Professional Documents
Culture Documents
.2010 ACOG Compendium
.2010 ACOG Compendium
of Selected Publications
THE AMERICAN COLLEGE OF
OBSTETRICIANS AND GYNECOLOGISTS
WOMENS HEALTH CARE PHYSICIANS
The Compendium of Selected Publications CD-ROM contains all Committee Opinions,
Practice Bulletins, Policy Statements, and Technology Assessments published by the
American College of Obstetricians and Gynecologists (the College) as of December 31,
2009. The information in these documents should not be viewed as establishing standards
or dictating rigid rules. The guidelines are general and intended to be adapted to many
different situations, taking into account the needs and resources particular to the locality, the
institution, or the type of practice. Variations and innovations that improve the quality of
patient care are to be encouraged rather than restricted. The purpose of these guidelines will
be well served if they provide a firm basis on which local norms may be built.
Copyright 2010 by the American College of Obstetricians and Gynecologists. All rights
reserved. No part of this publication may be reproduced, stored in a retrieval system,
posted on the Internet, or transmitted, in any form or by any means, electronic, mechanical,
photocopying, recording, or otherwise, without prior written permission from the publisher.
The American College of Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
ISBN: 978-1-934946-88-6
Publications can be ordered through the College Distribution Center by calling toll free
800-762-2264. To receive order forms via facsimile, call (732) 885-6364 and follow the audio
instructions. Publications also can be ordered from the College web site at www.acog.org.
The following resources from the College also contain College practice
guidelines and should be considered adjuncts to the documents in the
Compendium of Selected Publications CD-ROM.
Guidelines for Perinatal Care, Sixth Edition
Guidelines for Womens Health Care, Third Edition
Health Care for Adolescents
Special Issues in Womens Health
These documents are available online to members at www.acog.org
iii
FOREWORD xi
THE SCOPE OF PRACTICE OF OBSTETRICS AND GYNECOLOGY xii
CODE OF PROFESSIONAL ETHICS xiii
COMMITTEE OPINIONS
COMMITTEE ON ADOLESCENT HEALTH CARE
302 Guidelines for Adolescent Health Research 3
310 Endometriosis in Adolescents 7
314 Meningococcal Vaccination for Adolescents 14
344 Human Papillomavirus Vaccination
(Joint with the ACOG Working Group on Immunization) 17
349 Menstruation in Girls and Adolescents: Using the Menstrual Cycle as a Vital Sign
(Joint with the American Academy of Pediatrics) 24
350 Breast Concerns in the Adolescent 30
351 The Overweight Adolescent: Prevention, Treatment, and ObstetricGynecologic Implications 38
355 Vaginal Agenesis: Diagnosis, Management, and Routine Care 50
392 Intrauterine Device and Adolescents 55
415 Depot Medroxyprogesterone Acetate and Bone Effects
(Joint with Committee on Gynecologic Practice) 58
417 Addressing Health Risks of Noncoital Sexual Activities
(Joint with Committee on Gynecologic Practice) 62
*448 Menstrual Manipulation for Adolescents with Disabilities 65
*451 Von Willebrand Disease in Women
(Joint with Committee on Gynecologic Practice) 69
COMMITTEE ON CODING AND NOMENCLATURE
205 Tubal Ligation with Cesarean Delivery 77
249 Coding Responsibility 78
250 Inappropriate Reimbursement Practices by Third-Party Payers 79
COMMITTEE ON ETHICS
297 Nonmedical Use of Obstetric Ultrasonography 85
321 Maternal Decision Making, Ethics, and the Law 87
341 Ethical Ways for Physicians to Market a Practice 98
347 Using Preimplantation Embryos for Research 102
352 Innovative Practice: Ethical Guidelines 115
358 Professional Responsibilities in ObstetricGynecologic Education 122
Contents
*Published in 2009
SEARCH
COMPENDIUM OF SELECTED PUBLICATIONS iv
COMMITTEE ON ETHICS (continued)
359 Commercial Enterprises in Medical Practice 126
360 Sex Selection 129
362 Medical Futility 133
363 Patient Testing: Ethical Issues in Selection and Counseling 137
364 Patents, Medicine, and the Interests of Patients (Joint with Committee on Genetics) 140
365 Seeking and Giving Consultation 145
368 Adoption 150
369 Multifetal Pregnancy Reduction 154
370 Institutional Responsibility to Provide Legal Representation 159
371 Sterilization of Women, Including Those With Mental Disabilities 161
373 Sexual Misconduct 165
374 Expert Testimony 169
377 Research Involving Women 171
385 The Limits of Conscientious Refusal in Reproductive Medicine 177
389 Human Immunodeficiency Virus 183
390 Ethical Decision Making in Obstetrics and Gynecology 189
395 Surgery and Patient Choice 198
397 Surrogate Motherhood 203
401 Relationships With Industry 209
403 End-of-Life Decision Making 215
409 Direct-to-Consumer Marketing of Genetic Testing (Joint with Committee on Genetics) 222
410 Ethical Issues in Genetic Testing (Joint with Committee on Genetics) 224
422 At-Risk Drinking and Illicit Drug Use: Ethical Issues in Obstetric and Gynecologic Practice 232
*439 Informed Consent 244
COMMITTEE ON GENETICS
318 Screening for TaySachs Disease 255
324 Perinatal Risks Associated With Assisted Reproductive Technology
(Joint with Committees on Obstetric Practice and Gynecologic Practice) 257
325 Update on Carrier Screening for Cystic Fibrosis 261
338 Screening for Fragile X Syndrome 265
393 Newborn Screening 268
399 Umbilical Cord Blood Banking (Joint with Committee on Obstetric Practice) 272
*430 Preimplantation Genetic Screening for Aneuploidy 275
*432 Spinal Muscular Atrophy 277
*442 Preconception and Prenatal Carrier Screening for Genetic Diseases
in Individuals of Eastern European Jewish Descent 280
*446 Array Comparative Genomic Hybridization in Prenatal Diagnosis 284
*449 Maternal Phenylketonuria 287
1 Genetics and Molecular Diagnostic Testing 289
*Published in 2009
Technology Assessment
v
CONTENTS
COMMITTEE ON GYNECOLOGIC PRACTICE
240 Statement on Surgical Assistants (Joint with Committee on Obstetric Practice) 311
253 Nongynecologic Procedures 312
278 Avoiding Inappropriate Clinical Decisions Based
on False-Positive Human Chorionic Gonadotropin Test Results 313
280 The Role of the Generalist ObstetricianGynecologist in the Early
Detection of Ovarian Cancer (Joint with Society of Gynecologic Oncologists) 316
313 The Importance of Preconception Care in the Continuum of Womens Health Care 319
319 The Role of the ObstetricianGynecologist in the Assessment and Management of Obesity 321
322 Compounded Bioidentical Hormones 326
323 Elective Coincidental Appendectomy 328
332 Hepatitis B and Hepatitis C Virus Infections in ObstetricianGynecologists 330
334 Role of the ObstetricianGynecologist in the Screening and Diagnosis of Breast Masses 332
336 Tamoxifen and Uterine Cancer 334
337 Noncontraceptive Uses of the Levonorgestrel Intrauterine System 338
345 Vulvodynia (Joint with American Society for Colposcopy and Cervical Pathology) 342
372 The Role of Cystourethroscopy in the Generalist ObstetricianGynecologist Practice 346
375 Brand Versus Generic Oral Contraceptives 350
378 Vaginal Rejuvenation and Cosmetic Vaginal Procedures 352
384 Colonoscopy and Colorectal Cancer Screening and Prevention 354
387 Pharmaceutical Compounding 358
388 Supracervical Hysterectomy 360
396 Intraperitoneal Chemotherapy for Ovarian Cancer 363
405 Ovarian Tissue and Oocyte Cryopreservation 366
407 Low Bone Mass (Osteopenia) and Fracture Risk 368
408 Professional Liability and Gynecology-Only Practice
(Joint with Committees on Obstetric Practice and Professional Liability) 371
411 Routine Human Immunodeficiency Virus Screening 372
412 Aromatase Inhibitors in Gynecologic Practice 375
413 Age-Related Fertility Decline (Joint with American Society for Reproductive Medicine) 378
420 Hormone Therapy and Heart Disease 381
*434 Induced Abortion and Breast Cancer Risk 385
*440 The Role of Transvaginal Ultrasonography in the Evaluation of Postmenopasual Bleeding 387
*444 Choosing the Route of Hysterectomy for Benign Diseases 390
*450 Increasing Use of Contraceptive Implants and Intrauterine Devices to Reduce
Unintended Pregnancy (Joint with the Long Acting Reversible Contraception Working Group) 393
*452 Primary and Preventive Care: Periodic Assessments 398
4 Hysteroscopy 406
5 Sonohysterography 410
*6 Robot-Assisted Surgery 413
*Published in 2009
Technology Assessment
COMPENDIUM OF SELECTED PUBLICATIONS vi
COMMITTEE ON HEALTH CARE FOR UNDERSERVED WOMEN
307 Partner Consent for Participation in Womens Reproductive Health Research 419
312 Health Care for Homeless Women 422
316 Smoking Cessation During Pregnancy (Joint with Committee on Obstetric Practice) 428
317 Racial and Ethnic Disparities in Womens Health 434
343 Psychosocial Risk Factors: Perinatal Screening and Intervention 438
361 Breastfeeding: Maternal and Infant Aspects (Joint with Committee on Obstetric Practice) 447
391 Health Literacy 449
414 Human Immunodeficiency Virus and Acquired Immunodeficiency
Syndrome and Women of Color 452
416 The Uninsured 456
*423 Motivational Interviewing: A Tool for Behavior Change 460
*424 Abortion Access and Training 464
*425 Health Care for Undocumented Immigrants 468
*428 Legal Status: Health Impact for Lesbian Couples 472
*429 Health Disparities for Rural Women 476
*437 Community Involvement and Volunteerism 480
COMMITTEE ON INTERNATIONAL AFFAIRS
*427 Misoprostol for Postabortion Care 485
COMMITTEE ON OBSTETRIC PRACTICE
125 Placental Pathology 491
234 Scheduled Cesarean Delivery and the Prevention of Vertical Transmission of HIV Infection 492
260 Circumcision 495
267 Exercise During Pregnancy and the Postpartum Period 497
268 Management of Asymptomatic Pregnant or Lactating Women Exposed to Anthrax 500
275 Obstetric Management of Patients with Spinal Cord Injuries 503
276 Safety of Lovenox in Pregnancy 506
279 Prevention of Early-Onset Group B Streptococcal Disease in Newborns 508
281 Rubella Vaccination 516
284 Nonobstetric Surgery in Pregnancy 517
295 Pain Relief During Labor (Joint with American Society of Anesthesiologists) 518
299 Guidelines for Diagnostic Imaging During Pregnancy 519
305 Influenza Vaccination and Treatment During Pregnancy 524
315 Obesity in Pregnancy 526
326 Inappropriate Use of the Terms Fetal Distress and Birth Asphyxia 531
333 The Apgar Score (Joint with American Academy of Pediatrics) 533
339 Analgesia and Cesarean Delivery Rates 537
340 Mode of Term Singleton Breech Delivery 539
*Published in 2009
CONTENTS vii
COMMITTEE ON OBSTETRIC PRACTICE (continued)
342 Induction of Labor for Vaginal Birth After Cesarean Delivery 542
346 Amnioinfusion Does Not Prevent Meconium Aspiration Syndrome 545
348 Umbilical Cord Blood Gas and Acid-Base Analysis 548
376 Nalbuphine Hydrochloride Use for Intrapartum Analgesia 552
379 Management of Delivery of a Newborn With Meconium-Stained Amniotic Fluid 553
381 Subclinical Hypothyroidism in Pregnancy 554
382 Fetal Monitoring Prior to Scheduled Cesarean Delivery 556
394 Cesarean Delivery on Maternal Request 557
402 Antenatal Corticosteroid Therapy for Fetal Maturation 561
404 Late-Preterm Infants 564
418 Prenatal and Perinatal Human Immunodeficiency Virus Testing:
Expanded Recommendations 568
419 Use of Progesterone to Reduce Preterm Birth
(Joint with Society for Maternal Fetal Medicine) 572
421 Antibiotic Prophylaxis for Infective Endocarditis 575
*433 Optimal Goals for Anesthesia Care in Obstetrics
(Joint with American Society of Anesthesiologists) 577
*435 Postpartum Screening for Abnormal Glucose Tolerance in Women Who Had
Gestational Diabetes Mellitus 580
*438 Update on Immunization and Pregnancy: Tetanus, Diphtheria, and Pertussis Vaccination 583
*441 Oral Intake During Labor 586
*443 Air Travel During Pregnancy 587
*445 Antibiotics for Preterm Labor (Joint with Society for Maternal Fetal Medicine) 589
COMMITTEE ON PROFESSIONAL LIABILITY
380 Disclosure and Discussion of Adverse Events (Joint with Committee on Patient Safety and
Quality Improvement) 593
406 Coping With the Stress of Medical Professional Liability Litigation 595
COMMITTEE ON PATIENT SAFETY AND QUALITY IMPROVEMENT
320 Partnering With Patients to Improve Safety 599
327 Do Not Use Abbreviations 602
328 Patient Safety in the Surgical Environment 604
329 Tracking and Reminder Systems 609
331 Safe Use of Medication 612
353 Medical Emergency Preparedness 616
366 Disruptive Behavior 619
367 Communication Strategies for Patient Handoffs 621
398 Fatigue and Patient Safety 624
400 Technologic Advances to Reduce Medication-Related Errors 627
*447 Patient Safety in Obstetrics and Gynecology 631
*Published in 2009
COMPENDIUM OF SELECTED PUBLICATIONS viii
READING THE MEDICAL LITERATURE 637
PRACTICE BULLETINS
COMMITTEE ON PRACTICE BULLETINSOBSTETRICS
4 Prevention of Rh D Alloimmunization 647
6 Thrombocytopenia in Pregnancy 655
9 Antepartum Fetal Surveillance 666
12 Intrauterine Growth Restriction 677
13 External Cephalic Version 689
17 Operative Vaginal Delivery 696
19 Thromboembolism in Pregnancy 704
20 Perinatal Viral and Parasitic Infections 714
22 Fetal Macrosomia 727
24 Management of Recurrent Early Pregnancy Loss 738
29 Chronic Hypertension in Pregnancy 750
30 Gestational Diabetes 759
31 Assessment of Risk Factors for Preterm Birth 773
33 Diagnosis and Management of Preeclampsia and Eclampsia 781
36 Obstetric Analgesia and Anesthesia 790
37 Thyroid Disease in Pregnancy 805
38 Perinatal Care at the Threshold of Viability 815
40 Shoulder Dystocia 823
43 Management of Preterm Labor 829
44 Neural Tube Defects 838
48 Cervical Insufficiency 849
49 Dystocia and Augmentation of Labor 858
52 Nausea and Vomiting of Pregnancy 868
54 Vaginal Birth After Previous Cesarean Delivery 881
55 Management of Postterm Pregnancy 891
56 Multiple Gestation: Complicated Twin, Triplet, and High-Order Multifetal Pregnancy
(Joint with Society for MaternalFetal Medicine) 899
60 Pregestational Diabetes Mellitus 914
68 Antiphospholipid Syndrome 925
71 Episiotomy 934
75 Management of Alloimmunization During Pregnancy 940
76 Postpartum Hemorrhage 948
77 Screening for Fetal Chromosomal Abnormalities
(Joint with Committee on Genetics and the Society for MaternalFetal Medicine) 957
78 Hemoglobinopathies in Pregnancy 968
80 Premature Rupture of Membranes 977
*Published in 2009
CONTENTS ix
COMMITTEE ON PRACTICE BULLETINSOBSTETRICS (continued)
82 Management of Herpes in Pregnancy 990
86 Viral Hepatitis in Pregnancy 1000
88 Invasive Prenatal Testing for Aneuploidy (Joint with Committee on Genetics) 1015
90 Asthma in Pregnancy 1024
92 Use of Psychiatric Medications During Pregnancy and Lactation 1032
95 Anemia in Pregnancy 1052
97 Fetal Lung Maturity 1059
*100 Critical Care in Pregnancy 1069
*101 Ultrasonography in Pregnancy 1077
*102 Management of Stillbirth 1088
*105 Bariatric Surgery and Pregnancy 1102
*106 Intrapartum Fetal Heart Rate Monitoring: Nomenclature, Interpretation, and General
Management Principles 1111
*107 Induction of Labor 1122
251 Obstetric Aspects of Trauma Management 1134
COMMITTEE ON PRACTICE BULLETINSGYNECOLOGY
11 Medical Management of Endometriosis 1143
14 Management of Anovulatory Bleeding 1156
15 Premenstrual Syndrome 1164
28 Use of Botanicals for Management of Menopausal Symptoms 1173
34 Management of Infertility Caused by Ovulatory Dysfunction 1184
35 Diagnosis and Treatment of Cervical Carcinomas 1196
39 Selective Estrogen Receptor Modulators 1209
42 Breast Cancer Screening 1219
46 Benefits and Risks of Sterilization 1231
50 Osteoporosis 1243
51 Chronic Pelvic Pain 1257
53 Diagnosis and Treatment of Gestational Trophoblastic Disease
(Joint with Society of Gynecologic Oncologists) 1274
57 Gynecologic Herpes Simplex Virus Infections 1287
59 Intrauterine Device 1294
61 Human Papillomavirus 1304
63 Urinary Incontinence in Women 1318
65 Management of Endometrial Cancer
(Joint with Society of Gynecologic Oncologists) 1331
67 Medical Management of Abortion 1344
69 Emergency Contraception 1356
72 Vaginitis 1367
73 Use of Hormonal Contraception in Women With Coexisting Medical Conditions 1379
*Published in 2009
COMPENDIUM OF SELECTED PUBLICATIONS x
COMMITTEE ON PRACTICE BULLETINSGYNECOLOGY (continued)
81 Endometrial Ablation 1399
83 Management of Adnexal Masses 1415
84 Prevention of Deep Vein Thrombosis and Pulmonary Embolism 1429
85 Pelvic Organ Prolapse 1441
89 Elective and Risk-Reducing Salpingo-oophorectomy 1454
91 Treatment of Urinary Tract Infections in Nonpregnant Women 1465
93 Diagnosis and Management of Vulvar Skin Disorders 1475
94 Medical Management of Ectopic Pregnancy 1486
96 Alternatives to Hysterectomy in the Management of Leiomyomas 1493
99 Management of Abnormal Cervical Cytology and Histology 1507
*103 Hereditary Breast and Ovarian Cancer Syndrome (Joint with the Committee on Genetics
and the Society of Gynecologic Oncologists) 1533
*104 Antibiotic Prophylaxis for Gynecologic Procedures 1543
*108 Polycystic Ovary Syndrome 1553
*109 Cervical Cytology Screening 1567
POLICY STATEMENTS
AAFPACOG Joint Statement on Cooperative Practice and Hospital Privileges
(July 1980, Revised and Retitled, March 1998) 1581
Abortion Policy (January 1993, Reaffirmed July 2007) 1583
Access to Womens Health Care (July 1988, Reaffirmed July 2009) 1586
Certification and Procedural Credentialing (February 2008) 1587
Cervical Cancer Prevention in Low-Resource Settings (March 2004) 1589
Home Births in the United States (May 4, 2007) 1591
Joint Statement of ACOG/AAP on Human Immunodeficiency
Virus Screening (May 1999, Reaffirmed July 2006) 1592
Joint Statement of Practice Relationships Between ObstetricianGynecologists
and Certified Nurse-Midwives/Certified Midwives (October 2002) 1594
Midwifery Education and Certification (February 2006, Amended February 2007) 1595
The Role of Obstetrician-Gynecologists in Cosmetic Procedures (November 2008) 1596
Tobacco Marketing Aimed at Women and Adolescents
(July 1990, Amended July 2009) 1597
APPENDIX CONTENTS FROM OTHER COLLEGE RESOURCES
Guidelines for Perinatal Care, Sixth Edition 1601
Guidelines for Womens Health Care, Third Edition 1603
Health Care For Adolescents 1604
Special Issues in Womens Health 1604
Committee Opinions List of Titles 1605
Practice Bulletins List of Titles 1611
*Published in 2009
xi
Foreword
The Compendium of Selected Publications CD-ROM is a compilation of all Committee Opinions, Practice Bulletins,
Policy Statements, and Technology Assessments current as of December 31, 2009:
Committee Opinions: Brief focused documents that address clinical issues of an urgent or emergent
nature or nonclinical topics such as policy, economics, and social issues that relate to obstetrics and
gynecology. They are consensus statements that may or may not be based on scientific evidence.
Practice Bulletins: Evidence-based guidelines developed to indicate a preferred method of diagnosis
and management of a condition. The evidence is graded, and peer-reviewed research determines the
recommendations in the document.
Policy Statements: Position papers on key issues approved by the Executive Board.
Technology Assessments in Obstetrics and Gynecology: Documents that describe specific technolo-
gies and their application.
These series are developed by committees of experts and reviewed by leaders in the specialty and the College.
Each document is reviewed periodically and either reaffirmed, replaced, or withdrawn to ensure its continued
appropriateness to practice. The contribution of the many groups and individuals who participated in the process is
gratefully acknowledged.
Each section of the Compendium is devoted to a particular series, and includes those documents considered
current at the time of publication. A comprehensive table of contents has been added for ease of use with titles listed
numerically by committee. Those published within 2009 are indicated with an asterisk. Also provided are current
Committee Opinion and Practice Bulletin lists of titles, grouped by committee in order of publication.
As the practice of medicine evolves, so do College documents. As a part of the continuing process of review
and revision, many documents initially published as a separate installment of a series evolve to become a part of a
broader effort to educate and inform our Fellows. Books such Guidelines for Perinatal Care or Guidelines for Womens
Health Care carry equal weight as practice guidelines and should be considered adjuncts to the documents in the series.
For ease of reference, the contents of these volumes are included in the appendix.
The Compendium of Selected Publications CD-ROM and the companion 2010 Compendium of Selected
Publications, which includes only 20082009 series documents current as of December 31, 2009, can be purchased by
calling 800-762-2264 (Compendium CD-ROM only: $104, $59 [members]; 2010 Compendium and CD-ROM: $226,
$99 [members]).
Throughout the year, new documents will be published in the Colleges official journal, Obstetrics & Gynecology.
Single copies can be obtained from the Resource Center (202-863-2518), and the series are available for sale as
complete sets or subscriptions (call 800-762-2264 to order). These documents also are available to members on our web
site: www.acog.org. To verify the status of documents, contact the Resource Center or check our web site.
We are making every effort to provide health professionals with current, quality information on the practice of
obstetrics and gynecology. The Compendium of Selected Publications CD-ROM and the 2010 Compendium of Selected
Publications represent still other ways to disseminate material designed to promote womens health.
Ralph W. Hale, MD, Executive Vice President
COMPENDIUM OF SELECTED PUBLICATIONS xii
Obstetrics and gynecology is a discipline dedicated to the broad, integrated medical and surgical
care of womens health throughout their lifespan. The combined discipline of obstetrics and gyne-
cology requires extensive study and understanding of reproductive physiology, including the phys-
iologic, social, cultural, environmental and genetic factors that influence disease in women. This
study and understanding of the reproductive physiology of women gives obstetricians and gyne-
cologists a unique perspective in addressing gender-specific health care issues.
Preventive counseling and health education are essential and integral parts of the practice of obste-
tricians and gynecologists as they advance the individual and community-based health of women
of all ages.
Obstetricians and gynecologists may choose a scope of practice ranging from primary ambulatory
health care to concentration in a focused area of specialization.
Approved by the Executive Board
February 6, 2005
The Scope of Practice of
Obstetrics and Gynecology
xiii
of the American College of
Obstetricians and Gynecologists
Codeof Professional Ethics
Obstetrician-gynecologists, as members of the medical profession, have ethical responsibili-
ties not only to patients, but also to society, to other health professionals and to themselves.
The following ethical foundations for professional activities in the field of obstetrics and
gynecology are the supporting structures for the Code of Conduct. The Code implements
many of these foundations in the form of rules of ethical conduct. Certain documents of the
American College of Obstetricians and Gynecologists also provide additional ethical rules,
including documents addressing the following issues: seeking and giving consultation,
informed consent, sexual misconduct, patient testing, human immunodeficiency virus, rela-
tionships with industry, commercial enterprises in medical practice, and expert testimony.
Noncompliance with the Code, including the above-referenced documents, may affect an
individuals initial or continuing Fellowship in the American College of Obstetricians and
Gynecologists. These documents may be revised or replaced periodically, and Fellows should
be knowledgeable about current information.
Ethical Foundations
I. The patientphysician relationship: The welfare of the patient (beneficence) is central
to all considerations in the patientphysician relationship. Included in this relation-
ship is the obligation of physicians to respect the rights of patients, colleagues, and
other health professionals. The respect for the right of individual patients to make
their own choices about their health care (autonomy) is fundamental. The principle of
justice requires strict avoidance of discrimination on the basis of race, color, religion,
national origin, or any other basis that would constitute illegal discrimination (justice).
II. Physician conduct and practice: The obstetriciangynecologist must deal honestly
with patients and colleagues (veracity). This includes not misrepresenting himself or
herself through any form of communication in an untruthful, misleading, or decep-
tive manner. Furthermore, maintenance of medical competence through study,
application, and enhancement of medical knowledge and skills is an obligation of
practicing physicians. Any behavior that diminishes a physicians capability to prac-
tice, such as substance abuse, must be immediately addressed and rehabilitative
services instituted. The physician should modify his or her practice until the dimin-
ished capacity has been restored to an acceptable standard to avoid harm to patients
(nonmaleficence). All physicians are obligated to respond to evidence of questionable
conduct or unethical behavior by other physicians through appropriate procedures
established by the relevant organization.
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
COMPENDIUM OF SELECTED PUBLICATIONS xiv
III. Avoiding conflicts of interest: Potential conflicts of interest are inherent in the practice of medicine.
Physicians are expected to recognize such situations and deal with them through public disclosure.
Conflicts of interest should be resolved in accordance with the best interest of the patient, respecting a
womans autonomy to make health care decisions. The physician should be an advocate for the patient
through public disclosure of conflicts of interest raised by health payer policies or hospital policies.
IV. Professional relations: The obstetriciangynecologist should respect and cooperate with other physicians,
nurses, and health care professionals.
V. Societal responsibilities: The obstetriciangynecologist has a continuing responsibility to society as a
whole and should support and participate in activities that enhance the community. As a member of soci-
ety, the obstetriciangynecologist should respect the laws of that society. As professionals and members
of medical societies, physicians are required to uphold the dignity and honor of the profession.
Code of Conduct
I. PatientPhysician Relationship
1. The patientphysician relationship is the central focus of all ethical concerns, and the welfare of the
patient must form the basis of all medical judgments.
2. The obstetriciangynecologist should serve as the patients advocate and exercise all reasonable
means to ensure that the most appropriate care is provided to the patient.
3. The patientphysician relationship has an ethical basis and is built on confidentiality, trust, and hon-
esty. If no patientphysician relationship exists, a physician may refuse to provide care, except in
emergencies. Once the patientphysician relationship exists, the obstetriciangynecologist must
adhere to all applicable legal or contractual constraints in dissolving the patientphysician relation-
ship.
4. Sexual misconduct on the part of the obstetriciangynecologist is an abuse of professional power and
a violation of patient trust. Sexual contact or a romantic relationship between a physician and a cur-
rent patient is always unethical.
5. The obstetriciangynecologist has an obligation to obtain the informed consent of each patient. In
obtaining informed consent for any course of medical or surgical treatment, the obstetriciangyne-
cologist must present to the patient, or to the person legally responsible for the patient, pertinent
medical facts and recommendations consistent with good medical practice. Such information should
be presented in reasonably understandable terms and include alternative modes of treatment and the
objectives, risks, benefits, possible complications, and anticipated results of such treatment.
6. It is unethical to prescribe, provide, or seek compensation for therapies that are of no benefit to the
patient.
7. The obstetriciangynecologist must respect the rights and privacy of patients, colleagues, and others
and safeguard patient information and confidences within the limits of the law. If during the process
of providing information for consent it is known that results of a particular test or other information
must be given to governmental authorities or other third parties, that must be explained to the
patient.
8. The obstetriciangynecologist must not discriminate against patients based on race, color, national
origin, religion, or any other basis that would constitute illegal discrimination.
II. Physician Conduct and Practice
1. The obstetriciangynecologist should recognize the boundaries of his or her particular competencies
and expertise and must provide only those services and use only those techniques for which he or she
is qualified by education, training, and experience.
CODE OF PROFESSIONAL ETHICS XV xv
2. The obstetriciangynecologist should participate in continuing medical education activities to main-
tain current scientific and professional knowledge relevant to the medical services he or she renders.
The obstetriciangynecologist should provide medical care involving new therapies or techniques only
after undertaking appropriate training and study.
3. In emerging areas of medical treatment where recognized medical guidelines do not exist, the obste-
triciangynecologist should exercise careful judgment and take appropriate precautions to protect
patient welfare.
4. The obstetriciangynecologist must not publicize or represent himself or herself in any untruthful,
misleading, or deceptive manner to patients, colleagues, other health care professionals, or the public.
5. The obstetriciangynecologist who has reason to believe that he or she is infected with the human
immunodeficiency virus (HIV) or other serious infectious agents that might be communicated to
patients should voluntarily be tested for the protection of his or her patients. In making decisions
about patient-care activities, a physician infected with such an agent should adhere to the fundamen-
tal professional obligation to avoid harm to patients.
6. The obstetriciangynecologist should not practice medicine while impaired by alcohol, drugs, or phys-
ical or mental disability. The obstetriciangynecologist who experiences substance abuse problems or
who is physically or emotionally impaired should seek appropriate assistance to address these prob-
lems and must limit his or her practice until the impairment no longer affects the quality of patient
care.
III. Conflicts of Interest
1. Potential conflicts of interest are inherent in the practice of medicine. Conflicts of interest should be
resolved in accordance with the best interest of the patient, respecting a womans autonomy to make
health care decisions. If there is an actual or potential conflict of interest that could be reasonably con-
strued to affect significantly the patients care, the physician must disclose the conflict to the patient.
The physician should seek consultation with colleagues or an institutional ethics committee to deter-
mine whether there is an actual or potential conflict of interest and how to address it.
2. Commercial promotions of medical products and services may generate bias unrelated to product
merit, creating or appearing to create inappropriate undue influence. The obstetriciangynecologist
should be aware of this potential conflict of interest and offer medical advice that is as accurate, bal-
anced, complete, and devoid of bias as possible.
3. The obstetriciangynecologist should prescribe drugs, devices, and other treatments solely on the
basis of medical considerations and patient needs, regardless of any direct or indirect interests in or
benefit from a pharmaceutical firm or other supplier.
4. When the obstetriciangynecologist receives anything of substantial value, including royalties, from
companies in the health care industry, such as a manufacturer of pharmaceuticals and medical
devices, this fact should be disclosed to patients and colleagues when material.
5. Financial and administrative constraints may create disincentives to treatment otherwise recom-
mended by the obstetriciangynecologist. Any pertinent constraints should be disclosed to the
patient.
IV. Professional Relations
1. The obstetriciangynecologists relationships with other physicians, nurses, and health care profes-
sionals should reflect fairness, honesty, and integrity, sharing a mutual respect and concern for the
patient.
2. The obstetriciangynecologist should consult, refer, or cooperate with other physicians, health care
professionals, and institutions to the extent necessary to serve the best interests of their patients.
COMPENDIUM OF SELECTED PUBLICATIONS xvi
Copyright January 2008, The American College of Obstetricians and Gynecologists, 409 12th Street,
SW, PO Box 96920, Washington, DC 20090-6920. This document provides rules for ethical conduct for
obstetricians and gynecologists.
V. Societal Responsibilities
1. The obstetriciangynecologist should support and participate in those health care programs, prac-
tices, and activities that contribute positively, in a meaningful and cost-effective way, to the welfare of
individual patients, the health care system, or the public good.
2. The obstetriciangynecologist should respect all laws, uphold the dignity and honor of the profes-
sion, and accept the professions self-imposed discipline. The professional competence and conduct
of obstetriciangynecologists are best examined by professional associations, hospital peer-review
committees, and state medical and licensing boards. These groups deserve the full participation and
cooperation of the obstetriciangynecologist.
3. The obstetriciangynecologist should strive to address through the appropriate procedures the status of
those physicians who demonstrate questionable competence, impairment, or unethical or illegal behav-
ior. In addition, the obstetriciangynecologist should cooperate with appropriate authorities to prevent
the continuation of such behavior.
4. The obstetriciangynecologist must not knowingly offer testimony that is false. The
obstetriciangynecologist must testify only on matters about which he or she has knowledge and
experience. The obstetriciangynecologist must not knowingly misrepresent his or her credentials.
5. The obstetriciangynecologist testifying as an expert witness must have knowledge and experience
about the range of the standard of care and the available scientific evidence for the condition in ques-
tion during the relevant time and must respond accurately to questions about the range of the stan-
dard of care and the available scientific evidence.
6. Before offering testimony, the obstetriciangynecologist must thoroughly review the medical facts of
the case and all available relevant information.
7. The obstetriciangynecologist serving as an expert witness must accept neither disproportionate
compensation nor compensation that is contingent upon the outcome of the litigation.
COMMITTEE OPINIONS
COMMITTEE ON ADOLESCENT HEALTH CARE
COMMITTEE OPINIONS
COMMITTEE ON ADOLESCENT HEALTH CARE
3
Committee on
Adolescent Health Care
ACOG
Number 302, October 2004
Committee
Opinion
The Committee wishes to thank
Abigail English, JD; S. Paige
Hertweck, MD; Susan Kornetsky,
MPH; Audrey Rogers, PhD,
MPH; and John Santelli, MD,
MPH for their assistance in the
development of this opinion. This
document reflects emerging clini-
cal and scientific advances as of
the date issued and is subject to
change. The information should
not be construed as dictating an
exclusive course of treatment or
procedure to be followed.
Copyright October 2004
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of
this publication may be repro-
duced, stored in a retrieval sys-
tem, or transmitted, in any form
or by any means, electronic,
mechanical, photocopying,
recording, or otherwise, without
prior written permission from
the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Guidelines for adolescent health
research. ACOG Committee Opinion
No. 302. American College of
Obstetricians and Gynecologists.
Obstet Gynecol 2004;104:899902.
Guidelines for Adolescent Health
Research
ABSTRACT: The risks of exposure to violence, human immunodeficiency
virus, and other sexually transmitted diseases; alcohol, tobacco, and pre-
scribed and illicit drug use; and unintended pregnancy, among others, threat-
en the health and well-being of adolescents in the United States. Research is
needed in these and other areas to improve adolescent health care and to aid
in health policy decisions. Adolescents often are prevented from participating
in such research because of inadequate understanding of their legal status
and the ethical considerations regarding their participation in research.
There is confusion about what constitutes appropriate levels of protection for
studies involving adolescents as research subjects and uncertainty about the
need for parental permission. This document is designed to clarify the
informed consent and parental permission issues as they pertain to adolescent
health research.
Background
A basic criterion for ethical research is the protection of the rights and wel-
fare of people participating in research. The U.S. federal government has pro-
mulgated regulations that govern research involving human subjects when the
research is supported, conducted, or otherwise subject to regulation by the
federal government (1). These federal regulations on protection of human
subjects in research, known as the Code of Federal Regulations: Title 45-
Public Welfare; Part 46: Protection of Human Subjects (45 CFR Part 46), pro-
vide for a nationwide system of local Institutional Review Boards (IRBs).
These IRBs must review and approve all federally funded research involving
human subjects and are regulated by the Office for Human Research
Protections in the Department of Health and Human Services. Most universi-
ties and research institutions apply these regulations to privately funded
research as well. These regulations serve as guidelines for IRB review and
approval. They require that risks to research participants are minimized and
that they are reasonable relative to the anticipated benefits and the importance
of the knowledge that may be expected to result from the research. The reg-
ulations also require that the selection of research participants is equitable and
that informed consent is provided from each prospective research participant
COMPENDIUM OF SELECTED PUBLICATIONS 4
or the participants legally authorized representative.
Informed consent is the ability to understand the
risks and benefits of ones participation in a research
activity and to authorize ones participation in this
activity freely (2). General requirements for in-
formed consent are described in 45 CFR Part 46,
Section 116 (1). Finally, the regulations require that
the research plan makes adequate provisions for
ensuring the safety of research participants and that
adequate provisions are made to protect the privacy
of research participants and to maintain the confiden-
tiality of data. Subpart D of 45 CFR Part 46 contains
special protections for children who participate as
subjects in research.
Research involving adolescents, especially
regarding behaviors related to sexuality, often raises
questions about how to obtain adequate informed
consent and protection of the research participants
confidential receipt of health care services. The
Society for Adolescent Medicine provided early
leadership to address these concerns. In 1995, they
led the development of consensus guidelines to pro-
mote the ethical conduct of health research involv-
ing adolescents as research participants (3). The
society recently issued a revised position statement
to support the guidelines (4); the Society for
Adolescent medicine also established a code of
research ethics to encourage, enhance, and promote
ethical standards for the conduct of research in ado-
lescent health (5).
When considering the legal complexities of ado-
lescent health research, it is important to recognize
that the age of majority in almost every state is 18
years, and all states recognize the concept of eman-
cipated minors, who generally are allowed to consent
for their own health care. In addition, every state has
enacted some minor consent laws that allow minors
to consent for their own health care, whether or not
they are legally emancipated. Such laws may be
based on the status of the minor or the services they
are seeking. Minors who may consent for their own
health care based on their status include those who
are married, are members of the armed forces, live
apart from their parents, and are parents of a child. In
addition, all states allow adolescents who are minors
to consent for some categories of health care such as
sexually transmitted disease (STD) services (all
states), drug and alcohol care (almost all states), con-
traceptive services and pregnancy related care (a
majority of states), outpatient mental health counsel-
ing (about one half of states), or sexual assault care
(a few states). Some states specify the age at which a
minor can begin to consent (6). Researchers in ado-
lescent health should be familiar with current state
statutes regarding age of majority and emancipation,
as well as with minor consent statutes. An up-to-date
listing of these statutes can be found online at
http://www.guttmacher.org/pubs/spib.html.
Regulations
In the federal regulations governing research, chil-
dren are defined in 45 CFR 46 Section 102(a) as
persons who have not attained the legal age for
consent to treatments or procedures involved in the
research, under the applicable law of the jurisdiction
in which the research will be conducted(1). This
definition refers to laws, primarily state laws related
to consent for treatment of minors, age of majority,
and emancipation status.
Federal regulations governing human subject
research require parental permission and child
assent for subjects who meet the regulatory defini-
tion of children, ie, those who are younger than the
state-mandated age at which people may give legal-
ly effective informed consent for treatments or pro-
cedures involved in the research. Assent means a
child has given affirmative agreement to participate
in research. Mere failure to object should not, absent
affirmative agreement, be construed as assent.
Assent is required when, in the judgment of the IRB,
the children are capable of providing it (1).The fed-
eral regulations deliberately use the terms permis-
sion and assent to differentiate this process from
the usual informed consent process. An individual
can provide consent only for himself or herself.
Therefore, parents give only permission for their
child to be involved in research, not consent. Assent
recognizes the importance of the emerging capacity
of children to give informed consent for themselves,
as well as the ethical importance of obtaining their
agreement to participate even if they are not legally
authorized to give informed consent.
In 1977, the National Commission for the
Protection of Human Subjects of Biomedical and
Behavioral Research recommended that individual
IRBs be allowed to determine that parental permis-
sion is not appropriate in certain research studies,
including research involving assessment for or care
related to contraception and drug abuse (7).
According to the federal regulations (1), informed
consent may be waived under 45 CFR Part 46
Section 116(d) and parental permission may be
waived under 45 CFR Part 46 Section 408(c).
5 COMMITTEE OPINIONS
Four criteria set forth by 45 CFR Part 46 116(d)
allow an IRB to waive the requirement to obtain the
informed consent for adult research subjects or per-
mission of a parent or guardian for research subjects
who are children if: 1) the research involves no more
than minimal risk (which means that the probabil-
ity and magnitude of harm or discomfort anticipated
in the research are not greater in and of themselves
than those ordinarily encountered in daily life or
during the performance of routine physical or psy-
chologic examinations or tests [1]), 2) the waiver
will not adversely affect the rights and welfare of the
subjects, 3) the research could not practically be car-
ried out without a waiver, and 4) whenever appropri-
ate, the subjects will be provided with additional
pertinent information after participation (1). This
section is commonly used when waiving informed
consent for research involving existing data such as
medical records.
In addition, 45 CFR Part 46 Section 408(c)
specifically allows for a waiver of parental permis-
sion under Subpart D, which addresses research with
children. Section 408(c) of 45 CFR Part 46 states:
if an IRB determines that a research protocol is
designed for conditions or a subject population for
which parental permission is not a reasonable
requirement to protect subjects (eg, neglected or
abused children), it may waive consent requirements
provided an appropriate mechanism for protecting
the children who will participate as research subjects
is substituted and provided the waiver is not incon-
sistent with federal, state, or local law. The choice
of an appropriate mechanism would depend on the
nature and purpose of the activities described in the
protocol, the risk and anticipated benefit to the
research subjects, and their age, maturity, status, and
condition (1). In discussing the waiver of parental
permission, the National Commission cited as exam-
ples of when the requirement might not be a reason-
able one: [r]esearch designed to identify factors
related to the incidence or treatment of certain con-
ditions in adolescents for which, in certain jurisdic-
tions, they legally may receive treatment without
parental consent; [and] research in which the sub-
jects are mature minors and the procedures
involved entail essentially no more than minimal
risk that such individuals might reasonably assume
on their own (7).
Based on these criteria, either 45 CFR Part 46
Section 408(c) or 45 CFR Part 46 Section 116(d)
may be used to waive parental permission in a vari-
ety of studies, including, for example, surveys of
adolescents. It is important to note that if these sur-
veys are conducted in a school setting, federal edu-
cational law governing certain research conducted in
schools may apply. Health researchers working in
schools are, therefore, advised to become knowl-
edgeable about these laws.
Section 408(c) of 45 CFR Part 46 also may be
used to waive parental permission for research areas
including STDs, birth control usage, high-risk
behaviors, HIV prevention, and situations in which
obtaining parental consent may be dangerous to the
child (abuse situations). Finally, in certain research
studies, adolescent minors would not be considered
children and parental permission would not be
required. Such research includes certain clinical
studies involving pregnancy, family planning, and
treatment of STDs where the adolescent minor can
legally consent to such services. Again, familiarity
with current state statutes on the rights of minors to
consent to health care services is essential.
Researchers conducting and IRBs reviewing
research involving adolescents should be knowl-
edgeable of the federal regulations and the ethical
principles that underlie these regulations. They
should understand when parental permission is
required and when it may be waived. Personal
beliefs and attitudes should not enter into this deci-
sion. The Society for Adolescent Medicines
Guidelines for Adolescent Health Research (4) pro-
vide a comprehensive approach to understanding
these issues. Parental permission should not be a
barrier to the inclusion of adolescents in studies that
meet federal regulations and are designed to
improve their health.
Conclusions
1. Researchers developing study protocols and
materials for submission for IRB review and
approval and the IRBs themselves should be
familiar with, and adhere to, current federal reg-
ulations, 45 CFR Part 46 (1), and federal and
state laws that affect research (including laws
regarding age of majority and emancipation,
minor consent statutes, and federal educational
law governing certain research conducted in
schools).
2. Investigators will communicate better with IRB
panels regarding the involvement of adolescent
participants in research if they understand the
purpose of human subject protection regulations
COMPENDIUM OF SELECTED PUBLICATIONS 6
with respect to minors and review the guidelines
provided by the Society for Adolescent
Medicine (35).
3. Under the following circumstances it is reason-
able to waive parental permission when adoles-
cents are involved in studies: a) the waiver
would not adversely affect the rights and wel-
fare of the adolescent, b) the study poses no
more than a minimal risk to adolescents, c) the
study could not be practically carried out with-
out a waiver, and d) requiring permission may
not be reasonable to protect subjects. Parental
permission is not a requirement for research
involving the provision of health care for which
adolescents do not legally need parental con-
sent. It is important to review 45 CFR Part 46
for the necessary details.
References
1. Protection of human subjects. 45 C.F.R 46 (2003). Avail-
able at http://www.access.gpo.gov/nara/cfr/cfr-tablesearch.
html#page1. Retrieved July 8, 2004.
2. American College of Obstetricians and Gynecologists.
Ethics in obstetrics and gynecology. 2nd ed. ACOG:
Washington, DC; 2004.
3. Guidelines for adolescent health research. 1995. Society
for Adolescent Medicine. J Adolesc Health 2003;33:
4105.
4. Santelli JS, Smith Rogers A, Rosenfeld WD, DuRant RH,
Dubler N, Morreale M, et al. Guidelines for adolescent
health research: A position paper of the Society for
Adolescent Medicine. J Adolesc Health 2003;33:
396409.
5. Code of Research Ethics: position paper of the Society for
Adolescent Medicine. J Adolesc Health 1999;24:27782;
discussion 283.
6. English A, Kenney KE. State minor consent laws: a sum-
mary. 2nd Ed. Chapel Hill (NC): Center for Adolescent
Health & the Law; 2003.
7. The National Commission for the Protection of Human
Subjects of Biomedical and Behavioral Research.
Research involving children: report and recommenda-
tions. Bethesda (MD): U.S. Department of Health Educa-
tion and Welfare; 1977.
7 COMMITTEE OPINIONS
ACOG Committee on
Adolescent Health Care
ACOG
Number 310, April 2005
Committee
Opinion
This document reflects emerging
clinical and scientific advances as
of the date issued and is subject
to change. The information
should not be construed as dictat-
ing an exclusive course of treat-
ment or procedure to be followed.
The Committee wishes to thank
Marc R. Laufer, MD; Joseph
Sanfilippo, MD; and Jonathon
Solnik, MD; for their assistance
in the development of this docu-
ment.
Copyright April 2005
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of
this publication may be repro-
duced, stored in a retrieval sys-
tem, or transmitted, in any form
or by any means, electronic,
mechanical, photocopying,
recording, or otherwise, without
prior written permission from
the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Endometriosis in adolescents. ACOG
Committee Opinion No. 310.
American College of Obstetricians
and Gynecologists. Obstet Gynecol
2005;105:9217.
Endometriosis in Adolescents
ABSTRACT: Historically thought of as a disease that affects adult women,
endometriosis increasingly is being diagnosed in the adolescent population.
This disorder, which was originally described more than a century ago, still
represents a vague and perplexing entity that frequently results in chronic
pelvic pain, adhesive disease, and infertility. The purpose of this Committee
Opinion is to highlight the differences in adolescent and adult types of
endometriosis. Early diagnosis and treatment during adolescence may decrease
disease progression and prevent subsequent infertility.
Incidence
It has been difficult to establish accurate prevalence rates of endometriosis in
adult and adolescent women. Documented rates in adolescent patients under-
going laparoscopy for chronic pelvic pain range from 19% to 73%. Goldstein
et al (1) reported a 47% prevalence of endometriosis found at laparoscopy in
a prospective study of adolescent females with pelvic pain. Other studies have
shown that 2538% of adolescents with chronic pelvic pain have endometrio-
sis (2, 3). In addition, it has been shown that 5070% of adolescents with
pelvic pain not responding to combination hormone therapy (such as oral
contraceptive pills [OCPs]) and nonsteroidal antiinflammatory drugs
(NSAIDs) have endometriosis at the time of laparoscopy (4, 5).
Endometriosis also has been identified in premenarcheal girls who have
started puberty and have some breast development (6, 7). The occurrence of
endometriosis before menarche contributes to the argument that one etiology
for endometriosis lies in the theory of embryonic mllerian rests or coe-
lomic metaplasia as opposed to retrograde menses. Based on the occurrence
of early endometriosis, some authors have argued that thelarche be recog-
nized as a developmental benchmark, after which endometriosis is included
in the differential diagnosis of chronic pelvic pain (6).
It is common for adult women who have endometriosis to bring in their
adolescent daughters for evaluation and early diagnosis. Data from the
Endometriosis Association indicate that 66% of adult women reported the
onset of pelvic symptoms before age 20 years. Forty-seven percent of these
women reported they had to see a doctor five times or more before receiving
the diagnosis of endometriosis or referral. As the age of the onset of symp-
COMPENDIUM OF SELECTED PUBLICATIONS 8
toms decreases, the number of doctors having to be
seen to reach a diagnosis increases. Specifically, an
average of 4.2 doctors were seen for patients whose
symptoms began before age 15 years compared with
an average of 2.64 doctors for patients whose symp-
toms began between the ages of 30 years and 34
years. There are, on average, 9.28 years from the
onset of symptoms to the diagnosis (8). Endome-
triosis is believed to be a progressive disease be-
cause the prevalence and severity of the stage of the
disease significantly increase with age (9, 10). With
early diagnosis and treatment, it is hoped that dis-
ease progression and infertility can be limited, but
this remains to be proved with prospective research.
Presentation and Characteristics
The typical presentation of an adolescent with
endometriosis may be different from that of an adult.
One significant difference is that adolescents pri-
marily seek medical attention because of pain rather
than a concern for infertility. The most common
symptom noted among published reviews is
acquired or progressive dysmenorrhea, which was
encountered in 6494% of patients (4, 11). Other
common symptoms included acyclic pain (3691%),
dyspareunia (1425%), and gastrointestinal com-
plaints (246%) (11). Adolescents found to have
endometriosis most commonly present with both
cyclic and acyclic pain (62.6%), as opposed to
acyclic pain alone (28.1%), or cyclic pain alone
(9.4%) (11).
In young women, pelvic pain associated with
endometriosis often interferes with school atten-
dance as well as physical and social activities.
Prompt diagnosis and adequate therapy, therefore,
may return normal psychosocial development and
self-esteem, improve scholastic performance, and
lead to a return to normal daily activities.
Diagnosis
History and Physical Examination
A thorough review of history and physical examina-
tion are necessary to assess a variety of differential
diagnoses of pelvic pain such as appendicitis, pelvic
inflammatory disease, mllerian anomalies or out-
flow obstruction, bowel disease, hernias, musculo
skeletal disorders, and psychosocial complaints.
Pelvic examination may be difficult, especially in
patients who have not had vaginal intercourse.
When evaluating an adolescent for suspected
endometriosis or dysmenorrhea, the clinician should
aim to rule out a pelvic mass or a congenital anom-
aly of the reproductive tract. A bimanual examina-
tion may not be necessary to evaluate pelvic pain,
especially in adolescents who are virgins. If a bi-
manual examination cannot be performed or is
declined, a rectalabdominal examination in the dor-
sal lithotomy position may be helpful to determine if
a pelvic mass is present, and a cotton-tipped swab
can be inserted into the vagina to evaluate for the
presence of a transverse vaginal septum, vaginal
agenesis, or agenesis of the lower vagina. If a biman-
ual examination is performed, the clinician should
check for the existence of both diffuse and focal
pelvic tenderness, and evaluate the pelvis for a dis-
placed uterus or an adnexal mass. An ultrasound
examination may be helpful in evaluating the pelvis
of a young adolescent who declines a bimanual or
rectalabdominal examination.
Imaging Studies and Serum Markers
Ultrasonography and magnetic resonance imaging
are helpful in evaluating anatomical structures, but
are not specific for diagnosing endometriosis. An
adolescent will rarely have a pelvic mass from an
endometrioma or uterosacral nodularity. CA 125,
although very sensitive, is not specific and, thus, is
not helpful in the diagnosis of adolescent endo-
metriosis. No data exist regarding the use of CA 125
to monitor the clinical progression or regression of
disease in adolescents with endometriosis.
Empiric Therapy
If an adolescent younger than 18 years has persistent
pain while taking combination hormone therapy and
NSAIDs, endometriosis should be suspected and she
should be offered a laparoscopic evaluation (discus-
sion follows in section on Surgical Diagnosis). If,
however, she is older than 18 years and had a nega-
tive assessment for an ovarian mass or tumor, she
can be offered an empiric trial of gonadotropin-
releasing hormone (GnRH) agonist therapy (12, 13).
If the pain subsides with the use of GnRH agonist,
then a diagnosis of endometriosis can be made. An
empiric trial of GnRH agonist is not routinely
offered to patients younger than 18 years because
the effects of these medications on bone formation
and long-term bone density have not been ade-
quately studied. For patients younger than 18 years
or who decline empiric therapy, diagnostic and ther-
9 COMMITTEE OPINIONS
apeutic laparoscopy can be initiated. An algorithm
for therapy is provided in Figure 1 (14).
Surgical Diagnosis
After a comprehensive preoperative evaluation and
trial of combination hormone therapy and NSAIDs
to treat dysmenorrhea, laparoscopy should be rec-
ommended for diagnosing and treating presumed
endometriosis in an adolescent. Laparoscopy can be
safely performed in adolescents. At the time of sur-
gical diagnosis, most adolescents have Stage I dis-
ease as classified by the American Society for
Reproductive Medicine classification system (15).
Goldstein et al commented that almost 60% of the
Fig. 1. Protocol for evaluation and treatment of adolescent pelvic pain and endometriosis. (Modified with permission
from Bandera CA, Brown LR, Laufer MR. Adolescents and endometriosis. Clin Consult Obstet Gynecol 1995;7:206.)
History
Physical examination
Consider radiologic imaging
Pain diary
Cyclic CHT and NSAIDs
Empiric GnRH agonist (if older than 18 years)
If improveddiagnosis is endometriosis
If persistent pain
Laparoscopy
Diagnosis of endometriosis by visualization or biopsy
Surgical treatment (ablation/resection/laser)
of endometriosis
Endometriosis identified visually or by pathology No endometriosisvisually and histologically negative
Gastrointestinal or urologic evaluation
Pain management service
<16 years
No pain Continued pain
Continuous CHT
Symptoms persist
GnRH agonist
( add-back)*
OR
Continuous CHT
>16 years
Continuous CHT
Continue CHT Laparoscopy with resection of endometriosis
and/or
Long-term GnRH agonist with add-back
and
Pain management service
Complementary or alternative therapies
Abbreviations: NSAIDs, nonsteroidal antiinflammatory drugs; CHT, combination hormone therapy (oral contraceptive pills, estrogen/progestin
patch, estrogen/progestin vaginal ring, norethindrone acetate, medroxyprogesterone acetate); GnRH, gonadotropin-releasing hormone.
*Add-back indicates use of estrogen and progestin or norethindrone acetate alone.
COMPENDIUM OF SELECTED PUBLICATIONS 10
patients in their cohort had Stage I disease (1),
whereas 80% of the cases reported by other
researchers had minimal to mild disease (4).
Gynecologic surgeons who perform laparoscopy in
adolescents with pelvic pain should be familiar with
the typical lesions of endometriosis in adolescents,
which tend to be red, clear, or white (15) as opposed
to the powder-burn lesions seen commonly in adults
who have endometriosis. The use of a liquid medium
in the pelvis may facilitate the identification of clear
lesions, which are very common in adolescents (11).
Mllerian Anomalies and Endometriosis
The development of endometriosis in adolescent
patients has been associated with mllerian anom-
alies with outflow tract obstruction. The published
incidence of anomalies of the reproductive system
and associated endometriosis has been reported to
be as high as 40%, but most studies quote a rate of
56%. The clinical outcome in patients with outflow
tract obstructions has been reported to differ from
those without such obstruction because regression of
disease usually has been observed once surgical cor-
rection of the anomaly has been accomplished (16).
Treatment
The premise for treating the symptomatic adolescent
is based on the concept that endometriosis has been
shown to be a progressive disease without a known
cure. A physician treating an adolescent with endo-
metriosis should adopt a multidimensional approach
and consider the use of the following components:
surgery, hormonal manipulation, pain medications,
mental health support, complementary and alterna-
tive therapies, and education.
Patients younger than 18 years with persistent
pelvic pain while taking combination hormone ther-
apy should routinely be offered a laparoscopic pro-
cedure for diagnosis and surgical management of
endometriosis. The gynecologic surgeon must be
familiar with the appearance of endometriosis in
adolescents and should remove or destroy all visi-
ble lesions of endometriosis. Only procedures that
preserve fertility options should be applied; oophor-
ectomy or hysterectomy should not be offered to
adolescents.
Long-term follow-up studies of treatments for
adolescent endometriosis have not been performed.
Current treatments for adolescents have been extrap-
olated and adapted from the literature of adult cases
of endometriosis. The goal of therapy for adolescent
endometriosis should be suppression of pain, sup-
pression of disease progression, and preservation of
fertility. Consequently, after surgery, all adolescents
who have endometriosis should be treated with med-
ical therapy until they have completed child bearing
to suppress pain, progression of disease, and result-
ing potential infertility.
First-line treatment modalities should involve
the use of NSAIDs and hormone therapy. Because
red lesions have been shown to be active producers
of prostaglandins, and adolescents with endometrio-
sis typically report severe dysmenorrhea, NSAIDs
may be used in conjunction with hormonal men-
strual suppressive therapy to provide sufficient
relief. Most pharmacologic agents bring about relief
by inducing an anovulatory or a hypoestrogenic
state or both. Continuous combination hormone
therapy (OCPs, combination hormonal contracep-
tive patch, or vaginal ring) for menstrual suppression
can be used to create a pseudopregnancy state,
which was described more than 40 years ago (17).
This method routinely has been promoted for ado-
lescents who have endometriosis. Although this
method may provide effective relief, the Cochrane
Database Review 2003 provided data suggesting
that further studies are needed to prove long-term
benefits (18). Most clinicians advocate continuous
use of combination hormone therapy to induce
amenorrhea, but this modality can result in signifi-
cant breakthrough bleeding. One randomized con-
trolled trial compared a 28-day regimen with contin-
uous combination oral contraceptives and found no
increase in spotting days after 9 months of therapy,
with fewer total bleeding days in the group taking
continuous combination oral contraceptives (19).
Thus, continuous use of combination hormone ther-
apy is believed to be both safe and effective for ado-
lescents with endometriosis-related pain and, thus, is
the first-line hormone therapy for adolescents
younger than 16 years with endometriosis. Gonado-
tropin-releasing hormone agonists are not offered as
first-line therapy for adolescents in this age range.
Progestin-only protocols have been used for the
treatment of adult endometriosis with mixed results.
In a recent critical review, progestins were shown to
be as effective as danazol or GnRH agonists (20).
Common side effects include irregular bleeding and
weight gain. Some studies suggest that these side
effects are well tolerated (20), however in a data set
of 3,751 women who have endometriosis, treatment
11 COMMITTEE OPINIONS
with medroxyprogesterone acetate or depot medroxy-
progesterone acetate was the least well tolerated and
was the least effective in treating pain compared
with combination OCPs, GnRH agonists, and pain
medications (8). Furthermore, depot medroxyprog-
esterone acetate used for longer than 2 years has
been shown to decrease bone density in adolescents
(21, 22, 23). The U.S. Food and Drug Administra-
tion has warned against the long-term use of depot
medroxyprogesterone acetate because of adverse
affects on bone density (24).
Danazol, an androgenic and antiestrogenic
agent, is extremely effective in treating symptomatic
endometriosis in adults. Doses of 400800 mg daily
have been advocated for 6 months followed by con-
tinuous OCP use for maintenance suppression of the
hypothalamicpituitary ovarian axis. This choice of
pharmacotherapy was more common in the 1980s,
but the androgenic side effects have made this a poor
option for adolescents.
Gonadotropin-releasing hormone agonists cre-
ate a hypoestrogenic state by downregulating the
hypothalamicpituitary axis. Whereas these agents
are greatly effective in the treatment of endometrio-
sis-related pain in adolescents, their use alone (with-
out add-back therapy described in the following
paragraph) usually is limited to 6 months because of
the resultant profound hypoestrogenic state and its
subsequent effect on bone mineralization. This is a
major issue for an adolescent who is accruing peak
bone mineral density. Therefore, it has been suggest-
ed that this therapy not be offered as a first-line treat-
ment for adolescents younger than 16 years (14). At
6 months, GnRH agonist induces a 5% loss in tra-
becular bone mineral density and a 2% loss in
femoral neck bone mineral density in adult women.
In a cross-sectional study, researchers collected bone
mineral density test results of 265 females, aged
850 years (25). They determined that the majority
of bone mass growth is achieved by age 20 years and
that after the age 18 years, no significant differences
in bone mass or bone mineral density were noted at
most skeletal sites. This emphasizes that a drug-
induced hypoestrogenic state could significantly
affect peak bone mineralization that occurs during
adolescence, particularly in females younger than 16
years.
Investigators have determined that to reduce the
symptoms and bone loss related to a hypoestrogenic
state, add-back therapy with norethindrone acetate
(5 mg per day) or conjugated estrogens/medroxy-
progesterone acetate (0.625/2.5 mg per day) can
help preserve bone density (26, 27). Add-back ther-
apy has been shown not to influence the primary
therapeutic effect and resulted in less bone loss
12 months after cessation of therapy in adult
women. There is some evidence in adults to suggest
that immediate add-back therapy may result in even
less bone loss (28). No data exist on the long-term
effects of GnRH agonist use with add-back therapy
in the adolescent population and, thus, it should be
reserved for adolescents refractory to continuous
combination hormone therapy (14, 29). Lifestyle
modifications, such as adequate physical exercise
and calcium and vitamin D intake, also are essential
to maintaining proper bone health when taking
GnRH agonists (with or without add-back therapy).
Aside from medical management, surgery also
has proved to be an effective form of treatment for
adult patients with pain (30). Surgery for the man-
agement of endometriosis-related pain is an impor-
tant option for adolescents, but clearly, radical
procedures (oophorectomy, bilateral oophorectomy,
or hysterectomy) should be avoided in this age
group, even in rare cases of severe endometriosis. A
double-blinded randomized controlled trial com-
pared laser vaporization of endometriosis and laser
uterosacral nerve ablation with controls in 63 adult
patients with proven endometriosis. At 6 months of
follow-up, 63% of patients reported significant relief
compared with 23% of controls (31). Patients with
more advanced disease had better outcomes in pain
management compared with those with minimal dis-
ease. At 1-year follow-up, 90% of those in the treat-
ment arm who initially responded had continued
pain relief (32). Among the symptomatic controls,
an even distribution of patients was noted to have
progression, regression, and maintenance of disease.
Both new and recurrent disease was noted at second
look. In a Cochrane review of these data, adult
patients were almost 5 times more likely to benefit
from surgical management of endometriosis com-
pared with controls (33). One study demonstrated, in
a prospective review of 643 patients with pain, or
infertility, or both, that there was a significant rela-
tionship between pain and the depth of infiltration of
the endometriosis implants (9). This study also con-
firmed that red implants were more common in
younger patients and that the depth of invasion
increased with age, suggesting that endometriosis is
a progressive disease. The concept that endometrio-
sis is a progressive disease supports the recommen-
COMPENDIUM OF SELECTED PUBLICATIONS 12
dation for long-term medical treatment for pain
management of adolescent endometriosis and until
a woman has completed childbearing. Long-term
studies are needed to determine if medical treatment
can inhibit the progression of endometriosis diag-
nosed in adolescents and preserve future fertility.
In addition to surgery and hormonal manipula-
tion, complementary and alternative medicine has
been used for the treatment of endometriosis. A mul-
tidisciplinary pain management service, including
support groups and age-appropriate educational
information, may be beneficial for an adolescent with
chronic pelvic pain caused by endometriosis.
Summary
Endometriosis can be a debilitating disease that
affects adolescent girls and young women. Pediatri-
cians, adolescent health care providers, and gynecol-
ogists should recognize that thelarche and the
presence of endogenous estrogen can be considered
a developmental milestone and benchmark for inclu-
sion of adolescent endometriosis in the differential
diagnosis of postpubertal girls and young women
with chronic pelvic pain. Adolescent patients typi-
cally present with progressive and severe dysmenor-
rhea, but also may present with acylic pelvic pain.
Standard therapy (combination hormone therapy
and NSAIDs) for dysmenorrhea should be initiated,
and if symptoms do not resolve after 3 months, fur-
ther evaluation for endometriosis is indicated.
Prompt evaluation and consideration of the adverse
effects of endometriosis is, therefore, essential in
this age group.
Findings of the physical examination of adoles-
cents may vary from the adult population because
uterosacral nodularity and endometriomas are found
in more advanced disease and, thus, are uncommon
in adolescents. A bimanual pelvic examination may
not be necessary for further evaluation of pelvic pain
and should not be a requirement before the diagno-
sis of endometriosis and initiation of therapy for
adolescents. It is important to evaluate the vagina for
a possible obstructive anomaly and the ovaries for a
possible ovarian mass. This can be accomplished
with an evaluation of the vagina with a cotton-tipped
swab and an ultrasound examination of the pelvis.
Endometriosis in adolescents typically presents
as early disease (Stage I) and clear, red, and white
lesions are the most common. Treatment should
focus on conservative measures with surgical and
medical interventions. Only procedures that preserve
fertility options should be applied. Long-term endo-
metriosis treatment may be required for chronic pain
relief. Because there is no cure for endometriosis,
long-term treatment should continue until desired
family size is reached or fertility no longer needs to
be preserved. A multidisciplinary team approach to
the adolescent who has endometriosis may be the
most rewarding for the adolescent, her family, and
the clinician.
Resources
Endometriosis Association
(www.endometriosisassn.org)
The Center for Young Womens Health
(www.youngwomenshealth.org)
References
1. Goldstein DP, De Cholnoky C, Emans SJ. Adolescent
endometriosis. J Adolesc Health Care 1980;1:3741.
2. Vercellini P, Fedele L, Arcaini L, Bianchi S, Rognoni MT,
Candiani GB. Laparoscopy in the diagnosis of chronic
pelvic pain in adolescent women. J Reprod Med 1989;34:
82730.
3. Kontoravdis A, Hassan E, Hassiakos D, Botsis D,
Kontoravdis N, Creatsas G. Laparoscopic evaluation and
management of chronic pelvic pain during adolescence.
Clin Exp Obstet Gynecol 1999;26:767.
4. Reese KA, Reddy S, Rock JA. Endometriosis in an ado-
lescent population: the Emory experience. J Pediatr Adolesc
Gynecol 1996;9:1258.
5. Laufer MR, Goitein L, Bush M, Cramer DW, Emans SJ.
Prevalence of endometriosis in adolescent girls with
chronic pelvic pain not responding to conventional thera-
py. J Pediatr Adolesc Gynecol 1997;10:199202.
6. Batt RE, Mitwally MF. Endometriosis from thelarche to
midteens: pathogenesis and prognosis, prevention and
pedagogy. J Pediatr Adolesc Gynecol 2003;16:33747.
7. Marsh EE, Laufer MR. Endometriosis in premenarcheal
girls without an associated obstructive anomaly. Fertil
Steril 2005;83:75860.
8. Ballweg ML. Big picture of endometriosis helps provide
guidance on approach to teens: comparative historical
data show endo starting younger, is more severe. J Pediatr
Adolesc Gynecol 2003;16(suppl):S216.
9. Koninckx PR, Meuleman C, Demeyere S, Lesaffre E,
Comillie FJ. Suggestive evidence that pelvic endometrio-
sis is a progressive disease, whereas deeply infiltrating
endometriosis is associated with pelvic pain. Fertil Steril
1991;55:75965.
10. DHooghe TM, Bambra CS, Raeymaekers BM, Koninckx
PR. Serial laparoscopies over 30 months show that
endometriosis in captive baboons (Papio anubis, Papio
cynocephalus) is a progressive disease. Fertil Steril 1996;
65:6459.
13 COMMITTEE OPINIONS
11. Laufer MR. Identification of clear vesicular lesions of
atypical endometriosis: a new technique. Fertil Steril 1997;
68:73940.
12. Ling FW. Randomized controlled trial of depot leuprolide
in patients with chronic pelvic pain and clinically suspect-
ed endometriosis. Pelvic Pain Study Group. Obstet
Gynecol 1999;93:518.
13. American College of Obstetricians and Gynecologists.
Medical management of endometriosis. ACOG Practice
Bulletin 11. Washington, DC: ACOG; 1999.
14. Laufer MR, Sanfilippo J, Rose G. Adolescent endometrio-
sis: diagnosis and treatment approaches. J Pediatr Adolesc
Gynecol 2003;16(suppl):S311.
15. Revised American Society for Reproductive Medicine
classification of endometriosis: 1996. Fertil Steril 1997;
67:81721.
16. Sanfilippo JS, Wakim NG, Schikler KN, Yussman MA.
Endometriosis in association with uterine anomaly. Am J
Obstet Gynecol 1986;154:3943.
17. Kistner RW. The treatment of endometriosis by inducing
pseudopregnancy with ovarian hormones. Fertil Steril
1959;10:53956.
18. Moore J, Kennedy S, Prentice A. Modern combined oral
contraceptives for pain associated with endometriosis.
The Cochrane Database of Systematic Reviews 1997,
Issue 4. Art. No.: CD001019. DOI: 10.1002/14651858.
CD001019.
19. Miller L, Hughes JP. Continuous combination oral contra-
ceptive pills to eliminate withdrawal bleeding: a random-
ized trial. Obstet Gynecol 2003;101:65361.
20. Vercellini P, Cortesi I, Crosignani PG. Progestins for
symptomatic endometriosis: a critical analysis of the evi-
dence. Fertil Steril 1997;68:393401.
21. Cromer BA, Blair JM, Mahan JD, Zibners L, Naumovski
Z. A prospective comparison of bone density in adoles-
cent girls receiving depot-medroxyprogesterone acetate
(Depo-Provera), levonorgestrel (Norplant), or oral contra-
ceptives. J Pediatr 1996;129:6716.
22. Berenson AB, Radecki CM, Grady JJ, Rickert VI, Thomas
A. A prospective, controlled study of the effects of hor-
monal contraception on bone mineral density. Obstet
Gynecol 2001;98:57682.
23. Lara-Torre E, Edwards CP, Perlman S, Hertweck SP. Bone
mineral density in adolescent females using depot
medroxyprogesterone acetate. J Pediatr Adolesc Gynecol
2004;17:1721.
24. Black box warning added concerning long-term use of
depo-provera contraceptive injection. FDA talk paper.
Rockville (MD): U.S. Food and Drug Administration;
2004. Available at: http://www.fda.gov/bbs/topics/ANSWERS
/2004/ANS01325.html. Retrieved December 8, 2004.
25. Matkovic V, Jelic T, Wardlaw GM, Ilich JZ, Goel PK,
Wright JK, et al. Timing of peak bone mass in Caucasian
females and its implication for the prevention of osteo-
porosis: inference from a cross-sectional model. J Clin
Invest 1994;93:799808.
26. Barbieri RL. Hormone treatment of endometriosis: the
estrogen threshold hypothesis. Am J Obstet Gynecol
1992;166:7405.
27. Surrey ES, Hornstein MD. Prolonged GnRH agonist and
add-back therapy for symptomatic endometriosis: long-
term follow-up. Obstet Gynecol 2002;99:70919.
28. Kiesel L, Schweppe KW, Sillem M, Siebzehnrubl E.
Should add-back therapy for endometriosis be deferred
for optimal results? Br J Obstet Gynaecol 1996;103(suppl
14):157.
29. Lubianca JN, Gordon CM, Laufer MR. Add-back ther-
apy for endometriosis in adolescents. J Reprod Med 1998;
43:16472.
30. Abbott J, Hawe J, Hunter D, Holmes M, Finn P, Garry R.
Laparoscopic excision of endometriosis: a randomized,
placebo-controlled trial. Fertil Steril 2004;82:87884.
31. Sutton CJ, Ewen SP, Whitelaw N, Haines P. Prospective,
randomized, double-blind, controlled trial of laser
laparoscopy in the treatment of pelvic pain associated
with minimal, mild and moderate endometriosis. Fertil
Steril 1994;62:696700.
32. Sutton CJ, Pooley AS, Ewen SP, Haines P. Follow-up
report on a randomized controlled trial of laser laparos-
copy in the treatment of pelvic pain associated with
minimal to moderate endometriosis. Fertil Steril 1997;68:
10704.
33. Jacobson TZ, Barlow DH, Garry R, Koninckx PR.
Laparoscopic surgery for pelvic pain associated with
endometriosis. The Cochrane Database of Systematic
Reviews 2001, Issue 4. Art. No.: CD001300. DOI: 10.1002/
14651858.CD001300.
COMPENDIUM OF SELECTED PUBLICATIONS 14
Committee on
Adolescent Health Care
ACOG
Number 314, September 2005
Committee
Opinion
This information should not be
construed as dictating an exclu-
sive course of treatment or proce-
dure to be followed.
Copyright September 2005
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of this
publication may be reproduced,
stored in a retrieval system, or
transmitted, in any form or by any
means, electronic, mechanical,
photocopying, recording, or other-
wise, without prior written per-
mission from the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Meningococcal vaccination for adoles-
cents. ACOG Committee Opinion No.
314. American College of Obstetricians
and Gynecologists. Obstet Gynecol
2005;106:6679.
Meningococcal Vaccination for
Adolescents
ABSTRACT: Every year in the United States, approximately 1,4002,800 indi-
viduals are infected with meningococcal disease. The Advisory Committee on
Immunization Practices (ACIP) to the Centers for Disease Control and
Prevention (CDC) released recommendations in early 2005 to reduce the inci-
dence of meningococcal disease during adolescence and young adulthood. To
achieve this goal, routine vaccination of preadolescents with meningococcal
conjugate vaccine (MCV4) is now recommended. For adolescents who have
not received MCV4, the CDC now recommends vaccination before entry into
high school, at approximately 15 years of age. The American College of
Obstetricians and Gynecologists supports these recommendations and encour-
ages all health care providers caring for adolescent and young adult patients
to provide meningococcal vaccination with MCV4 when appropriate. This
includes vaccination of college freshmen who live in dormitories. Pregnant
women may be vaccinated with meningococcal polysaccharide vaccine
(MPSV4) as indicated. Health care providers also are encouraged to discuss
meningococcal vaccination with patients whose children have reached pread-
olescence, adolescence, or young adulthood and to increase awareness of the
signs and symptoms of meningococcal disease.
Background
Meningococcal disease is caused by bacteria (Neisseria meningitidis) that
infect the bloodstream and the meninges, resulting in serious illness. Every
year in the United States, approximately 1,4002,800 individuals are infect-
ed with meningococcal disease. Neisseria meningitidis has become a leading
cause of bacterial meningitis in the United States. Ten percent to 14% of indi-
viduals with meningococcal disease die, and 1119% percent of those who
survive have permanent disabilities, such as mental retardation, hearing loss,
and loss of limbs (1). The disease often begins with generalized symptoms
that can be mistaken for a common illness, such as the flu. Meningococcal
disease is particularly dangerous because it progresses rapidly and can be
fatal within hours (2). Therefore, it is important to prevent the disease,
through use of meningococcal vaccination, for individuals at highest risk.
Two meningococcal vaccines are available in the United States, meningo-
coccal polysaccharide vaccine (MPSV4) and meningococcal conjugate vac-
15 COMMITTEE OPINIONS
cine (MCV4). Studies indicate that both vaccines can
prevent four types of meningococcal disease
(serogroups A, C, Y, W-135). Of all cases of
meningococcal disease among individuals 11 years
and older, 75% are caused by serogroups C, Y, or W-
135. Both vaccines protect approximately 90% of
individuals vaccinated.
Meningococcal polysaccharide vaccine is a
tetravalent meningococcal polysaccharide vaccine
that has been available in the United States since the
1970s. Each dose consists of purified bacterial cap-
sular polysaccharides (50 g each) from serogroups
A, C, Y, and W-135. Meningococcal polysaccharide
vaccine is available in single-dose (0.5 mL) and 10-
dose (5 mL) vials (1).
Meningococcal conjugate vaccine is a tetrava-
lent meningococcal conjugate vaccine that was
licensed for use in the United States in January
2005. A 0.5-mL single dose of vaccine contains 4 g
each of capsular polysaccharide from serogroups A,
C, Y, and W-135 conjugated to 48 g of diphtheria
toxoid. Meningococcal conjugate vaccine is avail-
able only in single-dose vials and is expected to be
more effective, longer lasting, and more capable of
preventing transmission of the disease from person
to person (1).
These vaccines have been shown to be highly
effective at reducing meningococcal disease.
However, they do not protect individuals against
meningococcal disease caused by serogroup B of
N meningitidis. This type of bacteria causes one
third of all meningococcal cases. More than half of
the cases among infants younger than 1 year are
caused by serogroup B, for which no vaccine is
available in the United States (1).
Studies of vaccination with MPSV4 during
pregnancy have not documented adverse effects
among either pregnant women or newborns. On the
basis of these data, the Centers for Disease Control
and Prevention (CDC) states that pregnancy should
not preclude vaccination with MPSV4, if indicated.
No data are available on the safety of MCV4 during
pregnancy (1).
Recommendations of the Advisory
Committee on Immunization Practices to
the Centers for Disease Control and
Prevention
The Advisory Committee on Immunization Prac-
tices (ACIP) to the CDC released recommendations
in early 2005 to reduce meningococcal disease dur-
ing adolescence and young adulthood. Routine vac-
cination of preadolescents 1112 years of age with
MCV4 is now recommended. For adolescents who
have not received MCV4, the CDC now recom-
mends vaccination before entry into high school, at
approximately 15 years of age. The goal is to imple-
ment, within 3 years, routine vaccination with
MCV4 of all preadolescents beginning at 11 years of
age. Other adolescents and young adults who want
to decrease their risk for meningococcal disease also
can be given the immunization. The recommenda-
tions state that MCV4 is preferred, but MPSV4 is
acceptable (1).
Meningococcal vaccination also is recom-
mended for other high-risk groups including (1):
Anyone traveling to or living in a part of the
world where meningococcal disease is endemic
Anyone who is asplenic or has a damaged
spleen
Anyone who has terminal complement compo-
nent deficiency (an immune system disorder)
Anyone possibly exposed to meningitis during
an outbreak
Young men and women entering the military
College freshmen living in dormitories
College freshmen who live in dormitories are at
higher risk for meningococcal disease than other
individuals of the same age because lifestyle factors
common among freshman college students appear to
be linked to the disease. These factors include: living
in crowded housing, going to bars, smoking, and
having irregular sleeping habits. Because of the fea-
sibility constraints in targeting freshmen in dormito-
ries, the CDC indicates that colleges may elect to
target their vaccination campaigns to all matriculat-
ing freshmen. The risk for meningococcal disease
among nonfreshmen college students is similar to
that for the general population of similar age (1824
years). However, the vaccines are safe and immuno-
genic and can be provided to nonfreshmen college
students who want to reduce their risk for meningo-
coccal disease (1).
ACOG Recommendations
The American College of Obstetricians and Gyne-
cologists supports the recommendations of the ACIP
for routine vaccination of preadolescents against
meningococcal disease. Several medical profes-
COMPENDIUM OF SELECTED PUBLICATIONS 16
sional organizations, including the American Acad-
emy of Pediatrics, the Society for Adolescent
Medicine, and the American Academy of Family
Physicians also support the recommendations of the
ACIP (35). The American College of Obstetricians
and Gynecologists encourages all health care
providers caring for adolescent and young adult
patients to provide meningococcal vaccination with
MCV4 when appropriate. Because of the lack of
data regarding the safety of MCV4 during preg-
nancy, MPSV4 can be considered for adolescents
and young adults who are pregnant and those having
unprotected sex who may be at risk for unintended
pregnancy. Health care providers are encouraged to
discuss meningococcal vaccination with patients
whose children have reached preadolescence, ado-
lescence, or young adulthood. It is important to
increase parents, adolescents, and young adults
awareness of the signs and symptoms of meningo-
coccal disease even though they are frequently non-
specific. This can result in earlier medical care and
improved clinical outcomes.
References
1. Bilukha OO, Rosenstein N. Prevention and control of
meningococcal disease. Recommendations of the
Advisory Committee on Immunization Practices (ACIP).
National Center for Infectious Diseases, Centers for
Disease Control and Prevention (CDC). MMWR
Recomm Rep 2005;54(RR-7):1-21. Available at: http://
www.cdc.gov/mmwr/preview/mmwrhtml/rr5407a1.htm.
Retrieved June 6, 2005.
2. Centers for Disease Control and Prevention. Menin-
gococcal vaccines: what you need to know. Available at
http://www.cdc.gov/nip/publications/vis/vis-mening.rtf.
Retrieved May 18, 2005.
3. American Academy of Family Physicians. Meningo-
coccal immunization. Available at: http://www.aafp.org/
x34406.xml. Retrieved June 8, 2005.
4. Middleman AB, Rickert VI, Rosenthal SL. Menin-
gococcal vaccine: position statement of the Society for
Adolescent Medicine. J Adolesc Health 2005;37:262.
5. Prevention and control of meningococcal disease: recom-
mendations for use of meningococcal vaccines in pedi-
atric patients. Pediatrics 2005;116:496505.
17 COMMITTEE OPINIONS 17 17
Committee on
Adolescent Health Care
and
The ACOG Working
Group on Immunization
ACOG
Number 344, September 2006
Committee
Opinion
This information should not be
construed as dictating an exclusive
course of treatment or procedure
to be followed.
The College wishes to thank
Eduardo Lara-Torre, MD, Marc
R. Laufer, MD, Abigail English,
JD, Jennifer E. Dietrich, MD,
MSc, Richard S. Guido, MD,
John Santelli, MD, MPH, Stanley
Gall, MD, and Barbara Moscicki,
MD, for their assistance in the
development of this document.
Copyright September 2006
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of this
publication may be reproduced,
stored in a retrieval system,
posted on the Internet, or trans-
mitted, in any form or by any
means, electronic, mechanical,
photocopying, recording, or oth-
erwise, without prior written per-
mission from the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Human papillomavirus vaccination.
ACOG Committee Opinion No. 344.
American College of Obstetricians
and Gynecologists. Obstet Gynecol
2006;108:699705.
Human Papillomavirus Vaccination
ABSTRACT: The U.S. Food and Drug Administration recently approved a
quadrivalent human papillomavirus (HPV) vaccine for females aged 926
years. The American College of Obstetricians and Gynecologists recom-
mends the vaccination of females in this age group. The Advisory Committee
on Immunization Practices has recommended that the vaccination routinely
be given to girls when they are 11 or 12 years old. Although obstetrician
gynecologists are not likely to care for many girls in this initial vaccination
target group, they are critical to the widespread use of the vaccine for
females aged 1326 years. The quadrivalent HPV vaccine is most effective if
given before any exposure to HPV infection, but sexually active women can
receive and benefit from the vaccination. Vaccination with the quadrivalent
HPV vaccine is not recommended for pregnant women. It can be provided to
women who are breastfeeding. The need for booster vaccination after 5 years
has not been established. Health care providers are encouraged to discuss
with their patients the benefits and limitations of the quadrivalent HPV vac-
cine and the need for continued routine cervical cytology screening.
The relationship between infection with human papillomavirus (HPV) and
both cervical cancer and genital warts has been recognized for many years
(1). More than 100 genotypes of HPV have been discovered to date with
approximately 30 found in the genital mucosa. However, only 15 have been
shown to be associated with cervical cancer. Approximately 70% of cervical
cancers result from infection with HPV genotypes 16 and 18, and 90% of
cases of genital warts result from infection with HPV genotypes 6 and 11 (2).
The American Cancer Society estimates there will be 9,710 new cases of
cervical cancer and 3,700 deaths from cervical cancer in the United States in
2006 (3). Cervical cancer is the second largest cause of female cancer mor-
tality worldwide (4). Worldwide, an estimated 493,000 new cases occur each
year and of these cases, 274,000 women die annually from cervical cancer
(5). Eighty percent of these deaths occur where resources are the most limit-
ed (6). Although the implementation of cervical cytology screening programs
and treatment of precancerous lesions has led to a decrease in cervical cancer
deaths in the United States, there continues to be a significant population of
women not receiving adequate screening. In 2003, only 67% of uninsured
women aged 1864 years obtained cervical cytology screening within the
past 3 years compared with 86% of insured women in that age group (7).
COMPENDIUM OF SELECTED PUBLICATIONS 18 18 18
The U.S. Food and Drug Administration (FDA)
recently licensed the first vaccine shown to be
effective at preventing infection with some genotypes
of HPV. The prophylactic quadrivalent human papil-
lomavirus L1 virus-like particle vaccine offers pro-
tection against cervical cancer, cervical dysplasias,
vulvar or vaginal dysplasias, and genital warts asso-
ciated with HPV genotypes 6, 11, 16, and 18. The
FDA approval is for administration of this three-dose
vaccine to females aged 926 years at intervals of 0,
2, and 6 months (see the box). The need for booster
doses remains to be demonstrated (8). To date, pro-
tection has been shown to last at least 5 years (9).
A second, bivalent formulation of an HPV vac-
cine is in development. Results of initial studies of
this vaccine indicate that it offers protection similar
to the quadrivalent vaccine against HPV infections
caused by genotypes 16 and 18 (10, 11).
Studies of the quadrivalent HPV vaccine have
shown that in subjects naive to the vaccine geno-
types who followed protocol, the vaccine was 100%
effective in preventing cervical intraepithelial neo-
plasia (CIN) 2, CIN 3, and condylomatous vulvar
disease related to the HPV genotypes covered by the
vaccine (8). In contrast, for a woman with current or
past HPV infection, there is no evidence of protec-
tion from disease caused by the HPV genotypes with
which she was infected. There is, however, evidence
of protection from disease caused by the remaining
HPV vaccine genotypes (8, 12).
To be maximally effective against all HPV
genotypes included in the quadrivalent vaccine, it
should be given before any exposure to HPV infec-
tion. If the vaccine is given after the onset of sexual
activity, patients may have already been infected
with HPV and develop abnormal cervical cytology
related to the HPV genotypes in the vaccine as well
as to those genotypes not included in the vaccine.
Recommendations
Vaccination of Girls, Adolescents, and Young
Women
The American College of Obstetricians and
Gynecologists (ACOG) Committee on Adolescent
Health Care and the ACOG Working Group on
Immunization recommend the vaccination of
females aged 926 years against HPV. The Advisory
Committee on Immunization Practices has recom-
mended the initial vaccination target of females aged
11 or 12 years (13). Although obstetriciangynecol-
Key Information Regarding Gardasil
Dosage:
The quadrivalent human papillomavirus (HPV) vaccine
should be administered intramuscularly as three sepa-
rate 0.5-mL doses according to the following schedule:
First dose: at elected date
Second dose: 2 months after the first dose
Third dose: 6 months after the first dose
Storage:
The quadrivalent vaccine should be refrigerated at 28C
(3646F). It should not be frozen and should be pro-
tected from light.
Contraindications:
Hypersensitivity to the active substances or to any of
the excipients of the quadrivalent vaccine. Individuals
who develop symptoms indicative of hypersensitivity
after receiving a dose of quadrivalent vaccine should
not receive further doses of the product.
Precautions:
As with any vaccine, vaccination may not result in
protection in all vaccine recipients.
The quadrivalent vaccine is not intended to be used
for treatment of active genital warts; cervical cancer;
cervical intraepithelial neoplasia, vulvar intraepithelial
neoplasia, or vaginal intraepithelial neoplasia.
The quadrivalent vaccine has not been shown to pro-
tect against disease due to nonvaccine HPV types.
The vaccine is not recommended for use in pregnant
women. The manufacturer maintains a pregnancy reg-
istry to monitor fetal outcomes of pregnant women
exposed to the vaccine. Any exposure to it during
pregnancy can be reported by calling 800-986-8999.
Vaccine Adverse Event Reporting:
To report an adverse event associated with administra-
tion of the quadrivalent vaccine, go to
http://vaers.hhs.gov/.
Advisory Committee on Immunization Practices
Recommendations:
For current recommendations by the Advisory
Committee on Immunization Practices, go to
http://www.cdc.gov/nip/ACIP/.
CPT Code:
The American Medical Association has established a
Current Procedural Terminology* code of 90649 for
quadrivalent HPV vaccination.
*Current Procedural Terminology (CPT) is copyright 2006
American Medical Association. All rights reserved. No fee sched-
ules, basic units, relative values or related listings are included
in CPT. The AMA assumes no liability for the data contained
herein. CPT is a trademark of the American Medical Association.
19 COMMITTEE OPINIONS 19 19
ogists are not likely to care for many girls in this ini-
tial vaccination target group, they are critical to the
widespread use of the vaccine for females aged
1326 years. The American College of Obstetricians
and Gynecologists has recommended that the first
adolescent reproductive health care visit take place
between ages 13 years and 15 years (14). Adoles-
cents and young women aged 1626 years who are
in the vaccination age groups visit obstetrician
gynecologists for primary care, contraceptive or
other gynecologic needs, or pregnancy-related serv-
ices. These visits are a strategic time to discuss HPV
and the potential benefit of the HPV vaccine and to
offer vaccination to those who have not already
received it. During a health care visit with a girl or
woman in the age range for vaccination, an assess-
ment of the patients HPV vaccine status should be
conducted and documented in the patient record.
Cervical Cytology Screening
Current cervical cytology screening recommenda-
tions remain unchanged and should be followed
regardless of vaccination status (1, 1417). Cervical
cancer screening should begin approximately 3
years after the onset of vaginal intercourse or no
later than age 21 years (16). After the first screening,
annual cervical cytology screening should be con-
ducted for women younger than 30 years (17). It
must be emphasized that the currently approved
quadrivalent vaccine protects against acquisition
of HPV genotypes that account for only 70% of
HPV-related cervical cancer and only 90% of geni-
tal warts cases (2). The vaccine is a preventive tool
and is not a substitute for cancer screening.
Human Papillomavirus Testing
Testing for HPV is currently not recommended
before vaccination. Testing for HPV DNA would not
identify past HPV infections, only current HPV
infections. Serologic assays for HPV are unreliable
and currently not commercially available. Requiring
any type of screening test would raise the cost of
vaccination programs dramatically and reduce the
cost-effectiveness of vaccination.
Vaccination of Sexually Active Women
Sexually active women can receive the quadrivalent
HPV vaccine. Women with previous abnormal cer-
vical cytology or genital warts also can receive the
quadrivalent HPV vaccine. These patients should be
counseled that the vaccine may be less effective in
women who have been exposed to HPV before vac-
cination than in women who were HPV naive at the
time of vaccination (8, 12). Women with previous
HPV infection will benefit from protection against
disease caused by the HPV vaccine genotypes with
which they have not been infected. The need for annu-
al cervical cytology screening should be emphasized.
Vaccination of Women With Previous Cervical
Intraepithelial Neoplasia
There is concern that provision of the vaccination to
women with previous CIN may create a false sense
of protection, potentially deterring patients from
continuing their regular screening and management.
The quadrivalent vaccine can be given to patients
with previous CIN, but practitioners need to empha-
size that the benefits may be limited, and cervical
cytology screening and corresponding management
based on ACOG recommendations must continue.
Vaccination Is Not Treatment
The quadrivalent HPV vaccine is not intended to
treat patients with cervical cytologic abnormalities
or genital warts. Patients with these conditions
should undergo the appropriate evaluation and treat-
ment. It is important to note that many early cyto-
loic abnormalities can be detected and managed
conservatively given the significant rate of regres-
sion. This is especially true in adolescents and
young women (15, 18).
Vaccination of Pregnant and Lactating Women
The quadrivalent HPV vaccine has been classified
by the FDA as pregnancy category B. Although its
use in pregnancy is not recommended, no terato-
genic effects have been reported in animal studies.
In clinical studies, the proportion of pregnancies
with an adverse outcome were comparable in
women who received the quadrivalent HPV vac-
cine and in women who received a placebo (8).
The manufacturers pregnancy registry should be
contacted if pregnancy is detected during the vac-
cination schedule. Completion of the series should
be delayed until pregnancy is completed. It is not
known whether vaccine antigens or antibodies
found in the quadrivalent vaccine are excreted in
human milk (8). Lactating women can receive the
quadrivalent HPV vaccine because inactivated vac-
cines such as this vaccine do not affect the safety
of breastfeeding for mothers or infants (19).
COMPENDIUM OF SELECTED PUBLICATIONS 20 20 20
Vaccination of Immunosuppressed Patients
The presence of immunosuppression, like that expe-
rienced in patients with HIV infection, is not a con-
traindication to the quadrivalent HPV vaccine.
However, the immune response may be smaller in
the immunocompromised patient than in immuno-
competent patients (8).
Vaccination of Women Older Than 26 Years
and Males
Research regarding vaccination of women older than
26 years and males is currently under way. Data
available are insufficient to make recommendations
for these populations.
Other Methods for Prevention of HPV Infection
Abstinence from sexual activity is the most effective
way to avoid sexually transmitted diseases (STDs),
including HPV infection. Limiting the number of
sexual partners also may decrease ones risk for
STDs, including HPV. Use of latex condoms is the
only method currently available for sexually active
individuals to reduce the likelihood of HPV acquisi-
tion and HPV-related cervical dysplasia (20, 21).
Research Needs
ACOG supports additional research to evaluate the
need for booster vaccination, the effectiveness of
vaccination in women older than 26 years, and the
effectiveness of vaccination of males.
Educational Efforts
The quadrivalent HPV vaccine is a major break-
through in efforts to prevent cervical cancer; obste-
triciangynecologists can play a critical role in its
widespread use. It is important for clinicians to pro-
vide patient education about HPV-related disease
and be prepared to respond to questions from
patients regarding the HPV vaccine. Studies have
shown that physician recommendation plays an
important role in the acceptance of the vaccine by
patients (22). Limitations of the currently approved
quadrivalent vaccine also should be discussed,
including that it provides coverage for only two of
the 15 HPV genotypes associated with cancer and
only two of the genotypes that cause genital warts.
In addition, the health care provider can discuss with
patients that despite the high prevalence of HPV
infection, few infections result in cervical cancer.
As the HPV vaccines have been developed, mar-
ket research has addressed the acceptability of HPV
vaccination by parents, guardians, and patients. A
study of 880 females aged 1545 years demonstrat-
ed that more than 80% of mothers would support
vaccinating their daughters. In most additional stud-
ies, a higher level of acceptability was associated
with educating mothers and patients about the con-
sequences of HPV disease and the potential for
decreased rates of cervical cancer (2325). Profes-
sional recommendations for HPV vaccination are
essential in ensuring widespread acceptance and use
of the vaccine. Requiring vaccination for child care,
school, or college attendance and multicomponent
interventions that include community education
have been effective in improving the use of vaccina-
tion (26, 27).
Consent for HPV Vaccination
As for all immunizations, consent for HPV vaccina-
tion must be obtained from someone who is legally
authorized to provide it. Generally, for children and
adolescents who are minors, typically those younger
than 18 years, the consent of a parent is required for
medical care, including vaccinations. There are,
however, numerous exceptions to this requirement
(28). For example, individuals other than a parent
are sometimes authorized to consent for a child or
adolescents care. These may include a legal
guardian, a judge, or an individual who has been
authorized either by a parent or by a court to consent
for a minors care. In addition, in certain situations,
adolescents who are minors are legally allowed to
consent to their own care. This is usually determined
by state law and varies by state. Depending on the
state, certain minors are allowed to consent for care
because of their status; these may include minors
who have reached a certain age or are pregnant, mar-
ried, parents, living apart from their parents, or
emancipated (28). In all states, minors are allowed to
consent for diagnosis and treatment for STDs; how-
ever, many of the laws that authorize them to do so
do not mention vaccinations (28).
Clinicians should be familiar with state and
local statutes regarding the rights of minors to health
care services and the federal and state laws that
affect confidentiality. When necessary, they should
seek appropriate legal advice. Careful analysis
would be required to determine the circumstances in
which an adolescent minor might be able to consent
for her own HPV vaccination in a particular state.
Often, state medical societies can be helpful in this
capacity. A list of state medical society web sites is
21 COMMITTEE OPINIONS 21 21
available at http://www.ama-assn.org/ama/pub/
category/7630.html.
Advocacy Efforts
In the United States, cervical cancer rates are high-
est for low income and uninsured women. Third
party payers and government agencies are encour-
aged to assist in covering the costs of HPV vaccina-
tion to patients, even if they are underinsured or
uninsured. Pharmaceutical companysponsored
patient assistance programs for vaccines should be
implemented as well as the provision of the vaccine
at significantly discounted rates to the Vaccines for
Children (VFC) program. The VFC program
provides free vaccines to children who are
Medicaid-eligible, uninsured, Native American, or
underinsured children who visit federally qualified
or rural health centers. Health care providers are
encouraged to become VFC providers. (For more
information, go to http://www.cdc.gov/nip/vfc/.)
References
1. Human papillomavirus. ACOG Practice Bulletin No. 61.
American College of Obstetricians and Gynecologists.
Obstet Gynecol 2005;105:90518.
2. Bosch FX, Manos MM, Munoz N, Sherman M, Jansen
AM, Peto J, et al. Prevalence of human papillomavirus in
cervical cancer: a worldwide perspective. International
biological study on cervical cancer (IBSCC) Study
Group. J Natl Cancer Inst 1995;87:796802.
3. American Cancer Society. Cancer facts and figures 2006.
Atlanta (GA): ACS; 2006. Available at: http://www.
cancer.org/downloads/STT/CAFF2006PWSecured.pdf.
Retrieved June 29, 2006.
4. World Health Organization. State of the art new vaccines:
research and development. Initiative for Vaccine
Research. Geneva: WHO; 2003. Available at: http://
www.who.int/vaccine_research/documents/en/stateofart_
excler.pdf. Retrieved November 21, 2003.
5. International Agency for Research on Cancer. GLOBO-
CAN 2002 database. Lyon (FR): IARC; 2002.
6. Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide
incidence of eighteen major cancers in 1985. Int J Cancer
1993;54:594606.
7. National Center for Health Statistics. Health, United
States, 2005 with chartbook on trends in the health of
Americans. Hyattsville (MD): NCHS; 2005.
8. Prescribing information for GARDASIL. Whitehouse
Station (NJ): Merck & Co., Inc.; 2006. Available at:
http://www.merck.com/product/usa/pi_circulars/g/
gardasil/gardasil_pi.pdf. Retrieved June 26, 2006.
9. Centers for Disease Control and Prevention. HPV and
HPV vaccineinformation for healthcare providers.
Available at: http://www.cdc.gov/std/HPV/STDFact-HPV-
vaccine-hcp.htm#hpvvaccine. Retrieved July 7, 2006.
10. Harper DM, Franco EL, Wheeler C, Ferris DG, Jenkins D,
Schuind A, et al. Efficacy of a bivalent L1 virus-like par-
ticle vaccine in prevention of infection with human papil-
lomavirus types 16 and 18 in young women: a randomised
controlled trial. GlaxoSmithKline HPV Vaccine Study
Group. Lancet 2004;364:175765.
11. Harper DM, Franco EL, Wheeler CM, Moscicki AB,
Romanowski B, Roteli-Martins CM, et al. Sustained effi-
cacy up to 4.5 years of a bivalent L1 virus-like particle
vaccine against human papillomavirus types 16 and 18:
follow-up from a randomised control trial. Lancet
2006;367:124755.
12. Mao C, Koutsky LA, Ault KA, Wheeler CM, Brown DR,
Wiley DJ, et al. Efficacy of human papillomavirus-16 vac-
cine to prevent cervical intraepithelial neoplasia: a ran-
domized controlled trial [published erratum appears in
Obstet Gynecol 2006;107:1425]. Obstet Gynecol 2006;
107:1827.
13. Centers for Disease Control and Prevention. HPV vaccine
[human papillomavirus (HPV) and the HPV vaccine].
Atlanta (GA): CDC. Available at: http://www.cdc.gov/
nip/vaccine/hpv/. Retrieved July 26, 2006.
14. American College of Obstetricians and Gynecologists.
Primary and preventive health care for female adoles-
cents. In: Health care for adolescents. Washington, DC:
ACOG; 2003. p. 124.
15. Evaluation and management of abnormal cervical cytol-
ogy and histology in the adolescent. ACOG Committee
Opinion No. 330. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2006:107:9638.
16. Cervical cancer screening in adolescents. ACOG
Committee Opinion No. 300. American College of
Obstetricians and Gynecologists. Obstet Gynecol 2004;
104:8859.
17. Cervical cytology screening. ACOG Practice Bulletin No.
45. American College of Obstetricians and Gynecologists.
Obstet Gynecol 2003;102:41727.
18. Moscicki AB, Shiboski S, Broering J, Powell K, Clayton
L, Jay N, et al. The natural history of human papillo-
mavirus infection as measured by repeated DNA testing in
adolescent and young women. J Pediatr 1998;132:
27784.
19. Atkinson WL, Pickering LK, Schwartz B, Weniger BG,
Iskander JK, Watson JC. General recommendations on
immunization. Recommendations of the Advisory
Committee on Immunization Practices (ACIP) and the
American Academy of Family Physicians (AAFP).
Centers for Disease Control and Prevention. MMWR
Recomm Rep 2002;51(RR-2):135.
20. Hogewoning CJ, Bleeker MC, van den Brule AJ,
Voorhorst FJ, Snijders PJ, Berkhof J, et al. Condom use
promotes regression of cervical intraepithelial neoplasia
and clearance of human papillomavirus: a randomized
clinical trial. Int J Cancer 2003;107:8116.
21. Winer RL, Hughes JP, Feng Q, OReilly S, Kiviat NB,
Holmes KK, et al. Condom use and the risk of genital
human papillomavirus infection in young women. N Engl
J Med 2006;354:264554.
22. Zimet GD, Mays RM, Winston Y, Kee R, Dickes J, Su L.
Acceptability of human papillomavirus immunization. J
Womens Health Gend Based Med 2000;9:4750.
COMPENDIUM OF SELECTED PUBLICATIONS 22 22 22
23. Lazcano-Ponce E, Rivera L, Arillo-Santillan E, Salmeron
J, Hernandez-Avila M, Munoz N. Acceptability of a
human papillomavirus (HPV) trial vaccine among moth-
ers of adolescents in Cuernavaca, Mexico. Arch Med Res
2001;32:2437.
24. Hoover DR, Carfioli B, Moench EA. Attitudes of adoles-
cent/young adult women toward human papillomavirus
vaccination and clinical trials. Health Care Women Int
2000;21:37591.
25. Davis K, Dickman ED, Ferris D, Dias JK. Human papil-
lomavirus vaccine acceptability among parents of 10- to
15-year-old adolescents. J Low Genit Tract Dis 2004;
8:18894.
26. Centers for Disease Control and Prevention. The guide to
community preventive services. Effectiveness of multi-
component interventions that include education to
increase vaccination coverage. Atlanta (GA): CDC; 2003.
Available at: http://www.thecommunityguide.org/vaccine/
vpd-int-demand-multicomponent-ed.pdf. Retrieved July
11, 2006.
27. Centers for Disease Control and Prevention. The guide to
community preventive services. Effectiveness of requiring
vaccinations for child care, school, and college attendance to
increase vaccination coverage. Atlanta (GA): CDC; 2003.
Available at: http://www.thecommunityguide.org/vaccine/
vpd-int-demand-require.pdf. Retrieved July 11, 2006.
28. English A, Kenney KE. State minor consent laws: a sum-
mary. 2nd ed. Chapel Hill (NC): Center for Adolescent
Health & the Law; 2003.
Resources
ACOG Resources
American College of Obstetricians and Gynecologists. Cmo
prevenir las enfermedades de transmisin sexual. ACOG
Patient Education Pamphlet SP009. Washington, DC: ACOG;
2005.
American College of Obstetricians and Gynecologists. Genital
HPV (human papillomavirus) in adolescents fact sheet.
Washington, DC: ACOG; 2005.
American College of Obstetricians and Gynecologists. How to
prevent sexually transmitted diseases. ACOG Patient
Education Pamphlet AP009. Washington, DC: ACOG; 2005.
American College of Obstetricians and Gynecologists. Human
papillomavirus infection. ACOG Patient Education Pamphlet
AP073. Washington, DC: ACOG; 2003.
American College of Obstetricians and Gynecologists. Tool kit
for teen care. Washington, DC: ACOG; 2003.
Cervical cancer screening in adolescents. ACOG Committee
Opinion No. 300. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2004;104:8859.
Cervical cytology screening. ACOG Practice Bulletin No. 45.
American College of Obstetricians and Gynecologists. Obstet
Gynecol 2003;102:41727.
Human papillomavirus. ACOG Practice Bulletin No. 61.
American College of Obstetricians and Gynecologists. Obstet
Gynecol 2005;105:90518.
Sexually transmitted diseases in adolescents. ACOG Com-
mittee Opinion No. 301. American College of Obstetricians
and Gynecologists. Obstet Gynecol 2004;104:8918.
Other Resources
The following lists are for information purposes only. Referral
to these sources and web sites does not imply the endorsement
of ACOG. These lists are not meant to be comprehensive. The
exclusion of a source or web site does not reflect the quality of
that source or web site. Please note that web sites are subject to
change without notice. Furthermore, ACOG does not endorse
any commercial products that may be advertised or available
from these organizations or on these web sites.
American Cancer Society
1599 Clifton Rd. NE
Atlanta, GA 30329
1-800-ACS-2345 (or 1-866-228-4327 for TTY)
http://www.cancer.org
The American Social Health Association
PO Box 13827
Research Triangle Park, NC 27709
(919) 361-8400
(919) 361-8488: National Herpes Hotline
http://www.ashastd.org
http://www.iwannaknow.org
http://www.ashastd.org/hpvccrc
American Society for Colposcopy and Cervical Pathology
20 West Washington St., Suite 1
Hagerstown, MD 21740
(301) 733-3640
1-800-787-7227
http://www.asccp.org
Center for Young Womens Health
Childrens Hospital Boston
333 Longwood Ave., 5th Floor
Boston, MA 02115
(617) 355-2994
http://www.youngwomenshealth.org
Centers for Disease Control and Prevention
1600 Clifton Rd.
Atlanta, GA 30333
(404) 639-3311
1-800-311-3435
http://www.cdc.gov
http://www.cdc.gov/std/hpv/STDFact-HPV-vaccine.htm
Go Ask Alice!
Columbia University
7th Floor, Lerner Hall
2920 Broadway, Mail Code 2608
New York, NY 10027
(212) 854-5453
http://www.goaskalice.columbia.edu
Merck Inc.
Make the Connection
1-888-447-8266
http://www.maketheconnection.org
23 COMMITTEE OPINIONS 23 23
National Cervical Cancer Public Education Campaign
1-866-280-6605
http://www.cervicalcancercampaign.org
National Womens Health Resource Center
157 Broad St., Suite 315
Red Bank, NJ 07701
(732) 530-3425
1-877-986-9472
http://www.healthywomen.org
Planned Parenthood Federation of America
434 West 33rd St.
New York, NY 10001
1-800-230-7526
http://www.plannedparenthood.org
http://www.teenwire.org
Society for Adolescent Medicine
1916 Copper Oaks Circle
Blue Springs, MO 64015
(816) 224-8010
http://www.adolescenthealth.org
http://www.adolescenthealth.org/cme/program_hpv
Society of Obstetricians and Gynaecologists of Canada
780 Echo Drive
Ottawa, ON K1S 5R7
Canada
(613) 730-4192
1-800-561-2416
http://www.sogc.org
http://www.sexualityandu.ca
U.S. Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857-0001
1-888-INFO-FDA (1-888-463-6332)
http://www.fda.gov/cber/products/hpvmer060806.htm
http://www.fda.gov/womens/getthefacts/hpv.html
COMPENDIUM OF SELECTED PUBLICATIONS 24 24 24
Committee on
Adolescent Health Care
Committee on Adolescence
Reaffirmed 2009
ACOG
Number 349, November 2006
Committee
Opinion
This document reflects emerging clin-
ical and scientific advances as of the
date issued and is subject to change.
The information should not be con-
strued as dictating an exclusive
course of treatment or procedure to
be followed.
The committees would like to thank
Lesley Breech, MD; Angela Diaz,
MD; S. Paige Hertwick, MD; Paula
Adams Hillard, MD; and Marc
Laufer, MD, for their assistance in
the development of this document.
Copyright November 2006
by the American Academy of
Pediatrics and the American College
of Obstetricians and Gynecologists.
All rights reserved. No part of this
publication may be reproduced,
stored in a retrieval system, posted on
the Internet, or transmitted, in any
form or by any means, electronic,
mechanical, photocopying, recording,
or otherwise, without prior written
permission from the publisher.
Requests for authorization to make
photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Menstruation in girls and adolescents:
using the menstrual cycle as a vital
sign. ACOG Committee Opinion No.
349. American Academy of Pediatrics;
American College of Obstetricians
and Gynecologists. Obstet Gynecol
2006;108:13238.
Menstruation in Girls and
Adolescents: Using the Menstrual
Cycle as a Vital Sign
ABSTRACT: Young patients and their parents often are unsure about what
represents normal menstrual patterns, and clinicians also may be unsure
about normal ranges for menstrual cycle length and amount and duration of
flow through adolescence. It is important to be able to educate young
patients and their parents regarding what to expect of a first period and
about the range for normal cycle length of subsequent menses. It is equally
important for clinicians to have an understanding of bleeding patterns in
girls and adolescents, the ability to differentiate between normal and abnor-
mal menstruation, and the skill to know how to evaluate young patients con-
ditions appropriately. Using the menstrual cycle as an additional vital sign
adds a powerful tool to the assessment of normal development and the exclu-
sion of serious pathologic conditions.
Young patients and their parents frequently have difficulty assessing what
constitutes normal menstrual cycles or patterns of bleeding. Girls may be
unfamiliar with what is normal and may not inform their parents about men-
strual irregularities or missed menses. Additionally, girls often are reluctant
to discuss this very private topic with a parent, although they may confide in
another trusted adult. Some girls will seek medical attention for cycle varia-
tions that actually fall within the normal range. Others are unaware that their
bleeding patterns are abnormal and may be attributable to significant under-
lying medical issues with the potential for long-term health consequences.
Clinicians also may be unsure about normal ranges for menstrual cycle
length and for amount and duration of flow through adolescence. Clinicians
who are confident in their understanding of early menstrual bleeding patterns
may convey information to their patients more frequently and with less
prompting; girls who have been educated about menarche and early men-
strual patterns will experience less anxiety when they occur (1). By includ-
ing an evaluation of the menstrual cycle as an additional vital sign, clinicians
reinforce its importance in assessing overall health status for both patients
and parents. Just as abnormal blood pressure, heart rate, or respiratory rate
may be key to the diagnosis of potentially serious health conditions, identi-
American Academy
of Pediatrics
DEDICATED TO THE HEALTH OF ALL CHILDREN
25 COMMITTEE OPINIONS 25 25
fication of abnormal menstrual patterns through
adolescence may permit early identification of
potential health concerns for adulthood.
Normal Menstrual Cycles
Menarche
From the early 1800s to the mid-1950s, menarche
occurred at increasingly younger ages in the United
States, but there has been no further decline in the
past 4050 years. This finding also has been seen in
international studies of other developed urban popu-
lations (2). The U.S. National Health and Nutrition
Examination Surveys have found no significant
change in the median age at menarche over the past
30 years except among the non-Hispanic black pop-
ulation, which has a 5.5-month earlier age at menar-
che than it did 30 years ago (3). Age at menarche
varies internationally and especially in less devel-
oped countries; in Haiti, for example, the mean age
at menarche is 15.37 years (4, 5). This knowledge
may be especially pertinent for practitioners with a
large number of immigrant families in their patient
population. Although onset of puberty and menarche
typically occur at a later age in females from less
well-developed nations, two large studies have con-
firmed that a higher gain in body mass index (BMI)
during childhood is related to an earlier onset of
puberty (6, 7). This earlier onset of puberty may
result from attainment of a minimal requisite body
mass at a younger age. Other possible explanations
for the perceived trend in timing and progression of
puberty are environmental factors, including socio-
economic conditions, nutrition, and access to pre-
ventive health care (8).
Despite variations worldwide and within the
U.S. population, median age at menarche has
remained relatively stable, between 12 and 13 years,
across well-nourished populations in developed
countries. The median age of females when they have
their first period or menarche is 12.43 years (see the
box) (3). Only 10% of females are menstruating at
age 11.11 years; 90% are menstruating by age 13.75
years. The median age at which black females begin
to menstruate is earlier (12.06 years) than the median
age for Hispanic females (12.25 years) and non-
Hispanic white females (12.55 years) (3). Although
black girls start to mature earlier than non-Hispanic
white and Hispanic girls, U.S. females complete sec-
ondary sexual development at approximately the
same ages (9). Menarche typically occurs within 23
years after thelarche (breast budding), at Tanner stage
IV breast development, and is rare before Tanner
stage III development (10). Menarche correlates with
age at onset of puberty and breast development. In
girls with early onset of breast development, the
interval to menarche is longer (3 years or more) than
in girls with later onset (1113). By age 15 years,
98% of females will have had menarche (3, 14).
Traditionally, primary amenorrhea has been defined
as no menarche by age 16 years; however, many
diagnosable and treatable disorders can and should
be detected earlier, using the statistically derived
guideline of age 1415 years (3, 14). Thus, an evalu-
ation for primary amenorrhea should be considered
for any adolescent who has not reached menarche by
15 years or has not done so within 3 years of the-
larche. Accordingly, lack of breast development by
age 13 years also should be evaluated (15).
Cycle Length and Ovulation
Menstrual cycles often are irregular through adoles-
cence, particularly the interval from the first to the
second cycle. According to the World Health Organi-
zations international and multicenter study of 3,073
girls, the median length of the first cycle after menar-
che was 34 days, with 38% of cycle lengths exceed-
ing 40 days. Variability was wide: 10% of females
had more than 60 days between their first and second
menses, and 7% had a first-cycle length of 20 days
(16). Most females bleed for 27 days during their
first menses (1719). Early menstrual life is charac-
terized by anovulatory cycles (20, 21), but the fre-
quency of ovulation is related to both time since
menarche and age at menarche (2123). Early
menarche is associated with early onset of ovulatory
cycles. When age at menarche is younger than 12
years, 50% of cycles are ovulatory in the first gyne-
cologic year (year after menarche).
By contrast, it may take 812 years after menar-
che until females with later-onset menarche are fully
Normal Menstrual Cycles in Young Females
Menarche (median age): 12.43 years
Mean cycle interval: 32.2 days in first gynecologic
year
Menstrual cycle interval: typically 2145 days
Menstrual flow length: 7 days or less
Menstrual product use: three to six pads or tampons
per day
COMPENDIUM OF SELECTED PUBLICATIONS 26 26 26
ovulatory (23). Despite variability, most normal
cycles range from 21 to 45 days, even in the first
gynecologic year (1618), although short cycles of
fewer than 20 days and long cycles of more than 45
days may occur. Because long cycles most often
occur in the first 3 years postmenarche, that overall
trend is toward shorter and more regular cycles with
increasing age. By the third year after menarche,
6080% of menstrual cycles are 2134 days long, as
is typical of adults (16, 18, 24). An individuals nor-
mal cycle length is established around the sixth
gynecologic year, at a chronologic age of approxi-
mately 19 or 20 years (16, 18).
Two large studies, one cataloging 275,947
cycles in 2,702 females and another reporting on
31,645 cycles in 656 females, support the observa-
tion that menstrual cycles in girls and adolescents
typically range from 21 to approximately 45 days,
even in the first gynecologic year (25, 26). In the
first gynecologic year, the fifth percentile for cycle
length is 23 days and the 95th percentile is 90 days.
By the fourth gynecologic year, fewer females are
having cycles that exceed 45 days, but anovulation is
still significant for some, with the 95th percentile for
cycle length at 50 days. By the seventh gynecologic
year, cycles are shorter and less variable, with the
fifth percentile for cycle length at 27 days and the
95th percentile at only 38 days. Thus, during the
early years after menarche, cycles may be somewhat
long because of anovulation, but 90% of cycles will
be within the range of 2145 days (16).
Abnormal Menstrual Cycles
Prolonged Interval
A number of medical conditions can cause irregular
or missed menses. Although secondary amenorrhea
has been defined as the absence of menses for 6
months, it is statistically uncommon for girls and
adolescents to remain amenorrheic for more than 3
months or 90 daysthe 95th percentile for cycle
length. Thus, it is valuable to begin evaluation of
secondary amenorrhea after the absence of menses
for 90 days. Therefore, girls and adolescents with
chaotically irregular cycles with more than 3 months
between periods should be evaluated, not reassured
that it is normal to have irregular periods in the
first gynecologic years.
Irregular menses may be associated with many
conditions, including pregnancy, endocrine disorders,
and acquired medical conditions because all of these
conditions are associated with derangement of hypo-
thalamicpituitary endocrine function (see the box).
Commonly, polycystic ovary syndrome (PCOS) caus-
es prolonged intervals between menstrual periods,
especially in patients with signs of androgen excess.
The pathogenesis of PCOS is unclear; many experts
believe that PCOS results from primary functional
intraovarian overproduction of androgen. Others
believe that excessive luteinizing hormone secretion
from the pituitary gland, which stimulates a sec-
ondary ovarian androgen excess, has a role in causing
the disorder. Still others hypothesize that PCOS may
be related to hyperinsulinism. Whatever its origins,
PCOS accounts for 90% of hyperandrogenism among
females and, by definition, is characterized by amen-
orrhea and oligomenorrhea. Before the diagnosis is
confirmed, hyperprolactinemia, adrenal and ovarian
tumors, and drug effects (such as those caused by
danazol and several psychotropic medications) must
be ruled out. Additionally, although uncommon in the
general population, congenital adrenal hyperplasia
should be ruled out by a negative 17-hydroxypro-
gesterone test result (serum concentrations of less
than 1,000 ng/dL) (27). Treatment of PCOS should
target menstrual irregularities, hirsutism if present,
obesity, or insulin resistance.
Menstrual irregularities can be caused by distur-
bance of the central gonadotropin-releasing hormone
pulse generator as well as by significant weight loss,
strenuous exercise, substantial changes in sleeping
or eating habits, and severe stressors. Menstrual dis-
turbances also occur with chronic diseases, such as
Causes of Menstrual Irregularity
Pregnancy
Endocrine causes
Poorly controlled diabetes mellitus
Polycystic ovary syndrome
Cushings disease
Thyroid dysfunction
Premature ovarian failure
Late-onset congenital adrenal hyperplasia
Acquired conditions
Stress-related hypothalamic dysfunction
Medications
Exercise-induced amenorrhea
Eating disorders (both anorexia and bulimia)
Tumors
Ovarian tumors
Adrenal tumors
Prolactinomas
27 COMMITTEE OPINIONS 27 27
poorly controlled diabetes mellitus; with genetic and
congenital conditions, such as Turners syndrome;
and with other forms of gonadal dysgenesis. The
diagnosis of pregnancy always should be excluded,
even if the history suggests the patient has not been
sexually active.
Excessive Menstrual Flow
A females first period usually is reported to be of
medium flow, and the need for menstrual hygiene
products is not typically excessive. Although experts
typically report that the mean blood loss per menstru-
al period is 30 mL per cycle and that chronic loss
of more than 80 mL is associated with anemia, this
has limited clinical utility because most females are
unable to measure their blood loss. However, a recent
study in adult women confirms that the perception of
heavy menstrual flow is correlated with a higher
objective volume of blood loss (28).
Attempts to measure menstrual blood loss on
the basis of the number of pads or tampons used per
day or the frequency of pad changes are subject to
variables such as the individuals fastidiousness, her
familiarity or comfort with menstrual hygiene prod-
ucts, and even variation among types and brands
of pads or tampons (29). Most report changing a pad
approximately three to six times a day, although
external constraints such as school rules and limited
time between classes may make menstrual hygiene
more problematic for adolescents than for adults.
Menstrual flow requiring changes of menstrual
products every 12 hours is considered excessive,
particularly when associated with flow that lasts
more than 7 days at a time. This type of acute men-
orrhagia, although most often associated with
anovulation, also has been associated with the diag-
nosis of hematologic problems, including von
Willebrands disease and other bleeding disorders,
or other serious problems, including hepatic failure
and malignancy (3033).
The prevalence of von Willebrands disease is
1% in the general population. Von Willebrands
disease is the most common medical disorder asso-
ciated with menorrhagia at menarche (34). As many
as one in six girls presenting to an emergency
department with acute menorrhagia may have von
Willebrands disease (30). Therefore, hematologic
disorders should be considered in patients present-
ing with menorrhagiaespecially those presenting
acutely at menarche. Hormonal treatment, in the
form of estrogen therapy, may affect hematologic
factors and mask the diagnosis. Blood collection to
screen for hematologic disorders should be obtained
before initiating treatment. Evaluating the patient
may include referral to a hematologist or a special-
ized hemophilia treatment center for appropriate
screening.
Anticipatory Guidance
Because development of secondary sex characteris-
tics begins at ages as young as 8 years, primary care
clinicians should include pubertal development in
their anticipatory guidance to children and parents
from this age on. Clinicians should take an ongoing
history and perform a complete annual examination,
including the inspection of the external genitalia. It
is important to educate children and parents about
the usual progression of puberty. This includes the
likelihood that a childs initial breast growth may be
unilateral and slightly tender. Breast development
will likely then become bilateral, but some asymme-
try is normal. Young females and their parents
should understand that the progression of puberty
also includes the development of pubic hair, which
will increase in amount over time and become thick-
er and curlier. Additionally, clinicians should convey
that females will likely begin to menstruate approx-
imately 22.5 years after breast development begins,
keeping in mind that recent studies have suggested
that the onset of both breast development and
menarche may occur slightly earlier for black girls
than for white girls (35). Young females should
understand that menstruation is a normal part of
development and should be instructed on use of fem-
inine products and on what is considered normal
menstrual flow. Ideally, both parents and clinicians
can participate in this educational process.
Evaluation
Once young females begin menstruating, evaluation
of the menstrual cycle should be included with an
assessment of other vital signs. By including this
information with the other vital signs, clinicians
emphasize the important role of menstrual patterns
in reflecting overall health status. Clinicians should
ask at every visit for the first date of the patients last
menstrual period. Clinicians should convey that the
menstrual cycle is from the first day of a period to the
first day of the next period and may vary in length.
COMPENDIUM OF SELECTED PUBLICATIONS 28 28 28
Both the American Academy of Pediatrics and
the American College of Obstetricians and Gynecol-
ogists recommend preventive health visits during
adolescence to begin a dialogue and establish an envi-
ronment where a patient can feel good about taking
responsibility for her own reproductive health and
feel confident that her concerns will be addressed in
a confidential setting (36, 37). These visits are also
an opportunity to provide guidance to young females
and their parents on adolescent physical development
based on data that define normal pubertal develop-
ment, menarche, and menstrual cyclicity (38). Even
during visits with adult patients who interact with
adolescents or have children, education about appro-
priate expectations and normal patterns for the men-
strual cycle may be helpful guidance in the decision
to consider evaluation.
Asking the patient to begin to chart her menses
may be beneficial, especially if the bleeding history is
too vague or considered to be inaccurate. Although
uncommon, abnormalities do occur. Confirming nor-
mal internal and external genital anatomy with a
pelvic examination or ultrasonography can rule out
significant abnormalities. Therefore, one might con-
sider the menstrual cycle as a type of vital sign and an
indicator of other possible medical problems. Using
menarche or the menstrual cycle as a sensitive vital
sign adds a powerful tool to the assessment of normal
hormonal development and the exclusion of serious
abnormalities, such as anorexia nervosa, inflammato-
ry bowel disease, and many other chronic illnesses.
Menstrual conditions that suggest the need for further
evaluation are listed in the box.
Because menarche is such an important mile-
stone in physical development, it is important to be
able to educate young females and their parents
regarding what to expect of a first period and about
the range for normal cycle length of subsequent
menses. Girls who have been educated about early
menstrual patterns will experience less anxiety as
development progresses (1). It is equally important
for clinicians to have an understanding of bleeding
patterns of young females, the ability to differentiate
between normal and abnormal menstruation, and the
skill to know how to evaluate the young female
patient appropriately.
References
1. Frank D, Williams T. Attitudes about menstruation among
fifth-, sixth-, and seventh-grade pre- and post-menarcheal
girls. J Sch Nurs 1999;15:2531.
2. Wyshak G, Frisch RE. Evidence for a secular trend in age
of menarche. N Engl J Med 1982;306:10335.
3. Chumlea WE, Schubert CM, Roche AF, Kulin HE, Lee
PA, Himes JH, et al. Age at menarche and racial compar-
isons in US girls. Pediatrics 2003;111:1103.
4. Thomas F, Renaud F, Benefice E, de Meeus T, Guegan JF.
International variability of ages at menarche and meno-
pause: patterns and main determinants. Hum Biol 2001;
73:27190.
5. Barnes-Josiah D, Augustin A. Secular trend in the age at
menarche in Haiti. Am J Hum Biol 1997;7:35762.
6. He Q, Karlberg J. BMI in childhood and its association
with height gain, timing of puberty and final height.
Pediatr Res 2001;49:24451.
7. Wang Y. Is obesity associated with early sexual matura-
tion? A comparison of the association in American boys
versus girls. Pediatrics 2002;110:90310.
8. Apter D, Hermanson E. Update on female pubertal devel-
opment. Curr Opin Obstet Gynecol 2002;14:47581.
9. Sun SS, Schubert CM, Chumlea WC, Roche AF, Kulin
HE, Lee PA, et al. National estimates of the timing of sex-
ual maturation and racial differences among US children.
Pediatrics 2002;110:9119.
10. Marshall WA, Tanner JM. Variations in pattern of puber-
tal changes in girls. Arch Dis Child 1969;44:291303.
11. Marti-Henneberg C, Vizmanos B. The duration of puber-
ty in girls is related to the timing of its onset. J Pediatr
1997;131:61821.
12. Llop-Vinolas D, Vizmanos B, Closa Monasterolo R,
Escribano Subias J, Fernandez-Ballart JD, Marti-Henne-
berg C. Onset of puberty at eight years of age in girls
determines a specific tempo of puberty but does not affect
adult height. Acta Paediatr 2004;93:8749.
Menstrual Conditions That
May Require Evaluation
Menstrual periods that:
Have not started within 3 years of thelarche
Have not started by 13 years of age with no signs of
pubertal development
Have not started by 14 years of age with signs of
hirsutism
Have not started by 14 years of age with a history
or examination suggestive of excessive exercise or
eating disorder
Have not started by 14 years of age with concerns
about genital outflow tract obstruction or anomaly
Have not started by 15 years of age
Are regular, occurring monthly, and then become
markedly irregular
Occur more frequently than every 21 days or less fre-
quently than every 45 days
Occur 90 days apart even for one cycle
Last more than 7 days
Require frequent pad or tampon changes (soaking
more than one every 12 hours)
29 COMMITTEE OPINIONS 29 29
13. Largo RH, Prader A. Pubertal development in Swiss girls.
Helv Paediatr Acta 1983;38:22943.
14. National Center for Health Statistics. Age at menarche:
United States. Rockville (MD): NCHS; 1973. Available
at: http://www.cdc.gov/nchs/data/series/sr_11/sr11_133.
pdf. Retrieved June 26, 2006.
15. Reindollar RH, Byrd JR, McDonough PG. Delayed sexu-
al development: a study of 252 patients. Am J Obstet
Gynecol 1981;140:37180.
16. World Health Organization multicenter study on men-
strual and ovulatory patterns in adolescent girls. II.
Longitudinal study of menstrual patterns in the early post-
menarcheal period, duration of bleeding episodes and
menstrual cycles. World Health Organization Task Force
on Adolescent Reproductive Health. J Adolesc Health
Care 1986;7:23644.
17. Flug D, Largo RH, Prader A. Menstrual patterns in ado-
lescent Swiss girls: a longitudinal study. Ann Hum Biol
1984;11:495508.
18. Widholm O, Kantero RL. A statistical analysis of the
menstrual patterns of 8,000 Finnish girls and their moth-
ers. Acta Obstet Gynecol Scand Suppl 1971;14:(suppl
14):136.
19. Zacharias L, Rand WM, Wurtman RJ. A prospective study
of sexual development and growth in American girls: the
statistics of menarche. Obstet Gynecol Surv 1976;31:
32537.
20. Venturoli S, Porcu E, Fabbri R, Magrini O, Paradisi R,
Pallotti G, et al. Postmenarchal evolution of endocrine
pattern and ovarian aspects in adolescents with menstrual
irregularities. Fertil Steril 1987;48:7885.
21. Venturoli S, Porcu E, Fabbri R, Magrini O, Grammi L,
Paradisi R, et al. Longitudinal evaluation of the different
gonadotropin pulsatile patterns in anovulatory cycles of
young girls. J Clin Endocrinol Metab 1992;74:83641.
22. Apter D, Vihko R. Early menarche, a risk factor for breast
cancer, indicates early onset of ovulatory cycles. J Clin
Endocrinol Metab 1983;57:826.
23. Vihko R, Apter D. Endocrine characteristics of adolescent
menstrual cycles: impact of early menarche. J Steroid
Biochem 1984;20:2316.
24. Hickey M, Balen A. Menstrual disorders in adolescence:
investigation and management. Hum Reprod Update
2003;9:493504.
25. Treloar AE, Boynton RE, Behn BG, Brown BW. Variation
of the human menstrual cycle through reproductive life.
Int J Fertil 1967;12:77126.
26. Vollman RF. The menstrual cycle. Major Probl Obstet
Gynecol 1977;7:1193.
27. Cowan JT, Graham MG. Polycystic ovary syndrome:
more than a reproductive disorder. Patient Care 2003;37:
2333.
28. Warner PE, Critchley HO, Lumsden MA, Campbell-
Brown M, Douglas A, Murray GD. Menorrhagia I: mea-
sured blood loss, clinical features, and outcome in women
with heavy periods: a survey with follow-up data. Am J
Obstet Gynecol 2004;190:121623.
29. Grimes DA. Estimating vaginal blood loss. J Reprod Med
1979;22:1902.
30. Claessens E, Cowell CA. Acute adolescent menorrhagia.
Am J Obstet Gynecol 1981;139:27780.
31. Bevan JA, Maloney KW, Hillery CA, Gill JC, Mont-
gomery RR, Scott JP. Bleeding disorders: a common
cause of menorrhagia in adolescents. J Pediatr 2001;138:
85661.
32. Ellis MH, Beyth Y. Abnormal vaginal bleeding in adoles-
cence as the presenting symptom of a bleeding diathesis.
J Pediatr Adolesc Gynecol 1999;12:12731.
33. Duflos-Cohade C, Amandruz M, Thibaud E. Pubertal
metrorrhagia. J Pediatr Adolesc Gynecol 1996;9:1620.
34. Castaman G, Federici AB, Rodeghiero F, Mannucci PM.
Von Willebrands disease in the year 2003: towards com-
plete identification of gene defects for correct diagnosis
and treatment. Haematologica 2003;88:94108.
35. Herman-Giddens ME, Slora EJ, Wasserman RC, Bour-
dony CJ, Bhapkar MV, Koch GG, et al. Secondary sexual
characteristics and menses in young girls seen in office
practice: a study from the Pediatric Research in Office
Settings Network. Pediatrics 1997;99:50512.
36. American Academy of Pediatrics. Guidelines for health
supervision III. Elk Grove Village (IL): AAP; 2002.
37. American College of Obstetricians and Gynecologists.
Health care for adolescents. Washington, DC: ACOG;
2003.
38. Adams Hillard PJ. Menstruation in young girls: a clinical
perspective. Obstet Gynecol 2002;99:65562.
COMPENDIUM OF SELECTED PUBLICATIONS 30 30 30
Committee on
Adolescent Health Care
ACOG
Number 350, November 2006
Committee
Opinion
This document reflects emerging
clinical and scientific advances as
of the date issued and is subject
to change. The information should
not be construed as dictating an
exclusive course of treatment or
procedure to be followed.
The Committee would like to
thank Nichole Zidenberg, MD,
and Patricia S. Simmons, MD,
for their assistance in the devel-
opment of this document.
Copyright November 2006
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of this
publication may be reproduced,
stored in a retrieval system,
posted on the Internet, or trans-
mitted, in any form or by any
means, electronic, mechanical,
photocopying, recording, or oth-
erwise, without prior written per-
mission from the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Breast concerns in the adolescent.
ACOG Committee Opinion No. 350.
American College of Obstetricians
and Gynecologists. Obstet Gynecol
2006;108:132936
Breast Concerns in the Adolescent
ABSTRACT: Breast disease in the adolescent female encompasses an expan-
sive array of topics. Benign disease overwhelmingly dominates the differen-
tial diagnosis and dictates a different protocol for care in the adolescent
compared with the adult patient to avoid inappropriately high assessments of
risk and unnecessary diagnostic procedures and surgery. There also are
emerging issues pertaining to the care of the adolescent breast, such as
breast augmentation, nipple piercing, and management of the adolescent
patient with a family history of breast cancer.
Breast disease in the adolescent female encompasses an expansive array of
topics. Common presenting signs and symptoms in the adolescent patient are
breast pain, nipple discharge, and the discovery of a mass (1, 2). Benign dis-
ease overwhelmingly dominates the differential diagnosis and dictates a dif-
ferent protocol for care in the adolescent compared with the adult patient.
Family practitioners, pediatricians, nurse practitioners, and obstetrician
gynecologists most commonly encounter and manage adolescent patients
with breast disease. Many of these adolescents are referred for evaluation to
general surgeons and breast centers with little experience with or familiarity
with the data for this population. Their adult frame of reference can lead to
inappropriately high assessments of risk and unnecessary diagnostic proce-
dures and surgery.
Breast Development
As growth of the pubertal breast begins, it is often asymmetric. A unilateral
breast lump just beneath the areola in an 810-year-old patient is invariably
a developing breast bud. Biopsy in prepubertal girls or girls in early puberty
is rarely indicated and should almost always be avoided because it can irre-
versibly damage the breast bud. It is estimated that approximately 25% of
adolescent females have breast asymmetry that persists into adulthood (3). In
addition to the most common cause of breast asymmetry, normal variation in
breast size, the differential diagnosis includes unilateral hypoplasia or amas-
tia, unilateral hypertrophy or large breast mass, and Polands syndrome (con-
genital underdevelopment or absence of the chest muscle on one side of the
body). Failure of bilateral development of the breasts can be caused by
delayed puberty or rarely by bilateral hypoplasia or amastia. Careful assess-
31 COMMITTEE OPINIONS 31 31
ment of unilateral or bilateral breast hypoplasia is
important before any surgical intervention is initiated.
Common Adolescent Breast Concerns
Mastalgia
Breast pain, or mastalgia, is a common symptom in
the adolescent. Symptoms also may include mild
swelling and palpable nodularity, consistent with
fibrocystic changes, usually in the upper outer quad-
rant. The symptoms are typically cyclic and worse
premenstrually. Supportive measures and reassur-
ance are the best treatment. For adolescent patients
who are smokers, smoking cessation should be
encouraged because nicotine has been shown to
increase breast pain. Some studies suggest that
dietary modifications, such as eliminating coffee,
tea, and caffeinated sodas, can reduce breast pain (4,
5). A well fitting bra, particularly a sports bra dur-
ing exercise has been shown to reduce pain during
movement. Analgesics such as naproxen sodium or
ibuprofen alleviate the symptoms. Oral contracep-
tives also may be helpful with fibrocystic changes.
Nipple discharge
Nipple discharge in the adolescent can be white,
clear, red, yellow, green, or brown and is usually
benign in nature. Nipple discharge often is sec-
ondary to local irritation or stimulation, pregnancy,
or use of medications such as antipsychotics, oral
contraceptives, or opiates. Ductal ectasia is a benign
and common finding in the developing breast. It con-
sists of dilation of the mammary ducts, periductal
fibrosis and inflammation. The patient may present
with nipple discharge that may be bloody or dark
brown in nature, or a mass, or both. A bloody nipple
discharge, when associated with a mass, can be seen
in papilloma or papillomatosis and should be evalu-
ated because of the malignant potential of these con-
ditions. Ultrasonography is often used to assist in the
diagnosis and to reassure the patient of her status.
Except in papilloma or papillomatosis, observation
is recommended. As in adults, hyperprolactinemia
can cause galactorrhea in adolescents, thus the
appropriate laboratory and imaging studies should
be ordered in the evaluation process. Treatment is
directed by the results of the history, physical exam-
ination, and laboratory studies. As indicated, use of
the offending drugs is stopped, hypothyroidism is
treated, and prolactin tumors are managed medic-
ally or surgically. Typically, the patient should be
educated regarding behavioral changes to avoid nip-
ple stimulation, and observation is recommended.
Breast Mass
Of all breast masses diagnosed in adolescents, recent
retrospective chart reviews demonstrate that approx-
imately 67% are fibroadenomas, 15% are fibrocystic
changes, and 3% are abscess or mastitis (see the
box) (6). In one longitudinal study of adolescent
females with a breast mass, follow-up over a 79
month period demonstrated that 77% of adolescents
had lesions that either resolved or did not enlarge,
and no malignancies were diagnosed (7).
Breast Masses in the Adolescent Female
Benign
Fibroadenoma
Fibrocystic changes or cysts
Unilateral thelarche
Hemangioma
Intramammary lymph node
Fat necrosis
Abscess
Mastitis
Lipoma
Hematoma
Hamartoma
Micromastia (juvenile hypertrophy)
Galactocele
Intraductal papilloma
Juvenile papillomatosis
Lymphangioma
Malignant
Malignant cystosarcoma phyllodes
Breast carcinoma
Metastatic disease
Lymphoma, neuroblastoma, sarcoma, rhabdomyosar-
coma, acute leukemia
Data from Dehner LP, Hill DA, Deschryver K. Pathology
of the breast in children, adolescents, and young adults.
Semin Diagn Pathol 1999;16:23547; Simmons PS.
Diagnostic considerations in breast disorders of children
and adolescents. Obstet Gynecol Clin North Am 1992;
19:91102; and Laufer MR, Goldstein DP. The breast:
examination and lesions. In: Emans SJ, Laufer MR,
Goldstein DP, editors. Pediatric and adolescent gyne-
cology. 5th ed. Philadelphia (PA): Lippincott Williams &
Wilkins; 2005. p. 72959.
COMPENDIUM OF SELECTED PUBLICATIONS 32 32 32
Breast Hypertrophy
Idiopathic breast hypertrophy occurs in adolescents
and adults. When noted in adolescents, it is referred
to as juvenile or virginal breast hypertrophy.
Juvenile breast hypertrophy involves the uncon-
trolled overgrowth of breast tissue that occurs in
adolescents whose breasts develop normally during
puberty, but then continue to grow. This rapid
growth can be unilateral or bilateral and usually
occurs shortly after thelarche.
For many adolescents, breast hypertrophy and
persistent significant asymmetry can result in both
psychologic and physical consequences. These ado-
lescents often receive negative attention, experience
difficulties with athletics, and have more socializa-
tion problems that may lead to poor self-esteem and
isolation from family and peers (8). These conse-
quences have resulted in the development of eating
disorders in some adolescent females to compensate
for their breast size (9).
Surgical correction by enlarging one breast with
an implant, surgical reduction of the larger breast,
or a bilateral reduction mammoplasty can improve
the quality of life considerably. Studies have demon-
strated that the improvement of self-esteem seems to
be the most significant benefit of breast surgery (10,
11). Studies also have demonstrated that breast
reduction in adolescents with large breasts relieves
back, shoulder, and neck pain (10, 12).
Postoperatively, adolescent patients have the
same short- and long-term potential complications as
adult patients, including incisional separation, scar-
ring, sensory loss, and infection. Long-term compli-
cations, such as the possible inability to breastfeed,
also have been described in adults undergoing reduc-
tion mammoplasty; however, there are numerous sur-
gical techniques, some of which preserve the ability
to breastfeed (8). One study of adolescent patients
who underwent reduction mammoplasty between the
ages of 15 years and 17 years, found that these
patients subsequently breastfed their infants with
complication rates similar to those in the general
population (13). Overall, the most commonly cited
short-term complication is pain; the long-term com-
plications cited are related to scarring (10, 12). The
adolescent patient population reports satisfaction
with reduction mammoplasty exceeding 75%, even
when surveyed several years postoperatively (11, 12).
In one study of adolescent patients who underwent
bilateral breast reduction, 94% would recommend it
to a teenaged friend with a similar condition (10).
There is no definitive guideline for when breast
reduction should be suggested. An assessment of the
adolescents emotional, psychologic, and physical
maturity is recommended to guide this decision.
Breast development is variable, and several recom-
mendations regarding the timing of surgery have
been made, including postponing surgery until
breast maturity is reached, waiting for 6 months with
no change in bra size, or after the age of 18 years.
Surgery can be considered earlier when severe symp-
toms are encountered (14). The incidence of breast
regrowing after initial reduction during adolescence
is not known, but it has been reported (15). A psy-
chologic evaluation is a reasonable surgical prereq-
uisite because the plastic surgeon needs to fully
understand the motivation, maturity, and psychoso-
cial and emotional attributes of the patient seeking
this surgery. The plastic surgeon should be confident
that the adolescent has realistic goals and fully
understands the risks and benefits, including the lim-
itations of breast surgery (14).
Breast Augmentation
Plastic surgery involving augmentation of adoles-
cent breasts stimulates debate both socially and
medically. Over the past several years, the number of
cosmetic surgical procedures performed in patients
aged 18 years or younger has increased substantially
(16). Breast augmentations were less than 5% of the
total number of cosmetic surgical procedures per-
formed on this age group.
The number of adolescent females seeking
breast augmentation for aesthetic purposes is consid-
erable. This can be attributed to factors such as
media influence and distorted perceptions of an ideal
body type. In response to this trend, the American
Society for Plastic Surgery has adopted guidelines
for the appropriate selection of adolescents for aes-
thetic breast surgery (17). The guidelines acknowl-
edge that the U.S. Food and Drug Administration
considers the use of breast implants for aesthetic
breast augmentation in patients younger than 18
years to be an off-label use. They state that adoles-
cent candidates for purely aesthetic breast augmenta-
tion should be at least 18 years of age and recognize
that aesthetic breast surgery in the adolescent female
encompasses unique mental and physical com-
ponents. The adolescent and her parent should be
counseled regarding risks, activity restrictions, and
recovery time for the procedure being considered.
33 COMMITTEE OPINIONS 33 33
It is important to understand that for some ado-
lescents, breast augmentation leads to a successful
outcome. A less mature adolescent may have unre-
alistic expectations and be disappointed by the out-
come. For example, self-esteem issues may not
be resolved. An assessment of an adolescents
emotional, psychologic, and physical maturity is,
therefore, a reasonable surgical prerequisite. The
adolescent and her parent should be counseled that
breast implants are not typically associated with
breastfeeding difficulties or an increased risk of
breast cancer. The surgery may, however, make
future mammographic screening more difficult.
Nipple Piercing
Nipple piercing has become increasingly popular
and an emerging concern, particularly for the adoles-
cent. There is a paucity of research in the area of nip-
ple piercing, specifically addressing prevalence and
complications. The most common health risks asso-
ciated with piercing include infections, pain, bleed-
ing, hematoma, cyst formation, allergic reaction, and
keloid formation (18, 19). Nipple piercing has been
associated with a transmission risk for hepatitis B
and hepatitis C (20) and human immunodeficiency
virus (HIV) (21). There also are a growing number
of case reports of development of a breast abscess
after nipple piercing. A recent review of the literature
reports 10 cases of breast abscess after nipple pierc-
ing (22). The average time from piercing to diagno-
sis is 5 months because of a prolonged incubation
and wound healing time for nipple piercing. The
healing time after nipple piercing is 36 months,
which is longer than piercing of some other sites
(Table 1). In addition, patients may delay seeking
treatment after nipple piercing. Major complications
associated with an abscess after nipple piercing can
include endocarditis, heart valve injury, cardiac pros-
thesis infection, metal foreign body reaction in
breast tissue, or recurrent infections. Undue anxiety
may be caused by an incorrect initial diagnosis of
breast cancer in the pierced breast. Based on current
data, clinical recommendations for patients with
postpiercing infections should include antibiotic
treatment and removal of the nipple ring; screening
for hepatitis B, hepatitis C, and HIV; and glucose
testing to exclude diabetes mellitus, with its risk of
increased infection rate (22). Given the increasing
popularity of piercing, clinicians should routinely
screen adolescents for intent to undergo a piercing.
For those who intend to undergo a piercing, educa-
tion should be provided regarding safer piercing
strategies. Clinicians also should encourage these
individuals to become immunized against hepatitis B
and tetanus before the piercing, if they are not
already immune. Adolescents who have any of the
following factors should be advised to avoid nipple
piercing: alcohol or substance intoxication, metal
allergies (especially to nickel), anticoagulant ther-
apy, a history of chronic or acute infections, steroid
therapy, diabetes, and heart valve defects or any
other causes of immune suppression. For many
adolescents seeking advice regarding nipple pierc-
ing, the Internet is often their primary and sole
reference (see Resources). It is common for adoles-
cents to present with piercing complications and
quote or follow the advice provided on these
Internet web sites. Information on many of the
Internet web sites on nipple piercing conflict with
expert medical opinion.
Breast cancer
Primary breast cancer occurs rarely in the adolescent
patient. During the period 19982002, the incidence
of breast cancer in patients younger than 20 years
was 0 per 100,000. During the same period, the inci-
dence of breast cancer in women younger than 24
years of age was 1.3 per 100,000 (23). Malignancies
that occur in the adolescent breast are more likely
metastatic from another primary malignancy (24).
Although primary breast cancer is uncommon, risk
Table 1. Healing Time for Piercing by Body Part
Pierced Body Part Time It Takes to Heal
Nipple 36 months
Ear lobe 68 weeks
Ear cartilage 4 months to 1 year
Eyebrow 68 weeks
Nostril 24 months
Nasal septum 68 months
Nasal bridge 810 weeks
Tongue 4 weeks
Lip 23 months
Navel 4 months to 1 year
Female genitalia 410 weeks
Male genitalia 4 weeks to 6 months
Center for Young Womens Health, Childrens Hospital Boston. Body
piercing: a guide for teens. Available at: http://www.youngwomen-
shealth.org/body-piercing.html. Retrieved June 13, 2006. Copyright
2006. All rights reserved. Modified and reprinted with permission.
COMPENDIUM OF SELECTED PUBLICATIONS 34 34 34
factors for malignancy of the breast should be
assessed. Clinical evidence demonstrates that radia-
tion exposure, such as that seen with the treatment
of childhood cancer, to the prepubertal and pubertal
breast of females between the ages of 10 years and
30 years is associated with the greatest risk of radi-
ation-induced breast cancer later in life (25).
Clinical Management of a Breast
Abnormality
Ultrasonography generally is the best imaging
modality to study the adolescent breast (26, 27).
Mammography is not indicated in adolescents
because it offers poor image quality and is associ-
ated with both false-positive and false-negative
results due to the dense nature of the fibroglandular
tissues (28). Mammography also has been associ-
ated with unnecessary surgery and the increased risk
of radiation-induced malignant changes (2931).
Although aspiration for relief of pain of cysts can
be useful in the adolescent with a breast mass, fine
needle aspiration for diagnostic purposes has not
been well established in adolescents and should be
discouraged.
Most breast masses diagnosed in adolescents are
fibroadenomas. The majority of longitudinal studies
on fibroadenomas demonstrate that most lesions
decrease in size, and many even completely resolve
and, therefore, should not be excised. Specifically, a
large epidemiologic study of benign breast tumor
cases showed a 13.9% incidence of fibroadenomas
at registration, an increase in fibroadenoma after 5
years, and then a gradual decrease in fibroadenoma
over 8 years (32). Over a 5-year period, one study
examined 25 fibroadenomas and found that 52%
became smaller, 16% remained the same size, and
32% became larger (33). Another study found an
actuarial probability of disappearance of 46% of
lesions at 5 years and 69% at 9 years. It was found
that women 20 years and younger had a higher prob-
ability of resolution of a fibroadenoma than women
older than 20 years. Size or multiplicity of lesions
did not affect the probability of resolution (34).
Given the low risk of malignancy, high likelihood
of spontaneous resolution, and risks of deformity in
the growing breast, conservative, nonsurgical man-
agement is most often appropriate. Excisional biopsy
and surgery should be reserved for breast masses
that are enlarging or associated with overlying skin
changes, abscesses not responding to medical ther-
apy, or suspicious masses presenting in an adoles-
cent with a history of a previous malignancy.
Family History of Breast Cancer
One area of growing interest to gynecologists is the
management of the adolescent patient with a family
history of breast cancer. It is important to be aware
of the complexities of genetic testing, screening rec-
ommendations, and preventive health guidelines.
Currently, a woman living in the United States has a
13.2% lifetime risk of developing breast cancer (35).
A significant risk factor for the development of
breast cancer is a family history of the disease. The
risk in a patient with a first-degree relative affected
by breast cancer increases twofold to threefold (36).
The cumulative risk of breast cancer in women with
BRCA1 or BRCA2 genes ranges from 3.2% at 30
years to 85% at 70 years of age (37). The daughter
of a woman or man who is a BRCA carrier has a 50%
chance of having inherited the gene mutation.
Decisions regarding genetic testing in the adolescent
are complex and should include consideration of the
medical and psychologic implications of genetic
testing for each individual patient and her family.
Referral for genetic counseling by an appropriately
qualified individual is advised for patients consider-
ing genetic testing. Current recommendations out-
lined by the Cancer Genetics Studies Consortium do
not recommend radiographic surveillance for
BRCA1 carriers until 2535 years of age (38). The
National Cancer Institutes most recent summary
(April 2005) concludes that bilateral prophylactic
mastectomy is associated with a reduction in breast
cancer by as much as 90% in adult women with an
increased risk of breast cancer because of strong
family history. However, because of the physical and
psychologic effects of this surgery and its perma-
nence, decisions on this matter are usually deferred
until the individual is at least 35 years of age and has
completed childbearing (39). Therefore, there is no
urgency for testing the adolescent patient. The role
of BRCA1 and BRCA2 testing in adolescents is an
area of much needed research for both evidence-
based management and ethical practice (1).
Prevention of Breast Cancer
Effective and accurate counseling for adolescents
and their parents regarding breast cancer prevention
should be a routine component of preventive health
35 COMMITTEE OPINIONS 35 35
services for adolescents. Smoking, alcohol consump-
tion, and exposure to treatment with ionizing radia-
tion during adolescence have all been associated with
an increase in breast cancer in adulthood (40). It is
prudent to advise adolescents to avoid these expo-
sures. Additional preventive health guidance in all
adolescents should include encouraging exercise in
1224-year-old females because physical activity has
been shown to reduce the risk of breast cancer signif-
icantly (41). There are no rigorous recent scientific
data to support an association between abortions and
breast cancer. One recent prospective study examined
44,000 women with breast cancer from 53 studies
and 16 countries. This study demonstrated that preg-
nancies that end in therapeutic abortion do not
increase a womans risk of developing breast cancer
later in life (42). Some parents and patients are
opposed to oral contraceptive use because of a fear of
associated breast cancer. The National Institute of
Child Health evaluated the risk of breast cancer in
more than 4,500 women who were current or past
users of oral contraceptives. The study found no sig-
nificant increased risk of breast cancer when oral con-
traceptive users were compared with controls (43).
A casecontrol study found that oral contracep-
tive use before age 30 years and oral contraceptive
use for more than 5 years were associated with an
increased risk of breast cancer for BRCA1 carriers,
but not in BRCA2 carriers (44). A more recent cohort
study focused on cases of breast cancer diagnosed
before age 40 years and included a substantial num-
ber of BRCA1 and BRCA2 mutation carriers (45).
Compared with nonuse of oral contraceptives, use of
current low-dose oral contraceptive formulations did
not increase the risk of breast cancer in carriers of
BRCA1 or BRCA2 mutations. A positive family his-
tory of breast cancer, including BRCA1 or BRCA2
mutations, should not be regarded as contraindica-
tions to oral contraceptive use (46).
Breast Self-Examination
Historically, experts have recommended teaching
adolescents to perform breast self-examination for a
variety of reasons, including cancer detection, teach-
ing self-detection for future application, and con-
tributing to greater understanding and comfort with
their changing bodies. There are currently no data to
support these rationales. More recently, experts
observe that it might actually be ill advised to en-
courage breast self-examination in the adolescent
because girls who identify a breast mass themselves
may experience multiple physician visits, invasive
testing, and perhaps unwarranted surgery. These
extensive and expensive evaluations usually lead to
benign findings and unnecessary angst (47). The
American College of Obstetricians and Gynecol-
ogists states that, despite a lack of definitive data for
or against breast self-examination, breast self-exam-
ination may be recommended beginning at age 19
years. Counseling regarding breast self-examination
for those aged 1318 years is not recommended
(48). Some experts have recommended teaching
breast self-examination to adolescent females whose
mothers carry the BRCA1 or BRCA2 gene, begin-
ning at age 1821 years. Early breast self-examina-
tion has been recommended in those at high risk for
breast cancer, such as those with a personal history
of malignancy. Women with previous exposure to
therapeutic chest radiation therapy are advised to
begin breast self-examination 10 years after radia-
tion therapy (1, 2, 49).
Conclusion
Breast disorders in the adolescent female can
cause increased anxiety for the patient and her
family and pose a clinical challenge for her
health care provider.
Malignancy is rare in the adolescent breast. A
different emphasis for care in the adolescent
compared with the adult patient is, therefore,
recommended. Conservative, nonsurgical man-
agement is most often appropriate.
To increase the likelihood of satisfactory out-
comes from breast-reduction or augmentation
surgery, the surgeon should assess the adoles-
cents emotional, psychologic, and physical
maturity.
Given the increasing popularity of piercing,
including nipple piercing, clinicians should rou-
tinely screen adolescents for intent to undergo a
piercing. Preventive counseling and relevant
immunizations should be offered to adolescents
interested in piercing. For patients with post-
piercing infections, prompt treatment of infec-
tions and appropriate screening and testing is
essential.
Further investigation is needed to better counsel
adolescent patients about genetic testing for
breast cancer and the role of breast self-exami-
nation.
COMPENDIUM OF SELECTED PUBLICATIONS 36 36 36
Resources
ACOG Resources
American College of Obstetricians and Gynecologists.
Detecting and treating breast problems. ACOG Patient
Education Pamphlet AP026. Washington, DC: ACOG; 2004.
American College of Obstetricians and Gynecologists.
Fibrocystic breast changes. ACOG Patient Education Pamphlet
AP138. Washington, DC: ACOG; 2000.
Role of the obstetriciangynecologist in the screening and
diagnosis of breast masses. ACOG Committee Opinion No.
334. American College of Obstetricians and Gynecologists.
Obstet Gynecol 2006;107:12134.
Other Resources
The following lists are for informational purposes only.
Referral to these sources and web sites does not imply the
endorsement of ACOG. These lists are not meant to be compre-
hensive. The exclusion of a source or web site does not reflect
the quality of that source or web site. Please note that web sites
are subject to change without notice.
Association of Professional Piercers
PO Box 1287
Lawrence, KS 66044
Web: www.safepiercing.org
Resources for Your Patients
American Academy of Family Physicians
11400 Tomahawk Creek Parkway
Leawood, KS 66211-2672
Tel: (913) 906-6000
Web: www.aafp.org
American Academy of Pediatrics
NY Chapter 2
420 Lakeville Road, Suite 244
New Hyde Park, NY 11042
Web: www.ny2aap.org/tattoos.html
AWARE Foundation
1015 Chestnut Street
Philadelphia, PA 19107-4302
Tel: (215) 955-9847
Web: www.awarefoundation.org
Center for Young Womens Health
Childrens Hospital Boston
333 Longwood Avenue, 5th floor
Boston, MA 02115
Tel: (617) 355-CYWH (2994)
Web: www.youngwomenshealth.org
Go Ask Alice! (by Columbia University Health
Education Program)
Lerner Hall
2920 Broadway, 7th Floor
MC 2608
New York, NY 10027
Tel: (212) 854-5453
Web: www.goaskalice.columbia.edu
References
1. Simmons PS. Breast disorders in adolescent females. Curr
Opin Obstet Gynecol 2001;13:45961.
2. Templeman C, Hertweck SP. Breast disorders in the pedi-
atric and adolescent patient. Obstet Gynecol Clin North
Am 2000;27:1934.
3. Beach RK. Routine breast exams: a chance to reassure,
guide, and protect. Contemp Pediatr 1987;4:70100.
4. Minton JP, Foecking MK, Webster DJ, Matthews RH.
Caffeine, cyclic nucleotides, and breast disease. Surgery
1979;86:1059.
5. Abraham GE. Nutritional factors in the etiology of the
premenstrual tension syndromes. J Reprod Med 1983;
28:44664.
6. Laufer MR, Goldstein DP. The breast: examination and
lesions. In: Emans SJ, Laufer MR, Goldstein DP, editors.
Pediatric and adolescent gynecology. 5th ed. Philadelphia
(PA): Lippincott Williams & Wilkins; 2005. p. 72959.
7. Neinstein LS, Atkinson J, Diamant M. Prevalence and
longitudinal study of breast masses in adolescents. J
Adolesc Health 1993;14:27781.
8. Corriveau S, Jacobs JS. Macromastia in adolescence. Clin
Plast Surg 1990;17:15160.
9. Losee JE, Serletti JM, Kreipe RE, Caldwell EH.
Reduction mammoplasty in patients with bulimia nervosa.
Ann Plast Surg 1997;39:4436.
10. McMahan JD, Wolfe JA, Cromer BA, Ruberg RL. Lasting
success in teenage reduction mammoplasty. Ann Plast
Surg 1995;35:22731.
11. McGrath MH, Mukerji S. Plastic surgery and the teenage
patient. J Pediatr Adolesc Gynecol 2000;13:10518.
12. Lee MC, Lehman JA Jr, Tantri MD, Parker MG, Wagner
DS. Bilateral reduction mammoplasty in an adolescent
population: adolescent bilateral reduction mammoplasty.
J Craniofac Surg 2003;14:6915.
13. Aillet S, Watier E, Chevrier S, Pailheret JP, Grall JY.
Breast feeding after reduction mammaplasty performed
during adolescence. Eur J Obstet Gynecol Reprod Biol
2002;101:7982.
14. McGrath MH, Schooler WG. Elective plastic surgical pro-
cedures in adolescence. Adolesc Med Clin 2004;15:
487502.
15. Mayl N, Vasconez LO, Jurkiewicz MJ. Treatment of
macromastia in the actively enlarging breast. Plast
Reconstr Surg 1974;54:612.
16. American Society of Plastic Surgeons. National
Clearinghouse of Plastic Surgery Statistics. Procedural
statistics trends 1992-2005. Available at: http://www.plas-
ticsurgery.org/public_education/Statistical-Trends.cfm.
Retrieved June 12, 2006.
17. American Society of Plastic Surgeons. Plastic surgery for
teenagers. Available at: http://www.plasticsurgery.org/
news_room/loader.cfm?url=/commonspot/security/get-
file.cfm&PageID=14990. Retrieved June 12, 2006.
18. Mayers LB, Moriarty BW, Judelson DA, Rundell KW.
Complications of body art. Consultant 2002;42:174452.
19. Braithwaite RL, Stephens T, Sterk C, Braithwaite K.
Risks associated with tattooing and body piercing. J
Public Health Policy 1999;20:45970.
20. Conry-Cantilena C, VanRaden M, Gibble J, Melpolder J,
Shakil AO, Viladomiu L, et al. Routes of infection,
37 COMMITTEE OPINIONS 37 37
viremia, and liver disease in blood donors found to have
hepatitis C virus infection. N Engl J Med 1996;334:
16916.
21. Pugatch D, Mileno M, Rich JD. Possible transmission of
human immunodeficiency virus type 1 from body pierc-
ing. Clin Infect Dis 1998;26:7678.
22. Jacobs VR, Golombeck K, Jonat W, Kiechle M. Mastitis
nonpeurperalis after nipple piercing: time to act. Int J
Fertil Womens Med 2003;48:22631.
23. Ries LA, Eisner MP, Kosary CL, Hankey BF, Miller BA,
Clegg L, et al, editors. SEER cancer statistics review,
19752002. Bethesda (MD): National Cancer Institute;
2005. Available at: http://seer.cancer.gov/csr/1975_2002.
Retrieved June 13, 2006.
24. Simmons PS, Wold LE. Surgically treated breast disease
in adolescent females: a retrospective review of 185 cases.
Adolesc Pediatr Gynecol 1989;2:958.
25. Goss PE, Sierra S. Current perspectives on radiation-
induced breast cancer. J Clin Oncol 1998;16(1):33847.
26. Boothroyd A, Carty H. Breast masses in childhood and
adolescence. A presentation of 17 cases and a review of
the literature. Pediatr Radiol 1994;24:814.
27. Adler DD. Ultrasound of benign breast conditions. Semin
Ultrasound CT MR1989;10:10618.
28. Hart BL, Steinbock RT, Mettle FA, Jr, Pathak DR, Bartow
SA. Age and race related changes in mammographic
parenchymal patterns. Cancer 1989;63:25379.
29. Feig SA. Radiation risk from mammography: is it clinic-
ally significant? AJR Am J Roentgenol 1984;143:46975.
30. Eddy DM, Hasselblad V, McGivney W, Hendee W. The
value of mammography screening in women under age 50
years. JAMA 1988;259:15129.
31. Brenner DJ, Sawant SG, Hande MP, Miller RC, Elliston
CD, Fu Z, et al. Routine screening mammography: how
important is the radiation-risk side of the benefit-risk
equation? Int J Radiat Biol 2002;78:10657.
32. Arihiro K. Trends in benign breast tumors in Japanese
women, 19731995: experience of Hiroshima Tumor
Tissue Registry. Jpn J Cancer Res 2002;93:6105.
33. Carty NJ, Carter C, Rubin C, Ravichandran D, Royle GT,
Taylor I. Management of fibroadenoma of the breast. Ann
R Coll Surg Engl 1995;77:12730.
34. Cant PJ, Madden MV, Coleman MG, Dent DM. Non-
operative management of breast masses diagnosed as
fibroadenoma. Br J Surg 1995;82:7924.
35. American Cancer Society. Breast cancer facts & figures
20052006. Atlanta (GA): ACS; 2005. Available at: http://
www.cancer.org/downloads/STT/CAFF2005BrF.pdf.
Retrieved June 12, 2006.
36. Ottman R, Pike MC, King MC, Henderson BE. Practical
guide for estimating risk for familial breast cancer. Lancet
1983;2:5568.
37. Ford E, Easton DF, Bishop DT, Narod SA, Goldgar DE.
Risk of cancer in BRCA1-mutation carriers: Breast
Cancer Linkage Consortium. Lancet 1994;343:6925.
38. NIH consensus conference. Ovarian cancer. Screening,
treatment, and follow-up. NIH Consensus Development
Panel on Ovarian Cancer. JAMA 1995;273:4917.
39. Seeber B, Driscoll DA. Hereditary breast and ovarian can-
cer syndrome: should we test adolescents? J Pediatr
Adolesc Gynecol 2004;17:1617.
40. Marcus PM, Newman B, Millikan RC, Moorman PG,
Baird DD, Qaqish B. The associations of adolescent
cigarette smoking, alcoholic beverage consumption, envi-
ronmental tobacco smoke, and ionizing radiation with
subsequent breast cancer risk (United States). Cancer
Causes Control 2000;11:2718.
41. Lagerros YT, Hseih SF, Hsieh CC. Physical activity in
adolescence and young adulthood and breast cancer risk:
a quantitative review. Eur J Cancer Prev 2004;13:512.
42. Beral V, Bull D, Dell R, Peto R, Reeves G. Breast cancer
and abortion: collaborative reanalysis of data from 53 epi-
demiological studies, including 83,000 women with
breast cancer from 16 countries. Collaborative Group on
Hormonal Factors in Breast Cancer. Lancet 2004;363:
100716.
43. Marchbanks PA, McDonald JA, Wilson HG, Folger SG,
Mandel MG, Daling JR, et al. Oral contraceptives and the
risk of breast cancer. N Engl J Med 2002;346:202532.
44. Narod SA, Dube MP, Klijn J, Lubinski J, Lynch HT,
Ghadirian P, et al. Oral contraceptives and the risk of
breast cancer in BRCA1 and BRCA2 mutation carriers. J
Natl Cancer Inst 2002;94:17739.
45. Milne RL, Knight JA, John EM, Dite GS, Balbuena R,
Ziogas A, et al. Oral contraceptive use and risk of early-
onset breast cancer in carriers and noncarriers of BRCA1
and BRCA2 mutations. Cancer Epidemiol Biomarkers
Prev 2005;14:3506.
46. Use of hormonal contraception in women with coexisting
medical conditions. ACOG Practice Bulletin No. 73.
American College of Obstetricians and Gynecologists.
Obstet Gynecol 2006;107:145372.
47. Goldbloom RB. Self-examination by adolescents.
Pediatrics 1985;76:1268.
48. Primary and preventive care: periodic assessments.
ACOG Committee Opinion No. 292. American College of
Obstetricians and Gynecologists. Obstet Gynecol 2003;
102:11724.
49. Burke W, Daly M, Garber J, Botkin J, Kahn MJ, Lynch P,
et al. Recommendations for follow-up care of individuals
with an inherited predisposition to cancer. II. BRCA1 and
BRCA2. Cancer Genetics Studies Consortium. JAMA
1997;277:9971003.
COMPENDIUM OF SELECTED PUBLICATIONS 38 38 38
Committee on
Adolescent Health Care
ACOG
Number 351, November 2006
Committee
Opinion
This information should not be
construed as dictating an exclu-
sive course of treatment or proce-
dure to be followed.
The Committee wishes to thank
Nichole Zidenberg, MD; Mary
McKenna, PhD; and William H.
Dietz, MD, PhD, for their assis-
tance in the development of this
document.
Copyright November 2006
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of this
publication may be reproduced,
stored in a retrieval system,
posted on the Internet, or trans-
mitted, in any form or by any
means, electronic, mechanical,
photocopying, recording, or oth-
erwise, without prior written per-
mission from the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
The overweight adolescent: preven-
tion, treatment, and obstetricgyneco-
logic implications. ACOG Committee
Opinion No. 351. American College
of Obstetricians and Gynecologists.
Obstet Gynecol 2006;108:133748.
The Overweight Adolescent:
Prevention, Treatment, and Obstetric
Gynecologic Implications
ABSTRACT: The number of overweight adolescents has grown to epidemic
proportions in the United States. Adolescent females who are overweight
have significant health sequelae. The American College of Obstetricians and
Gynecologists recommends that all adolescents be screened annually for
overweight by determining weight and stature, calculating a body mass index
for age percentile, and asking about body image and eating patterns. Health
care providers should promote healthy eating and physical activity to
adolescent patients and their parents during routine preventive health care
visits. Adolescents with a body mass index greater than or equal to the 95th
percentile for age should have an in-depth dietary and health assessment to
determine psychosocial morbidity and risk for future cardiovascular disease.
Obstetriciangynecologists are strongly encouraged to provide this assess-
ment. Additional research is needed to determine the most appropriate
approach for the successful prevention and treatment of overweight adoles-
cents. Until this research has been completed, it is best to extrapolate an
approach from data and studies pertaining to children and adults, while
remaining cognizant of the special needs that surround adolescent growth
and development. Sound nutritional recommendations and regular physical
activity are essential components of prevention and treatment plans.
The number of overweight adolescents has grown to epidemic proportions in
the United States. The overweight female adolescent faces unique challenges
with her medical, psychologic, and reproductive health. Early intervention is
paramount to prevent associated short- and long-term morbidities. The goal
of this document is to review the most timely and pertinent information
regarding the overweight adolescent, as well as to provide prevention and
treatment strategies to guide the practitioner in providing gynecologic and
obstetric care for such a patient.
39 COMMITTEE OPINIONS 39 39
Definitions of Overweight and Obesity
The discussion of overweight or obesity in ado-
lescents is complicated by the inconsistent use of
definitions in clinical practice, research, and publi-
cations. These definitions have been applied to adults
and adolescents. The term obesity is now used less
frequently to avoid the associated negative connota-
tions, especially for children and adolescents. Body
mass index (BMI) is the most widely used tool for
assessment of overweight and obesity. It is calculated
using the following formula: weight in kilograms
divided by height in meters squared (weight [kg] /
height squared [m
2
]). There are now teen BMI calcu-
lators available online. A link to one such calculator
can be found at http://www.acog.org/goto/teens. This
calculator determines the teens BMI for age per-
centile. Alternatively, Figures 1 and 2 can be used.
The Centers for Disease Control and Prevention
(CDC) defines an adolescent as overweight if she has
a BMI greater than or equal to the 95th percentile for
age. For example, a girl aged 16 years whose height is
60 inches and weight is 155 pounds has a BMI of
30.3, as can be seen in Figure 1. By looking at Figure
2, it can be determined that this girls BMI is above
the 95th percentile; therefore, she is considered to be
overweight. An adolescent whose BMI is equal to or
greater than the 85th percentile for age, but less than
the 95th percentile for age is considered by the CDC
to be at risk for becoming overweight. Adult obesity
is defined by the CDC as a BMI greater than or equal
to 30 and the term overweight is used to describe a
BMI greater than or equal to 25, but less than or equal
to 29.9 (see Table 1) (1). (An adult BMI calculator is
available at http://www.nhlbisupport.com/bmi/.) The
American College of Obstetricians and Gynecologists
(ACOG) uses the CDC definitions.
Prevalence and Trends
According to National Health and Nutrition
Examination Survey 20032004 data, 16% of
females aged 1219 years were considered over-
weight. Thirty-two percent of adolescent females
were either overweight or at risk of becoming over-
weight (2). By comparison, only 6% of females aged
1219 years were considered overweight in the
NHANES study conducted in 19711974 (see
Figure 3) (3). There are substantial racial differences
in the prevalence of overweight for adolescents.
Specifically, Latino, Mexican-American, Asian/
Pacific Islander, and black populations were more
likely to be overweight or at risk for overweight in
adolescence than the white population (2, 4).
Health Risks of Overweight Adolescents
Overweight status in the adolescent female popula-
tion has been associated with lower educational
achievement and income, even after controlling for
intelligence and socioeconomic status at baseline (5).
These effects persisted even if the adolescent lost
weight and was no longer considered overweight (6).
Overweight adolescents often experience significant
low self-esteem and depression (79). Overweight
white girls are more likely to develop a negative body
image, and are at greater risk of developing eating
disorders. Overweight adolescent females have
reported experiences with intentional weight-related
teasing, jokes, and derogatory name calling, as well
as less intentional, potentially hurtful comments by
peers, family members, employers, strangers, and
health care providers. Overweight adolescents report
that others often make negative assumptions about
them, including that they are inactive or lazy, do not
have feelings, and are unclean (10).
Among adults who were overweight during
childhood, there is an increased relative risk of 1.5 of
all-cause mortality and 2.0 of cardiovascular disease
mortality (11). Adolescents who are at risk of
becoming overweight or who are overweight have a
significantly higher prevalence of moderate to severe
asthma when compared with a peer group (12).
Hypertension, sleep apnea, dyslipidemia, increased
fasting insulin levels, and sudden death have been
associated with being overweight (1316). More
recently, overweight adolescents have been shown to
be at increased risk of type 2 diabetes (17).
Furthermore, a variety of orthopedic complications
occur in overweight adolescents, such as slipped
capital femoral epiphysis and Blounts disease (a
growth disorder of the shin bone that causes the
lower leg to angle inward) (18). Finally, overweight
adolescents face increased morbidity and mortality
later in their reproductive lives.
Obstetric and Gynecologic Implications
for Overweight Adolescents
Irregular Menses
Overweight adolescents often report amenorrhea,
oligomenorrhea, or menometrorrhagia to their
COMPENDIUM OF SELECTED PUBLICATIONS 40 40 40
F
i
g
.
1
.
B
o
d
y
m
a
s
s
i
n
d
e
x
c
h
a
r
t
f
o
r
c
h
i
l
d
r
e
n
a
n
d
a
d
o
l
e
s
c
e
n
t
s
.
(
F
o
r
m
o
r
e
i
n
f
o
r
m
a
t
i
o
n
o
n
b
o
d
y
m
a
s
s
i
n
d
e
x
f
o
r
a
d
o
l
e
s
c
e
n
t
s
,
v
i
s
i
t
t
h
e
C
e
n
t
e
r
s
f
o
r
D
i
s
e
a
s
e
C
o
n
t
r
o
l
a
n
d
P
r
e
v
e
n
t
i
o
n
w
e
b
s
i
t
e
a
t
w
w
w
.
c
d
c
.
g
o
v
/
n
c
c
d
p
h
p
/
d
n
p
a
/
b
m
i
/
c
h
i
l
d
r
e
n
s
_
B
M
I
/
a
b
o
u
t
_
c
h
i
l
d
r
e
n
s
_
B
M
I
.
h
t
m
.
)
41 COMMITTEE OPINIONS 41 41
12
14
16
18
20
22
24
26
28
30
32
34
BMI
kg/m
2
12
14
16
18
20
22
24
26
28
30
32
34
BMI
kg/m
2
85th
90th
95th
75th
50th
25th
10th
5th
Overweight
(95th percentile and above)
At Risk of
Overweight
(85th94th
percentile)
Underweight
(5th percentile and below)
Fig. 2. Body mass index for age percentiles: Girls, aged 220 years. (Developed by the National Center for Health
Statistics in collaboration with the National Center for Chronic Disease Prevention and Health Promotion [2000].)
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Age (years)
COMPENDIUM OF SELECTED PUBLICATIONS 42 42 42
health care providers. Being an overweight adoles-
cent is associated with elevated levels of free estro-
gens through increased peripheral aromatization of
androgens to estrogens, decreased sex hormone
binding globulin, and increased insulin levels that
can stimulate ovarian stromal tissue production of
androgen. The elevated peripheral estrogen levels are
associated with disruption of normal ovulation and
subsequent irregular menstrual cycles. Higher de-
grees of overweight have been associated with high-
er probabilities of menstrual cycle disturbances (19).
Polycystic Ovary Syndrome
Obesity has been reported to occur in one half of
adult patients with polycystic ovary syndrome
(PCOS). Obesity in adult patients with PCOS is
characterized by an increased waist-to-hip ratio or
android appearance as opposed to truncal obesity.
The presence of obesity compounds clinical risk in
adult patients with PCOS for several reasons.
Obesity is associated with decreased sex hormone-
binding globulin, which increases circulating free
testosterone and estradiol in adults (20). Obese
adults have an increased likelihood of dyslipidemia,
raising concern for future cardiovascular events
(21). Finally, obesity is associated with insulin resis-
tance, which may progress to diabetes mellitus in
adult patients with PCOS (22).
Lifestyle modification is recommended as first-
line management for overweight female adolescents
with PCOS. Dietary intervention studies have con-
sistently demonstrated the benefit of weight reduc-
tion in obese adult females with PCOS to normalize
menstrual cycles and hyperandrogenism and
improve metabolic variables (23).
Oral contraceptives are the standard therapy for
PCOS to provide hormonal suppression of ovarian
androgen production. Metformin has been approved
by the U.S. Food and Drug Administration for use in
patients with type 2 diabetes and is the most com-
mon insulin-sensitizing agent used in studies on
PCOS even though the use of metformin in these
patients is currently considered off label. Some
investigators state that based on current data, use of
metformin can be justified in overweight adoles-
cents with PCOS and insulin resistance to improve
metabolic and hormonal alterations and possibly
prevent long-term sequelae (24). The role of insulin-
reduction therapies in treating PCOS is evolving
and has substantial efficacy in restoring regularity of
menstrual cycles. These therapies usually are associ-
ated with initial weight loss, are less effective in the
treatment of hirsutism, and may cause gastrointesti-
nal side effects (25).
Table 1. Definitions
At Risk for
Population Becoming Overweight Overweight Obesity
Adolescent Body mass index is equal to or Body mass index greater than or Term not typically used
greater than the 85th percentile equal to 95th percentile for age
for age, but less than the 95th based on growth charts by the
percentile for age based on growth Centers for Disease Control
charts by the Centers for Disease and Prevention
Control and Prevention
Adult Term not typically used Body mass index greater than or Body mass index greater
equal to 25, but less than or equal than or equal to 30
to 29.9
P
r
e
v
e
l
a
n
c
e
o
f
o
v
e
r
w
e
i
g
h
t
(
p
e
r
c
e
n
t
a
g
e
o
f
p
o
p
u
l
a
t
i
o
n
)
20
15
10
5
0
19711974 19761980 19881994 19992002 20032004
Years of NHANES study
Females aged 1219 years
Fig. 3. Overweight adolescent females aged 1219 years.
National Center for Health Statistics. Health, United
States, 2005 with chartbooks on trends in the health of
Americans. Hyattsville (MD): 2005. Ogden CL, Carroll
MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM.
Prevalence of overweight and obesity in the United States,
1999-2004. JAMA 2006;295:154955.
43 COMMITTEE OPINIONS 43 43
Hormonal Contraception
Recent studies suggest that women weighing more
than 70.5 kg have an increased risk of unintended
pregnancy while using combination oral contracep-
tives compared with women who have normal body
mass (relative risk 1.6) (26, 27). Another study
demonstrated that women with BMIs greater than
32.2 had a higher risk of accidental pregnancy while
using combination oral contraceptives than did
women who have normal body mass (27). Several
mechanisms have been proposed to account for the
elevated failure rates in obese adult women. It has
been theorized that obese adult women metabolize
steroids differently than lean women possibly
because of a larger blood volume to transport steroid
hormones and fat cells sequestering steroid hor-
mones (28). In obese adult users of combination oral
contraceptives, the risk of thromboembolism is
increased (29). For overweight adolescents at risk of
pregnancy, it is important to balance the risks and
benefits of combination oral contraceptives, includ-
ing the risks from pregnancy. Consideration should
be given to progestin-only oral contraceptives and
intrauterine methods when counseling overweight
adolescents regarding contraceptive choices. Women
who weigh more than 90 kg may have a dispropor-
tionately higher likelihood of contraceptive failure
with the transdermal contraceptive patch (30).
Serum levonorgestrel levels are lower in obese
adult women compared with nonobese adult women
using a two-rod implant (not yet commercially avail-
able). Yet, effective contraception is thought to last 5
years regardless of weight (31). The effectiveness of
the etonogestrel single-rod implant that has been
recently approved by the U.S. Food and Drug
Administration for use in overweight women has not
been adequately studied. However, serum concentra-
tions of the synthetic progestin etonogestrel are
inversely related to body weight and decrease with
time after insertion. It is, therefore, possible that with
time this single-rod implant may be less effective in
overweight women (32). No changes in efficacy have
been shown with the vaginal ring regardless of
patient weight. Although injectable contraception
has not been demonstrated to decrease contraceptive
efficacy based on weight, it has been associated with
weight gain (see Table 2).
Intrauterine Device
The effectiveness of the intrauterine device (IUD) in
obese adult women is similar to that demonstrated in
adults of average weight. Insertion of an IUD can be
technically challenging in the obese adult woman
and often requires the use of a larger speculum for
adequate visualization of the cervix. Placing a con-
dom with the tip removed over the speculum blades
can aid in exposure. Ultrasonography also may be a
useful tool both before and during IUD insertion
(33). This information may be applied to the adoles-
cent population until other data are available.
Pregnancy-Related Issues
Maternal obesity (BMI greater than or equal to 30)
is an important obstetric risk factor independent of
maternal age (34). Nearly all complications of preg-
nancy, except intrauterine growth restriction, are
more frequent in obese adult women (35). In a
recent prospective Danish study, overweight and
obese adult women had increased risks of diabetes,
hypertension, preeclampsia, and cesarean delivery
(36). Obesity is associated with a more than doubled
risk of stillbirth (odds ratio, 2.8; 95% confidence
interval [CI], 1.55.3) and neonatal death (odds
ratio, 2.6; 95% CI, 1.25.8) compared with women
of normal weight. Much of these data are based on
adult women, but may be applied to the pregnant
adolescent population until other data are available.
Most adolescent pregnancies (80%) are unin-
tended (37). This precludes the physician from pro-
viding preconception counseling that would address
diet and exercise. The goals of this counseling
include avoiding specific pregnancy complications,
such as macrosomia, operative deliveries, late fetal
deaths, neural tube defects, gestational hyperten-
sion, and gestational diabetes. There is a significant
increase in cesarean deliveries in primiparous ado-
lescents with BMIs greater than or equal to 30 com-
pared with those with BMIs less than or equal to 20
(38). Maternal weight also has an effect on the child.
Regardless of maternal age, maternal obesity in the
first trimester of pregnancy is associated with elevat-
ed risk of overweight in the child. Specifically, the
relative risk of overweight in the child was 2.0 (95%
CI, 1.72.3) at age 2 years, 2.3 (95% CI, 2.02.6) at
age 3 years, and 2.3 (95% CI, 2.02.6) at age 4 years
(39).
African-American adolescents who are over-
weight before their first pregnancy become more
overweight; on average, 3.3 years following the
index pregnancy. They also are at increased risk of
retaining gestational weight gain (40). The associa-
tion between ethnicity, overweight, and obstetric and
COMPENDIUM OF SELECTED PUBLICATIONS 44 44 44
neonatal outcomes needs further exploration in the
adolescent population.
Information regarding pregnancy termination
also is scarce. In second trimester dilation and evac-
uation abortions, obesity has been linked with tech-
nical difficulty, longer operating times, and more
blood loss (41, 42).
Prevention
The American College of Obstetricians and Gyne-
cologists recommends that all adolescents be
screened annually for overweight by determining
weight and stature, calculating a BMI for age, and
asking about body image and eating patterns (43).
The U.S. Preventive Services Task Force concluded
that there is insufficient evidence to recommend for
or against routine screening for overweight in ado-
lescents in primary care settings (44). This is based
on the lack of evidence that screening and therapeu-
tic intervention improve health outcomes for over-
weight adolescents. Although ACOG recognizes the
recent report and the limitations in the data, ACOG
continues to support the screening of adolescents
because screening and interventions may demon-
strate benefit if used in combination with several
modalities.
Although the research on prevention of over-
weight status in adolescents has resulted in few
effective recommendations, some prevention strate-
gies have been generated. Parents play a significant
role. A surgeon general report highlights the proba-
ble protective benefit of breastfeeding in preventing
overweight in children and adults (45). Health care
providers should promote healthy eating and physi-
cal activity to adolescent patients and their parents
during routine preventive health care visits (43, 45).
Parents can help their children and adolescents to
follow the Dietary Guidelines for Americans at
home and at school. These guidelines include recom-
mendations to decrease consumption of fat,
saturated fat, sodium, and added sugars; increase
Table 2. The Effect of Weight on Birth Control Methods
Average Associated Does weight affect how well
Birth Control Method Weight Gain it prevents pregnancy?
Abstinence None No
Male condom None No
Female condom None No
Emergency contraception None No
Vaginal spermicide None No
Diaphragm None If gain or loss of 10 pounds or more
occurs, it may need to be refitted
Cervical cap None If gain or loss of 10 pounds or more
occurs, it may need to be refitted
Combination oral None If weight is 176 pounds or
contraceptives more, it may not prevent pregnancy
as well
Progestin-only oral None If weight is 176 pounds or
contraceptives (mini pills) more, it may not prevent pregnancy
as well
Contraceptive injection 5 pounds in first year of use No
Vaginal ring None No
Patch None If weight is 176 pounds or more, it
may not prevent pregnancy as well
Copper T intrauterine device None No
Mirena intrauterine system None No
Sterilization None No
Created by the SAFE Study: Computer-Aided Counseling to Prevent Teen Pregnancy/STDs, Principal Investigator:
Melanie A. Gold, D.O., University of Pittsburgh School of Medicine, supported by NICHD grant #HD41058.
Modified and reprinted with permission.
45 COMMITTEE OPINIONS 45 45
consumption of fruit, vegetables, whole grains, and
other foods that are rich in fiber; increase the con-
sumption of milk or other foods or beverages that are
good sources of calcium; and participate in at least
60 minutes of physical activity on most, preferably
all, days of the week (45, 46). Adolescents can be
encouraged to increase the amount of regular daily
activity by making small lifestyle changes, such as
climbing the stairs instead of taking an elevator.
They also can be encouraged to choose an activity
that can become a part of their everyday life, such as
bicycling or walking. Leisure activities that are
sedentary, such as television viewing and playing
computer games, should be restricted to less than 2
hours per day. Parents also should be encouraged to
model healthy eating habits and physical activity
and should be informed that food should never be
used as a tool for punishment or reward. Eating
breakfast and regular meals is important to promot-
ing and maintaining a healthy weight. A recent study
funded by the National Institutes of Health moni-
tored nearly 2,400 females aged 919 years for 10
years and found that those who regularly ate break-
fast, particularly ones that included cereal, were
slimmer than those who skipped the morning meal
(47). Schools can support healthy behavior by using
several means, including the provision of instruc-
tion, the enactment of physical activity and nutrition
policies, and by ensuring that the school environ-
ment supports healthy eating and physical activity
(48).
Screening and Treatment
Adolescence can be a difficult time for assessing
weight status because of pubertal changes and dif-
ferences in individual patterns of growth. A dietary
and health assessment should be conducted on ado-
lescents with BMIs greater than or equal to the 85th
percentile for age, but less than the 95th percentile
for age to determine psychosocial morbidity and risk
for future cardiovascular disease if:
Their BMI has increased by two or more units
during the previous 12 months
They have a family history of premature heart dis-
ease, obesity, hypertension, or diabetes mellitus
They express concern about their weight
They have elevated blood pressure or serum
cholesterol levels (43)
Adolescents with a BMI greater than or equal to
the 95th percentile for age should have an in-depth
dietary and health assessment to determine psy-
chosocial morbidity and risk for future cardiovascu-
lar disease. Obstetriciangynecologists are strongly
encouraged to provide this assessment (43). Early
referral to a nutritional specialist skilled in adoles-
cent care may be warranted. The patient usually is
acutely aware of her weight issue and has likely
attempted many of her own weight loss strategies.
These adolescents need clear and direct support,
guidance, and encouragement. Also they need a bet-
ter understanding of the widespread nature of the
disease to feel less alone and isolated. Family
involvement in the treatment plan is critical. Any
proposed diet should be consistent with the Dietary
Guidelines for Americans and allow for individual-
ized caloric intake recommendations that support
gradual, not rapid, weight loss.
It is important to note that weight loss is recom-
mended only for adolescents in certain circumstances
(46). For example, older overweight adolescents who
have completed linear growth or those with com-
orbidities, may require weight loss (18, 49). More
often, the goal is to slow the rate of weight gain
while achieving normal growth and development.
Discussion of portion sizes, snacking, and eating at
restaurants and outside the home is helpful (46).
(See box for examples of healthy snacks.) Wake
Forest University has developed a web site
(http://www1.wfubmc.edu/Nutrition/Count+Your+
Calories/dtd.htm) that provides the nutritional and
caloric information of several of the largest fast food
chains in the United States. This web site may be
useful to adolescent patients and their parents.
There are sufficient adult data indicating that
physical activity contributes to weight loss, both
Healthy Snacks
Providing some examples of healthy snacks may be
useful when discussing the dietary needs of an over-
weight adolescent female. These examples may include:
A bean burrito
A cheese quesadilla with salsa and lettuce
A yogurt and fruit smoothie with graham crackers
A bowl of whole-grain cereal topped with sliced fruit
and milk
A small salad with sliced deli meat, tuna or beans
Fruit, cheese, and whole-grain crackers
COMPENDIUM OF SELECTED PUBLICATIONS 46 46 46
alone and when it is combined with dietary therapy.
Efforts to achieve weight loss with physical activity
alone generally produce moderate weight loss. Even
so, increased physical activity is a useful adjunct to
low-calorie diets in promoting weight reduction.
Also, physical activity reduces obesity-associated
comorbidities (1).
The amount of time an adolescent spends per-
forming aerobic versus sedentary activities should
be assessed. As stated previously, it is recommended
that adolescents participate in at least 60 minutes
of physical activity on most, preferably all, days
of the week (46). Increased activity and decreased
television viewing has been shown to reduce an
adolescents weight (50). In children, family-based
programs that encompass diet, physical activity,
reduction of sedentary behavior, and behavioral ther-
apy have been shown to help children lose weight
compared with no treatment. It is important to pro-
vide recommendations on diet and physical activity
that are achievable given the patients family environ-
ment. It also is important to evaluate the adolescents
psychologic well-being (18). Often, collaboration
with a mental health professional is indicated.
There are limited data to document the efficacy
of prescription medications or over-the-counter
drugs for weight loss in adolescents. The role of sur-
gical intervention for overweight adolescents has yet
to be established, but some recent studies have sug-
gested that surgical weight loss improves the early
mortality experienced by these adolescents (51).
Bariatric surgery currently is recommended for ado-
lescents who have a BMI greater than 40 and have
comorbid conditions. Those who may be candidates
for bariatric surgery should be referred to a multidis-
ciplinary weight management team with expertise in
treating overweight adolescents (52). Long-term
studies are needed to determine the risk and benefits
of bariatric surgery in adolescents. Nationally, a new
paradigm has been proposed with an emphasis on
promoting a healthy lifestyle in overweight patients
instead of focusing solely on weight loss. This idea
of health at any size may encourage patients to
focus on their overall health improvement, rather
than only their weight status (53).
Conclusion
Adolescent females who are overweight have signifi-
cant health sequelae. There are limited evidence-based
data for the successful prevention and treatment of
overweight adolescents. Because additional research
is needed, our best tool is to extrapolate an approach
from data and studies pertaining to children and
adults, while remaining cognizant of the special
needs that surround adolescent growth and develop-
ment. Sound nutritional recommendations and regu-
lar physical activity are essential components for
overall good health because they convey myriad ben-
efits for growth, brain and cognitive development,
self-esteem, immunity, and disease prevention (54).
References
1. National Heart, Lung, and Blood Institute (NHLBI),
National Institute for Diabetes and Digestive and Kidney
Diseases (NIDDK). Clinical guidelines on the identifica-
tion, evaluation, and treatment of overweight and obesity
in adults. The evidence report. NIH Publication No. 98-
4083. Bethesda (MD): NIH; 1998. Available at: http://
www.nhlbi.nih.gov/guidelines/obesity/ob_gdlns.pdf.
Retrieved July 25, 2006.
2. Ogden CL, Carroll MD, Curtin LR, McDowell MA,
Tabak CJ, Flegal KM. Prevalence of overweight and obe-
sity in the United States, 1999-2004. JAMA 2006;295:
154955.
3. National Center for Health Statistics. Health, United
States, 2005 with chartbooks on trends in the health of
Americans. Hyattsville (MD): NCHS; 2005.
4. Haas JS, Lee LB, Kaplan CP, Sonneborn D, Phillips KA,
Liang S. The association of race, socioeconomic status,
and health insurance status with the prevalence of over-
weight among children and adolescents. Am J Public
Health 2003;93:210510.
5. Gortmaker SL, Must A, Perrin JM, Sobol AM, Dietz WH.
Social and economic consequences of overweight in ado-
lescence and young adulthood. N Engl J Med 1993;
329:100812.
6. Sargent JD, Blanchflower DG. Obesity and stature in ado-
lescence and earnings in young adulthood. Analysis of a
British birth cohort. Arch Pediatr Adolesc Med 1994;
148:6817.
7. Erickson SJ, Robinson TN, Haydel F, Killen JD. Are over-
weight children unhappy? Body mass index, depressive
symptoms, and overweight concerns in elementary school
children. Arch Pediatr Adolesc Med 2000;154:9315.
8. Strauss RS. Childhood obesity and self-esteem. Pediatrics
2000;105; e15.
9. Swallen KC, Reither EN, Haas SA, Meier AM.
Overweight, obesity, and health-related quality of life
among adolescents: the National Longitudinal Study of
Adolescent Health. Pediatrics 2005;115:3407.
10. American Obesity Association. Obesity in youth. AOA
fact sheet. Available at: http://www.obesity.org/subs/fast-
facts/obesity_youth.shtml. Retrieved April 3, 2006.
11. Must A, Strauss RS. Risks and consequences of childhood
and adolescent obesity. Int J Obes Relat Metab Disord
1999;23(suppl 2):S211.
12. Rodriguez MA, Winkelby MA, Ahn D, Sundquist J,
Kraemer HC. Identification of population subgroups of
47 COMMITTEE OPINIONS 47 47
children and adolescents with high asthma prevalence:
findings from the Third National Health and Nutrition
Examination Survey. Arch Pediatr Adolesc Med 2002;
156:26975.
13. Reinehr T, Andler W, Demer C, Siegried W, Mayer H,
Wabitsch M. Cardiovascular risk factors in overweight
German children and adolescents: relation to gender, age
and degree of overweight. Nutr Metab Cardiovasc Dis
2005;15;1817.
14. Wing YK, Hui SH, Pak WM, Ho CK, Cheung A, Li AM,
et al. A controlled study of sleep related disordered
breathing in obese children. Arch Dis Child 2003;88:
10437.
15. Viner RM, Segal TY, Lichtarowicz-Krynska E,
Hindmarsch P. Prevalence of the insulin resistance syn-
drome in obesity. Arch Dis Child 2005;90:104.
16. Bharati S, Lev M. Cardiac conduction system involve-
ment in sudden death of obese young people. Am Heart J
1995;129:27381.
17. Wabitsch M, Hauner H, Hertrampf M, Muche R, Hay B,
Mayer H, et al. Type II diabetes mellitus and impaired
glucose regulation in Caucasian children and adolescents
with obesity living in Germany. Int J Obes Relat Metabl
Disord 2004;28:30713.
18. Daniels SR, Arnett DK, Eckel RH, Gidding SS, Hayman
LL, Kumanyika S, et al. Overweight in children and ado-
lescents: pathophysiology, consequences, prevention, and
treatment. Circulation 2005;111:19992012.
19. Castillo-Martinez L, Lopez-Alvarenga JC, Villa AR,
Gonzalez-Barranco J. Menstrual cycle length disorders in
18-40-y-old obese women. Nutrition 2003;19:31720.
20. Chang RJ. A practical approach to the diagnosis of poly-
cystic ovary syndrome. Am J Obstet Gynecol 2004;
191:7137.
21. Guzick DS. Cardiovascular risk in women with polycystic
ovarian syndrome. Semin Reprod Endocrinol 1996:14:
459.
22. Legro, RS, Kunselman AR, Dodson WC, Dunaif A.
Prevalence and predictors of risk for type 2 diabetes mel-
litus and impaired glucose control in polycystic ovarian
syndrome: a prospective, controlled study in 254 affected
women. J Clin Endocrinol Metab 1999:84:1659.
23. Norman R, Davies M, Lord J, Moran LJ. The role of
lifestyle modification in polycystic ovarian syndrome.
Trends Endocrinol Metab 2002;13:2517.
24. Pelusi C, Pasquali R. Polycystic ovary syndrome in ado-
lescents: pathophysiology and treatment implications.
Treat Endocrinol 2003;2:21530.
25. Ehrmann DA. Polycystic ovary syndrome. N Engl J Med
2005;352:122336.
26. Holt VL, Cushing-Haugen KL, Daling JR. Body weight
and risk of oral contraceptive failure. Obstet Gynecol
2002;99:8207.
27. Holt VL, Scholes D, Wicklund KG, Cushing-Haugen KL,
Daling JR. Body mass index, weight, and oral contracep-
tive failure risk. Obstet Gynecol 2005;105:4652.
28. Speerhas R. Drug metabolism in malnutrition and obesi-
ty: clinical concerns. Cleve Clin J Med 1995;62:735.
29. Nightingale AL, Lawrenson RA, Simpson EL, Williams
TJ, MacRae KD, Farmer RD. The effects of age, body
mass index, smoking and general health on the risk of
venous thromboembolism in users of combined oral con-
traceptives. Eur J Contracept Rep Health Care 2000:
5:26574.
30. Zieman M, Guillebaud J, Weisberg E, Shangold GA,
Fisher AC, Creasy GW. Contraceptive efficacy and cycle
control with the Ortho Evra/Evra transdermal system: the
analysis of pooled data. Fertil Steril 2002;77(suppl):
S138.
31. Sivin I, Wan L, Ranta S, Alvarez F, Brache V, Mishell DR
Jr, et al. Levonorgestrel concentrations during 7 years of
continuous use of Jadelle contraceptive implants. Contra-
ception 2001;64:439.
32. Implanon [package insert]. Roseland (NJ): Organon:
2006. Available at: http://www.fda.gov/cder/foi/label/2006/
021529lbl.pdf. Retrieved Sepember 20, 2006.
33. Grimes DA, Shields WC. Family planning for obese
women: challenges and opportunities. Contraception
2005;72:14.
34. Kristensen J, Vestergaard M, Wisborg K, Kesmodel U,
Secher NJ. Pre-pregnancy weight and the risk of stillbirth
and neonatal death. BJOG 2005;112:4038.
35. Andreasen KR, Andersen ML, Schantz AL. Obesity and
pregnancy. Acta Obstet Gynecol Scand 2004;83:10229.
36. Rode L, Nilas L, Wojdemann K, Tabor A. Obesity-related
complications in Danish single cephalic term pregnancies.
Obstet Gynecol 2005;105:53742.
37. National Campaign to Prevent Teen Pregnancy. Teen sex-
ual activity, contraceptive use, pregnancy and childbear-
ing: general facts and stats. Washington, DC: NCPTP;
2003. Available at: http://www.teenpregnancy.org/resources/
reading/fact_sheets/genfacts.asp. Retrieved July 25, 2006.
38. Young TK, Woodmansee B. Factors that are associated
with cesarean delivery in a large private practice: the impor-
tance of prepregnancy body mass index and weight gain.
Am J Obstet Gynecol 2002;187:3128; discussion 31820.
39. Whitaker RC. Predicting preschooler obesity at birth: the
role of maternal obesity in early pregnancy. Pediatrics
2004;114:e2936.
40. Segel JS, McAnarney ER. Adolescent pregnancy and sub-
sequent obesity in African-American girls. J Adolesc
Health 1994;15:4914.
41. Dark AC, Miller L, Kothenbeutel RL, Mandel L. Obesity
and second-trimester abortion by dilation and evacuation.
J Reprod Med 2002;47:22630.
42. Marchiano DA, Thomas AG, Lapinski R, Balwan K, Patel
J. Intraoperative blood and gestational age at pregnancy
termination. Prim Care Update Ob Gyns 1998;5:2045.
43. American College of Obstetricians and Gynecologists.
Health care for adolescents. Washington, DC: ACOG; 2003.
44. Screening and interventions for overweight in children
and adolescents: recommendation statement. US Preventive
Services Task Force. Pediatrics 2005;116:2059.
45. U.S. Department of Health and Human Services. The
Surgeon Generals call to action to prevent and decrease
overweight and obesity. Rockville (MD): USDHHS;
2001. Available at: http://www.surgeongeneral.gov/top-
ics/obesity/calltoaction/CalltoAction.pdf. Retrieved July
18, 2006.
46. U.S. Department of Agriculture, U.S. Department of
Health and Human Services. Dietary guidelines for
Americans, 2005. 6th ed. Washington, DC: United States
Government Printing Office; 2005. Available at: http://
COMPENDIUM OF SELECTED PUBLICATIONS 48 48 48
www.health.gov/dietaryguidelines/dga2005/document/
pdf/DGA2005.pdf. Retrieved April 3, 2006.
47. Barton BA, Eldridge AL, Thompson D, Affenito SG,
Striegel-Moore RH, Franko DL, et al. The relationship of
breakfast and cereal consumption to nutrient intake and
body mass index: the National Heart, Lung, and Blood
Institute Growth and Health study. J Am Diet Assoc
2005;105:13839.
48. Wechsler H, McKenna ML, Lee SM, Dietz WH. The role
of schools in preventing childhood obesity. State Educ
Stand 2004;5:412.
49. Barlow SE, Dietz WH. Obesity evaluation and treatment:
expert committee recommendations. The Maternal and
Child Health Bureau, Health Resources and Services
Administration and the Department of Health and Human
Services. Pediatrics 1998;102:E29. Available at: http://
www.pediatrics.org/cgi/content/full/102/3/e29. Retrieved
July 25, 2006.
50. Austin SB, Field AE, Wiecha J, Peterson KE, Gortmaker
SL. The impact of a school-based obesity prevention trial
on disordered weight-control behaviors in early adoles-
cent girls. Arch Pediatr Adolesc Med 2005;159:22530.
51. Jain A. What works for obesity? A summary of the research
behind obesity interventions. London: BMJ Publishing
Group; 2004. Available at: http://www.unitedhealthfounda-
tion.org/obesity.pdf. Retrieved April 11, 2006.
52. Inge T, Krebs NF, Garcia VF, Skelton JA, Guice KS,
Strauss RS, et al. Bariatric surgery for severely over-
weight adolescents: concerns and recommendations.
Pediatrics 2004;114:21723.
53. ODea JA. Prevention of child obesity: first, do no harm.
Health Educ Res 2005;20:25965.
54. Berg F, Buechner J, Parham E. Guidelines for childhood
obesity prevention programs: promoting healthy weight in
children. Weight Realities Division of the Society for
Nutrition Education. J Nutr Educ Behav 2003;35:14.
Resources
ACOG Resources
American College of Obstetricians and Gynecologists. Eating
disorders. In: Health care for adolescents. Washington, DC:
ACOG; 2003. p.8194.
American College of Obstetricians and Gynecologists. Eating
disorders. ACOG Patient Education Pamphlet AP144.
Washington, DC: ACOG; 2000.
American College of Obstetricians and Gynecologists. Healthy
eating. ACOG Patient Education Pamphlet AP130. Washington,
DC: ACOG; 2006.
Obesity in pregnancy. ACOG Committee Opinion No. 315.
American College of Obstetricians and Gynecologists. Obstet
Gynecol 2005;106:6715.
American College of Obstetricians and Gynecologists. Primary
and preventive health care for female adolescents. In: Health
care for adolescents. Washington, DC: ACOG; 2003. p.124.
The role of the obstetriciangynecologist in the assessment and
management of obesity. ACOG Committee Opinion No. 319.
American College of Obstetricians and Gynecologists. Obstet
Gynecol 2005;106:8959.
American College of Obstetricians and Gynecologists. Tool kit
for teen care. Washington, DC: ACOG; 2003.
American College of Obstetricians and Gynecologists. Weight
& adolescent females. Fact Sheets for Teens FS019.
Washington, DC: ACOG; 2003.
American College of Obstetricians and Gynecologists. Weight
control: eating right and keeping fit. ACOG Patient Education
Pamphlet AP064. Washington, DC: ACOG; 2006.
Other Resources
We have provided information on the following organizations
and web sites because they have information that may be of
interest to our readers. The American College of Obstetricians
and Gynecologists does not necessarily endorse the views
expressed or the facts presented by these organizations or on
these web sites. Further, ACOG does not endorse any commer-
cial products that may be advertised or available from these
organizations or on these web sites.
American Academy of Family Physicians
11400 Tomahawk Creek Parkway
Leawood, KS 66211-2672
Telephone: 800-274-2237 or 913-906-6000
http://www.aafp.org
American Academy of Pediatrics
141 Northwest Point Boulevard
Elk Grove Village, IL 60007-1098
Telephone: 847-434-4000
http://www.aap.org/obesity
American Alliance for Health, Physical Education,
Recreation, and Dance
1900 Association Drive
Reston, VA 20191-1598
Telephone: 800-213-7193 or 703-476-3400
http://www.aahperd.org
American College of Sports Medicine
401 West Michigan Street
Indianapolis, IN 46202-3233
Telephone: 317-637-9200
http://www.acsm.org
American Dietetic Association
120 South Riverside Plaza, Suite 2000
Chicago, IL 60606-6995
Telephone: 800-877-1600
http://www.eatright.org
American Heart Association
7272 Greenville Avenue
Dallas, TX 75231
Telephone: 800-242-8721
http://www.americanheart.org
American Obesity Association
1250 24th Street NW, Suite 300
Washington, DC 20037
Telephone: 202-776-7711
http://www.obesity.org
49 COMMITTEE OPINIONS 49 49
AWARE Foundation
1015 Chestnut Street, Suite 1225
Philadelphia, PA 19107-4302
Telephone: 215-955-9847
http://www.awarefoundation.org
Centers for Disease Control and Prevention
Division of Adolescent and School Health
Healthy Youth
PO Box 8817
Silver Spring, MD 20907
Telephone: 800-CDC-INFO (800-232-4636)
http://www.cdc.gov/nccdphp/dash
Centers for Disease Control and Prevention
National Center for Chronic Disease Prevention and Health
Promotion
1600 Clifton Rd
Atlanta, GA 30333
Telephone: 404-639-3311 or 800-311-3435 or 800-232-4636
http://www.cdc.gov/nccdphp/dnpa/obesity
http://www.cdc.gov/nccdphp/dnpa/bmi/index.htm
Institute of Medicine
500 Fifth Street NW
Washington DC 20001
Telephone: 202-334-2352
http://www.iom.edu/
National Association for Health & Fitness
The Network of State and Governors Councils
c/o Be Active New York State
65 Niagara Square, Room 607
Buffalo NY 14202
Telephone: 716-583-0521
http://www.physicalfitness.org
National Heart, Lung, and Blood Institute
PO Box 30105
Bethesda, MD 20824-0105
Telephone: 301-592-5873
http://www.nhlbi.nih.gov/index.htm
Society for Adolescent Medicine
1916 NW Copper Oaks Circle
Blue Springs, MO 64015
Telephone: 816-224-8010
http://www.adolescenthealth.org
U.S. Surgeon General
Office of Surgeon General
5600 Fishers LaneRoom 18-66
Rockville MD 20857
301-443-4000
http://www.surgeongeneral.gov/topics/obesity/
calltoaction/fact_adolescents.htm
COMPENDIUM OF SELECTED PUBLICATIONS 50 50 50
Committee on
Adolescent Health Care
Reaffirmed 2009
ACOG
Number 355, December 2006 (Replaces No. 274, July 2002)
Committee
Opinion
This document reflects emerging
clinical and scientific advances as
of the date issued and is subject
to change. The information
should not be construed as dictat-
ing an exclusive course of treat-
ment or procedure to be followed.
The Committee would like to
thank Marc R. Laufer, MD, for
his assistance in the development
of this document.
Copyright December 2006
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of this
publication may be reproduced,
stored in a retrieval system,
posted on the Internet, or trans-
mitted, in any form or by any
means, electronic, mechanical,
photocopying, recording, or oth-
erwise, without prior written per-
mission from the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Vaginal agenesis: diagnosis, manage-
ment, and routine care. ACOG
Committee Opinion No. 355.
American College of Obstetricians
and Gynecologists. Obstet Gynecol
2006;108:16059.
Vaginal Agenesis: Diagnosis,
Management, and Routine Care
ABSTRACT: Vaginal agenesis occurs in 1 of every 4,00010,000 females.
The most common cause of vaginal agenesis is congenital absence of the
uterus and vagina, which also is referred to as mllerian aplasia, mllerian
agenesis, or MayerRokitanskyKsterHauser syndrome. The condition
usually can be successfully managed nonsurgically with the use of suc-
cessive dilators if it is correctly diagnosed and the patient is sufficiently
motivated. Besides correct diagnosis, effective management also includes
evaluation for associated congenital renal or other anomalies and careful
psychologic preparation of the patient before any treatment or intervention.
If surgery is preferred, a number of approaches are available; the most
common is the AbbeMcIndoe operation. Women who have a history of ml-
lerian agenesis and have created a functional vagina require routine gyne-
cologic care and can be considered in a similar category to that of women
without a cervix and thus annual cytologic screening for cancer may be
considered unnecessary in this population.
Vaginal agenesis is an uncommon, but not rare, condition. Given an inci-
dence ranging from 1 per 4,000 to 1 per 10,000 females (1), vaginal agene-
sis is a condition that general gynecologists will encounter once or twice
during their professional careers. The most common cause of vaginal agen-
esis is congenital absence of the uterus and vagina, which also is referred to
as mllerian aplasia, mllerian agenesis, or MayerRokitanskyKster
Hauser syndrome. The term mllerian aplasia will be used to describe this
congenital reproductive anomaly throughout this document. Mllerian apla-
sia is caused by embryologic growth failure of the mllerian duct, with
resultant anomalies in the mllerian structures. With absence of the vagina,
there is variation on the presence or absence of the uterus. A single mid-
line uterus can be present or uterine horns (with or without an endometrial
cavity) can exist. The ovaries, given their separate embryologic source, are
normal in structure and function.
To manage vaginal agenesis effectively, correct diagnosis of the under-
lying condition is important. Evaluation for associated congenital, renal, or
other anomalies also is essential. Both diagnosis and evaluation usually can
be completed without surgery. Patient counseling should be provided
51 COMMITTEE OPINIONS 51 51
before any treatment or intervention. Nonsurgical
creation of the neovagina should be the first-line
approach.
Differential Diagnosis
Patients with mllerian aplasia have a normal
46,XX karyotype, normal female phenotype, and
normal ovarian hormonal and oocyte function.
Puberty and development of secondary sexual char-
acteristics progress normally except that menarche
does not occur. Therefore, patients with mllerian
aplasia typically present in adolescence with prima-
ry amenorrhea. The practitioner should remember
that it is usually 23 years from the onset of breast
development until the first period. If menarche has
not occurred within 3 years of the onset of breast
development, further evaluation is indicated.
Mllerian aplasia is the second most common cause
of primary amenorrhea, with gonadal dysgenesis
being the most common cause (2).
On physical examination, patients with mller-
ian aplasia have normal breast development, normal
secondary sexual body proportions, body hair, and
hymenal tissue. A vagina is absent unless it has been
created by sexual encounters. Differential diagnosis
of vaginal agenesis includes congenital absence of
the vagina (with or without uterine structures),
androgen insensitivity (absence or alteration of
androgen-receptor function), 17 -hydroxylase
deficiency, a low transverse vaginal septum, and
imperforate hymen.
In cases of androgen insensitivity, the gonads are
testes, producing normal androgens in karyotypic
46,XY individuals. The lack of androgen tissue
receptors results in sparse or no pubic and axillary
hair. Patients with androgen insensitivity typically
have normal breast development because of periph-
eral conversion of circulating androgens to estrogens.
They may have a small lower vagina, or a normal
length vagina can occur; however, no uterus or
cervix is present. In pubertal females, the differen-
tial diagnosis between androgen insensitivity and
mllerian aplasia is easily made by assessing serum
testosterone levels. A testosterone level in the puber-
tal male range confirms the diagnosis of androgen
insensitivity.
In postpubertal patients, the presence of func-
tioning ovarian tissue seen on pelvic ultrasound
examinations may serve as a secondary confirma-
tion of the diagnosis of mllerian aplasia, excluding
the diagnosis of androgen insensitivity. Chromo-
somal studies, although more costly than a serum
testosterone level assessment, provide the diagnos-
tic tool to differentiate between mllerian aplasia in
genetic females and disorders of testosterone syn-
thesis in genetic males. Chromosomal analysis also
is helpful in prepubertal children who do not yet
have postpubertal sex steroid production.
In cases of 17 -hydroxylase deficiency, 46XY
individuals will have complete male pseudoher-
maphroditism with female external genitalia, a blind
short vaginal pouch, no uterus or fallopian tubes,
and intraabdominal testes. Affected males are usu-
ally raised as girls, with the underlying disorder
being recognized when the patient is evaluated for
lack of pubertal development (3, 4).
The differential diagnosis of vaginal agenesis
also includes imperforate hymen and low transverse
vaginal septum. Patients with these latter conditions
will have a normal cervix and uterus, both of which
may be palpable on rectal examination. In contrast
to most patients with mllerian aplasia, the patient
with an imperforate hymen will not have the typical
fringe of hymenal tissue. The patient with a low
transverse vaginal septum will have a normal
hymen, like the patient with mllerian aplasia.
Conventional ultrasonography, three-dimensional
ultrasonography, and magnetic resonance imaging
can be used to better define the mllerian structures
and are helpful in definitively defining anatomy.
Correct diagnosis of the underlying condition
affecting the genital anatomy is crucial before any
surgical intervention. If the patient undergoes an
operation because of an incorrect diagnosis (eg, an
incorrect preoperative diagnosis of an imperforate
hymen in cases of vaginal agenesis), it can be
extremely difficult to correct the anomaly because
of scar tissue.
Evaluation of the Patient With
Mllerian Aplasia
Most patients with mllerian aplasia have small
rudimentary mllerian bulbs without any endome-
trial activity. In 27% of patients with mllerian
aplasia, active endometrium is found in these uterine
structures (1). These patients will present with
cyclic or chronic abdominal pain. Magnetic reso-
nance imaging has been suggested to assess the
reproductive anatomy, although it is rarely needed in
the initial evaluation unless ultrasound evaluation
COMPENDIUM OF SELECTED PUBLICATIONS 52 52 52
for the presence of functional endometrium in a
mllerian structure is equivocal (5). Although
laparoscopy is not necessary to diagnose mllerian
aplasia, it may be useful in the evaluation of patients
with cyclic abdominal pain to exclude the possibil-
ity of endometrial activity in mllerian structures
(6). When obstructed hemi-uteri are identified (uter-
ine horns with the presence of active endometrium
without associated cervix and upper vagina), then
removal of the unilateral or bilateral obstructed uter-
ine structures should be performed. The removal of
the obstructed uterine structures can be accom-
plished laparoscopically (7, 8).
Patients with mllerian aplasia often have con-
comitant congenital malformations, especially of
the abdominal wall, urinary tract, and skeleton.
Inguinal hernias occur at an increased incidence in
patients with mllerian aplasia. Ultrasonography
can be used to screen for the more common find-
ings of renal agenesis or a pelvic kidney. This
evaluation can be performed during the study of
ovarian and mllerian structures. The implications
of ureteral duplication in the case of later abdomi-
nal or pelvic surgery can be discussed, or intra-
venous pyelography can be used to exclude this
possibility. Scoliosis is the most common skeletal
abnormality associated with mllerian aplasia. It
also should be noted that there is an increased, but
small, rate of hearing impairment in patients with
mllerian aplasia.
After the diagnosis of mllerian aplasia, the
adolescent should be offered counseling to empha-
size that a normal sex life will be possible after a
neovagina has been created. Ultimately, however,
infertility may be a more difficult aspect of this dis-
order for the patient to accept. Future fertility
options should be addressed with adolescents and
their parent(s) or guardian(s). Discussion of assisted
reproductive techniques and use of a gestational car-
rier (surrogate) is appropriate. Specifically, it is
important to explain that eggs can be harvested from
patients with mllerian aplasia and used in assisted
reproductive technology; daughters of women with
MayerRokitanskyKsterHauser syndrome con-
ceived by assisted reproductive technology have
been shown to have normal reproductive tracts (9).
This information allows teens to understand their
reproductive potential for becoming a biologic par-
ent and may help them accept the diagnosis and its
implications. Referral to a mental health profes-
sional is very worthwhile for some patients. The
best predictor of good emotional outcome after
diagnosis and vaginoplasty is a good relationship
between the patient and her parents or guardians and
the ability to share feelings with family and friends
(7). Contact with a support group or young women
with the same diagnosis may be helpful (6) (see
Resources).
Patients should be given a brief, written medical
summary of their condition, including a summary of
concomitant malformations. This information may
be useful if the patient requires urgent medical care
or emergency surgery from a health care provider
unfamiliar with mllerian aplasia.
Nonsurgical Creation of a Neovagina
Timing for nonsurgical or surgical creation of a neo-
vagina is elective; however, it is best planned when
the patient is emotionally mature. Nonsurgical cre-
ation of the vagina is the appropriate first-line
approach in most patients because it is the least mor-
bid procedure. In a recently reported series of
patients with mllerian aplasia, more than 90% were
able to achieve anatomic and functional success by
vaginal dilation (10).
Patients are asked to manually place successive
dilators on the perineal dimple for 30 minutes to 2
hours per day. Another option of sitting on a bicycle
seat stool provides the perineal pressure and allows
the patient to participate in simultaneous productive
activities, such as doing homework or practicing a
musical instrument (11). Many young women find
that sitting on the bicycle seat stool is too uncom-
fortable or awkward, thus they may have better suc-
cess using dilators while reclining on a bed after a
relaxing bath. Use of dilators in the management of
vaginal agenesis is appropriate and successful in
most patients. Mature, highly motivated patients
who wish to avoid surgery and are aware that it will
take several months to achieve their goal are likely
to be successful (11, 12). Because the nonoperative
approach is noninvasive and usually successful, it is
strongly recommended as first-line therapy.
Clinicians often use buddies, other patients
with vaginal agenesis who have successfully di-
lated, as support to the young woman attempting
dilation. Young married patients make excellent
buddies. If fertility issues are a major concern to
the patient or her family, it may be helpful to find
a buddy who has used assisted reproductive tech-
niques to become a mother.
53 COMMITTEE OPINIONS 53 53
Surgical Creation of a Neovagina
Surgery becomes an option for patients who are
unsuccessful with dilators or patients who prefer
surgery after a thorough discussion with the patient
and her parent(s) or guardian(s) of the risks and ben-
efits of the procedure and the available nonsurgical
alternatives. It should be stressed to the young
woman that a surgical vaginoplasty is not a quick
fix and that she will still need to use vaginal dila-
tors postoperatively to maintain her surgically cre-
ated vagina. The aim of surgery is the creation of a
vaginal canal in the correct axis of adequate size and
secretory capacity to allow intercourse to occur
without the need for continued postoperative dila-
tion. The timing of the surgery depends on the
patient and the type or procedure planned. Surgeries
often are performed in late adolescence (ages 1721
years) when the patient is more mature and better
able to adhere to postoperative dilation or instruc-
tions. Surgery usually is scheduled during summer
vacation to allow for an adequate recovery time
without missing school and to reduce questions
from peers (6, 13).
A number of operations are appropriate for the
correction of vaginal agenesis. The approach usu-
ally is based on the experience of the operating sur-
geon. Pediatric surgeons are more likely to use
bowel segments for the creation of a neovagina;
gynecologists are more likely to use a perineal
approach. Whatever technique is chosen, the sur-
geon must be experienced with the procedure
because the initial surgery is more likely to succeed
than follow-up procedures. Reoperation in these
cases increases the chance of operative injury to sur-
rounding tissues and the possibility of a poor func-
tional outcome. At present, there is no consensus in
the literature regarding the best option for surgical
correction (14).
The most common surgical procedure used by
U.S. gynecologists to create a neovagina is the
AbbeMcIndoe operation. This involves the dissec-
tion of a space between the rectum and bladder,
placement of a mold covered with a split-thickness
skin graft into the space, and the diligent use of
vaginal dilation postoperatively. Postoperative dila-
tion must be continued to prevent significant skin
graft contracture. This surgery is inappropriate if the
patient rejects the nonsurgical technique because
she has concerns about or objections to dilation. If
postoperative dilation is not done, the patient will
have a nonfunctional vagina. The dilators are used
long-term on a less frequent basis until the woman
is having vaginal intercourse because at that time
the penis will act as a dilator to maintain the length
of the vagina.
Other procedures for the creation of the neo-
vagina are the Vecchietti procedure and laparo-
scopic modifications of operations previously
performed by laparotomy. The Vecchietti procedure
involves the creation of a neovagina via dilation
with a traction device attached to the abdomen,
sutures placed subperitoneally via laparotomy, and a
plastic olive placed on the vaginal dimple. In the
laparoscopic modification, traction sutures are
placed laparoscopically. The two techniques are
comparable in terms of producing a functional neo-
vagina (15). Davydov developed a three-stage oper-
ation involving dissection of the rectovesical space
with abdominal mobilization of the peritoneum,
with creation of the vaginal fornices and attachment
of the peritoneum to the introitus. The newer adap-
tation involves dissection of the rectovaginal space,
with mobilization of the peritoneum from below and
laparoscopic assistance from above. This is fol-
lowed by closure of the abdominal end of the neo-
vagina with a laparoscopically placed pursestring
suture (8, 16, 17).
General Gynecologic Care
Women who have a history of mllerian agenesis
and have created a functional vagina do require rou-
tine gynecologic care. Annual pelvic examinations
should be performed to examine for vaginal stricture
or stenosis. Women with mllerian agenesis should
be aware that the neovagina has the same risk as a
native vagina for sexually transmitted diseases and
thus they should be appropriately screened. In addi-
tion, vaginal speculum examination and inspection
should be performed to look for possible malignan-
cies (in cases of skin graft or bowel vaginas), colitis
or ulceration (in cases of bowel vaginas), or other
problems. No data exists regarding the need or lack
of need for routine Pap testing in women with a neo-
vagina. It is reasonable to consider these women in
the same category as women without a cervix
because of hysterectomy for the treatment of benign
disease. Thus, annual cytologic screening for cancer
can be considered unnecessary, although no data are
available to support or oppose this concept.
COMPENDIUM OF SELECTED PUBLICATIONS 54 54 54
Conclusion
The most important steps in the effective manage-
ment of mllerian aplasia are correct diagnosis of
the underlying condition; evaluation for associated
congenital, renal, or other anomalies; and prepara-
tion of the patient before any treatment or interven-
tion. If any of these are neglected, the success of the
intervention will be compromised.
Laparoscopy is seldom required to make the
diagnosis but may be appropriate in the patient pre-
senting with pelvic pain. Nonsurgical creation of the
neovagina should be the first-line approach. In cases
in which surgical intervention is required, referrals
to centers with expertise in this area should be con-
sidered. Few surgeons have extensive experience in
construction of the neovagina, and the initial surgery
has the greatest chance for success. In addition,
experts at these centers may be more successful in
promoting the nonsurgical approach, given their
experience.
References
1. Evans TN, Poland ML, Boving RL. Vaginal malforma-
tions. Am J Obstet Gynecol 1981;141:91020.
2. Reindollar RH, Byrd JR, McDonough PG. Delayed sex-
ual development: a study of 252 patients. Am J Obstet
Gynecol 1981;140:37180.
3. New MI. Male pseudohermaphroditism due to 17 alpha-
hydroxylase deficiency. J Clin Invest 1970;49:193041.
4. Nieman LK, Kovacs WJ. Uncommon causes of congeni-
tal adrenal hyperplasia. In: Rose BD, editor. UpToDate.
Waltham (MA); 2006.
5. Fedele L, Dorta M, Brioschi D, Giudici MN, Candiani
GB. Magnetic resonance imaging in Mayer-Rokitansky-
Kuster-Hauser syndrome. Obstet Gynecol 1990;76:
5936.
6. Laufer MR, Goldstein DP, Hendren WH. Structural
abnormalities of the female reproductive tract. In: Emans
SJ, Laufer MR, Goldstein DP, editors. Pediatric and ado-
lescent gynecology. 5th ed. Philadelphia (PA): Lippincott
Williams & Wilkins; 2005. p. 334416.
7. Poland ML, Evans TN. Psychologic aspects of vaginal
agenesis. J Reprod Med 1985;30:3404.
8. Adamyan LV. Laparoscopic management of vaginal apla-
sia with or without functional noncommunicating rudi-
mentary uterus. In: Arregui ME, Fitzgibbons RJ Jr,
Katkhouda N, McKernan JB, Reich H, editors. Principles
of laparoscopic surgery: basic and advanced techniques.
New York (NY): SpringerVerlag; 1995. p. 64651.
9. Petrozza JC, Gray MR, Davis AJ, Reindollar RH.
Congenital absence of the uterus and vagina is not com-
monly transmitted as a dominant genetic trait: outcomes
of surrogate pregnancies. Fertil Steril 1997;67:3879.
10. Roberts CP, Haber MJ, Rock JA. Vaginal creation for
mllerian agenesis. Am J Obstet Gynecol 2001;
185:134952; discussion 13523.
11. Williams JK, Lake M, Ingram JM. The bicycle seat stool
in the treatment of vaginal agenesis and stenosis. J Obstet
Gynecol Neonatal Nurs 1985;14:14750.
12. Rock JA, Breech LL. Surgery for anomalies of the
Mllerian ducts. In: Rock JA, Jones HW 3rd, editors. Te
Lindes operative gynecology. 9th ed. Philadelphia (PA):
Lippincott Williams & Wilkins; 2003. p. 70552.
13. Templeman CL, Lam AM, Hertweck SP. Surgical man-
agement of vaginal agenesis. Obstet Gynecol Surv
1999;54:58391.
14. Laufer MR. Congenital absence of the vagina: in search
of the perfect solution. When, and by what technique,
should a vagina be created? Curr Opin Obstet Gynecol
2002;14:4414.
15. Borruto F, Chasen ST, Chervenak FA, Fedele L. The
Vecchietti procedure for surgical treatment of vaginal
agenesis: comparison of laparoscopy and laparotomy. Int
J Gynaecol Obstet 1999;64:1538.
16. Davydov SN, Zhvitiashvili OD. Formation of vagina
(colpopoiesis) from peritoneum of Douglas pouch. Acta
Chir Plast 1974;16:3541.
17. Adamyan LV. Therapeutic and endoscopic perspectives.
In: Nichols DH, Clarke-Pearson DL, editors. Gyneco-
logic, obstetric, and related surgery. 2nd ed. St. Louis
(MO): Mosby; 2000. p. 120917.
Resources
MRKH.org, Inc.
PO Box 301494
Jamaica Plain, MA 02130
Web: www.mrkh.org
The Center for Young Womens Health
Childrens Hospital Boston
333 Longwood Avenue, 5th Floor
Boston, MA 02115
(617) 730-0192
Web:www.youngwomenshealth.org
A guide to vaginal agenesis in teens. Available at
www.youngwomenshealth.org/vaginalagenesis.html
MRKH (Mayer Rokitansky Kuster Hauser Syndrome) and
vaginal agenesis: a guide for parents and guardians. Available
at www.youngwomenshealth.org/mrkh_parent.html
55 COMMITTEE OPINIONS 55
Intrauterine Device and Adolescents
ABSTRACT: The intrauterine device (IUD) is highly effective and widely used by
women throughout the world. Data support the safety of IUDs for most women, includ-
ing adolescents. This document addresses the major benefits of IUD use in adolescents,
a population at particular risk of unintended pregnancy.
Committee on
Adolescent Health
Care
The committee
would like to thank
Nicole Zidenberg, MD,
Nirupama DeSilva, MD,
Melissa Gilliam, MD,
and Eve Espey, MD, for
their contributions to
the development of this
document.
This document reflects
emerging clinical and sci-
entific advances as of the
date issued and is subject
to change. The informa-
tion should not be con-
strued as dictating an
exclusive course of treat-
ment or procedure to be
followed.
Number 392 December 2007
ACOG COMMITTEE OPINION
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Intrauterine devices (IUDs) are used by
fewer than 3% of reproductive-aged women
in the United States (1). Concerns about
pelvic inflammatory disease (PID), sexually
transmitted diseases (STDs), infertility, and
difficult insertion have limited the use of the
IUD in adolescents. Data support the safety
of IUDs for most women, including adoles-
cents. The World Health Organization sup-
ports the use of intrauterine contraception in
women from menarche to age 20 years, stat-
ing that the benefits of intrauterine contra-
ception generally outweigh the risks (2).
Importance of Appropriate
Contraception
Approximately 29% of ninth graders and
62% of 12th graders have engaged in inter-
course (3). Sexual activity and inconsistent
contraceptive use contribute to the high rate
of adolescent pregnancy in the United States,
which exceeds that of other industrialized
countries (4, 5). Intrauterine devices offer the
long-term, cost-effective, highly reliable, and
effective contraception needed by women,
especially adolescents (6, 7).
Common Misperceptions
The Intrauterine Device Does Not
Increase an Adolescents Risk of
Pelvic Inflammatory Disease and
Sexually Transmitted Diseases
Past experiences with the Dalkon Shield have
perpetuated the myth that IUDs cause pelvic
infections. The studies that showed a causal
relationship between pelvic infection and
IUDs were fraught with methodologic errors.
Confounding factors included inappropriate
comparison groups, overdiagnosis of salpin-
gitis in IUD users, and inability to control for
the effects of sexual behavior, leading to an
exaggeration of risk estimates (8). Ongoing
research continues to demonstrate the safety
of modern types of IUDs.
The risk of PID is increased above base-
line only at the time of insertion. Among
22,908 IUD users, within the first 20 days of
use, the risk of PID was 9.7 per 1,000 woman-
years; from 21 days to 8 years, the incidence of
PID was 1.4 per 1,000 woman-years, the
same as that in the general population (9).
Other multicenter randomized controlled
trials confirmed these findings (8, 10). The
risk of PID with IUD placement is 02%
when no infection is present at the time of
insertion and 05% when insertion occurred
with a documented infection. The absolute
risk of PID is very small in both groups (10).
Case reports also have shown that women
with positive chlamydia cultures identified at
the time of IUD insertion are unlikely to
develop PID if the infection is treated with
the IUD retained (11, 12).
The levonorgestrel-releasing intrauter-
ine system may lower the risk of PID by
thickening cervical mucus and thinning the
endometrium (13). Studies have demonstrat-
ed the reduced risk of PID using the lev-
onorgestrel-releasing intrauterine system as
compared with a copper IUD (14, 15).
Intrauterine Devices Do Not Affect
the Fertility of Adolescents
Compared with other methods, infertility
was not higher after cessation of IUD use ver-
sus cessation of other reversible methods of
contraception (8). In a casecontrol study
examining determinants of tubal infertility,
the presence of chlamydial antibodies was
associated with infertility in both users and
COMPENDIUM OF SELECTED PUBLICATIONS 56 56
nonusers of IUDs (16). Fecundity rapidly returns to nor-
mal after IUD removal (17, 18).
Discontinuation
Adolescents are more likely than adult women to discon-
tinue a range of contraceptive methods, including pills
and injectable contraception. In women younger than 25
years, discontinuation of the levonorgestrel-releasing
intrauterine system at 12 months was slightly higher
compared with older women (19). Among copper IUD
users, pain and bleeding led to discontinuation (20). The
rate of amenorrhea with the levonorgestrel-releasing
intrauterine system varies from 16.4% to 80% at 1 year
after insertion and may alleviate bleeding concerns (21).
Expulsion
Expulsion contributes to IUD failure with a risk of 1 in 20
(22). Younger age and previous IUD expulsion may con-
fer the greatest risk of failure (23). Prior expulsion should
not be considered a contraindication for a new IUD pro-
vided that patients undergo appropriate counseling and
have close follow-up (23).
Contraindications
Contraindications to IUD use include current pregnancy;
PID or puerperal or postabortion sepsis that is current or
within the past 3 months; current STDs; purulent cervici-
tis; undiagnosed abnormal vaginal bleeding; malignancy
of the genital tract; known uterine anomalies or leiomy-
omata distorting the uterine cavity in a way incompatible
with IUD insertion; or allergy to any component of the
IUD or Wilsons disease (for copper-containing IUDs)
(24). An asymptomatic patient may use an IUD within
3 months of a treated pelvic infection or septic abortion
(2, 18).
Emergency Contraception and
Menstrual Suppression
The copper IUD may be used for emergency contracep-
tion within 5 days of unprotected intercourse (24). The
IUD confers the additional benefit of serving as a long-
term contraceptive. One study found that 86% of parous
women and 80% of nulliparous women maintained the
IUD for long-term contraception after use as emergency
contraception (25).
In addition to providing contraception, the lev-
onorgestrel-releasing intrauterine system reduces men-
strual blood loss by 75% at 3 months. It offers the most
favorable side effect profile of the progesterone-only
methods. The levonorgestrel-releasing intrauterine system
offers an alternative to birth control pills for cycle control.
Confidentiality, Consent, and
Counseling
Practitioners must be familiar with federal, state, and
institutional guidelines governing consent by adolescents.
In many states, adolescents have the right to receive con-
fidential contraceptive services without parental permis-
sion (26). Confidential IUD insertion may be thwarted by
the cost or consent issues. Preinsertion counseling about
the IUD is paramount. Goals of counseling include
awareness of the long-term nature of the contraceptive,
side effects, risks, and benefits. Upon insertion of the
IUD, self-examination to confirm the presence of strings
should be taught, and condom use for STD prevention
should be encouraged. It is important for adolescents
using IUDs to be familiar with their anatomy and com-
fortable with checking for strings.
Insertion in the Nulliparous Patient
Discomfort with IUD insertion is common. In one study,
86% of adolescents reported mild to severe pain with
insertion (13). Misoprostol may soften a nulliparous
cervix before insertion (27). Studies of use of non-
steroidal antiinflammatory drugs for analgesia yielded
mixed results but they may be used (28). Less studied
methods of analgesia include paracervical blocks or pre-
insertion narcotics. Little data suggest that IUD insertion
is technically more difficult in adolescents.
Prophylactic antibiotics are not necessary for IUD
insertion (29). Because adolescents have the highest num-
ber of reported cases of chlamydia and coinfection with
gonorrhea frequently occurs (30), all adolescents should
be screened for gonorrhea and chlamydia before IUD
insertion (27, 31). Screening at the time of insertion expe-
dites contraceptive use. Patients with positive test results
have no adverse effects if treated promptly (1012).
Conclusion
The IUD is a highly effective method of contraception
that is underused in the United States. Because adoles-
cents contribute disproportionately to the epidemic of
unintended pregnancy in this country, top tier methods
of contraception, including IUDs and implants, should be
considered as first-line choices for both nulliparous and
parous adolescents. After thorough counseling regarding
contraceptive options, health care providers should
strongly encourage young women who are appropriate
candidates to use this method.
References
1. Mosher WD, Martinez GM, Chandra A, Abma JC, Willson
SJ. Use of contraception and use of family planning services
in the United States: 1982-2002. Adv Data 2004;350:136.
2. World Health Organization. Intrauterine devices. In:
Medical eligibility criteria for contraceptive use. 3rd ed.
Geneva: WHO; 2004. p. 117. Available at: http://www.
who.int/reproductive-health/publications/mec/7_iud.pdf.
Retrieved August 16, 2007.
3. Eaton DK, Kann L, Kinchen S, Ross J, Hawkins J, Harris
WA, et al. Youth risk behavior surveillanceUnited States,
2005. MMWR Surveill Summ 2006;55(5):1108.
57 COMMITTEE OPINIONS 57
4. Zibners A, Cromer BA, Hayes J. Comparison of continua-
tion rates for hormonal contraception among adolescents.
J Pediatr Adolesc Gynecol 1999;12:904.
5. Guttmacher Institute. In brief: facts on American teens sex-
ual and reproductive health. New York (NY): GI; 2006.
Available at: http://guttmacher.org/pubs/fb_ATSRH.html.
Retrieved August 16, 2007.
6. Trussell J, Vaughan B. Contraceptive failure, method-relat-
ed discontinuation and resumption of use: results from the
1995 National Survey of Family Growth. Fam Plann
Perspect 1999;31:6472, 93.
7. Chiou CF, Trussell J, Reyes E, Knight K, Wallace J, Udani J,
et al. Economic analysis of contraceptives for women.
Contraception 2003;68:310.
8. Grimes DA. Intrauterine device and upper-genital-tract
infection. Lancet 2000;356:10139.
9. Farley TM, Rosenberg MJ, Rowe PJ, Chen JH, Meirik O.
Intrauterine devices and pelvic inflammatory disease: an
international perspective. Lancet 1992;339:7858.
10. Mohllajee AP, Curtis KM, Peterson HB. Does insertion and
use of an intrauterine device increase the risk of pelvic
inflammatory disease among women with sexually trans-
mitted infection? A systematic review. Contraception
2006;73:14553.
11. Skjeldestad FE, Halvorsen LE, Kahn H, Nordbo SA, Saake K.
IUD users in Norway are at low risk for genital C. tra-
chomatis infection. Contraception 1996;54:20912.
12. Faundes A, Telles E, Cristofoletti ML, Faundes D, Castro S,
Hardy E. The risk of inadvertent intrauterine device inser-
tion in women carriers of endocervical Chlamydia tra-
chomatis. Contraception 1998;58:1059.
13. Suhonen S, Haukkamaa M, Jakobsson T, Rauramo I. Clinical
performance of a levonorgestrel-releasing intrauterine sys-
tem and oral contraceptives in young nulliparous women: a
comparative study. Contraception 2004;69:40712.
14. Andersson K, Odlind V, Rybo G. Levonorgestrel-releasing
and copper-releasing (Nova T) IUDs during five years of
use: a randomized comparative trial. Contraception 1994;
49:5672.
15. Toivonen J, Luukkainen T, Allonen H. Protective effect of
intrauterine release of levonorgestrel on pelvic infection:
three years comparative experience of levonorgestrel- and
copper-releasing intrauterine devices. Obstet Gynecol
1991;77:2614.
16. Hubacher D, Lara-Ricalde R, Taylor DJ, Guerra-Infante F,
Guzman-Rodriguez R. Use of copper intrauterine devices
and the risk of tubal infertility among nulligravid women.
N Engl J Med 2001;345:5617.
17. Hov GG, Skjeldestad FE, Hilstad T. Use of IUD and subse-
quent fertilityfollow-up after participation in a random-
ized clinical trial. Contraception 2007;75:8892.
18. Penney G, Brechin S, de Souza A, Bankowska U, Belfield T,
Gormley M, et al. FFPRHC Guidance (January 2004). The
copper intrauterine device as long-term contraception.
Faculty of Family Planning and Reproductive Health Care
Clinical Effectiveness Unit [published erratum appears in J
Fam Plann Reprod Health Care 2004;30:134]. J Fam Plann
Reprod Health Care 2004;30:2941; quiz 42.
19. Luukkainen T, Allonen H, Haukkamaa M, Holma P, Pyorala
T, Terho J, et al. Effective contraception with the lev-
onorgestrel-releasing intrauterine device: 12-month report
of a European multicenter study. Contraception 1987;36:
16979.
20. Rivera R, Chen-Mok M, McMullen S. Analysis of client
characteristics that may affect early discontinuation of the
TCu-380A IUD. Contraception 1999;60:15560.
21. Toma A, Jamieson MA. Revisiting the intrauterine contra-
ceptive device in adolescents. J Pediatr Adolesc Gynecol
2006;19:2916.
22. FFPRHC Guidance (April 2004). The levonorgestrel-releas-
ing intrauterine system (LNG-IUS) in contraception and
reproductive health. Faculty of Family Planning and
Reproductive Health Care Clinical Effectiveness Unit. J Fam
Plann Reprod Health Care 2004;30:99108; quiz 109.
23. Thonneau P, Almont T, de La Rochebrochard E, Maria B.
Risk factors for IUD failure: results of a large multicentre
case-control study. Hum Reprod 2006;21:26126.
24. Intrauterine device. ACOG Practice Bulletin No. 59.
American College of Obstetricians and Gynecologists.
Obstet Gynecol 2005;105:22332.
25. Zhou L, Xiao B. Emergency contraception with Multiload
Cu-375 SL IUD: a multicenter clinical trial. Contraception
2001;64:10712.
26. Guttmacher Institute. State policies in brief: minors access
to contraceptive services. New York (NY): GI; 2007.
Available at: http://www.guttmacher.org/statecenter/spibs/
spib_MACS.pdf. Retrieved September 6, 2007.
27. McNaught J. Adolescents and IUCDsNot a contraindica-
tion. J Pediatr Adolesc Gynecol 2006;19:3035.
28. Grimes DA, Hubacher D, Lopez LM, Schulz KF. Non-
steroidal anti-inflammatory drugs for heavy bleeding or
pain associated with intrauterine-device use. Cochrane
Database of Systematic Reviews 2006, Issue 4. Art. No.:
CD006034. DOI: 10.1002/14651858.CD006034.pub2.
29. Grimes DA, Schulz FK. Antibiotic prophylaxis for intrauter-
ine contraceptive device insertion. Cochrane Database of
Systematic Reviews 1999, Issue 3. Art. No.: CD001327. DOI:
10.1002/14651858.CD001327.
30. Centers for Disease Control and Prevention. Sexually trans-
mitted disease surveillance 2005. Atlanta (GA): CDC; 2006.
Available at: http://www.cdc.gov/std/stats/05pdf/Surv2005. pdf.
Retrieved August 16, 2007.
31. Lacy J. Clinic opinions regarding IUCD use in adolescents.
J Pediatr Adolesc Gynecol 2006;19:3013.
Copyright December 2007 by the American College of Obstet-
ricians and Gynecologists, 409 12th Street, SW, PO Box 96920,
Washington, DC 20090-6920. All rights reserved. No part of this pub-
lication may be reproduced, stored in a retrieval system, posted on
the Internet, or transmitted, in any form or by any means, electronic,
mechanical, photocopying, recording, or otherwise, without prior
written permission from the publisher. Requests for authorization to
make photocopies should be directed to: Copyright Clearance Center,
222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
Intrauterine device and adolescents. ACOG Committee Opinion No.
392. American College of Obstetricians and Gynecologists. Obstet
Gynecol 2007;110:14935.
ISSN 1074-861X
COMPENDIUM OF SELECTED PUBLICATIONS 58 58
Committee on
Adolescent Health
Care
Committee on
Gynecologic
Practice
This document reflects
emerging clinical and sci-
entific advances as of the
date issued and is subject
to change. The informa-
tion should not be con-
strued as dictating an
exclusive course of treat-
ment or procedure to be
followed.
Number 415 September 2008
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Depot medroxyprogesterone acetate (DMPA)
is a highly effective, long-acting contraceptive
injection used by more than two million
women annually in the United States, includ-
ing approximately 400,000 adolescents (1).
Convenient dose administration and privacy
are appealing to adolescents, and the expand-
ed use of DMPA has been credited for at least
part of the decrease in adolescent pregnancy
rates over the past decade (2, 3). Depot
medroxyprogesterone acetate prevents preg-
nancy by inhibiting the secretion of pituitary
gonadotropins resulting in anovulation,
amenorrhea, and a decreased production of
serum estrogen. Hypoestrogenism is associ-
ated with a decrease in bone mineral density
(BMD). In older women, low BMD consis-
tent with osteopenia or osteoporosis is asso-
ciated with an increased risk of fracture.
No studies have been conducted to examine
the association between BMD and fractures
in low-risk young women, including those
using DMPA or those experiencing the
physiologic hypoestrogenism of lactation.
Although DMPA is associated with BMD loss
during use, current evidence suggests that
partial or full recovery of BMD occurs at the
spine and at least partial recovery occurs at
the hip after discontinuation of DMPA.
Given the efficacy of DMPA, particularly for
populations such as adolescents for whom
contraceptive adherence can be challenging or
for those who feel they could not comply with
a daily contraceptive method or a method that
must be used with each act of intercourse, the
possible adverse effects of DMPA must be bal-
anced against the significant personal and pub-
lic health impact of unintended pregnancy.
Bone Mineral Density
A number of studies demonstrate the effect
of DMPA on BMD. Cross-sectional and lon-
gitudinal studies using dual-energy X-ray
absorptiometry (DXA) technology among
current users of DMPA (ages 1854 years)
demonstrate that DMPA use results in lower
BMD compared with nonusers regardless of
the anatomic site measured (410). Longi-
tudinal studies report BMD losses at the hip
and spine of 0.53.5% after 1 year of DMPA
use (5, 11) and a 5.77.5% loss in BMD after
2 years of use (8, 10).
Although few studies have examined
long-term use of DMPA, it appears that the
greatest BMD loss is experienced during the
first few years of use (7, 10, 11). In one 3-year
Depot Medroxyprogesterone Acetate and
Bone Effects
ABSTRACT: Although depot medroxyprogesterone acetate (DMPA) is associated
with bone mineral density (BMD) loss during use, current evidence suggests that partial
or full recovery of BMD occurs at the spine and at least partial recovery occurs at the hip
after discontinuation of DMPA. Given the efficacy of DMPA, particularly for populations
such as adolescents for whom contraceptive adherence can be challenging or for those
who feel they could not comply with a daily contraceptive method or a method that must
be used with each act of intercourse, the possible adverse effects of DMPA must be bal-
anced against the significant personal and public health impact of unintended pregnancy.
Concerns regarding the effect of DMPA on BMD should neither prevent practitioners from
prescribing DMPA nor limit its use to 2 consecutive years. Practitioners should not per-
form BMD monitoring solely in response to DMPA use because any observed short-term
loss in BMD associated with DMPA use may be recovered and is unlikely to place a
woman at risk of fracture during use or in later years.
ACOG COMMITTEE OPINION
59 COMMITTEE OPINIONS 59
longitudinal study, mean change in BMD at each
6-month interval decreased as the number of cumulative
months of DMPA use increased (7). Those using DMPA
for 12 months or less lost BMD at a faster rate than those
using DMPA for 13 months or more (7). Another recent
longitudinal study with a 4-year follow-up period
demonstrated that almost 75% of the BMD lost at the hip
and 90% lost at the spine occurred during the first
24 months of use (9). Women who continued DMPA use
beyond 24 months still lost additional bone, but the mag-
nitude of loss was smaller with each subsequent year of
use (9).
A recent prospective study of BMD monitored
DMPA users and nonhormonal contraceptive users
2025 years of age for up to 5 years of use and for up to 2
years after discontinuation. Despite BMD loss during use,
total hip BMD among DMPA users had returned almost
to baseline levels at 2 years after discontinuation (from
-5.16% after 240 weeks of use to -0.2% at 96 weeks after
discontinuation), and BMD values in the lumbar spine
showed partial recovery (from -5.38% after 240 weeks of
use to -1.19% at 96 weeks after discontinuation) (12). As
in prior studies, the rate of BMD loss was greater in the
first year of treatment than in subsequent years.
Bone loss during the reproductive years is not unique
to DMPA use. Studies of adult women show a decrease in
BMD of 28% during pregnancy and 35% during
breastfeeding (13, 14). These losses are temporary; 612
months after birth or cessation of breast-feeding BMD
values increase to near preconception values in most
women (11). Similarly, studies suggest that at least some
of the bone loss experienced as a result of DMPA use is
recovered after discontinuation. However, studies differ in
their assessment of the speed and completeness of this
recovery (7, 9, 10, 12, 1517). Furthermore, the degree of
recovery appears to differ by site. A 3-year longitudinal
study of 1839-year-old DMPA users noted that women
experienced steady gains in BMD after discontinuation,
regardless of duration of DMPA use (7). Lumbar spine
BMD of DMPA users was similar to that of nonusers by
30 months after discontinuation (7). Increases in BMD at
the hip among those discontinuing use of DMPA also
were noted, but the gain in BMD at this location was
lower than that of nonusers 30 months after discontinua-
tion. Similarly, a 4-year study of first-time users of DMPA
1835 years of age demonstrated that the length of time
required for BMD values to return to baseline levels
depended on the site measured and the duration of
DMPA use. Complete recovery occurred at the spine
within 2730 months among those using DMPA up to 24
months. Recovery at the hip was slower; among those
women who used DMPA for 24 months or less, a return
to baseline values was not observed by 30 months after
discontinuation (9).
Bone mineral density normally increases during the
teenaged years. Therefore, a decrease or stabilization in
BMD during this period may be cause for concern. In a
study of DMPA users aged 1221 years, BMD decreased
an average of 3.1% (18). In contrast, adolescents who were
not using hormonal contraception gained BMD at an
average rate of 9.5% over 2 years (18). Among new DMPA
users aged 1418 years, a decrease of 5% at the spine
occurred after 24 months compared with an increase of
2.3% in nonusers (16). The decrease in BMD observed in
these studies may be mitigated by the short-term or inter-
mittent nature of DMPA use in many adolescents because
the discontinuation rate is 50% in the first year (19).
Furthermore, increases in BMD of 14% at the hip and
spine 12 months after discontinuation of DMPA have
been shown in adolescents aged 1418 years (16).
At least two cross-sectional studies provide reassur-
ing data that BMD in former adult DMPA users is similar
to that of never users (20, 21). A World Health
Organization study observed this lack of difference in
BMD in an international population of former DMPA
users and nonusers (20). Another study of post-
menopausal women in New Zealand indicated similar
BMD in former adult DMPA users compared with that of
never users (21).
Fracture Risk
Although many studies have examined the intermediate
outcome of decreased BMD related to DMPA, few inves-
tigations have examined the outcome of critical impor-
tance to womens healththat of fracture risk. Two studies
have examined DMPA use and fracture, both in high-risk
populations. A prospective, short-term study of female
military recruits found that, in white women only, history
of DMPA use was one of several factors associated with an
increased risk of stress fractures of the calcaneus (22).
This study was limited to women at high risk of fractures
and is not applicable to the general population. Another
recent study of developmentally delayed women suggests
an increased risk of fractures in those with a history of
DMPA use. This study is limited by its cross-sectional
design and its use of retrospective data (23).
There are no reported studies in which the risk of
osteoporosis or fractures has been examined in a low-risk
population of prior DMPA users. A recent Cochrane
review reveals that not a single randomized controlled
trial of DMPA and fracture risk has been performed (24).
The Black Box Warning
Concerns over the effect of DMPA use on BMD caused
the U.S. Food and Drug Administration to issue a black
box warning in November 2004. This warning stated
that prolonged use of DMPA may result in significant loss
of BMD, that the loss is greater the longer the drug is
used, and that the loss may not be completely reversible
after discontinuation. The warning cautions that use of
DMPA beyond 2 years should be considered only if other
contraceptive methods are inadequate. In a letter to
physicians, a manufacturer of DMPA suggested DXA
monitoring after 2 years of use.
COMPENDIUM OF SELECTED PUBLICATIONS 60 60
The U.S. Food and Drug Administration warning is
based on intermediate effects on BMD, which may or may
not be relevant to increased fracture risk. Because the evi-
dence suggests that the rate of BMD loss may slow with
longer term DMPA use, the rationale for restriction to
2 years of use or DXA monitoring is unclear. Practitioners
should not perform BMD monitoring solely in response
to DMPA use because any observed short-term losses in
BMD may be recovered and are unlikely to place women
at risk of fracture during DMPA use or in later years.
Risks of Bone Loss Versus the
Benefits of Contraception
Most women and adolescents use DMPA to avoid preg-
nancy. The failure rate in typical users is 23% for DMPA
(25). As a result, DMPA is widely used by women for
whom successful use of a daily or partner-dependent con-
traceptive method is difficult. Increased use of DMPA in
the past 15 years has been paralleled by a decrease in the
adolescent pregnancy rate (2, 3). Although there are many
factors contributing to the decrease in adolescent preg-
nancies, DMPA has likely played a role. It is important to
weigh the theoretical risk of future fracture from
decreased BMD in DMPA users against the very real risk
of pregnancy if contraceptive choices are limited (26). For
example, an adolescent who is at high risk for pregnancy
may be best served by the use of DMPA as a contraceptive
option; both pregnancy and DMPA are associated with
loss of BMD. The riskbenefit ratio might differ for a
noncontraceptive indication such as dysmenorrhea (23).
Counseling
Women initiating DMPA should be thoroughly counseled
about the benefits and the potential risks of DMPA. Daily
exercise and age-appropriate calcium and vitamin D
intake should be encouraged. No studies have shown that
these measures will offset loss of BMD during DMPA use,
but these recommendations can benefit general health,
and most adolescents do not ingest sufficient dietary cal-
cium. Although studies of adolescents and adult women
demonstrate that low-dose estrogen supplementation
limits BMD loss in DMPA users (27, 28), estrogen supple-
mentation during DMPA use is not currently recom-
mended. Most importantly, clinicians should provide
counseling regarding the side effects of DMPA, including
irregular bleeding, in order to attempt to reduce the high
rates of discontinuation of this method.
Conclusion
Depot medroxyprogesterone acetate is a safe and effective
means of long-term contraception, which has likely con-
tributed to a decrease in adolescent pregnancy rates over
the past decade. Concerns regarding the effect of DMPA
on BMD should neither prevent practitioners from pre-
scribing DMPA nor limit its use to 2 consecutive years.
Appropriate counseling with a discussion of current med-
ical evidence should occur before the initiation of this
medication and during prolonged use. Practitioners
should not perform BMD monitoring solely in response
to DMPA use because any observed short-term loss in
BMD associated with DMPA use may be recovered and is
unlikely to place a woman at risk of fracture during use or
in later years. Effective long-term contraceptive methods
that have no effect on BMD and have high continuation
rates, such as contraceptive implants and intrauterine
devices, should also be considered as first-line methods
for adolescents.
References
1. Mosher WD, Martinez GM, Chandra A, Abma JC, Willson
SJ. Use of contraception and use of family planning ser-
vices in the United States: 1982-2002. Adv Data 2004;(350):
136.
2. Santelli JS, Abma J, Ventura S, Lindberg L, Morrow B,
Anderson JE, et al. Can changes in sexual behaviors among
high school students explain the decline in teen pregnancy
rates in the 1990s? J Adolesc Health 2004;35:8090.
3. Santelli JS, Lindberg LD, Finer LB, Singh S. Explaining
recent declines in adolescent pregnancy in the United
States: the contribution of abstinence and improved contra-
ceptive use. Am J Public Health 2007;97:1506.
4. Cundy T, Cornish J, Roberts H, Elder H, Reid IR. Spinal
bone density in women using depot medroxyprogesterone
contraception. Obstet Gynecol 1998;92:56973.
5. Berenson AB, Radecki CM, Grady JJ, Rickert VI, Thomas A.
A prospective, controlled study of the effects of hormonal
contraception on bone mineral density. Obstet Gynecol
2001;98:57682.
6. Wanichsetakul P, Kamudhamas A, Watanaruangkovit P,
Siripakarn Y, Visutakul P. Bone mineral density at various
anatomic bone sites in women receiving combined oral
contraceptives and depot-medroxyprogesterone acetate for
contraception. Contraception 2002;65:40710.
7. Scholes D, LaCroix AZ, Ichikawa LE, Barlow WE, Ott SM.
Injectable hormone contraception and bone density: results
from a prospective study [published erratum appears in
Epidemiology 2002;13:749]. Epidemiology 2002;13:5817.
8. Berenson AB, Breitkopf CR, Grady JJ, Rickert VI, Thomas A.
Effects of hormonal contraception on bone mineral density
after 24 months of use. Obstet Gynecol 2004;103:899906.
9. Clark MK, Sowers M, Levy B, Nichols S. Bone mineral den-
sity loss and recovery during 48 months in first-time users
of depot medroxyprogesterone acetate. Fertil Steril 2006;
86:146674.
10. Clark MK, Sowers MR, Nichols S, Levy B. Bone mineral
density changes over two years in first-time users of depot
medroxyprogesterone acetate. Fertil Steril 2004;82:15806.
11. Ulrich CM, Georgiou CC, Snow-Harter CM, Gillis DE.
Bone mineral density in mother-daughter pairs: relations to
lifetime exercise, lifetime milk consumption, and calcium
supplements. Am J Clin Nutr 1996;63:729.
12. Kaunitz AM, Miller PD, Rice VM, Ross D, McClung MR.
Bone mineral density in women aged 25-35 years receiving
depot medroxyprogesterone acetate: recovery following dis-
continuation. Contraception 2006;74:909.
61 COMMITTEE OPINIONS 61
13. Karlsson C, Obrant KJ, Karlsson M. Pregnancy and lacta-
tion confer reversible bone loss in humans. Osteoporos Int
2001;12:82834.
14. Sowers M, Corton G, Shapiro B, Jannausch ML, Crutchfield
M, Smith ML, et al. Changes in bone density with lactation.
JAMA 1993;269:31305.
15. Cundy T, Cornish J, Evans MC, Roberts H, Reid IR.
Recovery of bone density in women who stop using
medroxyprogesterone acetate. BMJ 1994;308:2478.
16. Scholes D, LaCroix AZ, Ichikawa LE, Barlow WE, Ott SM.
Change in bone mineral density among adolescent women
using and discontinuing depot medroxyprogesterone
acetate contraception. Arch Pediatr Adolesc Med 2005;
159:13944.
17. Johnson CC, Burkman RT, Gold MA, Brown RT, Harel Z,
Bruner A, et al. Longitudinal study of depot medroxyprog-
esterone acetate (Depo-Provera) effects on bone health in
adolescents: study design, population characteristics and
baseline bone mineral density. Contraception 2008;77:
23948.
18. Cromer BA, Stager M, Bonny A, Lazebnik R, Rome E,
Ziegler J, et al. Depot medroxyprogesterone acetate, oral
contraceptives and bone mineral density in a cohort of ado-
lescent girls. J Adolesc Health 2004;35:43441.
19. Zibners A, Cromer BA, Hayes J. Comparison of continua-
tion rates for hormonal contraception among adolescents.
J Pediatr Adolesc Gynecol 1999;12:904.
20. Petitti DB, Piaggio G, Mehta S, Cravioto MC, Meirik O.
Steroid hormone contraception and bone mineral density:
a cross-sectional study in an international population. The
WHO Study of Hormonal Contraception and Bone Health.
Obstet Gynecol 2000;95:73644.
21. Orr-Walker BJ, Evans MC, Ames RW, Clearwater JM,
Cundy T, Reid IR. The effect of past use of the injectable
contraceptive depot medroxyprogesterone acetate on bone
mineral density in normal post-menopausal women. Clin
Endocrinol 1998;49:6158.
22. Lappe JM, Stegman MR, Recker RR. The impact of lifestyle
factors on stress fractures in female Army recruits.
Osteoporos Int 2001;12:3542.
23. Watson KC, Lentz MJ, Cain KC. Associations between frac-
ture incidence and use of depot medroxyprogesterone
acetate and anti-epileptic drugs in women with develop-
mental disabilities. Womens Health Issues 2006;16:34652.
24. Lopez LM, Grimes DA, Schulz KF, Curtis KM. Steroidal
contraceptives: effect on bone fractures in women.
Cochrane Database of Systematic Reviews 2006, Issue 4.
Art. No.: CD006033. DOI: 10.1002/14651858.CD006033
25. Trussell J. Contraceptive failure in the United States.
Contraception 2004;70:8996.
26. Cromer BA, Scholes D, Berenson A, Cundy T, Clark MK,
Kaunitz AM, et al. Depot medroxyprogesterone acetate and
bone mineral density in adolescentsthe Black Box
Warning: a Position Paper of the Society for Adolescent
Medicine. Society for Adolescent Medicine. J Adolesc
Health 2006;39:296301.
27. Cundy T, Ames R, Horne A, Clearwater J, Roberts H,
Gamble G, et al. A randomized controlled trial of estrogen
replacement therapy in long-term users of depot medroxy-
progesterone acetate. J Clin Endocrinol Metab 2003;88:
7881.
28. Cromer BA, Lazebnik R, Rome E, Stager M, Bonny A,
Ziegler J, et al. Double-blinded randomized controlled trial
of estrogen supplementation in adolescent girls who receive
depot medroxyprogesterone acetate for contraception. Am
J Obstet Gynecol 2005;192:427.
Copyright September 2008 by the American College of Obstet-
ricians and Gynecologists, 409 12th Street, SW, PO Box 96920,
Washington, DC 20090-6920. All rights reserved. No part of this pub-
lication may be reproduced, stored in a retrieval system, posted on
the Internet, or transmitted, in any form or by any means, electronic,
mechanical, photocopying, recording, or otherwise, without prior writ-
ten permission from the publisher. Requests for authorization to
make photocopies should be directed to: Copyright Clearance Center,
222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
Depot medroxyprogesterone acetate and bone effects. ACOG
Committee Opinion No. 415. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2008;112:72730.
ISSN 1074-861X
COMPENDIUM OF SELECTED PUBLICATIONS 62 62
Addressing Health Risks of Noncoital
Sexual Activity
ABSTRACT: Noncoital sexual behaviors, which include mutual masturbation, oral
sex, and anal sex, are common expressions of human sexuality. Couples may engage in
noncoital sexual activity instead of penilevaginal intercourse hoping to reduce the risk of
sexually transmitted diseases and unintended pregnancy. Although these behaviors carry
little or no risk of pregnancy, women engaging in noncoital behaviors may be at risk of
acquiring sexually transmitted diseases. Practitioners can assist by assessing patient risk
and providing risk reduction counseling for those participating in noncoital sexual activities.
Committee on
Adolescent Health
Care
Committee on
Gynecologic Practice
This document reflects
emerging clinical and scien-
tific advances as of the
date issued and is subject
to change. The information
should not be construed
as dictating an exclusive
course of treatment or
procedure to be followed.
Number 417 September 2008
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Noncoital sexual activities are common in
both adults and adolescents. The 2002
National Survey of Family Growth found
that 88% of females and 90% of males aged
2544 years, and 55% of males and 54% of
females aged 1519 years, have had oral sex
with an opposite-sex partner (1). Anal sex is
less common than oral or vaginal sex and is
commonly initiated at a later age; 35% of
females and 40% of males aged 2544 years
and 11% of male and female adolescents
aged 1519 years reported anal sex with an
opposite-sex partner (1). Comparison of
data on oral sex from the 2002 National
Survey of Family Growth with data from
three national surveys from the early and mid
1990s (the 1991 National Survey of Men, the
1992 National Health and Social Life Survey,
and the 1995 National Survey of Adolescent
Men) provides no evidence for a recent
increase in oral sex prevalence among adoles-
cents and young adults despite concerns
expressed in the popular media (1).
Noncoital behaviors commonly co-
occur with coital behaviors. Both oral sex
and anal sex are much more common
among adolescents who have already had
vaginal intercourse as compared with those
who have not (2). Likewise, the prevalence of
oral sex among adolescents jumps dramati-
cally in the first 6 months after initiation of
vaginal intercourse, suggesting that both are
often initiated at the same time and with the
same partner. Initiation of anal sex before
initiation of coitus is rare, and the preva-
lence of anal sex increases slowly after initia-
tion of coitus.
When engaging in oral sex, most indi-
viduals, including adolescents, are unlikely to
use barrier protection for a variety of rea-
sons, including a greater perceived safety of
noncoital sexual activity compared with
vaginal sex (3, 4). In the 2002 National
Survey of Family Growth, only 11% of
females and 15% of males aged 1517 years
who had ever engaged in oral sex reported
using a condom the most recent time that
they had engaged in oral sex (5).
Some sexually transmitted diseases
(STDs) may be transmitted during noncoital
sexual activity. Infections can be spread
through saliva, blood, vaginal secretions,
semen, and fecal material. Preexisting infec-
tions, open sores, abrasions, or any compro-
mise of the epithelial tissue can increase the
risk of transmission. Transmission of STDs is
organism specific, with certain infections
commonly infecting the oral or rectal cavity,
and many rarely doing so or causing infec-
tion without sequelae.
Human Immunodeficiency
Virus
Human immunodeficiency virus (HIV)
transmission is highly correlated with the
HIV viral load of the infected partner. In
addition, the risk of acquiring HIV varies
dramatically according to the specific sexual
ACOG COMMITTEE OPINION
63 COMMITTEE OPINIONS 63
behavior, especially whether it is insertive or receptive. The
U.S. Centers for Disease Control and Prevention (CDC)
estimates a 100-fold increase in risk from the safest to the
least safe behavior (Table 1). Human immunodeficiency
virus is most readily transmitted through anal sex.
Receptive anal sex with a partner who is infected with HIV
is the sexual behavior associated with the greatest risk of
HIV transmission. Condom use reduces HIV transmis-
sion by approximately 80% in HIV-serodiscordant cou-
ples (6). Although saliva appears to have components that
inactivate HIV, there are case reports of HIV acquisition in
men who engaged only in oral sex with other men (7).
Herpes Simplex Virus
Herpes infection is commonly transmitted through kiss-
ing and via oral, vaginal, and anal sex. Typically, herpes
simplex virus type 1 (HSV-1) is associated with oral
lesions, whereas herpes simplex virus type 2 (HSV-2) is
associated with genital lesions. However, both HSV-1 and
HSV-2 are capable of infecting oral, anal, and genital sites.
A study of university students seeking treatment for her-
pes found the percentage of HSV-1 genital herpes infec-
tions increased from 31% in 1993 to 78% in 2001 (8).
Therefore, older studies that based their results solely on
the presence of HSV-2 have underestimated the preva-
lence of genital herpes infections (9, 10).
Human Papillomavirus
Human papillomavirus (HPV) is a very common sexu-
ally transmitted virus that causes anogenital and oral can-
cers as well as the benign genital warts. There are more
than 100 strains of HPV, 40 of which selectively infect the
anogenital and oral areas. More than 90% of the HPV
infections resolve spontaneously without sequelae; how-
ever, persistent infection in the anogenital area or oral
cavity may cause cancer. Although the most efficient
means of transmission appear to be penilevaginal sex or
penileanal sex, oral transmission appears to occur as
well. However, data currently suggest that transmission is
less efficient to the oral cavity than to the genital area. The
digital spread of HPV is theoretically possible because
genital HPV DNA has been detected on the hand.
However, because this is only detection of DNA, it is not
proved that this DNA is infectious.
Hepatitis Viruses
Hepatitis B virus can be found in semen, saliva, and
feces and is commonly spread through sexual contact.
Hepatitis A is transmitted from fecal contamination of the
oral cavity, thus explaining the higher incidence of infec-
tion in homosexual men who engage in oralanal contact.
Sexual transmission of hepatitis C is uncommon but has
been associated with both preexisting hepatitis B and HIV
infection and with oralgenital contact (7).
Nonviral Sexually Transmitted
Diseases
A substantial number of recent primary and secondary
cases of syphilis reported in Chicago were attributable to
oral sex, with 86 of 627 (13.7%) individuals with syphilis
reporting oral sex as the only sexual exposure that could
account for their infection (11).
Most gonorrheal infections are sexually transmitted
and involve the urethra, cervix, rectum, or mouth (12).
Disseminated disease after oralgenital contact has been
documented. Although only 10% of isolated pharyngeal
gonorrheal infections are symptomatic, pharyngitis, with
or without fever or lymphadenopathy, should raise suspi-
cion for gonorrheal infection when all other etiologies
have been ruled out.
Chlamydia has been isolated from throat cultures in
both men and women. In women, pharyngeal infection is
associated with performing oral sex on men (12, 13).
Chancroid, shigellosis, salmonellosis, and other enteric
infections have been linked to oralgenital or oralanal
sex in a few case reports but appear to be relatively
uncommon. The role of noncoital sexual activity in the
transmission of other nonviral infections, such as vulvo-
vaginal candidiasis, bacterial vaginosis, and trichomonia-
sis remains unclear (12).
Patient Counseling
Noncoital sexual activity is not necessarily safe sex.
Because people define sexuality in a variety of ways, it is
important that practitioners ask direct questions regard-
ing sexual activity, including questions about oral or anal
sex and mutual masturbation, and questions about sex-
ual partners, including whether the patient has sex with
men, women, or both men and women.
A positive response to these questions indicates the
need for counseling regarding infection prevention strate-
gies specific to noncoital sexual activity. To individual-
ize counseling, the clinician must consider the womans
infection risk from partner factors (number of sexual part-
ners and her partners sexual behaviors, particularly multi-
ple sexual partnerships) and the community prevalence of
Table 1. Risk of Human Immunodeficiency Virus
Transmission According to Sexual Behavior
Sex Act Relative Risk*
Insertive fellatio 1
Receptive fellatio 2
Insertive vaginal sex 10
Insertive anal sex 13
Receptive vaginal sex 20
Receptive anal sex 100
*Refers to relative risk of acquiring human immunodeficiency virus (HIV) infection
among persons without HIV infection.
Varghese B, Maher JE, Peterman TA, Branson BM, Steketee RW. Reducing the risk
of sexual HIV transmission: quantifying the per-act risk for HIV on the basis of
choice of partner, sex act, and condom use. Sex Transm Dis 2002;29:3843.
COMPENDIUM OF SELECTED PUBLICATIONS 64 64
STDs. Because most women who engage in noncoital sex-
ual activity also are engaging in penilevaginal intercourse,
the clinician needs to consider whether noncoital behaviors
add any additional risks to those already posed by sexual
intercourse. When a young person engages in only oral or
anal sex, the likelihood of encountering a partner infected
with an STD should be considered. Correct and consistent
condom use should be encouraged, especially for anal sex
and vaginal sex. Practitioners also should consider the
patients history of STDs and patterns of barrier method
use with each partner. In brief, practitioners need to con-
sider the totality of the patients STD risk.
Counseling should focus on reducing STD risk factors
such as multiple partners. This may be more effective than
discouraging oral or anal sex. Risk-reduction strategies may
include engaging in safer behaviors (eg, oral sex often is
safer than vaginal intercourse, anal sex often is riskier than
penilevaginal sex), abstinence, mutual monogamy, limit-
ing the number of partners, STD testing before engaging in
sexual activity with a new partner, and correct and consis-
tent use of condoms, particularly for vaginal and anal sex.
Sex toys should be cleaned between uses. Couples counsel-
ing may be helpful for STD-serodiscordant couples.
Routine screening for chlamydia is recommended
annually for all sexually active women aged 25 years or
younger, and routine screening for gonorrhea is recom-
mended for all sexually active adolescents. Although the
2006 CDC STD Treatment Guidelines recommend
behavioral screening for anal and oral sex, they do not
make specific recommendations for routine oral or anal
STD laboratory screening (14). Selected laboratory test-
ing for oral and anal STDs should be based on clinical
symptoms and behavioral risks.
Lesbians and bisexual women should be screened for
STDs based on the same risk factors as other women.
Because most lesbians have been sexually active with men at
some point in their lives and because some STDs also can be
transmitted by sexual activity exclusively among lesbians, it
should not be assumed that STD screening is unnecessary.
Conclusion
Great efforts are needed to educate health care practition-
ers and the public regarding the potential health risks of
noncoital sexual activities and the importance of risk
reduction and barrier methods of protection. Practitioners
can assist by assessing patient risk and providing risk
reduction counseling for those participating in noncoital
sexual activities. Ultimately, additional research is needed
to determine the full impact of noncoital sexual activity
on the health of patients.
References
1. Mosher WD, Chandra A, Jones J. Sexual behavior and
selected health measures: men and women 1544 years of
age, United States, 2002. Adv Data 2005;(362):155.
2. Lindberg LD, Jones R, Santelli JS. Non-coital sexual activi-
ties among adolescents. J Adolesc Health 2008;42(suppl 1):
445.
3. Prinstein MJ, Meade CS, Cohen GL. Adolescent oral sex,
peer popularity, and perceptions of best friends sexual
behavior. J Pediatr Psychol 2003;28:2439.
4. Halpern-Felsher BL, Cornell JL, Kropp RY, Tschann JM.
Oral versus vaginal sex among adolescents: perceptions,
attitudes, and behavior. Pediatrics 2005;115:84551.
5. Terry-Humen E, Manlove J, Cottingham S. Trends and
recent estimates: sexual activity among U.S. teens. Child
Trends Research Brief No. 200608. Washington, DC: Child
Trends; 2006. Available at: http://childtrends.org/files/
sexualactivityrb.pdf. Retrieved April 23, 2008.
6. Weller SC, Davis-Beaty K. Condom effectiveness in reduc-
ing heterosexual HIV transmission. Cochrane Database of
Systematic Reviews 2002, Issue 1. Art. No.: CD003255. DOI:
10.1002/14651858.CD003255.
7. Edwards S, Carne C. Oral sex and the transmission of viral
STIs. Sex Transm Infect 1998;74:610.
8. Roberts CM, Pfister JR, Spear SJ. Increasing proportion of
herpes simplex virus type 1 as a cause of genital herpes infec-
tion in college students. Sex Transm Dis 2003;30:797800.
9. Cherpes TL, Meyn LA, Hillier SL. Cunnilingus and vaginal
intercourse are risk factors for herpes simplex virus type 1
acquisition in women. Sex Transm Dis 2005;32:849.
10. Lafferty WE, Downey L, Celum C, Wald A. Herpes simplex
virus type 1 as a cause of genital herpes: impact on surveil-
lance and prevention. J Infect Dis 2000;181:14547.
11. Centers for Disease Control and Prevention (CDC).
Transmission of primary and secondary syphilis by oral
sexChicago, Illinois, 1998-2002. MMWR Morb Mortal
Wkly Rep 2004;53:9668.
12. Edwards S, Carne C. Oral sex and transmission of non-viral
STIs. Sex Transm Infect 1998;74:95100.
13. Jones RB, Rabinovitch RA, Katz BP, Batteiger BE, Quinn TS,
Terho P, et al. Chlamydia trachomatis in the pharynx and
rectum of heterosexual patients at risk for genital infection.
Ann Intern Med 1985;102:75762.
14. Workowski KA, Berman SM. Sexually transmitted diseases
treatment guidelines, 2006. Centers for Disease Control and
Prevention [published erratum appears in: MMWR Morb
Mortal Wkly Rep 2006;55:997]. MMWR Recomm Rep
2006;55:194.
Copyright September 2008 by the American College of Obstet-
ricians and Gynecologists, 409 12th Street, SW, PO Box 96920,
Washington, DC 20090-6920. All rights reserved. No part of this pub-
lication may be reproduced, stored in a retrieval system, posted on
the Internet, or transmitted, in any form or by any means, electronic,
mechanical, photocopying, recording, or otherwise, without prior writ-
ten permission from the publisher. Requests for authorization to
make photocopies should be directed to: Copyright Clearance Center,
222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
Addressing health risks of noncoital sexual activity. ACOG Committee
Opinion No. 417. American College of Obstetricians and Gynecolo-
gists. Obstet Gynecol 2008;112:7357.
ISSN 1074-861X
65 COMMITTEE OPINIONS 65
ACOG COMMITTEE OPINION
Menstrual Manipulation for Adolescents
With Disabilities
ABSTRACT: Defining the reasons for intervention and the precise goal of treatment
are the most critical issues regarding use of interventions to alter menstrual flow in
adolescents with disabilities. Reasons for intervention may relate to abnormal uterine
bleeding, hygiene, mood issues, fear of pregnancy, and acute onset of other medical con-
ditions. Goals of treatment may include a decrease in the amount of bleeding, periodic
amenorrhea, or treatment of symptoms, such as mood issues or dysmenorrhea. First-line
treatment options should be safe, minimally invasive, and nonpermanent. Endometrial
ablation has not been studied in adolescents, has not been studied long-term, is consid-
ered irreversible and, therefore, is not recommended in teenagers.
Committee on
Adolescent Health
Care
The Committee would
like to thank Elisabeth
Quint, MD and Ann
Davis, MD for their
assistance in the develop-
ment of this document.
This document reflects
emerging clinical and sci-
entific advances as of the
date issued and is subject
to change. The information
should not be construed
as dictating an exclusive
course of treatment or pro-
cedure to be followed.
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Number 448 December 2009
For an adolescent with either physical or
developmental disabilities, menstruation can
provide significant challenges for the patient
and her caregivers. The hygiene component
of often irregular early bleeding episodes and
the behavioral concerns that accompany
menstrual periods especially in developmen-
tally delayed teenagers may cause significant
problems. In addition, concerns regarding
sexuality and vulnerability to abuse and preg-
nancy contribute to the worries of many par-
ents. Requests for amenorrhea or menstrual
manipulation will be presented to obstetri-
ciangynecologists, who then need to offer
information and counseling in this area. This
committee opinion focuses on the concerns,
assessment, and methods used for menstrual
manipulation in adolescents with disabilities.
Communication and Special
Considerations for History
Taking
Optimal gynecologic health care of adoles-
cents with disabilities is comprehensive;
maintains confidentiality, if possible; does
not treat the patient as infantile, affirms the
patients dignity; maximizes the patients
interests; and avoids harm. When possible,
the patient should have the opportunity to be
interviewed in private (1). Communication
should be directed to the teenager and not
to a family member or personal assistant.
Having knowledge of the teenagers mode of
communication and provider patience in the
process are critical.
Knowledge of puberty, menstruation,
sexual activity, safety, and the ability to con-
sent to any sexual act should be assessed.
Adolescents with disabilities often are thought
to be asexual, but they are as likely as other
teenagers without disabilities to be sexually
active, and are at greater risk for forced sex-
ual encounters (2). When knowledge deficits
are present, developmentally appropriate edu-
cation on hygiene, contraception, sexually
transmitted infections, and abuse prevention
measures should be provided. Most adoles-
cents who are able to use the toilet without
assistance can learn to use pads or tampons
or both appropriately.
When the obstetriciangynecologist
receives a request for amenorrhea or men-
strual manipulation, it is important to assess
the reason(s) for the request, especially if the
request does not directly come from the
patient. If the patient herself requests to have
her menstrual periods eliminated, her rea-
sons can be discussed directly with her. If her
caregiver requests this for the teenager, espe-
cially if the teenager has a significant devel-
opmental delay, the issues become more
complex. Before determining the next steps,
COMPENDIUM OF SELECTED PUBLICATIONS 66 66
the health care provider needs to ascertain whether the
request is based on convenience for the family or care-
givers, vulnerability for abuse and pregnancy, or menses
that truly affect the patients quality of life. If the adoles-
cent with disabilities cannot participate in her usual activ-
ities during her menses, this may be due to inadequate
help with her hygiene needs, behavioral issues during
menses, or dysmenorrhea.
Menstrual Concerns
Although all teenagers may have irregular cycles during
the first 25 years after menarche (3), adolescents with dis-
abilities may have additional reasons to experience men-
strual irregularities, including thyroid disease in teenagers
with trisomy 21, high prolactin levels due to mood stabi-
lizing medication, and polycystic ovary syndrome in
teenagers with seizure disorders (1020%) (4, 5).
Examination
With the new guidelines regarding cervical cytology
screening (6), a pelvic examination is rarely needed in a
teenager who is not sexually active and is only recom-
mended for specific indications, including abnormal
bleeding, vaginal discharge, suspicion of a vaginal foreign
object, or abuse evaluations, which may require an exam-
ination under anesthesia. Sexually transmitted infection
screening can be done by urine and blood testing. The
evaluation for abnormal bleeding is the same for adoles-
cents with disabilities as for other adolescents.
Treatment Options
If after an evaluation, the teenager, her family and health
care provider have decided that menstrual intervention is
warranted, the least invasive, reversible, and least harmful
intervention should be used. It is important to assess if pre-
dictable but potentially longer bleeding is easier to manage
than sporadic, irregular bleeding and counsel that total
amenorrhea is difficult to obtain. The following options are
available.
Nonsteroidal Antiinflammatory Drugs
Antiprostaglandin drugs in adequate dosages decrease
ovulatory bleeding by approximately 3040% with less
reduction in anovulatory cycles. Although this will not
stop menses, it may help with pain and bleeding (7).
Estrogen-Containing Methods
Combined Oral Contraceptives
Combined oral contraceptives (OCs) used cyclically
result in less menstrual blood loss in patients. Combined
OCs can be used continuously or for an extended period
to attempt to reduce the total days of menstrual flow.
This, however, increases the incidence of unscheduled
bleeding, especially early in use, but amenorrhea rates
may increase to 50%. There are only sparse data on how
to manage the unscheduled bleeding; however, one study
suggests that use of norethindrone acetate resulted in
more amenorrhea than levonorgestrel (8). There is a
chewable combined OC available to use with G-tubes or
patients who are unable to swallow pills.
Contraceptive Patch
Pharmacologic data indicate that estrogen exposure is
higher with use of the contraceptive patch than with oral
contraceptives or the vaginal ring. It is unclear how this
may affect the risk of deep vein thrombosis (DVT) (9,
10). Caution, therefore, is recommended for use of the
patch in nonmobile women (see following discussion of
DVT). In teenagers with developmental disabilities,
unscheduled removal of the patch may occur. Placement
of the patch on the buttocks or shoulder, where the indi-
vidual cannot reach it, may remedy this problem.
Contraceptive Ring
Contraceptive rings often are difficult for adolescents
with mobility issues or functional hand limitations to
insert. There are clear intimacy issues with using care-
givers to assist with inserting a ring, although some
women may feel comfortable with partner help. The ring
can be used for 3 weeks, with an interval free week, but
rings used for 4 weeks continuously lead to lighter bleed-
ing and more days of amenorrhea (11).
Estrogen Use and Risk of Deep Vein Thrombosis
Immobility is not listed as a contraindication to estrogen-
containing contraceptives by the World Health Organ-
ization and the American College of Obstetricians and
Gynecologists (12). However, there are minimal data on
the risk of DVT in women who take contraceptives with
or without exogenous estrogen and who use wheelchairs.
Clinicians, therefore, will want to assess patients for
hypercoagulability by obtaining a careful family history
(13) and encourage exercise of extremities in patients
who are physically able. Because there is a possible con-
cern about clotting risk with patches and combined OCs
with third-generation progestins (14), they may not be
the first choice for women who are immobile.
Progestin-Only Methods
Oral Medications
Cyclic progestins reduce blood loss in women with
anovulation, but do not work in this capacity for women
who are ovulatory (15). While taking the progestin only
minipill, patients will have ovulatory cycles approxi-
mately 40% of the time, short irregular cycles 40% of
time, or lack of cycles from amenorrhea to irregular
bleeding 20% of the time (16). Oral progestins in higher
doses than the progestin-only birth control pills can be
used daily to achieve amenorrhea. Occasional depressed
mood has been noted by clinicians, although, there is not
substantial data to support this.
Implants
Progestin contraceptive subdermal implants have an inci-
dence of unscheduled bleeding of up to 40% in the first
67 COMMITTEE OPINIONS 67
months after insertion (17) and need significant patient
cooperation or sedation for insertion.
Intramuscular Depot Medroxyprogesterone Acetate
Use of depot medroxyprogesterone acetate (DMPA)
results in relatively high rates of amenorrhea by the
fourth dose (approximately as high as 90% per 90-day
cycle in some studies) and has traditionally been used
extensively to suppress menses (18). There are two main
areas of concern for adolescents with disabilities.
1. Bone density: Although a decrease in bone density has
been described with DMPA use in teenagers, there is
evidence showing recovery of bone after DMPA is dis-
continued (19). However, in teenagers where the sup-
pression may need to be long term or when the risk for
very low bone density may be increased because of
immobility or being under weight or both, DMPA use
may be less advisable. Supplementation with calcium
and vitamin D should be considered. Several studies of
adolescents and women demonstrate that low-dose
estrogen supplementation limits bone mineral density
loss in DMPA users; however, estrogen supplementa-
tion during DMPA use is not currently recommended
(19).
2. Weight gain: Weight gain is variable but appears to be
particularly problematic for overweight patients
(20). For adolescents with disabilities who may be
dependent on their own strength or the help of care-
givers for transfers in and out of chairs and beds, a
relatively small weight gain may affect their indepen-
dence and should be closely monitored.
Progesterone-Releasing Intrauterine Contraception
The levonorgestrel intrauterine device (IUD) is utilized
outside of its contraceptive labeling as a method of men-
strual suppression (21). Irregular bleeding is common
initially, but amenorrhea rates increase over time and
overall blood loss is significantly decreased. One meta-
analysis of levonorgestrel IUD use in the general popula-
tion indicates a 7080% reduction of blood loss (22).
Ovulation is variable so amelioration of ovulatory symp-
tomatology will vary. Current data on the levonorgestrel
IUD is not specific to adolescents with disabilities. In ado-
lescents with disabilities, IUD insertion may need to be
done under anesthesia because of a higher likelihood of
nulligravid status (23), unpredictable cooperation, a nar-
row vagina, a small uterus, and significant contractures.
Special Consideration: Antiepileptic Drugs and
Hormone Use
Even though estrogen is a proconvulsant, combined OCs
have not been associated with an increase in seizures.
Irregular bleeding is common and contraceptive effec-
tiveness may be affected by enzyme inducing antiepileptic
drugs (24). Progestins increase seizure threshold and can
play an important role for women with epilepsy (25).
Estrogen or progesterone content may need to be
increased or DMPA may be used in 10-week intervals to
decrease irregular bleeding (26).
Surgical Methods
Endometrial Ablation
Endometrial ablation aims to treat heavy bleeding by
selectively destroying the endometrial lining while leaving
the uterus intact. It is generally recommended with con-
comitant contraception or sterilization, only if reproduc-
tion is no longer desired. The use of endometrial ablation
in adolescents with disabilities is not recommended
because of the following issues:
There is no real long-term outcome data (for exam-
ple, 2040 years) or data on adolescents.
Guardians and patients who request endometrial
ablation in adolescents with disabilities do so in the
hope to obtain amenorrhea, which occurs in approx-
imately 1347% of adults at 12 months (27).
Women younger than 45 years experience a signifi-
cantly higher failure rate of the procedure than older
women (28).
Although ablation is not considered sterilization by
many, the destruction of the endometrium will ren-
der the patient subfertile, if not infertile. In the event
that pregnancy ensues after an ablation, complica-
tions are likely (29).
Consent requirements for sterilization in adolescents
with disabilities who cannot give their own consent,
either because of age or developmental delay, should
apply to this procedure as well (1). Although there
are laws in some states protecting minors from steril-
ization procedures, it is unclear if these laws apply to
ablation.
Hysterectomy
Occasionally, a family may request a hysterectomy for
definitive amenorrhea in adolescents with disabilities.
Issues with hysterectomy in this situation include that this
method is always irreversible and has the highest poten-
tial for morbidity and mortality. In situations when
guardians request hysterectomy, it is critical to define
what benefits they desire. Hysterectomy is seen by some as
ideal for pregnancy prevention, and menstrual control
may be a secondary goal. It is critical for guardians to
understand that a hysterectomy will not protect the child
from the hazards of sexual abuse or sexually transmitted
infections. Only very rarely should a hysterectomy be con-
sidered for adolescents with disabilities, just as for
teenagers without disabilities, such as when they are done
for extreme situations like cancer. Abnormal bleeding is
almost always managed medically for a teenager without
disabilities. The same should be true for adolescents with
disabilities. Laws regarding minor sterilization, hysterec-
tomy, and consent issues vary from state to state.
COMPENDIUM OF SELECTED PUBLICATIONS 68 68
Guidelines are available from the American College of
Obstetricians and Gynecologists regarding consent (1).
References
1. Sterilization of women, including those with mental dis-
abilities. ACOG Committee Opinion No. 371. American
College of Obstetricians and Gynecologists. Obstet Gynecol
2007;110:21720.
2. Cheng MM, Udry JR. Sexual behaviors of physically dis-
abled adolescents in the United States. J Adolesc Health
2002;31:4858.
3. Menstruation in girls and adolescents: using the menstrual
cycle as a vital sign. ACOG Committee Opinion No. 349.
American College of Obstetricians and Gynecologists.
Obstet Gynecol 2006;108:13238.
4. Prasher VP. Down syndrome and thyroid disorders: a review.
Downs Syndr Res Pract 1999;6:2542.
5. Herzog AG, Schachter SC. Valproate and the polycystic
ovarian syndrome: final thoughts. Epilepsia 2001;42:3115.
6. Cervical cytology screening. ACOG Practice Bulletin No.
109. American College of Obstetricians and Gynecologists.
Obstet Gynecol 2009;114:140920.
7. Bonnar J, Sheppard BL. Treatment of menorrhagia during
menstruation: randomised controlled trial of ethamsylate,
mefenamic acid, and tranexamic acid. BMJ 1996;313:
57982.
8. Edelman AB, Koontz SL, Nichols MD, Jensen JT. Continuous
oral contraceptives: are bleeding patterns dependent on the
hormones given? Obstet Gynecol 2006; 107:65765.
9. Use of hormonal contraception in women with coexisting
medical conditions. ACOG Practice Bulletin No. 73.
American College of Obstetricians and Gynecologists.
Obstet Gynecol 2006;107:145372.
10. Phelps JY, Kelver ME. Confronting the legal risks of pre-
scribing the contraceptive patch with ongoing litigation.
Obstet Gynecol 2009;113:7126.
11. Sulak PJ, Smith V, Coffee A, Witt I, Kuehl AL, Kuehl TJ.
Frequency and management of breakthrough bleeding with
continuous use of the transvaginal contraceptive ring: a
randomized controlled trial. Obstet Gynecol 2008;112:
56371.
12. World Health Organization. Medical eligibility criteria for
contraceptive use. 3rd ed. Geneva: WHO; 2004.
13. Savelli SL, Kerlin BA, Springer MA, Monda KL, Thornton
JD, Blanchong CA. Recommendations for screening for
thrombophilic tendencies in teenage females prior to con-
traceptive initiation. J Pediatr Adolesc Gynecol 2006;19:3
136.
14. Girolami A, Spiezia L, Rossi F, Zanon E. Oral contraceptives
and venous thromboembolism: which are the safest prepara-
tions available? Clin Appl Thromb Hemost 2002;8: 15762.
15. Lethaby A, Irvine GA, Cameron IT. Cyclical progestogens
for heavy menstrual bleeding. Cochrane Database of
Systematic Reviews 2008, Issue 1. Art. No.: CD001016. DOI:
10.1002/14651858.CD001016.pub
16. Broome M, Fotherby K. Clinical experience with the
progestogen-only pill. Contraception 1990;42:48995.
17. Funk S, Miller MM, Mishell DR Jr, Archer DF, Poindexter A,
Schmidt J, et al. Safety and efficacy of Implanon, a single-
rod implantable contraceptive containing etonogestrel.
Implanon US Study Group. Contraception 2005;71:31926.
18. Speroff L, Fritz MA. Long-acting methods of contraception.
In: Clinical gynecologic endocrinology and infertility. 7th
ed. Philadelphia (PA): Lippincott Williams & Wilkins; 2005.
p. 94969.
19. Depot Medroxyprogesterone Acetate and Bone Effects.
ACOG Committee Opinion No.415. American College of
Obstetricians and Gynecologists. Obstet Gynecol 2008;
112:72730.
20. Bonny AE, Ziegler J, Harvey R, Debanne SM, Secic M,
Cromer BA. Weight gain in obese and nonobese adolescent
girls initiating depot medroxyprogesterone, oral contracep-
tive pills, or no hormonal contraceptive method. Arch
Pediatr Adolesc Med 2006;160:405.
21. Noncontraceptive uses of the levonorgestrel intrauterine
system. ACOG Committee Opinion No. 337. American
College of Obstetricians and Gynecologists. Obstet Gynecol
2006;107:147982.
22. Mansour D. Modern management of abnormal uterine
bleeding: the levonorgestrel intra-uterine system. Best Pract
Res Clin Obstet Gynaecol 2007;21:100721.
23. Suhonen S, Haukkamaa M, Jakobsson T, Rauramo I. Clinical
performance of a levonorgestrel-releasing intrauterine sys-
tem and oral contraceptives in young nulliparous women:
a comparative study. Contraception 2004;69:40712.
24. Foldvary-Schaefer N, Falcone T. Catamenial epilepsy:
pathophysiology, diagnosis, and management. Neurology
2003;61:S215.
25. Foldvary-Schaefer N, Harden C, Herzog A, Falcone T.
Hormones and seizures. Cleve Clin J Med 2004;71 Suppl
2:S118.
26. Quint EH. Menstrual issues in adolescents with physical
and developmental disabilities. Ann N Y Acad Sci 2008;
1135:2306.
27. Endometrial ablation. ACOG Practice Bulletin No. 81.
American College of Obstetricians and Gynecologists.
Obstet Gynecol 2007;109:123348.
28. El-Nashar SA, Hopkins MR, Creedon DJ, St Sauver JL,
Weaver AL, McGree ME, et al. Prediction of treatment out-
comes after global endometrial ablation. Obstet Gynecol
2009;113:97106.
29. Hare AA, Olah KS. Pregnancy following endometrial abla-
tion: a review article. J Obstet Gynaecol 2005;25:10814.
Copyright December 2009 by the American College of Obstetricians
and Gynecologists, 409 12th Street, SW, PO Box 96920, Washington,
DC 20090-6920. All rights reserved. No part of this publication may be
reproduced, stored in a retrieval system, posted on the Internet, or
transmitted, in any form or by any means, electronic, mechanical,
photocopying, recording, or otherwise, without prior written permis-
sion from the publisher. Requests for authorization to make photo-
copies should be directed to: Copyright Clearance Center, 222
Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
ISSN 1074-861X
Menstrual manipulation for adolescents with disabilities. ACOG
Committee Opinion No. 448. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2009;114:142831.
69 COMMITTEE OPINIONS 69
ACOG COMMITTEE OPINION
Number 451 December 2009
Von Willebrand Disease in Women
ABSTRACT: Approximately 3 million women in the United States have inherited
bleeding disorders. The prevalence of bleeding disorders is particularly high among
women with menorrhagia. Von Willebrand disease is the most common inherited bleed-
ing disorder. Once a diagnosis is made, collaboration with a hematologist is helpful for
long-term management. Women with von Willebrand disease may be at increased risk
for gynecologic and obstetric complications. Many treatments are available for the con-
trol of menorrhagia in women with von Willebrand disease, but the first-line therapy
remains combined hormonal contraception.
Committee on
Adolescent Health
Care
Committee on
Gynecologic
Practice
This document reflects
emerging clinical and sci-
entific advances as of the
date issued and is subject
to change. The informa-
tion should not be con-
strued as dictating an
exclusive course of treat-
ment or procedure to be
followed.
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Background
Approximately 3 million women in the
United States have inherited bleeding disor-
ders (1). Von Willebrand disease is the most
common inherited bleeding disorder, with a
prevalence of 0.61.3% (2, 3). Among women
with menorrhagia, the prevalence is greater,
and ranges from 5% to 15%. In particular,
von Willebrand disease appears to be more
prevalent among Caucasians with menorrha-
gia (4). One study suggests that 15.9% of
Caucasians were found to have von Wille-
brand disease, compared with 1.3% of African
Americans (5).
Von Willebrand disease is an autosoma-
lly inherited congenital bleeding disorder
involving a qualitative or quantitative defi-
ciency of von Willebrand factor (vWF).
Dominant and recessive patterns of transmis-
sion exist. Von Willebrand factor is a protein
that is critical for proper platelet adhesion
and protects against coagulant factor degra-
dation. There are three main types of von
Willebrand disease. Type 1 (deficiency of vWF),
the most common, usually is mild; type 2
(abnormal vWF) is less common; type 3
(complete absence of vWF) and pseudo von
Willebrand forms are rare, and the presenta-
tion signs and symptoms are variable (6).
Presenting Symptoms and
Signs
The most commonly reported symptom
among women with a diagnosis of von
Willebrand disease or suspected bleeding dis-
order is menorrhagia, but additional symp-
toms or signs also may be present (7, 8).
Other presenting symptoms may include
epistaxis, bleeding after dental extraction,
bleeding from minor cuts or abrasions, post-
operative bleeding, gingival bleeding, easy
bruising, postpartum hemorrhage, joint
bleeding, and gastrointestinal bleeding (7, 9).
Among women with a diagnosis of von
Willebrand disease, 48% reported easy bruis-
ing, 44% reported epistaxis, 51% reported
gingival bleeding, and 84% presented with
menorrhagia (8, 10). In one cross-sectional
study, women with von Willebrand disease
were also more likely than controls to report
other gynecologic conditions, including ovar-
ian cysts (52%), endometriosis (30%), leio-
myomas (32%), endometrial hyperplasia
(10%), polyps (8%), and hysterectomy (26%)
in addition to menorrhagia (8).
Up to 20% of women presenting with
menorrhagia at any time in life will have an
underlying bleeding disorder (2, 4, 5). The
onset of heavy menses at menarche is often
the first sign of von Willebrand disease.
Among a cohort of 38 women with type 1
von Willebrand disease, retrospective analysis
of bleeding symptoms revealed that menor-
rhagia at menarche was the most common
initial bleeding symptom, occurring in 53%
of women (11). The American College of
Obstetricians and Gynecologists recom-
mends that an initial reproductive health
visit occur between the ages of 13 years and
15 years. This gives many clinicians an oppor-
COMPENDIUM OF SELECTED PUBLICATIONS 70 70
tunity to inquire about menstrual history early in repro-
ductive life (12). This also provides an opportunity to dis-
cuss the use of a menstrual calendar to aid in patient
recall, which allows for clinicians to better differentiate
menorrhagia from irregular, anovulatory bleeding.
Anovulatory bleeding is more common during early ado-
lescence and generally does not raise suspicion of a bleed-
ing disorder (13, 14). Other screening tools for identifying
women with menorrhagia who should be evaluated for a
bleeding disorder include the pictorial bleeding assess-
ment chart. This tool is useful for women to specifically
record the number of pads or tampons used during their
menstrual periods as well as noting how many times they
may have passed clots or had flooding accidents. This tool
has been validated in adult women and demonstrates
greater than 80% sensitivity and specificity for scores
greater than 100 (15). When the pictorial bleeding assess-
ment chart tool is combined with a set of eight questions
that focus on bleeding history, the sensitivity increases to
95% for diagnosis of any underlying bleeding disorder
and 92% for von Willebrand disease; specificity is 72%
and 8%, respectively (16).
A recent study also highlights the varied presentation
of menorrhagia among women with von Willebrand dis-
ease of different age groups (5). One-hundred fifteen
women of all ages with diagnoses of menorrhagia were
evaluated for bleeding conditions. Nearly 50% of these
women were ultimately determined to have platelet dys-
function, von Willebrand disease, or coagulation factor
abnormalities. Importantly, bleeding disorders were
found to be just as prevalent in adolescents as they were
in adult women (5). The evaluation and management of
women presenting with abnormal uterine bleeding have
been addressed in other College publications as well (14).
Nonetheless, inherited and acquired disorders of coagula-
tion and hemostasis should be considered in the differen-
tial diagnosis of menorrhagia and abnormal uterine
bleeding regardless of age.
Diagnosis
The first step in the evaluation of women with suspected
bleeding disorders involves careful history and physical
examination (9, 17). Directed questions are useful in asses-
sing risk for inherited bleeding conditions (see Box 1) (9,
17). If red flags exist, then health care providers should
follow the National Heart, Lung, and Blood Institute
guidelines (9, 17). Family history of menorrhagia or other
bleeding problems is helpful in assessing the need for fur-
ther evaluation, even in the absence of a known bleeding
disorder diagnosis. In one study of 580 women with men-
orrhagia, 33.9% of women had a family history signifi-
cant for excessive bleeding, but less than 1% reported
knowing of a specific or known or diagnosed bleeding
condition within their families (5). Other important ini-
tial questions include personal history of bleeding prob-
lems, liver or kidney disorders, family history of
hysterectomy at an early age, history of postpartum hem-
orrhage, or use of anticoagulants. Positive responses to
initial questions should be followed by more probing
questions and physical examination. Physical examina-
tion findings suggestive of a bleeding disorder include
petechiae, ecchymoses, skin pallor, or swollen joints,
although absence of these signs does not exclude the pos-
sibility of an underlying bleeding condition (7, 18, 19).
In patients with a positive screening history, labora-
tory testing is indicated (see Fig. 1) (9, 17). Initial tests
should include complete blood count with platelets, pro-
thrombin time, and partial thromboplastin time (fibrino-
gen or thrombin time are optional); bleeding time is
neither sensitive nor specific, and is not indicated.
Depending on the results of initial tests, or if a patients
history is suggestive of an underlying bleeding condition,
specific tests for von Willebrand disease, including von
Willebrand-Ristocetin cofactor activity, von Willebrand
factor antigen, and factor VIII may be indicated (see
Fig. 1) (9, 17, 1921). These test results may be affected by
several variables such as age, race, family history, blood
type, stress, concurrent heavy bleeding, inflammation,
exogenous or endogenous hormones, pregnancy, time of
the menstrual cycle, sample processing, and quality of the
laboratory (9, 17, 1929). Because existing laboratory
assays have limitations and no single diagnostic test reli-
ably identifies the condition, this testing can be done in
conjunction with a hematologist if necessary (9, 17).
Furthermore, although certain types of von Willebrand
disease may be easily distinguished from other bleeding
Box 1. Bleeding Disorder Red Flags
Patient has a relative with an inherited bleeding condi-
tion
Prolonged bleeding, lasting more than 15 minutes,
from small injuries or wounds
Heavy prolonged and recurrent bleeding following
surgical procedures
Bruising with minimal or no trauma with palpable lump
under the bruise
Spontaneous nosebleeds
Prolonged bleeding following dental procedures
Blood in the stool or bleeding ulcer that required
urgent medical attention for cessation
History of anemia requiring blood transfusion
Heavy menses resulting in anemia or low iron stores
Passing clots more than 1 inch diameter with menses
or soaking more than one pad or tampon hourly
Heavy bleeding during or following childbirth
Adapted from the National Heart, Lung, and Blood Institute, The
Diagnosis, Evaluation, and Management of von Willebrand
Disease. NIH Pub. No. 08-5832. December, 2007.
71 COMMITTEE OPINIONS 71
Fig. 1. Laboratory tests for suspected bleeding disorders *Adapted from the National Heart, Lung, and Blood Institute,
The Diagnosis, Evaluation, and Management of von Willebrand Disease. NIH Pub. No. 08-5832. December, 2007.
Abbreviations: CBC, complete blood count; FVIII, factor VIII activity;
PT, prothrombin time; PTT, partial thromboplastin time; TT, thrombin
time; vWF:Ag, von Willebrand factor antigen; vWF:RCo, von
Willebrand factor ristocetin cofactor activity.
Positive initial screen by history
and physical examination
Initial hemostasis tests
CBC and platelet count
PT and PTT
Fibrinogen or TT (optional)
If bleeding history is strong, consider
performing initial von Willebrand
disease assays in conjunction with
hematologist
Other cause identified, eg, decreased
platelets, isolated abnormal PT, low
fibrinogen, and abnormal TT
Referral to hematologist for other
appropriate evaluation
Referral to hematologist for initial
von Willebrand disease assays
vWF:Ag
vWF:RCo
FVIII
Isolated prolonged PTT that
corrects on 1:1 mixing study, or no
abnormalities
conditions on the basis of laboratory testing, not all types
are as straightforward to diagnose. Genetic tests may be
necessary for confirmation of certain von Willebrand dis-
ease types (9, 17).
Management
Once a diagnosis has been established, a variety of treat-
ments exist. Treatments include ways to increase endoge-
nous plasma concentration of vWF, replace vWF, or
promote hemostasis without affecting vWF. With mild
von Willebrand disease and menorrhagia, combination
hormonal contraceptives are first-line treatments. In
a study involving women with a diagnosis of von
Willebrand disease, 88% reported improvement in men-
orrhagia with oral contraceptives alone (7, 18). In addi-
tion, the levonorgestrel-releasing intrauterine device has
been proved effective for the reduction of menorrhagia
symptoms in adult women with bleeding disorders (30).
Intrauterine devices containing levonorgestrel have been
used in the adolescent population as well, especially in
cases of traditional hormonal management failure.
Although other contraceptives such as the contraceptive
patch and contraceptive ring have not yet been studied in
this population, theoretically, they would exhibit similar
control of menstrual bleeding. Extended cycle combined
hormonal contraceptives or depot medroxyprogesterone
acetate are other options for consideration to help control
heavy menses, although patients should still be warned
about breakthrough spotting (14).
Newer hemostatic agents include antifibrinolytics,
such as -aminocaproic acid and tranexamic acid (31).
These are agents that inhibit the conversion of plasmino-
gen to plasmin, inhibiting fibrinolysis, and thereby help
stabilize clots. These agents also may be used alone or in
conjunction with hormones to control menstrual bleed-
ing, especially in the event a definitive diagnosis of von
Willebrand disease has not yet been established. Because
tranexamic acid is not yet approved for treatment of men-
orrhagia, this medication should be used with the guid-
ance of a hematologist (9, 17, 31).
Therapies generally prescribed in conjunction with a
hematologist once a diagnosis of von Willebrand disease-
COMPENDIUM OF SELECTED PUBLICATIONS 72 72
has been established include desmopressin acetate and
Recombinant Factor 8 and vWF complex infusion (9, 17).
Desmopressin acetate is a synthetic derivative of the anti-
diuretic hormone vasopressin and works by stimulating
the release of vWF from endothelial cells (21). Recom-
binant factor VIII and vWF complex infusion are a plas-
ma-derived concentrate used to replace vWF and factor
VIII. Patients also should be reminded that products that
prevent platelet adhesion, such as aspirin or non-
steroidal antiinflammatory drugs, should be avoided once
von Willebrand disease is diagnosed (9, 17).
Special Considerations
Gynecologic concerns in women with von Willebrand
disease include ruptured ovarian cysts, menstrual bleed-
ing, endometriosis, and leiomyomas. Patients with heavy
menstrual bleeding or hemorrhagic ovarian cysts may be
easily managed with the introduction of a combined con-
traceptive regimen, by preventing both heavy menstrual
bleeding or the development of hemorrhagic cysts (10).
For the acute presentation of a ruptured ovarian cyst,
patients with von Willebrand disease may require surgical
intervention for hemostasis. In the presence of menor-
rhagia, patients with von Willebrand disease may require
hormonal treatment (oral or intravenous) in addition to
a hemostatic agent or desmopressin acetate and vWF
replacement (9, 10, 17).
Obstetric concerns include postpartum hemorrhage,
mode of delivery, operative delivery techniques, sponta-
neous abortion, and epidural management. Many experts
have advocated that women with von Willebrand disease
may have a vaginal delivery safely, with cesarean delivery
reserved as indicated (9, 17). Because von Willebrand dis-
ease is an inherited condition, traumatic vaginal delivery,
such as what may occur with the use of vacuum or rota-
tional forceps, should be avoided because of the potential
risk of traumatic injury to an infant with a possible
hereditary bleeding disorder (32). If surgery is planned,
it is important to coordinate care with a hematologist
because vWF replacement may be necessary. The same
considerations apply to epidural placement because this
may be dependent on severity of disease; therefore, con-
sultation with a hematologist is important. The rate of
spontaneous abortion is similar to that of the general
population. However, because patients may be at risk for
hemorrhage at the time of spontaneous incomplete abor-
tion, the use of vWF and factor VIII to control bleeding
may be required (32). Furthermore, in a recent large epi-
demiologic study, the risk of postpartum hemorrhage for
women with von Willebrand disease was 50% higher than
for women without a bleeding disorder (29). Von
Willebrand factor and factor VIII concentrates may be
required to control bleeding in this situation as well (9).
Once estrogen levels begin to decrease in the postpartum
period, some individuals with bleeding conditions may
present with delayed hemorrhage. Throughout pregnan-
cy, at the time of delivery, and in the event of postpartum
hemorrhage, vWF and factor VIII levels are important to
assess because some women may require replacement of
vWF and factor VIII for safe range maintenance (10, 32).
Any surgical procedure in a woman with von
Willebrand disease requires consultation with a hematol-
ogist because of the potential risk of hemorrhage.
Preprocedure vWF, vWF activity, and factor VIII levels
may be important in determining the need for and tim-
ing of infusion treatment preoperatively and postopera-
tively (21).
It is particularly important to diagnose bleeding dis-
orders early in children and adolescents because acciden-
tal trauma is the most common source of morbidity and
mortality in this age group. Early warning signs and fam-
ily history are critical for the acute treatment in these sit-
uations. Ensuring that families have adequate access to
care and encouraging use of medical alert bracelets are
important (9, 32).
Conclusion
Von Willebrand disease is a common cause of menorrhagia
and other bleeding problems. Obstetriciangynecologists
should keep von Willebrand disease and other bleeding
disorders in mind when evaluating patients with menor-
rhagia, especially at menarche. Once a diagnosis is made,
collaboration with a hematologist is helpful for the long-
term management of women with bleeding disorders
such as von Willebrand disease. Von Willebrand disease
affects the reproductive system as well as other body sys-
tems, so patients may need access to other health care
providers in addition to gynecologists. Many resources
exist for patients and health care providers through the
National Heart, Lung, and Blood Institute, National
Hemophilia Foundations Project Red Flag, and the
American Society for Hematology (9, 33).
References
1. National Womens Health Information Center. Bleeding
disorders: frequently asked questions. Washington, DC:
NWHIC; 2009. Available at: http://www.womenshealth.
gov/FAQ/bleeding-disorders.cfm. Retrieved August 14,
2009.
2. James AH. More than menorrhagia: a review of the obstet-
ric and gynaecological manifestations of bleeding disorders.
Haemophilia 2005;11:295307.
3. James AH. Von Willebrand disease. Obstet Gynecol Surv
2006;61:13645.
4. Shankar M, Lee CA, Sabin CA, Economides DL, Kadir RA.
von Willebrand disease in women with menorrhagia: a sys-
tematic review. BJOG 2004;111:73440.
5. Dilley A, Drews C, Miller C, Lally C, Austin H, Ramaswamy
D, et al. von Willebrand disease and other inherited bleed-
ing disorders in women with diagnosed menorrhagia.
Obstet Gynecol 2001;97:6306.
6. Pruthi RK. A practical approach to genetic testing for von
Willebrand disease. Mayo Clin Proc 2006;81:67991.
73 COMMITTEE OPINIONS 73
7. Valente MJ, Abramson N. Easy bruisability. South Med J
2006;99:36670.
8. Kirtava A, Crudder S, Dilley A, Lally C, Evatt B. Trends in
clinical management of women with von Willebrand dis-
ease: a survey of 75 women enrolled in haemophilia treat-
ment centres in the United States. Haemophilia 2004;
10:15861.
9. National Heart, Lung, and Blood Institute. The diagnosis,
evaluation, and management of von Willebrand disease.
NIH Publication No. 08-5832. Bethesda (MD): NHLBI;
2007. Available at: http://www.nhlbi.nih.gov/guidelines/vwd/
vwd.pdf. Retrieved August 14, 2009.
10. James AH, Kouides PA, Abdul-Kadir R, Edlund M, Federici
AB, Halimeh S, et al. Von Willebrand disease and other
bleeding disorders in women: consensus on diagnosis and
management from an international expert panel. Am J
Obstet Gynecol 2009;201:12.e112.e8.
11. Ragni MV, Bontempo FA, Hassett AC. von Willebrand dis-
ease and bleeding in women. Haemophilia 1999;5:3137.
12 The initial reproductive health visit. ACOG Committee
Opinion No. 335. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2006;107:12159.
13. Philipp CS, Faiz A, Dowling N, Dilley A, Michaels LA, Ayers
C, et al. Age and the prevalence of bleeding disorders in
women with menorrhagia. Obstet Gynecol 2005;105:616.
14. American College of Obstetricians and Gynecologists.
Management of anovulatory bleeding. ACOG Practice
Bulletin 14. Washington, DC: ACOG; 2000.
15. Lee CA. Women and inherited bleeding disorders: men-
strual issues. Semin Hematol 1999;36:217.
16. Philipp CS, Faiz A, Dowling NF, Beckman M, Owens S,
Ayers C, et al. Development of a screening tool for identify-
ing women with menorrhagia for hemostatic evaluation.
Am J Obstet Gynecol 2008;198:163.e1163.e8.
17. James AH, Manco-Johnson MJ, Yawn BP, Dietrich JE,
Nichols WL. Von Willebrand disease: key points from the
2008 National Heart, Lung, and Blood Institute guidelines.
Obstet Gynecol 2009;114:6748.
18. Kirtava A, Drews C, Lally C, Dilley A, Evatt B. Medical,
reproductive and psychosocial experiences of women diag-
nosed with von Willebrands disease receiving care in haemo-
philia treatment centres: a case-control study. Haemophilia
2003;9:2927.
19. Kouides PA. Current understanding of von Willebrands
disease in women - some answers, more questions. Haemo-
philia 2006;12(suppl 3):14351.
20. Jennings I, Kitchen S, Woods TA, Preston FE. Laboratory
performance of haemophilia centres in developing coun-
tries: 3 years experience of the World Federation of Hemo-
philia External Quality Assessment Scheme. Haemophilia
1998;4:73946.
21. Foster PA. The reproductive health of women with von
Willebrand Disease unresponsive to DDAVP: results of an
international survey. On behalf of the Subcommittee on
von Willebrand Factor of the Scientific and Standardization
Committee of the ISTH. Thromb Haemost 1995;74:
78490.
22. Miller CH, Dilley AB, Drews C, Richardson L, Evatt B.
Changes in von Willebrand factor and factor VIII levels dur-
ing the menstrual cycle. Thromb Haemost 2002;87: 10823.
23. Miller CH, Haff E, Platt SJ, Rawlins P, Drews CD, Dilley AB,
et al. Measurement of von Willebrand factor activity: rela-
tive effects of ABO blood type and race. J Thromb Haemost
2003;1:21917.
24. Miller CH, Dilley A, Richardson L, Hooper WC, Evatt BL.
Population differences in von Willebrand factor levels affect
the diagnosis of von Willebrand disease in African-
American women. Am J Hematol 2001;67:1259.
25. Keightley AM, Lam YM, Brady JN, Cameron CL, Lillicrap
D. Variation at the von Willebrand factor (vWF) gene locus
is associated with plasma vWF:Ag levels: identification of
three novel single nucleotide polymorphisms in the vWF
gene promoter. Blood 1999;93:427783.
26. Gralnick HR, McKeown LP, Wilson OM, Williams SB, Elin
RJ. von Willebrand factor release induced by endotoxin. J
Lab Clin Med 1989;113:11822.
27. Conlan MG, Folsom AR, Finch A, Davis CE, Sorlie P,
Marcucci G, et al. Associations of factor VIII and von
Willebrand factor with age, race, sex, and risk factors for
atherosclerosis. The Atherosclerosis Risk in Communities
(ARIC) Study. Thromb Haemost 1993;70:3805.
28. Ruggeri ZM, Ware J. von Willebrand factor. FASEB J 1993;
7:30816.
29. James AH, Jamison MG. Bleeding events and other compli-
cations during pregnancy and childbirth in women with
von Willebrand disease. J Thromb Haemost 2007;5:11659.
30. Kingman CE, Kadir RA, Lee CA, Economides DL. The use
of levonorgestrel-releasing intrauterine system for treat-
ment of menorrhagia in women with inherited bleeding
disorders. BJOG 2004;111:14258.
31. Fraser IS, Porte RJ, Kouides PA, Lukes AS. A benefit-risk
review of systemic haemostatic agents: part 2: in excessive or
heavy menstrual bleeding. Drug Saf 2008;31:27582.
32. Demers C, Derzko C, David M, Douglas J. Gynaecological
and obstetric management of women with inherited bleed-
ing disorders. Society of Obstetricians and Gynecologists of
Canada. J Obstet Gynaecol Can 2005;27:70732.
33. National Hemophilia Foundation. von Willebrand disease.
Available at: http://www.hemophilia.org/NHFWeb/MainPgs/
MainNHF.aspx?menuid=182&contentid=47&rptname=
bleeding. Retrieved August 14, 2009.
Copyright December 2009 by the American College of Obstetricians
and Gynecologists, 409 12th Street, SW, PO Box 96920, Washington,
DC 20090-6920. All rights reserved. No part of this publication may be
reproduced, stored in a retrieval system, posted on the Internet, or
transmitted, in any form or by any means, electronic, mechanical,
photocopying, recording, or otherwise, without prior written permis-
sion from the publisher. Requests for authorization to make photo-
copies should be directed to: Copyright Clearance Center, 222
Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
ISSN 1074-861X
Von Willebrand disease in women. ACOG Committee Opinion No.
451. American College of Obstetricians and Gynecologists. Obstet
Gynecol 2009;114:143943.
COMMITTEE OPINIONS
COMMITTEE ON NOMENCLATURE
COMMITTEE OPINIONS
COMMITTEE ON NOMENCLATURE
77
Committee
on Coding and
Nomenclature
Number 205, August 1998
This document reflects emerg-
ing clinical and scientific ad-
vances as of the date issued and
is subject to change. The infor-
mation should not be construed
as dictating an exclusive course
of treatment or procedure to be
followed. Requests for authori-
zation to make photocopies
should be directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
Copyright August 1998
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Tubal Ligation with Cesarean
Delivery
Tubal ligation at the time of cesarean delivery requires significant additional
physician work even though the technical work of the procedure is brief.
Informed consent by the patient requires considerably more counseling by
the physician regarding potential risks and benefits of this procedure than is
necessary with alternative means of sterilization and contraception. Also,
many states require completion of special informed consent documents in
addition to the customary consent forms required by hospitals. These forms
must be completed before scheduling the procedure.
Patients have the right to change their minds. Thus, it is important to
reconfirm the patients decision shortly before the operation.
Tubal ligation with cesarean delivery involves removal of a segment of
fallopian tube, which is sent for histologic confirmation. With most cesarean
deliveries, tissue is not evaluated by a pathologist. Accordingly, it is impor-
tant for the surgeon to verify the pathology report, which adds an additional
component to post-service work.
The risk of professional liability for operative complications is increased
with this procedure. This risk is low, but real. Furthermore, sterilization fail-
ure occurs in about 1 in 100 cases even though the operation was performed
properly. This failure also carries a liability risk.
Because tubal ligation is a discrete extra service, it should be coded
accordingly: 59510 or 59618routine obstetric care including antepartum
care, cesarean delivery, and postpartum careand 58611ligation or tran-
section of fallopian tube(s) done at the time of cesarean delivery or intra-
abdominal surgery.
Committee
Opinion
ACOG
COMPENDIUM OF SELECTED PUBLICATIONS 78 78
Committee on
Coding and
Nomenclature
Reaffirmed 2005
ACOG
Number 249, January 2001
Committee
Opinion
Copyright January 2001
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of
this publication may be repro-
duced, stored in a retrieval sys-
tem, or transmitted, in any form
or by any means, electronic,
mechanical, photocopying,
recording, or otherwise, without
prior written permission from
the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Coding Responsibility
Physicians are responsible for accurately coding the services they provide
to their patients. Likewise, insurers are obligated to process all legitimate
insurance claims for covered services accurately and in a timely manner.
It is inappropriate for physicians to code or for insurers to process claims
incorrectly in order to enhance or reduce reimbursement. When either
party engages in such a practice intentionally and repetitively, it should
be considered dishonest and may be subject to civil and criminal
penalties.
79 COMMITTEE OPINIONS 79
Committee on
Coding and
Nomenclature
ACOG
Number 250, January 2001
Committee
Opinion
Copyright January 2001
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of this
publication may be reproduced,
stored in a retrieval system, or
transmitted, in any form or by any
means, electronic, mechanical,
photocopying, recording, or other-
wise, without prior written per-
mission from the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Inappropriate Reimbursement
Practices by Third-Party Payers
The American College of Obstetricians and Gynecologists (ACOG)
Committee on Coding and Nomenclature believes that physicians must
code accurately the services they provide and the diagnoses that justify
those services for purposes of appropriate payment. This requirement is
consistent with the rules established by the American Medical Association
(AMA) Current Procedural Terminology Editorial Panel and published as
the Current Procedural Terminology (CPT) and with those established by
the International Classification of Diseases, Ninth Revision, Clinical
Modification (ICD-9-CM), which are published in the American Hospital
Associations ICD-9-CM Coding Clinic. In fairness, payers should be equal-
ly obligated to pay physicians based on the CPT standards and accept for
processing all ICD-9-CM codes recorded on the claim. Currently, no such
obligation for payers exists.
Inappropriate Billing Denials
Five frequently encountered billing situations account for most payers inap-
propriate first-time total or partial denials of correctly coded services. Each
of these situations can inappropriately deny payment to physicians for med-
ically indicated and correctly coded services because of payers payment
policies.
1. Inappropriately bundling correctly coded multiple surgical procedures
Current Procedural Terminology clearly describes surgical procedures that
may be performed to treat various conditions. Each CPT code describes a
specific procedure that was valued under the Resource Based Relative
Value Scale (RBRVS) on the basis of a description of the work it entails.
Many patients, especially those with complex clinical situations, need
more than one surgical procedure to be performed at an operative session.
For instance, a patient may require a vaginal hysterectomy because of
severe irregular bleeding, but also might require repair of a symptomatic
cystocele and rectocele. Because no single CPT code describes this com-
bination of procedures, the physician should apply multiple CPT codes
with appropriate modifiers to the secondary procedures as mandated by
COMPENDIUM OF SELECTED PUBLICATIONS 80 80
CPT rules. Furthermore, the physician should
expect reimbursement for all of the provided ser-
vices defined by the CPT codes.
Despite the accuracy of the above statement
regarding reimbursement for multiple procedures,
payers often cite the efforts of Medicare to reduce
payments for inappropriately unbundled CPT
codes by physicians as justification for denial of
physician claims for appropriately coded services.
Indeed, the Health Care Financing Administration
has established the Correct Coding Initiative
(CCI), a process for bundling together many ser-
vices that should not be paid separately. The
process continues to undergo refinement with
input from the AMA and medical specialty soci-
eties.
Unfortunately, some commercial software
products that do not adhere to either CPT or CCI
guidelines are being used by third-party payers to
identify CPT codes for services that will not be
reimbursed when coded together. For example,
some of these products incorrectly bundle anterior
and posterior colporrhaphy with enterocele repair
into the code for vaginal hysterectomy, presum-
ably because all of these procedures are performed
through a vaginal approach. The AMA Correct
Coding and Policy Committee, with input from
ACOG staff, has identified many instances of
inappropriate denial of reimbursement with some
of these commercial bundling products. Physi-
cians should appeal such denials (see the box) and
cite the content of this document in requesting
appropriate payment for these services.
2. Ignoring modifiers that explain qualifying circum-
stancesCurrent Procedural Terminology modi-
fiers provide a coding shorthand that helps explain
situations for which either increased or reduced
payment is justified. There is, at present, no insur-
ance industry standard for recognizing modifiers.
The American College of Obstetricians and
Gynecologists believes that third-party payers
should follow existing CPT guidelines and coding
options, including recognition of all CPT modi-
fiers, to ensure that all circumstances concerning
the service performed are recognized. Payers who
ignore correctly applied CPT modifiers inappro-
priately underreimburse physicians for the ser-
vices provided.
3. Denying payment for diagnostic and therapeutic
procedures performed on the same day of
serviceIn certain clinical situations, a diagnostic
surgical procedure is performed to determine
Seven Steps for Appealing Denied Claims
Take these steps when appealing inappropriate reim-
bursement practices by third-party payers:
1. Keep in mind that this is a negotiation process
that will succeed only if the insurer is con-
vinced that a charge is fair for the patient and
the physician. It is important to use accepted
coding standards when attempting to show
that an insurers policy is wrong. Polite but
direct communication is more likely to achieve
desired results than confrontation.
2. Have your staff contact the claims department
of the insurer and discuss the reason for denial
with the claims processor. These discussions
should be based on clinical facts that rely on
the Current Procedural Terminology (CPT)
code definition of the service and the standard
of care implied by the CPT code as it was val-
ued under the Medicare Resource Based
Relative Value Scale (RBRVS) system.
Document all communication with the insurer
(date, person from office making the call, per-
son spoken with, results).
3. If staff is unsuccessful, contact the medical
director of the payer yourself. Maintain open
lines of communication with the medical direc-
tor to discuss inappropriate payment policies
and accepted coding standards.
4. Involve the state medical society in disputes
with insurers. Many state societies will become
very involved when patterns of abuse emerge.
5. Contact the American College of Obstetricians
and Gynecologists (ACOG) for assistance in
dealing with inappropriately denied medically
indicated services that are covered by the
patients insurance policy and clearly were cor-
rectly reported. Contact ACOGs Department of
Health Economics by fax or mail after down-
loading a complaint form from ACOGs web
site (www.acog.org), or call (202) 863-2447
for assistance.
6. Send a copy of any correspondence between
the practice and the payer dealing with unre-
solved problems to the insurance commis-
sioner or equivalent regulatory authority in
your state.
7. Involve your patient when inappropriate billing
problems cannot be resolved in other ways.
Physicians are not responsible for the insur-
ance plan selected by the patient. Many third-
party payers will revise their payment policies
when they receive a complaint from the patient
or patients employer or union.
81 COMMITTEE OPINIONS 81
whether a therapeutic surgical procedure is
required. When this occurs, it often is appropriate
for the two procedures to be done at one time rather
than at two distinct times. For example, if a diag-
nostic laparoscopy for a suspected benign condi-
tion reveals cancer, the physician may decide to
perform a laparotomy to remove the cancer at the
same operative session. In such a situation, many
payers deny payment for the diagnostic lapa-
roscopy even though performance of both the diag-
nostic and therapeutic procedures at the same time
is medically indicated and requires additional
physician work above that of the therapeutic proce-
dure alone. In accordance with CPT guidelines,
both procedures should be coded and the physician
should be paid for both when the procedures have
been documented appropriately and coded correct-
ly. In the example, proper coding for the diagnostic
service in addition to a therapeutic procedure
would at the present time require the use of modi-
fier 59 to identify the diagnostic procedure as
distinct. In addition, however, the diagnostic proce-
dure must be justified with a specific ICD-9-CM
diagnostic code, which may or may not be the
same as the ICD-9-CM code for the therapeutic
procedure.
The practice by payers of bundling diagnostic
and therapeutic procedures to reduce physicians
payment is inappropriate. Physicians have a legal
obligation to code correctly. Insurers are equally
obligated not to alter coding by physicians that is
in accordance with approved CPT guidelines.
4. Precertifying consultations at a predetermined
levelSome payers require precertification of a
consultation and typically authorize a predeter-
mined level of service based on the diagnostic
information provided by the physician who
requested the consultation. By contrast, the CPT
guidelines state that the correct level of consulta-
tion is determined by the extent of the history,
physical examination, and complexity of the med-
ical decision-making process for each patient. This
definition of services was used by Medicare under
RBRVS to assign the relative value for physician
consultation. Each patient who requires a consulta-
tion does so with a medical history typically
including co-morbidities that can dramatically alter
the physician work required to provide this service.
Often such co-morbidities will necessitate a more
thorough history and physical examination and
involve more complex medical decision making
than required in their absence. For example, a
request for a consultation to assess fetal well-being
in an otherwise healthy patient who has had an
uneventful pregnancy will not resemble a consulta-
tion for this same problem when the patient has
preexisting complications of pregnancy, such as
cardiac disease, uncontrolled diabetes mellitus, or
a history of poor obstetric outcomes.
Because it is not possible to determine prospec-
tively the level of service that will be required to
evaluate and recommend treatment based on the
uniqueness of each patients problems, payers
should precertify for an unspecified level of con-
sultation that is paid at the appropriate level once
the service has been provided.
5. Denying diagnostic tests or studies performed at
the same encounter as a distinct evaluation and
management serviceThe CPT manual states:
The actual performance and/or interpreta-
tion of diagnostic tests/studies ordered dur-
ing a patient encounter are not included in
the levels of [evaluation and management
(E/M)] services. Physician performance of
diagnostic tests/studies for which specific
CPT codes are available may be reported
separately, in addition to the appropriate
E/M code.
With this statement, CPT has clarified that diag-
nostic tests and studies, including colposcopies,
biopsies, diagnostic ultrasound examinations, and
cystometrics, are ordered on the basis of clinical
criteria for each patient and not as a routine ser-
vice. This definition means that tests performed at
the time of an outpatient or other E/M encounter
are not to be paid as part of the E/M service, but
rather are to be paid separately. The E/M codes in
CPT were valued under the Medicare RBRVS fee
schedule on the basis of the CPT guidelines; these
values do not include any diagnostic tests or studies.
The payer may deny reimbursement of diagnos-
tic tests or studies at the time of an E/M encounter
because the payers payment policies might have
been formulated with a lack of understanding of
CPT coding standards that separate physician
work included with the E/M service from the diag-
nostic test or study. This lack of understanding
may lead the payer to inappropriately include all
services provided to the patient at the E/M
encounter as part of that service. The payer also
may deny payment because the physician failed to
add a modifier 25 to the billed E/M code to by-
pass the payers established coding edits to ensure
appropriate payment for both services.
COMPENDIUM OF SELECTED PUBLICATIONS 82 82
Possible Remedies
The physician should ensure that his or her billing
staff are knowledgeable about:
What is normally included and what is excluded
from the service being billed (This information is
provided in the most current edition of ACOGs
OB-GYN Coding Manual: Components of Correct
Procedural Coding.*)
How to link each service billed with one or more
specific ICD-9-CM diagnostic codes that specifi-
cally justifies the reason for the service (This infor-
mation is available in the most current edition of
ACOGs ICD-9-CM: Diagnostic Coding in
Obstetrics and Gynecology.*)
* These resources are available from the American College of
Obstetricians and Gynecologists.
The correct application of CPT modifiers, when
indicated (This information may be found in the
appendixes of the current AMA CPT manual and
in the current edition of ACOGs CPT Coding in
Obstetrics and Gynecology.*)
Billing rules established by individual payers
The billing office should communicate clearly
the indication for performing all coded services on
the same date of service by reporting the most specif-
ic ICD-9-CM diagnostic codes. In some encounters,
the justification for all services rendered may be doc-
umented by a single ICD-9-CM code. When a patient
has multiple complaints or problems, multiple ICD-
9-CM codes should be used.
COMMITTEE OPINIONS
COMMITTEE ON ETHICS
COMMITTEE OPINIONS
COMMITTEE ON ETHICS
85
Committee on
Ethics
Reaffirmed 2009
ACOG
Number 297, August 2004
Committee
Opinion
Copyright August 2004
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of
this publication may be repro-
duced, stored in a retrieval sys-
tem, or transmitted, in any form
or by any means, electronic,
mechanical, photocopying,
recording, or otherwise, without
prior written permission from
the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Nonmedical use of obstetric ultra-
sonography. ACOG Committee
Opinion No. 297. American College
of Obstetricians and Gynecologists.
Obstet Gynecol 2004;104:4234.
Nonmedical Use of Obstetric
Ultrasonography
ABSTRACT: The American College of Obstetricians and Gynecologists
(ACOG) has endorsed the Prudent Use statement from the American
Institute of Ultrasound in Medicine (AIUM) discouraging the use of obstetric
ultrasonography for nonmedical purposes (eg, solely to create keepsake pho-
tographs or videos). The ACOG Committee on Ethics provides reasons in
addition to those offered by AIUM for discouraging this practice.
The American College of Obstetricians and Gynecologists (ACOG) has
endorsed the following statement from the American Institute of Ultrasound
in Medicine (AIUM) discouraging the use of obstetric ultrasonography for non-
medical purposes (eg, solely to create keepsake photographs or videos) (1):
The AIUM advocates the responsible use of diagnostic ultrasound. The AIUM
strongly discourages the non-medical use of ultrasound for psychosocial or enter-
tainment purposes. The use of either two-dimensional (2D) or three-dimensional
(3D) ultrasound to only view the fetus, obtain a picture of the fetus or determine the
fetal gender without a medical indication is inappropriate and contrary to responsi-
ble medical practice. Although there are no confirmed biological effects on patients
caused by exposures from present diagnostic ultrasound instruments, the possibili-
ty exists that such biological effects may be identified in the future. Thus ultrasound
should be used in a prudent manner to provide medical benefit to the patient.
In addition to the concerns noted by AIUM, the ACOG Committee on Ethics
believes that nonmedical use of ultrasonography should be discouraged for
the following reasons:
Nonmedical ultrasonography may falsely reassure women. Even though
centers that perform nonmedical ultrasonography and create keepsake
photographs and videos of the fetus may offer disclaimers about the
limitations of their product, customers may interpret an aesthetically
pleasing image or entertaining video as evidence of fetal health and
appropriate development. Ultrasonography performed for psychosocial
or entertainment purposes may be limited by the extent and duration of
the examination, the training of those acquiring the images, and the qual-
ity control in place at the ultrasound facility. Women may incorrectly
believe that the limited scan is, in fact, diagnostic.
COMPENDIUM OF SELECTED PUBLICATIONS 86 86
Abnormalities may be detected in settings that
are not prepared to discuss and provide follow-
up for concerning findings. Without the ready
availability of appropriate prenatal health care
professionals, customers at sites for nonmedical
ultrasonography may be left without necessary
support, information, and follow-up for con-
cerning findings. For example, customers may
interpret a minor finding (eg, an echogenic
intracardiac focus) as a major abnormality,
resulting in unnecessary anxiety and concern.
Conversely, in the event of concerning findings
(eg, oligohydramnios), women may not receive
appropriate follow-up. Obstetric ultrasonogra-
phy is most appropriately obtained as part of an
integrated system for delivering prenatal care.
Reference
1. American Institute of Ultrasound in Medicine. Prudent use.
AIUM Official Statements. Laurel (MD): AIUM; 1999.
Available at http://www.aium.org/provider/statements/
_statementSelected.asp?statement=2. Retrieved May 19, 2004.
87 COMMITTEE OPINIONS 87
Committee on
Ethics
ACOG
Number 321, November 2005
Committee
Opinion
Copyright November 2005
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of this
publication may be reproduced,
stored in a retrieval system, or
transmitted, in any form or by any
means, electronic, mechanical,
photocopying, recording, or other-
wise, without prior written per-
mission from the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Maternal decision making, ethics, and
the law. ACOG Committee Opinion
No. 321. American College of
Obstetricians and Gynecologists.
Obstet Gynecol 2005;106:112737.
Maternal Decision Making, Ethics,
and the Law
ABSTRACT: Recent legal actions and policies aimed at protecting the fetus
as an entity separate from the woman have challenged the rights of pregnant
women to make decisions about medical interventions and have criminalized
maternal behavior that is believed to be associated with fetal harm or
adverse perinatal outcomes. This opinion summarizes recent, notable legal
cases; reviews the underlying, established ethical principles relevant to the
highlighted issues; and considers six objections to punitive and coercive
legal approaches to maternal decision making. These approaches 1) fail to
recognize that pregnant women are entitled to informed consent and bodily
integrity, 2) fail to recognize that medical knowledge and predictions of out-
comes in obstetrics have limitations, 3) treat addiction and psychiatric illness
as if they were moral failings, 4) threaten to dissuade women from prenatal
care, 5) unjustly single out the most vulnerable women, and 6) create the
potential for criminalization of otherwise legal maternal behavior. Efforts to
use the legal system to protect the fetus by constraining pregnant womens
decision making or punishing them erode a womans basic rights to privacy
and bodily integrity and are not justified. Physicians and policy makers
should promote the health of women and their fetuses through advocacy of
healthy behavior; referral for substance abuse treatment and mental health
services when indicated; and development of safe, available, and efficacious
services for women and families.
Ethical issues that arise in the care of pregnant women are challenging to
physicians, politicians, lawyers, and ethicists alike. One of the fundamental
goals of medicine and society is to optimize the outcome of pregnancy.
Recently, some apparent attempts to foster this goal have been characterized
by legal action and policies aimed at specifically protecting the fetus as an
entity separate from the woman. These actions and policies have challenged
the rights of pregnant women to make decisions about medical interventions
and have criminalized maternal behavior that is believed to be associated
with fetal harm or adverse perinatal outcomes.
Practitioners who care for pregnant women face particularly difficult
dilemmas when their patients reject medical recommendations, use illegal
COMPENDIUM OF SELECTED PUBLICATIONS 88 88
drugs, or engage in a range of other behaviors that
have the potential to cause fetal harm. In such situ-
ations, physicians, hospital representatives, and
others have at times resorted to legal actions to
impose their views about what these pregnant
patients ought to do or to effect particular interven-
tions or outcomes. Appellate courts have held, how-
ever, that a pregnant womans decisions regarding
medical treatment should take precedence regard-
less of the presumed fetal consequences of those
decisions. In one notable 1990 decision, a District
of Columbia appellate court vacated a lower courts
decision to compel cesarean delivery in a critically
ill woman at 26 weeks of gestation against her
wishes, stating in its opinion that in virtually all
cases the question of what is to be done is to be
decided by the patientthe pregnant womanon
behalf of herself and the fetus (1). Furthermore,
the court stated that it could think of no extremely
rare and truly exceptional case in which the state
might have an interest sufficiently compelling to
override a pregnant patients wishes (2). Amid often
vigorous debate, most ethicists also agree that a
pregnant womans informed refusal of medical
intervention ought to prevail as long as she has the
ability to make medical decisions (3, 4).
Recent legislation, criminal prosecutions, and
legal cases much discussed in both courtrooms and
newsrooms have challenged these precedents, rais-
ing the question of whether there are circumstances
in which a woman who has become pregnant may
have her rights to bodily integrity and informed con-
sent overridden to protect her fetus. In Utah, a
woman who had used cocaine was charged with
homicide for refusing cesarean delivery of a fetus
that was ultimately stillborn. In Pennsylvania, physi-
cians obtained a court order for cesarean delivery in
a patient with suspected fetal macrosomia. Across
the country, pregnant women have been arrested and
prosecuted for being pregnant and using drugs or
alcohol. These cases and the publicity they have
engendered suggest that it is time to revisit the ethi-
cal issues involved.
The ethics of caring for pregnant women and an
approach to decision making in the context of the
maternalfetal relationship have been discussed in
previous statements by the American College of
Obstetricians and Gynecologists (ACOG) Commit-
tee on Ethics. After briefly reiterating those discus-
sions, this opinion will summarize recent, notable
cases; review the underlying, established ethical
principles relevant to the highlighted issues; con-
sider objections to punitive and coercive legal
approaches to maternal decision making; and sum-
marize recommendations for attending to future
ethical matters that may arise.
Recent Cases
In March 2004, a 28-year-old woman was charged
with first-degree murder for refusing to undergo an
immediate cesarean delivery because of concerns
about fetal well-being and later giving birth to a girl
who tested positive for cocaine and a stillborn boy.
According to press reports, the woman was mentally
ill and intermittently homeless and had been brought
to Utah by a Florida adoption agency to give birth to
the infants and give them up. She ultimately pled
guilty to two counts of child endangerment.
In January 2004, a woman who previously had
given birth vaginally to six infants, some of whom
weighed close to 12 pounds, refused a cesarean deliv-
ery that was recommended because of presumed
macrosomia. A Pennsylvania hospital obtained a
court order to perform the cesarean delivery and gain
custody of the fetus before and after delivery, but the
woman and her husband fled to another hospital,
where she reportedly had an uncomplicated vaginal
delivery of a healthy 11-pound infant.
In September 2003, a 22-year-old woman was
prosecuted after her son tested positive for alcohol
when he was born in Glens Falls, New York. A few
days after the birth, the woman was arrested and
charged with two counts of child endangerment for
knowingly feeding her blood, containing alcohol, to
her fetus via the umbilical cord. Several months later,
her lawyers successfully appealed her conviction.
In May 1999, a 22-year-old woman who was
homeless regularly used cocaine while pregnant and
gave birth to a stillborn infant in South Carolina. She
became the first woman in the United States to be
tried and convicted of homicide by child abuse
based on her behavior during pregnancy and was
given a 12-year prison sentence. The conviction was
upheld in the South Carolina Supreme Court, and
the U.S. Supreme Court recently refused to hear her
appeal. At a postconviction relief hearing, expert tes-
timony supported arguments that the woman had
had inadequate representation, but the court held
that there was no ineffective assistance of counsel
and that she is not entitled to a new trial. This deci-
sion is being appealed.
89 COMMITTEE OPINIONS 89
Ethical Considerations
Framing Ethics in Perinatal Medicine
It is likely that the interventions described in the pre-
ceding cases were motivated by a shared concept
that a fetus can and should be treated as separable
and legally, philosophically, and practically inde-
pendent from the pregnant woman within whom it
resides. This common method of framing ethical
issues in perinatal medicine is not surprising given a
number of developments in the past several decades.
First, since the 1970s, the development of tech-
niques for imaging, testing, and treating fetuses has
led to the widespread endorsement of the notion that
fetuses are independent patients, treatable apart
from the pregnant women upon whom their
existence depends (5). Similarly, some bioethical
models now assert that physicians have moral oblig-
ations to fetal patients that are separate from their
obligations to pregnant women (6). Finally, a num-
ber of civil laws, discussed later in this section, aim
to create fetal rights separate from a pregnant
womans rights.
Although frameworks that treat the woman and
fetus as separable and independent are meant to sim-
plify and clarify complex issues that arise in obstet-
rics, many writers have noted that such frameworks
tend to distort, rather than illuminate, ethical and
policy debates (7). In particular, these approaches
have been criticized for their tendency to emphasize
the divergent rather than shared interests of the preg-
nant woman and fetus. This emphasis results in a
view of the maternalfetal relationship as paradig-
matically adversarial, when in fact in the vast major-
ity of cases, the interests of the pregnant woman and
fetus actually converge.
In addition, these approaches tend to ignore the
moral relevance of relationships, including the phys-
ically and emotionally intimate relationship between
the woman and her fetus, as well as the relationships
of the pregnant woman within her broader social
and cultural networks. The cultural and policy con-
text, for example, suggests a predominantly child-
centered approach to maternal and child health,
which has influenced current perspectives on the
fetus. The prototype for the federal Maternal and
Child Health Bureau dates back to 1912, when the
first organization was called into existence by
reformers such as Florence Kelley, who stated that
the U.S. should have a bureau to look after the child
crop, and Julia Lathrop, who said that the final
purpose of the Bureau is to serve all children, to try
to work out standards of care and protection which
shall give to every child his fair chance in the world.
The current home page of the Maternal and Child
Health Bureau web site cites as its vision an equal-
ly child-centered goal (8).
At times, in the current clinical and policy con-
texts, when the woman and fetus are treated as
separate individuals, the woman and her medical
interests, health needs, and rights as moral agent,
patient, and research subject fade from view. Con-
sider, first, womens medical interests as patients.
Researchers performing fetal surgerynovel
interventions to correct fetal anatomic abnormali-
tieshave been criticized recently not only for their
tendency to exaggerate claims of success with
regard to fetal and neonatal health, but also for their
failure to assess the impact of surgery on pregnant
women, who also undertake the risks of the major
surgical procedures (9). As a result, several centers
performing these techniques now use the term ma-
ternalfetal surgery to explicitly recognize the fact
that a womans bodily integrity and health are at
stake whenever interventions directed at her fetus
are performed. Furthermore, a study sponsored by
the National Institute of Child Health and Human
Development comparing maternalfetal surgery
with postnatal repair of myelomeningocele (the
Management of Myelomeningocele Study) is now
assessing maternal as well as fetal outcomes,
including measurement of reproductive and health
outcomes, depression testing, and economic and
family health outcomes in women who participate
in the clinical trial.
Similarly, new civil laws that aim to treat the
fetus as separate and independent have been criti-
cized for their failure both to address the health
needs of the woman within whose body the fetus
resides and to recognize the converging interests of
the woman and fetus. In November 2002, a revision
of the state child health insurance program (sCHIP)
that expanded coverage to individual(s) under the
age of 19 including the period from conception until
birth was signed into law. The program does not
cover pregnant women older than 18 years except
when medical interventions could directly affect the
well-being of their fetuses. For example, under
sCHIP, intrapartum anesthesia is covered, according
to the U.S. Department of Health and Human
Services, only because if a womans pain during a
labor and delivery is not reduced or properly
COMPENDIUM OF SELECTED PUBLICATIONS 90 90
relieved, adverse and sometimes disastrous effects
can occur for the unborn child (10).
Furthermore, for beneficiaries of sCHIP, many
significant womens health issues, even those that
are precipitated by pregnancy (eg, molar gestation,
postpartum depression, or traumatic injury from
intimate partner violence not impacting the fetus),
are not covered as a part of routine antenatal care
(11). This approach has been criticized not only for
its failure to address the health needs of women,
but also for its failure to achieve the narrow goal
of improving child health because it ignores the
fact that maternal and neonatal interests converge.
For instance, postpartum depression is associated
with adverse effects in infants, including impaired
maternalinfant interaction, delayed cognitive and
emotional development, increased anxiety, and de-
creased self-esteem (12, 13). Thus, the law ignores
the fact that a critical component of ensuring the
health of newborns is the provision of comprehen-
sive care for their mothers.
Likewise, in April 2004, the Unborn Victims of
Violence Act was signed into law, creating a separate
federal offense if, during the commission of certain
federal crimes, an individual causes the death of, or
bodily injury to, a fetus at any stage of pregnancy.
The law, however, does not categorize the death of
or injury to a pregnant woman as a separate federal
offense, or create sentence enhancement for those
who assault or murder a woman while pregnant. The
statutes sponsors explicitly rejected proposals that
had virtually identical criminal penalties but recog-
nized the pregnant woman as the victim, despite the
fact that murder is responsible for more pregnancy-
associated deaths in the United States than any other
cause, including hemorrhage and thromboembolic
events (14, 15).
Beyond its impact on maternal and child health,
a failure to recognize the interconnectedness of the
pregnant woman and fetus has important ethical and
legal implications. Because an intervention on a
fetus must be performed through the body of a preg-
nant woman, an assertion of fetal rights must be rec-
onciled with the ethical and legal obligations toward
pregnant women as women, persons in their own
right. Discussions about rights of the unborn often
have failed to address these obligations. Regardless
of what is believed about fetal personhood, claims
about fetal rights require an assessment of the rights
of pregnant women, whose personhood within the
legal and moral community is indisputable.
Furthermore, many writers have noted a moral
injury that arises from abstracting the fetus from
the pregnant woman, in its failing to recognize the
pregnant woman herself as a patient, person, and
rights-bearer. This approach disregards a fundamen-
tal moral principle that persons never be treated
solely as means to an end, but as ends in themselves.
Within the rhetoric of conflict and fetal rights, the
pregnant woman has at times been reduced to a ves-
seleven a fortress holding the fetus prisoner
(16). As George Annas aptly described, Before birth,
we can obtain access to the fetus only through its
mother, and in the absence of her informed consent,
can do so only by treating her as a fetal container, a
nonperson without rights to bodily integrity (3).
Some writers have argued that at the heart of the
distorting influence of the two-patient model of
the maternalfetal dyad is the fact that, according to
traditional theories that undergird medical ethics, the
very notion of a person or a patient is someone who
is physically separate from others. Pregnancy, how-
ever, is marked by a particular and particularly
thoroughgoing kind of intertwinement (17). Thus,
the pregnant woman and fetus fit awkwardly at best
into what the term patient is understood to mean.
They are neither physically separate, as persons are
understood to be, nor indistinguishably fused. A
framework that instead defines the professional eth-
ical obligations with a deep sensitivity to relation-
ships of interdependency may help to avoid the
distorting influence of the two-patient model as tra-
ditionally understood (18). Although this opinion
does not specifically articulate a novel comprehen-
sive conceptual model for perinatal ethics, in the dis-
cussion that follows, the Committee on Ethics takes
as morally central the essential connection between
the pregnant woman and fetus.
Ethics Committee Opinions and the Maternal
Fetal Relationship
In the context of a framework that recognizes the
interconnectedness of the pregnant woman and fetus
and emphasizes their shared interests, certain opin-
ions previously published by the ACOG Committee
on Ethics are particularly relevant. These include:
Informed Consent (19)
Patient Choice in the MaternalFetal Relation-
ship (20)
At-Risk Drinking and Illicit Drug Use: Ethical
Issues in Obstetric and Gynecologic Practice
(21)
91 COMMITTEE OPINIONS 91
One fundamental ethical obligation of health
care professionals is to respect patients autonomous
decision making and to adhere to the requirement
for informed consent for medical intervention. In
January 2004, the Committee on Ethics published a
revised edition of Informed Consent in which the
following points are defended:
Requiring informed consent is an expression of
respect for the patient as a person; it particular-
ly respects a patients moral right to bodily
integrity, to self-determination regarding sex-
uality and reproductive capacities, and to the
support of the patients freedom within caring
relationships.
The ethical requirement for informed consent
need not conflict with physicians overall ethical
obligation to a principle of beneficence; that is,
every effort should be made to incorporate a
commitment to informed consent within a com-
mitment to provide medical benefit to patients
and thus respect them as whole and embodied
persons.
Pregnancy does not obviate or limit the require-
ment to obtain informed consent. Intervention on
behalf of the fetus must be undertaken through the
body and within the context of the life of the preg-
nant woman, and therefore her consent for medical
treatment is required, regardless of the treatment
indication. However, pregnancy presents a special
set of issues. The issues associated with informed
refusal of care by pregnant women are addressed in
the January 2004 opinion Patient Choice in the
MaternalFetal Relationship (20). This opinion
states that in cases of maternal refusal of treatment
for the sake of the fetus, court-ordered intervention
against the wishes of a pregnant woman is rarely if
ever acceptable. The document presents a review of
general ethical considerations applicable to pregnant
women who do not follow the advice of their physi-
cians or do not seem to make decisions in the best
interest of their fetuses. Although the possibility of a
justifiable court-ordered intervention is not com-
pletely ruled out, the document presents several rec-
ommendations that strongly discourage coercive
measures:
The obstetricians response to a patients
unwillingness to cooperate with medical advice
. . . should be to convey clearly the reasons for
the recommendations to the pregnant woman,
examine the barriers to change along with her,
and encourage the development of health-pro-
moting behavior.
[Even if] a womans autonomous decision
[seems] not to promote beneficence-based
obligations (of the woman or the physician) to
the fetus, . . . the obstetrician must respect the
patients autonomy, continue to care for the
pregnant woman, and not intervene against the
patients wishes, regardless of the conse-
quences.
The obstetrician must keep in mind that med-
ical knowledge has limitations and medical
judgment is fallible and should therefore take
great care to present a balanced evaluation of
expected outcomes for both [the woman and the
fetus].
Obstetricians should consider the social and
cultural context in which these decisions are
made and question whether their ethical judg-
ments reinforce gender, class, or racial inequal-
ity.
In addition to revisiting questions of how practi-
tioners should address refusal of treatment in the
clinic and delivery room, the four cases outlined pre-
viously illustrate punitive and coercive policies
aimed at pregnant women who engage in behaviors
that may adversely affect fetal well-being. The 2004
opinion At-Risk Drinking and Illicit Drug Use:
Ethical Issues in Obstetric and Gynecologic
Practice (21) specifically addresses addiction and
the prosecution of women who use drugs and alco-
hol during pregnancy and recommends strongly
against punitive policies:
Addiction is not primarily a moral weakness, as
it has been viewed in the past, but a brain dis-
ease that should be included in a review of sys-
tems just like any other biologic disease
process.
Recommended screening . . . connected with
legally mandated testing or reporting . . . endan-
ger[s] the relationship of trust between physician
and patient, place[s] the obstetrician in an adver-
sarial relationship with the patient, and possibly
conflict[s] with the therapeutic obligation.
Punitive policies are unjust in that they indict
the woman for failing to seek treatment that
actually may not be available to her and in that
they are not applied evenly across sex, race,
and socioeconomic status.
COMPENDIUM OF SELECTED PUBLICATIONS 92 92
Physicians must make a substantial effort to
treat the patient with a substance abuse prob-
lem with dignity and respect in order to form a
therapeutic alliance.
Finally, recent legal decisions affirm that physi-
cians have neither an obligation nor a right to per-
form prenatal testing for alcohol or drug use without
a pregnant womans consent (22, 23). This includes
consent to testing of the woman that could lead to
any form of reporting, both to legal authorities for
purposes of criminal prosecution and to civil child
welfare authorities.
Against Coercive and Punitive Legal Approaches
to the MaternalFetal Relationship
This section addresses specifically the ethical issues
associated with the cases outlined previously and
delineates six reasons why restricting patients liber-
ty and punishing pregnant women for their actions
during pregnancy that may affect their fetuses is nei-
ther wise nor justifiable. Each raises important
objections to punishing pregnant women for actions
during pregnancy; together they provide an over-
whelming rationale for avoiding such approaches.
1. Coercive and punitive legal approaches to preg-
nant women who refuse medical advice fail to
recognize that all competent adults are entitled to
informed consent and bodily integrity.
A fundamental tenet of contemporary medical ethics
is the requirement for informed consent, including
the right of competent adults to refuse medical inter-
vention. The Committee on Ethics affirms that
informed consent for medical treatment is an ethical
requirement and is an expression of respect for the
patient as a person with a moral right to bodily
integrity (19).
The crucial difference between pregnant and
nonpregnant individuals, though, is that a fetus is
involved whose health interests could arguably be
served by overriding the pregnant womans wishes.
However, in the United States, even in the case of
two completely separate individuals, constitutional
law and common law have historically recognized
the rights of all adults, pregnant or not, to informed
consent and bodily integrity, regardless of the
impact of that persons decision on others. For
instance, in 1978, a man suffering from aplastic ane-
mia sought a court order to force his cousin, who
was the only compatible donor available, to submit
to bone marrow harvest. The court declined,
explaining in its opinion:
For our law to compel the Defendant to submit to an
intrusion of his body would change every concept
and principle upon which our society is founded. To
do so would defeat the sanctity of the individual and
would impose a rule which would know no limits. . . .
For a society that respects the rights of one individ-
ual, to sink its teeth into the jugular vein or neck of
its members and suck from it sustenance for another
member, is revolting to our hard-wrought concepts of
jurisprudence. Forcible extraction of living body tis-
sues causes revulsion to the judicial mind. Such
would raise the specter of the swastika and the
Inquisition, reminiscent of the horrors this portends.
(24)
Justice requires that a pregnant woman, like any
other individual, retain the basic right to refuse med-
ical intervention, even if the intervention is in the
best interest of her fetus. This principle was chal-
lenged unsuccessfully in June 1987 with the case of
a 27-year-old woman who was at 25 weeks of gesta-
tion when she became critically ill with cancer.
Against the wishes of the woman, her family, and
her physicians, the hospital obtained a court order
for a cesarean delivery, claiming independent rights
of the fetus. Both mother and infant died shortly
after the cesarean delivery was performed. Three
years later, the District of Columbia Court of
Appeals vacated the court-ordered cesarean delivery
and held that the woman had the right to make health
care decisions for herself and her fetus, arguing that
the lower court had erred in subordinating her right
to bodily integrity in favor of the states interest in
potential life (1).
2. Court-ordered interventions in cases of informed
refusal, as well as punishment of pregnant women
for their behavior that may put a fetus at risk,
neglect the fact that medical knowledge and pre-
dictions of outcomes in obstetrics have limitations.
Beyond its importance as a means to protect the
right of individuals to bodily integrity, the doctrine
of informed consent recognizes the right of individ-
uals to weigh risks and benefits for themselves.
Women almost always are best situated to understand
the importance of risks and benefits in the context
of their own values, circumstances, and concerns.
Furthermore, medical judgment in obstetrics itself
has limitations in its ability to predict outcomes. In
this document, the Committee on Ethics has argued
that overriding a womans autonomous choice,
whatever its potential consequences, is neither ethi-
93 COMMITTEE OPINIONS 93
cally nor legally justified, given her fundamental
rights to bodily integrity. Even those who challenge
these fundamental rights in favor of protecting the
fetus, however, must recognize and communicate
that medical judgments in obstetrics are fallible (25).
And fallibilitypresent to various degrees in all
medical encountersis sufficiently high in obstetric
decision making to warrant wariness in imposing
legal coercion. Levels of certainty underlying med-
ical recommendations to pregnant women are
unlikely to be adequate to justify legal coercion and
the tremendous impact on the lives and civil liberties
of pregnant women that such intervention would
entail (26). Some have argued that court-ordered
intervention might plausibly be justified only when
certainty is especially robust and the stakes are espe-
cially high. However, in many cases of court-
ordered obstetric intervention, the latter criterion has
been met but not the former. Furthermore, evidence-
based medicine has revealed limitations in the abili-
ty to concretely describe the relationship of maternal
behavior to perinatal outcome. Criminalizing women
in the face of such scientific and clinical uncertainty
is morally dubious. Not only do these approaches fail
to take into account the standards of evidence-based
medical practice, but they are also unjust, and their
application is likely to be informed by bias and opin-
ion rather than objective assessment of risk.
Consider, first, the limitations of medical judg-
ment in predicting birth outcomes based on mode of
childbirth. A study of court-ordered obstetric inter-
ventions suggested that in almost one third of cases
in which court orders were sought, the medical judg-
ment was incorrect in retrospect (27). One clear
example of the challenges of predicting outcome is
in the management of risk associated with shoulder
dystocia in the setting of fetal macrosomiawhich
is, and should be, of great concern for all practition-
ers. When making recommendations to patients,
however, practitioners have an ethical obligation to
recognize and communicate that accurate diagnosis
of macrosomia is imprecise (20). Furthermore,
although macrosomia increases the risk of shoulder
dystocia, it is certainly not absolutely predictive; in
fact, most cases of shoulder dystocia occur unpre-
dictably among infants of normal birthweight. Given
this uncertainty, ACOG makes recommendations
about when cesarean delivery may be considered,
not about when it is absolutely indicated. Because of
the inability to determine with certainty when a sit-
uation is harmful to the fetus or pregnant woman and
the inability to guarantee that the pregnant woman
will not be harmed by the medical intervention,
great care should be exercised to present a balanced
evaluation of expected outcomes for both parties
(20). The decision about weighing risks and benefits
in the setting of uncertainty should remain the preg-
nant womans to make in the setting of supportive,
informative medical care.
Medical judgment also has limitations in that
the relationship of maternal behavior to pregnancy
outcome is poorly understood and may be exagger-
ated in realms often mistaken to be of moral rather
than medical concern, such as drug use. For
instance, recent child development research has not
found the effects of prenatal cocaine exposure that
earlier uncontrolled studies reported (28). It is now
understood that poverty and its concomitantspoor
nutrition and inadequate health carecan account
for many of the effects popularly attributed to
cocaine. Before these data emerged, the criminal
justice approach to drug addiction during pregnancy
was fueled to a great degree by what is now under-
stood to be the distorting image of the crack baby.
Such an image served as a convenient symbol for
an aggressive war on drug users [that] makes it eas-
ier to advocate a simplistic punitive response than to
address the complex causes of drug use (29). The
findings questioning the impact of cocaine on peri-
natal outcome are among many considerations that
bring sharply into question any possible justification
for a criminal justice approach, rather than a public
health approach, to drug use during pregnancy.
Given the incomplete understanding of factors
underlying perinatal outcomes in general and the
contribution of individual behavioral and socioeco-
nomic factors in particular, to identify homeless and
addicted women as personally, morally, and legally
culpable for perinatal outcomes is inaccurate, mis-
leading, and unjust.
3. Coercive and punitive policies treat medical prob-
lems such as addiction and psychiatric illness as
if they were moral failings.
Regardless of the strength of the link between an
individuals behaviors and pregnancy outcome,
punitive policies directed at women who use drugs
are not justified, because these policies are, in effect,
punishing women for having a medical problem.
Although once considered a sign of moral weakness,
addiction is now, according to evidence-based med-
icine, considered a diseasea compulsive disorder
COMPENDIUM OF SELECTED PUBLICATIONS 94 94
requiring medical attention (30). Pregnancy should
not change how clinicians understand the medical
nature of addictive behavior. In fact, studies over-
whelmingly show that pregnant drug users are very
concerned about the consequences of their drug
use for their fetuses and are particularly eager to
obtain treatment once they find out they are preg-
nant (31, 32). Despite evidence-based medical rec-
ommendations that support treatment approaches to
drug use and addiction (21), appropriate treatment is
particularly difficult to obtain for pregnant and par-
enting women and the incarcerated (29). Thus, a
disease process exacerbated by social circum-
stancenot personal, legal, or moral culpability
is at the heart of substance abuse and pregnancy.
Punitive policies unfairly make pregnant women
scapegoats for medical problems whose cause is
often beyond their control.
In most states, governmental responses to preg-
nant women who use drugs have upheld medical
characterizations of addiction. Consistent with long-
standing U.S. Supreme Court decisions recognizing
that addiction is an illness and that criminalizing it
violates the Constitutions Eighth Amendment prohi-
bitions against cruel and unusual punishment, no state
has adopted a law that specifically creates unique
criminal penalties for pregnant women who use drugs
(33). However, in South Carolina, using drugs or
being addicted to drugs was effectively criminalized
when the state supreme court interpreted the word
child in the states criminal child endangerment
statute to include viable fetuses, making the child
endangerment statute applicable to pregnant women
whose actions risk harm to a viable fetus (23). In all
states, women retain their Fourth Amendment free-
dom from unreasonable searches, so that pregnant
women may not be subject to nonconsensual drug
testing for the purpose of criminal prosecution.
Partly on the basis of the understanding of addic-
tion as a compulsive disorder requiring medical atten-
tion, medical professionals, U.S. state laws, and the
vast majority of courts do not support unique crimi-
nal penalties for pregnant women who use drugs.
4. Coercive and punitive policies are potentially
counterproductive in that they are likely to dis-
courage prenatal care and successful treatment,
adversely affect infant mortality rates, and under-
mine the physicianpatient relationship.
Even if the aforementioned ethical concerns could
be addressed, punitive policies would not be justifi-
able on utilitarian grounds, because they would like-
ly result in more harm than good for maternal and
child health, broadly construed. Various studies have
suggested that attempts to criminalize pregnant
womens behavior discourage women from seeking
prenatal care (34, 35). Furthermore, an increased
infant mortality rate was observed in South Carolina
in the years following the Whitner v State decision
(36), in which the state supreme court concluded
that anything a pregnant woman does that might
endanger a viable fetus (including, but not limited
to, drug use) could result in either charges of child
abuse and a jail sentence of up to 10 years or homi-
cide and a 20-year sentence if a stillbirth coincides
with a positive drug test (23). As documented previ-
ously (21), threats and incarceration have been inef-
fective in reducing the incidence of alcohol and drug
abuse among pregnant women, and removing chil-
dren from the home of an addicted mother may sub-
ject them to worse risks in the foster care system. In
fact, women who have custody of their children
complete substance abuse treatment at a higher rate
(3739).
These data suggest that punishment of pregnant
women might not result in women receiving the
desired message about the dangers of prenatal sub-
stance abuse; such measures might instead send an
unintended message about the dangers of prenatal
care. Ultimately, fear surrounding prenatal care
would likely undermine, rather than enhance, mater-
nal and child health. Likewise, court-ordered inter-
ventions and other coercive measures may result in
fear about whether ones wishes in the delivery room
will be respected and ultimately could discourage
pregnant patients from seeking care. Encouraging
prenatal care and treatment in a supportive environ-
ment will advance maternal and child health most
effectively.
5. Coercive and punitive policies directed toward
pregnant women unjustly single out the most vul-
nerable women.
Evidence suggests that punitive and coercive poli-
cies not only are ethically problematic in and of
themselves, but also unfairly burden the most vul-
nerable women. In cases of court-ordered cesarean
deliveries, for instance, the vast majority of court
orders have been obtained against poor women of
color (27, 40).
Similarly, decisions about detection and man-
agement of substance abuse in pregnancy are fraught
95 COMMITTEE OPINIONS 95
with bias, unfairly burdening the most vulnerable
despite the fact that addiction occurs consistently
across race and socioeconomic status (41). In the
landmark case of Ferguson v City of Charleston,
which involved selective screening and arrest of
pregnant women who tested positive for drugs, 29 of
30 women arrested were African American. Studies
suggest that affluent women are less likely to be
tested for use of illicit drugs than poor women of
color, perhaps because of stereotyped but demon-
strably inaccurate assumptions about drug use. One
study found that despite similar rates of substance
abuse across racial and socioeconomic status,
African American women were 10 times more like-
ly than white women to be reported to public health
authorities for substance abuse during pregnancy
(42). These data suggest that, as implemented, many
punitive policies centered on maternal behaviors,
including substance use, are deeply unjust in that
they reinforce social and racial inequality.
6. Coercive and punitive policies create the potential
for criminalization of many types of otherwise
legal maternal behavior.
In addition to raising concerns about race and
socioeconomic status, punitive and coercive policies
may have even broader implications for justice for
women. Because many maternal behaviors are asso-
ciated with adverse pregnancy outcome, these poli-
cies could result in a society in which simply being
a woman of reproductive potential could put an indi-
vidual at risk for criminal prosecution. For instance,
poorly controlled diabetes is associated with numer-
ous congenital malformations and an excessive rate
of fetal death. Periconceptional folic acid deficiency
is associated with an increased risk of neural tube
defects. Obesity has been associated in recent stud-
ies with adverse pregnancy outcomes, including
preeclampsia, shoulder dystocia, and antepartum
stillbirth (43, 44). Prenatal exposure to certain
medications that may be essential to maintaining a
pregnant womans health status is associated with
congenital abnormalities. If states were to consis-
tently adopt policies of punishing women whose
behavior (ranging from substance abuse to poor
nutrition to informed decisions about prescription
drugs) has the potential to lead to adverse perinatal
outcomes, at what point would they draw the line?
Punitive policies, therefore, threaten the privacy and
autonomy not only of all pregnant women, but also
of all women of reproductive potential.
Recommendations
In light of these six considerations, the Committee
on Ethics strongly opposes the criminal prosecution
of pregnant women whose activities may appear to
cause harm to their fetuses. Efforts to use the legal
system specifically to protect the fetus by constrain-
ing womens decision making or punishing them for
their behavior erode a womans basic rights to pri-
vacy and bodily integrity and are neither legally nor
morally justified. The ACOG Committee on Ethics
therefore makes the following recommendations:
In caring for pregnant women, practitioners
should recognize that in the majority of cases,
the interests of the pregnant woman and her
fetus converge rather than diverge. Promoting
pregnant womens health through advocacy of
healthy behavior, referral for substance abuse
treatment and mental health services when nec-
essary, and maintenance of a good physician
patient relationship is always in the best interest
of both the woman and her fetus.
Pregnant womens autonomous decisions
should be respected. Concerns about the impact
of maternal decisions on fetal well-being should
be discussed in the context of medical evidence
and understood within the context of each
womans broad social network, cultural beliefs,
and values. In the absence of extraordinary cir-
cumstances, circumstances that, in fact, the
Committee on Ethics cannot currently imagine,
judicial authority should not be used to imple-
ment treatment regimens aimed at protecting the
fetus, for such actions violate the pregnant
womans autonomy.
Pregnant women should not be punished for
adverse perinatal outcomes. The relationship
between maternal behavior and perinatal out-
come is not fully understood, and punitive
approaches threaten to dissuade pregnant
women from seeking health care and ultimately
undermine the health of pregnant women and
their fetuses.
Policy makers, legislators, and physicians
should work together to find constructive and
evidence-based ways to address the needs of
women with alcohol and other substance abuse
problems. This should include the development
of safe, available, and efficacious services for
women and families.
COMPENDIUM OF SELECTED PUBLICATIONS 96 96
References
1. In re A.C., 573 A.2d 1235 (D.C. 1990).
2. Annas GJ. Foreclosing the use of force: A.C. reversed.
Hastings Cent Rep 1990;20(4):279.
3. Annas GJ. Protecting the liberty of pregnant patients [edi-
torial]. N Engl J Med 1987;316:12134.
4. Rhoden NK. The judge in the delivery room: the emer-
gence of court-ordered cesareans. Calif Law Rev 1986;
74:19512030.
5. Bianchi DW, Crombleholme TM, DAlton ME. Fetology:
diagnosis and management of the fetal patient. New York
(NY): McGraw-Hill; 2000.
6. McCullough LB, Chervenak FA. Ethics in obstetrics and
gynecology. New York (NY): Oxford University Press;
1994.
7. Harris LH. Rethinking maternal-fetal conflict: gender
and equality in perinatal ethics. Obstet Gynecol 2000;96:
78691.
8. Maternal and Child Health Bureau. Mission statement.
Rockville (MD): MCHB; 2005. Available at: http://www.
mchb.hrsa.gov/about/default.htm. Retrieved June 17,
2005.
9. Lyerly AD, Gates EA, Cefalo RC, Sugarman J. Toward
the ethical evaluation and use of maternal-fetal surgery.
Obstet Gynecol 2001;98:68997.
10. State Childrens Health Insurance Program; eligibility for
prenatal care and other health services for unborn chil-
dren. Final rule. Centers for Medicare & Medicaid
Services (CMS), HHS. Fed Regist 2002;67:6195574.
11. Steinbock B. Health care coverage for not-yet-born chil-
dren. Hastings Cent Rep 2003;33(1):49.
12. Murray L, Cooper P. Effects of postnatal depression on
infant development. Arch Dis Child 1997;77:99101.
13. Murray L, Fiori-Cowley A, Hooper R, Cooper P. The
impact of postnatal depression and associated adversity
on early mother-infant interactions and later infant out-
come. Child Dev 1996;67:251226.
14. Horon IL, Cheng D. Enhanced surveillance for preg-
nancy-associated mortalityMaryland, 19931998.
JAMA 2001;285:14559.
15. Frye V. Examining homicides contribution to pregnancy-
associated deaths [editorial]. JAMA 2001;285:15101.
16. Phelan JP. The maternal abdominal wall: a fortress against
fetal health care? South Calif Law Rev 1991;65:46190.
17. Little MO. Abortion, intimacy, and the duty to gestate.
Ethical Theory Moral Pract 1999;2:295312.
18. Mattingly SS. The maternal-fetal dyad. Exploring the
two-patient obstetric model. Hastings Cent Rep 1992;22:
138.
19. Informed consent. In: American College of Obstetricians
and Gynecologists. Ethics in obstetrics and gynecology.
2nd ed. Washington, DC: ACOG; 2004. p. 917.
20. Patient choice in the maternalfetal relationship. In:
American College of Obstetricians and Gynecologists.
Ethics in obstetrics and gynecology. 2nd ed. Washington,
DC: ACOG; 2004. p. 346.
21. At-risk drinking and illicit drug use: ethical issues in
obstetric and gynecologic practice. ACOG Committee
Opinion No. 294. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2004;103:102131.
22. Ferguson v. City of Charleston, 532 U.S. 67 (2001).
23. Whitner v. State, 328 S.C. 1, 492 S.E.2n 777 (1997).
24. McFall v. Shimp, 10 Pa. D. & C.3d (C.P. 1978).
25. Rhoden NK. Informed consent in obstetrics: some special
problems. West N Engl Law Rev 1987;9:6788.
26. Nelson LJ, Milliken N. Compelled medical treatment of
pregnant women. Life, liberty, and law in conflict. JAMA
1988;259:10606.
27. Kolder VE, Gallagher J, Parsons MT. Court-ordered
obstetrical interventions. N Engl J Med 1987;316:11926.
28. Frank DA, Augustyn M, Knight WG, Pell T, Zuckerman
B. Growth, development, and behavior in early childhood
following prenatal cocaine exposure: a systematic review.
JAMA 2001;285:161325.
29. Chavkin W. Cocaine and pregnancytime to look at the
evidence [editorial]. JAMA 2001;285:16268.
30. Marwick C. Physician leadership on National Drug Policy
finds that addiction treatment works. JAMA 1998;279:
114950.
31. Murphy S, Rosenbaum M. Pregnant women on drugs:
combating stereotypes and stigma. New Brunswick (NJ):
Rutgers University Press; 1999.
32. Kearney MH, Murphy S, Rosenbaum M. Mothering on
crack cocaine: a grounded theory analysis. Soc Sci Med
1994;38:35161.
33. Harris LH, Paltrow L. MSJAMA. The status of pregnant
women and fetuses in US criminal law. JAMA 2003;
289:16979.
34. Poland ML, Dombrowski MP, Ager JW, Sokol RJ.
Punishing pregnant drug users: enhancing the flight from
care. Drug Alcohol Depend 1993;31:199203.
35. United States. General Accounting Office. Drug exposed
infants: a generation at risk: report to the chairman,
Committee on Finance, U.S. Senate. Washington, DC:
U.S. General Accounting Office; 1990.
36. The Annie E. Casey Foundation. 2004 kids count data
book: moving youth from risk to opportunity. Baltimore
(MD): AECF; 2004. Available at: http://www.aecf.org/
publications/data/kc2004_e.pdf. Retrieved June 17, 2005.
37. Haller DL, Knisely JS, Elswick RK Jr, Dawson KS,
Schnoll SH. Perinatal substance abusers: factors influenc-
ing treatment retention. J Subst Abuse Treat 1997;14:
5139.
38. Hohman MM, Shillington AM, Baxter HG. A comparison
of pregnant women presenting for alcohol and other drug
treatment by CPS status. Child Abuse Negl 2003;27:
30317.
39. Kissin WB, Svikis DS, Morgan GD, Haug NA.
Characterizing pregnant drug-dependent women in treat-
ment and their children. J Subst Abuse Treat 2001;21:
2734.
40. Nelson LJ, Marshall MF. Ethical and legal analyses of
three coercive policies aimed at substance abuse by preg-
nant women. Charleston (SC): Medical University of
South Carolina, Program in Bioethics; 1998.
41. Mathias R. NIDA survey provides first national data on drug
use during pregnancy. NIDA Notes 1995;10(1). Available
97 COMMITTEE OPINIONS 97
at: http://www.nida.nih.gov/NIDA_Notes/NNVol10N1/
NIDASurvey.html. Retrieved June 17, 2005.
42. Chasnoff IJ, Landress HJ, Barrett ME. The prevalence of
illicit-drug or alcohol use during pregnancy and discrep-
ancies in mandatory reporting in Pinellas County, Florida.
N Engl J Med 1990;322:12026.
43. Cedergren MI. Maternal morbid obesity and the risk of
adverse pregnancy outcome. Obstet Gynecol 2004;103:
21924.
44. Cnattingius S, Bergstrom R, Lipworth L, Kramer MS.
Prepregnancy weight and the risk of adverse pregnancy
outcomes. N Engl J Med 1998;338:14752.
COMPENDIUM OF SELECTED PUBLICATIONS 98 98
ACOG
Number 341, July 2006
Committee
Opinion
Copyright July 2006
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of this
publication may be reproduced,
stored in a retrieval system, post-
ed on the Internet, or transmitted,
in any form or by any means,
electronic, mechanical, photo-
copying, recording, or otherwise,
without prior written permission
from the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Ethical ways for physicians to market
a practice. ACOG Committee Opinion
No. 341. American College of
Obstetricians and Gynecologists.
Obstet Gynecol 2006;108:23942.
Ethical Ways for Physicians
to Market a Practice
ABSTRACT: It is ethical for physicians to market their practices through any
form of public communication provided that the communication is truthful
and not misleading or deceptive. Communications should not convey dis-
criminatory attitudes involving race, ethnicity, gender, or sexual orientation.
All paid advertising must be clearly identified as such. Producing fair and
accurate advertising of medical practices and services can be challenging. It
often is difficult to include detailed information because of cost and size
restrictions or the limitations of the media form that has been selected. If the
specific advertising form does not lend itself to clear and accurate descrip-
tion, an alternative media format should be selected. Finally, any advertis-
ing that seeks to denigrate the competence of other individual professionals
or group practices is always considered unethical.
Traditionally, physicians and medical societies have raised concerns that
advertising commercializes the practice of medicine and does not respect the
dignity of the profession. Physicians have been expected to generate refer-
rals from other physicians and from satisfied patients by providing good care
to their patients. In the past, some state and national professional medical
societies prohibited advertising in their code of ethics. In 1982, the Supreme
Court ruled in favor of the Federal Trade Commission (FTC) in its claim that
the American Medical Association was in restraint of trade because the
American Medical Associations Code of Ethics prohibited advertising (1).
The FTC argued that all businesses and professionals have the right to
inform the public of the services they provide and that all consumers have
the right to make informed choices based on truthful advertising. The pur-
pose of this Committee Opinion is to provide objective criteria to help mem-
bers of the American College of Obstetricians and Gynecologists determine
whether or not a certain advertisement or method of marketing is ethical. In
considering appropriate marketing practices, physicians should evaluate not
only their own actions but also those undertaken on their behalf by hospitals
or other health care centers that may be marketing their services.
It is ethical for physicians to market their practices through any form of
public communication provided that the communication is truthful and not
misleading or deceptive in any way. In addition, communications should not
Committee on
Ethics
Reaffirmed 2008
99 COMMITTEE OPINIONS 99
convey discriminatory attitudes involving race, eth-
nicity, gender, or sexual orientation.
Appropriate Forms of Communication
According to the FTC guidelines, physicians must
be allowed to make their services known through
advertising to assist the public in obtaining medical
services. A physician or practice should not be
restricted from using any form of public media to
market medical services, such as newspapers, mag-
azines, telephone directories, radio, web pages,
computer billboards, television, and direct mail. All
of these media formats have the potential for both
effective, ethical communication as well as misrep-
resentation, depending on their form and content.
Advertising in any format may be ethical but still
reflect poorly on the profession and undermine the
public impressions of the profession. For example,
use of a large billboard or television infomercials
to advertise services is not unethical, but still might
be considered by many to be unprofessional.
Physicians should consider not just the intent of the
advertisement but also its impact.
A paid advertisement promoting the activities of
a physician or practice must be clearly identified as
advertising. It is not ethical to compensate the com-
munication media in any way for publicity in a news
item. If a television infomercial is used to inform the
public of services available, it should be very clear at
all times that this is paid advertising and not part of
a news program.
Care should be taken to choose information
appropriate to the form of communication. The com-
plexity of medical terms and treatments may not
always lend itself to the restrictions of a particular
advertisement design or media format. For example,
the brevity of television and radio advertisements
may require omitting so much information that the
advertisement becomes misleading.
The location in which an advertisement is
placed also may contribute to deception. For exam-
ple, some readers may assume that a physician who
advertises his or her practice under the subheading
Infertility in the telephone directory has received
extensive subspecialty training in that area and reg-
ularly treats patients with these problems.
Advertisers should be careful not to imply subspe-
cialty training when none exists.
Actively approaching specific individuals, in
person or by phone, with the purpose of attracting
them as patients usually is not considered ethical
because the risk of undue pressure from the solicitor
is too great. Common expectations for a physi-
cianpatient relationship may make the prospective
patient feel obligated to respond affirmatively to the
encounter. Although many physicians view such
active approaches as always being unprofessional,
they may be ethical in rare circumstances if extraor-
dinary care is taken to avoid undue pressure. For
example, it may be appropriate to pass out cards to
potential clients at a community health fair.
Appropriate Content of Advertisements
Advertisements must be truthful and not deceptive
or misleading. Specifically, this means that all infor-
mation must be accurate and must not create false or
unjustified expectations. The omission of informa-
tion should not render the advertisement misleading.
Images and graphics can be as deceptive or mislead-
ing as text. Finally, the physician or clinic must be
able to substantiate all claims made in the advertise-
ment. Advertisements may include nondeceptive
information, such as address, phone numbers, web
site address, office hours, languages spoken, board
certification, contracted insurance plans, publica-
tions by physicians, teaching positions, hospital
affiliations, and methods of payment accepted.
Terms such as top, world-famous, world-
class, or even pioneer, usually are misleading and
designed to attract vulnerable patients. Statements
that rank the competence of physicians or the quali-
ty of medical services usually are not factually sup-
portable. If attributions of this type are used, the
advertisement must describe how these rankings
were established. The testimonial of one or two sat-
isfied patients may mislead the public into believing
that all patients, even those with dissimilar histories,
have similar outcomes. The designation Top
Doctor as voted by magazine readers, other doc-
tors, or specific groups may be used in promotional
material since the term is a factual statement of the
results of a survey. However, advertisements must
state if such a designation involved payment by the
physician. Furthermore, any advertising that seeks
to denigrate the competence of other individual pro-
fessionals or group practices always is considered
unethical.
Care must be taken in advertising procedures
that are experimental or have never been proved to
result in the desired outcome. It is deceptive to give
COMPENDIUM OF SELECTED PUBLICATIONS 100 100
the public the impression that experimental or
unstudied procedures are of proven value or accept-
ed practice.
Claims that a physician or group of physicians
have a unique skill or offer a unique test or treatment
often may be deceptive and rarely should be used. If
a physician has carefully verified that he or she is the
only practitioner to offer a certain treatment in a par-
ticular geographic area, then this information may
be dispersed. If the uniqueness results from a restric-
tive commercial agreement, this fact needs to be dis-
closed in the advertisement.
Specific outcomes should rarely be advertised
because the definition of a success rate, the selection
of eligible patients for consideration in calculating
rates, and the predictive value of rates are all impor-
tant in accurately assessing outcomes. Whereas
these should be discussed with an individual patient
in the context of her care, they cannot be interpreted
accurately by someone viewing an advertisement
and may be very confusing or misleading to the
patient trying to determine where to seek care. For
example, a fertility clinics success rate for assist-
ed reproductive technologies is dependent on the
patients age, the clinics patient selection and exclu-
sion policies, and the clinics criteria for cycle can-
cellation. Success may be stated in many ways,
each of which results in a different rate: as clinical
pregnancies, singleton pregnancies, or live births per
started cycle, per egg retrieval, or per embryo trans-
fer. Comparing hospitals by cesarean delivery rate is
similarly difficult because rates vary with the char-
acteristics of a patient population or the presence of
a neonatal intensive care unit or both. Furthermore,
a new program or site should not present the success
rates of the parent site as its own because its new
facilities are as yet untested. When advertisements
do involve success rates or other outcomes, all
claims must be supported by valid, reproducible
data, must clearly state the method used to calculate
outcomes, and must not lead patients or the public to
believe that outcomes are better than they are.
Fee structures and costs may be advertised, as
long as information is complete and titles for special
programs do not mislead or encourage inaccurate
assumptions. For example, promises of a money-
back guarantee are frequently misleading because
usually they refund only a portion of the patients
money if the desired outcome does not occur.
Shared-risk plans usually do not share risk
between the patient and the clinic, but among a
group of patients. Do one, get one free treatments
may involve extraordinary requirements and expens-
es for the initial treatment and may not truly save the
patient any money. A free initial consultation
should not contain any hidden costs or routinely
involve recommendations for expensive tests or
treatments. Any advertisements involving such
financial plans should contain enough information
so that the prospective patients are neither misled
nor unduly induced to seek services at that clinic.
Producing fair and accurate advertising of med-
ical practices and services can be challenging, even
with the best intentions. It often is difficult to
include detailed information because of cost and
size restrictions or the limitations of the media form
that has been selected. If the specific advertising
form does not lend itself to clear and accurate
description, an alternative media format should be
selected.
Concerns About Discrimination
Discriminatory attitudes about race, ethnicity, gen-
der, or sexual orientation in advertisements are not
acceptable. A line item stating that a provider speaks
Spanish or Cantonese accurately states the services
provided and would not be considered discrimina-
tory. Similarly, a factual statement that the providers
in a certain clinic are all women is ethical. However,
wording that suggests that health care provided sole-
ly by women is superior to health care for women by
men would be considered discriminatory and uneth-
ical in the absence of evidence supporting that
claim. If the intent of stating the facts is to imply a
value judgment rather than to offer supportable or
useful information about access, then even a state-
ment of fact may be unethical.
Vulnerable Groups
Certain individuals and groups of individuals may
be more easily misled by some claims made in
advertisements. Special care should be taken when
designing a marketing plan that targets these groups.
Perimenopausal and postmenopausal women, fear-
ful of cancer, may embrace natural therapies, even
when these therapies have not been evaluated ade-
quately for efficacy or risk. Patients with advanced
cancer may be more likely to pursue unapproved
procedures or pharmaceuticals. Patients with infer-
tility or recurrent pregnancy losses, desperate to
101 COMMITTEE OPINIONS 101
have a child, often are willing to pursue expensive
new treatments that are completely unproved.
Summary
Advertising by physicians or groups of physicians is
unethical when it contains material that is false,
unsubstantiated, deceptive, or misleading. Even if
the advertisement follows the guidelines covered in
this statement, the individual professional should be
the one who chooses a marketing plan he or she
believes respects the dignity of the profession.
Reference
1. American Medical Assoc. v. FTC, 455 U.S. 676 (1982).
Bibliography
American College of Obstetricians and Gynecologists. Code of
professional ethics of the American College of Obstetricians
and Gynecologists. Washington, DC: ACOG; 2004.
Guidelines for advertising by ART programs. Practice
Committee, Society for Assisted Reproductive Technology;
American Society for Reproductive Medicine. Fertil Steril
2004;82:5278.
COMPENDIUM OF SELECTED PUBLICATIONS 102 102
Committee on
Ethics
Reaffirmed 2008
ACOG
Number 347, November 2006
Committee
Opinion
Copyright November 2006
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of this
publication may be reproduced,
stored in a retrieval system,
posted on the Internet, or trans-
mitted, in any form or by any
means, electronic, mechanical,
photocopying, recording, or
otherwise, without prior written
permission from the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Using preimplantation embryos for
research. ACOG Committee Opinion
No. 347. American College of
Obstetricians and Gynecologists.
Obstet Gynecol 2006;108:130517.
Using Preimplantation Embryos
for Research*
ABSTRACT: Human embryonic stem cell research promises an increased
understanding of the molecular process underlying cell differentiation.
Transplantation of embryonic stem cells or their derivatives may, in the
future, offer therapies for human diseases. In this Committee Opinion, the
American College of Obstetricians and Gynecologists (ACOG) Committee
on Ethics presents an ethical framework for examining issues surrounding
research using preimplantation embryos and proposes ethical guidelines for
such research. The Committee acknowledges the diversity of opinions among
ACOG members and affirms that no physician who finds embryo research
morally objectionable should be required or expected to participate in such
research. The Committee supports embryo research within 14 days after evi-
dence of fertilization but limits it according to ethical guidelines. The
Committee recommends that cryopreserved embryos be the preferred source
for research but believes that the promise of somatic cell nuclear transfer is
such that research in this area is justified. The Committee opposes reproduc-
tive cloning. Intended parents for whom embryos are created should give
informed consent for the disposition of any excess embryos. The donors of
gametes or somatic cells used in the creation of such tissue should give con-
sent for donation of embryos for research. Abandoned embryos should not be
accepted for research. Potential research projects should be described to
potential donors as much as possible. Donation of embryos for stem cell
research requires specific consent. The Committee believes that compensa-
tion for egg donors for research is acceptable, consistent with American
Society for Reproductive Medicine guidelines.
The human embryo
or
after
7 Differentiation begins
or
after
Cell division ends
89 Implantation complete
Embryonic disc
or
after
1416 Embryogenesis begins; Primitive streak
differentiation has passed
point of twinning
*Both in vivo and in vitro except as noted.
In vivoorganizational structure as a blastocyst is requisite to beginning of implantation and persists after implantation (which may be
complete as early as 89 days after fertilization) until appearance of the primitive streak.
Cell division may end at any time in vivo or in vitro; it has not persisted in vitro beyond 69 days.
In vivo.
Fig. 2. Early in vivo and in vitro human development process.
COMPENDIUM OF SELECTED PUBLICATIONS 108 108
Why Pursue Embryo Research?
Most contemporary discussions about embryo
research center entirely on the question of the
embryos intrinsic moral statuswhether or not the
embryo meets specific criteria for moral personhood.
Based on the understanding of the degree to which an
embryo does or does not meet such criteria, these dis-
cussions have taken a stand about the permissibility
of options for embryo disposition. Bioethicist Patricia
King has noted that human embryo research policy
should do more than reflect mere abstract assertions
about the moral status of human embryos. Rather, the
moral underpinnings of human embryo research
should be derived from a range of values, including
the facilitation of human procreation, the advance-
ment of applied scientific knowledge, the reduction
of human suffering, and the protection of vulnerable
persons from coercion and exploitation (15).
There can be no compelling argument for
embryo research without the promise of benefit.
Potential benefits of embryo research include an
improved understanding of fertilization, implanta-
tion, and early pregnancy biology and, with this
understanding, possibly fewer undesired outcomes,
such as miscarriage. For infertile couples, embryo
research offers the possibility of more effective
therapies: research efforts helped optimize condi-
tions for intracytoplasmic sperm injection, embryo
culture, and cryopreservation, for example. For oth-
ers at risk for heritable genetic disease who feel
pregnancy termination is undesirable or inappropri-
ate, embryo research has led to the possibility of
early, accurate genetic diagnosis: PGD provides
diagnostic results at a point before implantation, so
pregnancy termination can be avoided. In addition
to these benefits of embryo research in general,
stem cell research promises additional potential
benefits, for such work may lead both to a better
understanding of the processes leading to tissue dif-
ferentiation and function and to possible therapies
by creating lines that can replace diseased or non-
functioning tissues. Those who donate gametes or
embryos for research are offered the rewards of
potentially extending scientific knowledge and,
apart from any current or future hope of improving
their own health, the opportunity to help others with
this knowledge. Indeed, in considering the fate of
excess embryos for which destruction is planned,
some have argued that donation for research
accords the embryo more respect than destruction
alone (16, 17).
Are There Alternatives to Using Preimplantation
Embryos for Research?
As with all human research, research on embryos
and embryonic stem cells should be engaged in only
when alternative means of developing knowledge
are inadequate. Whenever possible, animal models
or cell and tissue culture systems should be used to
advance the understanding of human biology.
However, direct extrapolation of results from in vitro
animal embryo studies to humans can be mislead-
ing. Unfertilized oocytes also do not offer the same
opportunities for investigating growth processes that
embryos do.
Some have argued that obtaining or using
embryonic stem cells is unnecessary because stem
cells have been or can be isolated from umbilical
cord blood or adult tissues, such as brain and skin.
Yet such adult stem cells, in contrast to embryonic
stem cells, have already progressed along the path of
differentiation and lack the plasticity of embryonic
stem cells. It is unlikely that once differentiated,
these cells can be induced to form the range of tis-
sues that can, by contrast, be produced by less-dif-
ferentiated embryonic stem cells (18, 19).
Umbilical cord blood stem cells have been
shown in some studies to transdifferentiate to a lim-
ited extent into nonhematopoietic cells, including
those of the brain, heart, liver, pancreas, bone, and
cartilage, in experimental culture and animal sys-
tems (20, 21). Some have speculated that, on the
basis of these observations, cord blood might serve
as a source of cells to facilitate tissue repair and
regeneration in the distant future. Research is need-
ed to clarify the role, if any, of cord blood in this
field of regenerative medicine.
For those with ethical objections, recent activity
in stem cell research has led to a vigorous search
for alternative sources of stem cells that might
obviate the need to use or destroy fresh or frozen
embryos (22). Suggested techniques include 1) extrac-
tion of cells from embryos already dead, 2) non-
harmful biopsy of a single blastomere from a living
embryo, 3) extraction of cells from artificially creat-
ed nonembryonic but embryolike cellular systems
(engineered to lack the essential elements of
embryogenesis but still capable of some cell division
and growth), and 4) dedifferentiation of somatic
cells back to pluripotency. The Committee on Ethics
recognizes that such techniques, if ultimately proved
to be productive, would avoid some but not all of the
arguments and objections that have been raised to
109 COMMITTEE OPINIONS 109
embryo and stem cell research. The Committee
believes, however, that until such hypothetical alter-
natives become realities for human tissues, their
possibility should not stand as a barrier to pursuing
available methods of demonstrated efficacy. Indeed,
technical barriers to these proposed alternatives are
not trivial, and the possibility of reprogramming
adult stem cells to achieve the same potential as
embryonic stem cells has been termed by experts as
exceedingly rare (23). It also is not clear that all
these suggestions are free from ethical concerns or
objections (eg, distinguishing when an embryo is
dead).
In considering embryonic stem cell research, it
is also important to indicate why progress requires
isolation of lines different from those already estab-
lished. Federal regulations prohibit funding for
investigations of the many new embryonic stem cell
lines created since August 2001, some of which have
been used by both international and U.S. researchers
to advance the field. Yet, advocates of stem cell
research note that in contrast to several of these
newer lines, all lines on the National Institutes of
Health (NIH) registry were cultured in contact with
mouse cells and bovine serum, which limits poten-
tial therapeutic applications. Furthermore, the U.S.
federal guidelines prohibit federal funding of
somatic cell nuclear transfer techniques (also
known as SCNT techniques) and research, which
may offer unique opportunities for human therapy
by creating cells tailored to an individuals genotype
and thus, in theory, requiring less need for immuno-
suppression if therapeutics can one day be created
from such individualized cell lines.
Are There Arguments Against Embryo Research?
Balanced against any potential benefits of embryo
research are known and potential risks. Embryo
research usually will involve destruction of embryos
and, as a result, most human embryo research will
not benefit the embryo that is usedenhancing nei-
ther its developmental potential nor its chance of sur-
vival. It is this potential harm that has led national
ethics advisory committees and commissions to eval-
uate the moral status of the embryo and has sharply
separated the two sides of the embryo research and
stem cell debate. Yet, as detailed previously, this doc-
ument views destruction of in vitro embryos as dif-
ferent from destruction of a human being.
Short of destruction, the manipulation of
embryos that are intended for transfer to the uterus
(as with embryo biopsy for PGD) raises concern for
potential manipulation-related damage in ongoing
pregnancies. Some embryo research can be validat-
ed scientifically and be beneficial clinically only if
there is a subsequent transfer of the embryo to a
womans uterus in an attempt to achieve pregnancy,
yet until such transfer is accomplished, it remains
unknown whether research interventions will
enhance or reduce the prospects for healthy life.
Women and couples who either participate in
research or donate gametes or embryos for research
also may be at risk. If a couple decides to donate
excess embryos for research, such as stem cell
extraction, they may be at risk for psychologic
harms such as uncertainty, stress, and anxiety. These
potential hazards are not exclusively related to the
option of donation of embryos for research purpos-
es and may accompany all decisions regarding the
disposition of frozen embryos. When research
requires hormonal stimulation and retrieval of
oocytes separate from plans for pregnancy (ie, tis-
sues obtained or created for research alone), the
oocyte donor faces risks similar to those involved in
oocyte donation for reproductive purposes. It is
essential to ensure that a womans or couples choice
is free of coercion and possible exploitation and that
the woman or couple gives informed consent.
Recognizing such risks, some have expressed
concern regarding the potential to exploit women as
oocyte donors. In part to answer such concerns,
some guidelines such as those proposed by the
National Academy of Sciences recommend no com-
pensation for oocyte donation for research other
than for out-of-pocket expenses (24). Such restric-
tions, however, seem inappropriate to the ACOG
Committee on Ethics and are inconsistent with pol-
icy and practice concerning compensation both to
oocyte donors for reproductive purposes and women
participating in other types of research protocols.
Compensation for oocyte donation for reproductive
purposes is supported by ASRM (25) and is custom-
ary in the United States, and there is no strong argu-
ment for distinguishing this practice from donation
in the research context. The risks to the woman and
the need to protect against potential abuses are sim-
ilar in the two situations. Payment to an oocyte
donor should be understood to be compensation for
the womans time, effort, risk, and discomfort and
not as payment for the eggs that may be recovered.
The level of compensation should be consistent with
ASRM guidelines intended to preclude payment lev-
COMPENDIUM OF SELECTED PUBLICATIONS 110 110
els that might be construed as exerting undue influ-
ence on the donor (25). In providing advice to those
seeking oocyte donors, ASRM guidelines also high-
light the importance of protecting vulnerable popu-
lations and providing compensation commensurate
with the time and effort involved.
Who Should Give Permission for Embryos to Be
Used for Research?
Individuals will differ in their beliefs about morality
of and appropriate limits for embryo research. This
is true for individuals or couples creating embryos as
part of infertility treatment and later making deci-
sions regarding frozen embryos, as well as for
gamete donors, who may in some cases be different
from the individuals for whom the embryos were
created (26, 27). In considering the question of who
should give consent for research using preimplanta-
tion embryos, it is important to recognize that such
research may occur long after gametes have been
donated and embryos created, and in addition, the
details of future research questions and protocols are
unlikely to be known at the time of donation. In
many cases, of course, those supplying the egg and
sperm will be the same as those for whom the
embryo is created, and these circumstances present
the easiest conditions for obtaining appropriate,
informed consent for research. In such cases, cou-
ples may indicate at the time the embryos are frozen
that they would be willing to consider future dona-
tion for research, but specific permission needs to be
obtained at the later time when custody is trans-
ferred to the research team. If details of the research
protocol are known at the time embryos are frozen,
couples should be so informed. Alternatively, some
couples will be willing to donate unused embryos to
an appropriate party (eg, those operating the labora-
tory or storage facility) for use in future research
projects as yet unformulated at the time of donation.
If such work includes projects in stem cell research,
this should be specifically discussed and the details
of stem cell research (eg, creation of immortal cell
lines) described insofar as they are known at the time
of donation. If both members of the couple have not
previously given consent at the time custody is trans-
ferred, embryos should not be used for research.
If gamete donors are different from those for
whom embryos were created, research should pro-
ceed only if gamete donors have been made aware of
the option of embryo research and have given their
consent to such research. Given the emotions and
discussion surrounding stem cell research, potential
research projects should be described as much as
possible. However, gamete donors need to recognize
that the details of future research projects are unlike-
ly to be available at the time of gamete donation, and
therefore donors need to be comfortable consenting
to research that is described only in general terms
(28). Abandoned embryos, as defined by the ASRM
Ethics Committee (29, 30), should not be accepted
for research.
When embryo research is conducted in anticipa-
tion of transfer (for example, PGD research), the
intended parents and, if different, the gamete donors
must be provided with adequate information regard-
ing the nature of the research, the risks to the embryo,
and the chances for a successful pregnancy resulting
in the birth of a healthy child, and they must provide
their informed consent (31). If research is to be done
on an embryo that is to be transferred eventually to a
third party (a gestational carriers uterus), this indi-
vidual also should give informed consent for the
research.
Finally, choices should be made in circum-
stances free of financial or other coercion. Full infor-
mation should, therefore, include assurance that
consent to donation of embryos for research is not a
condition for receiving services and that fee scales
are not contingent on consent to research. Moreover,
donors of embryos should understand that they will
receive no compensation for their donation of excess
embryos. The consent process also should cover any
possible identifiers that will be maintained with the
tissue to link it back to the donors, access to current
and future health information from donors, willing-
ness of donors to be contacted in the future, owner-
ship, patent rights, and commercial uses of stem cell
lines that may be developed from the embryo. All
providing consent also should understand that they
may withdraw their consent up to the time that the
donated tissues actually are used in research.
In the scenarios of adults donating gametes for
the creation of embryos solely for research and
adults donating somatic cells for somatic cell
nuclear transfer, special considerations must be
taken into account. The information provided to
donors for embryonic stem cell research must
acknowledge that the process of obtaining the
embryonic stem cell line from the inner cell mass of
the blastocyst will result in the destruction of the
embryo and also should indicate that the derived
stem cell lines may be propagated indefinitely. The
111 COMMITTEE OPINIONS 111
consent process also should cover the same elements
as consent obtained when unused embryos are
donated for research. A woman wishing to donate
oocytes for research must be informed of possible
risks to her in the process of controlled ovarian
hyperstimulation and retrieving oocytes, and egg
donor programs should set up medical and psycho-
logic screening procedures in order to safeguard
potential donors.
May Embryos Be Created for Research?
Many cryopreserved embryos exist in the United
States. When such embryos are appropriate to the
questions under investigation and appropriate con-
sent can be obtained, the ACOG Committee on
Ethics recommends that these embryos be the pre-
ferred resource for research. Not all frozen embryos
are available or appropriate for research, however,
and frozen embryos may not meet all criteria neces-
sary for some therapeutic applications (32). Investi-
gations of specific genetic defects, for example,
may require specific tissues not available in already
frozen embryos, and any future therapies using stem
cells (eg, somatic cell nuclear transfer) by design
may require that embryos and the derived embry-
onic stem cells have a genetic profile identical to
the intended recipient. The Committee on Ethics
believes that the promise of somatic cell nuclear
transfer as a technique to create important and
unique stem cell lines is such that research in this
area is justified, a finding consistent with the prac-
tices of the United Kingdoms Human Fertilisation
and Embryology Authority (33). Furthermore, the
Committee on Ethics can imagine a future day when
the creation of tissues via somatic cell nuclear trans-
fer to be used in the isolation of human stem cell
lines for therapeutic purposes will be possible and
needed; if so, the Committee on Ethics would con-
sider this process to be ethically appropriate.
Although there are no physical differences
between excess embryos from an IVF therapy and
created-for-research embryos, the moral distinc-
tion that many make seems to rest on the intent of
the creation of the embryo, whether for procreation
or research, and the special respect given to human
embryos. An embryo originally created for procre-
ation may be seen to be created for its own sake, as
an end in itself, whereas an embryo created for
research may appear to be a mere means to the
ends of others. For some, the respect given to the
human embryo differentiates the embryo from mere
human tissues or cells and necessitates greater oblig-
ation to justify valid scientific inquiry. Others judge
that the potential benefits of research for societal
health outweigh any limitations conferred by the
respect due to human embryos, whether they are
excess embryos or created for research.
There is a precedent for creation of embryos for
research purposes. The early work in human IVF by
Edwards and colleagues consisted of fertilizing hu-
man oocytes for research in order to study the nor-
mality of the zygotes thus created before transfer to
a woman was even considered (34). In 1994, the
NIH Human Embryo Research Panel approved the
creation of IVF embryos for research when the very
nature of the research itself required the fertilization
of oocytes and when a research project deemed to be
exceptionally important required a particular type of
embryo for its validity. Currently, there is little need
for the creation of embryos by fertilization for
research purposes, but in the future the supply of
available tissues, research questions, or therapeutic
paradigms may change. If a compelling need arises,
the question of creating embryos by fertilization for
use in research will need to be addressed carefully.
Does Experimental or Other Use of Stem Cells
Lend Support to Reproductive Cloning?
In the processes involved, associated risks, and
intended outcomes, work involving stem cells and
cloning for biomedical research with the intent of
developing future therapies (eg, somatic cell nuclear
transfer) may clearly be distinguished from repro-
ductive cloning. The former areas of research and
practice involve the isolation and manipulation of
cells from embryos that are not allowed to progress
past the 14-day stage and are not transferred to the
uterus. Because reproductive cloning is designed to
produce a human being, it raises a distinct set of
issues and concerns, and these are not the focus of
this Committee Opinion. The support expressed in
this Committee Opinion for embryo research and
cloning for research purposes does not imply
endorsement of reproductive cloning, which the
Committee on Ethics opposes.
Guidelines
The Committee on Ethics takes the position that
human embryo research can be justified under cer-
tain conditions. This position is based on an inter-
pretation of the moral status of the embryo as a
COMPENDIUM OF SELECTED PUBLICATIONS 112 112
living entity with a human genetic code, deserving
of some form of respect in itself and not solely for its
usefulness in research. But this position also recog-
nizes the value of the embryo as relative, in the sense
that it does not require the degree of protection and
absolute respect that is accorded human persons. In
other words, the embryo is humannot simply like
other human tissue (for it is genetically unique and
has human potential)but it also is not a human
person.
Risks of harm to the embryo in research can be
justified, but not without limits. Embryos, for exam-
ple, should not be subjected to trivial or poorly
designed research programs; if the embryos are des-
ignated for transfer to a womans uterus, the goals of
successful pregnancy should be given priority; and
the real and symbolic values of the embryo should
not be negated or trivialized. The Committee on
Ethics recommends the following guidelines for
clinical and laboratory research involving human
embryos.
1. Research will be conducted only by scientifi-
cally qualified individuals and in settings that
include appropriate and adequate resources and
protections. The design of the research and each
of its procedures should be clearly formulated in
a research protocol that is submitted to a special-
ly appointed independent committee for evalua-
tion, guidance, and approval.
2. The question to be explored must be scientifical-
ly valid; must take into account scientific work
to date, including animal studies; and cannot be
answered through research on animal embryos
or on unfertilized gametes.
3. The information sought should offer potential
scientific and clinical benefit in areas such as
embryonic development, human reproduction,
chromosomal and genetic conditions, or, for
embryonic stem cell lines, potential disease
therapies.
4. The research will be conducted using embryos
at the earliest possible developmental stage of
the embryo, not to exceed 14 days after evidence
of fertilization in any case.
5. Any embryo that has undergone research will be
transferred to a uterus only if the original
research was undertaken to prepare the embryo
for selection or placement or to improve its
chances for implantation and only if specific
consent for transfer is obtained.
6. Intended parents for whom embryos are created
(embryo donors) should be provided with the
opportunity to provide informed consent as to
the disposition of any excess embryos, whether
for eventual destruction, donation for attempted
implantation by another individual or couple, or
scientific research. This presupposes an explicit
policy on the part of the researchers and their
sponsoring institutions that facilitates communi-
cation of options and provides for informed
donor choice. If gamete donors differ from the
embryo donors, then embryos may be donated
for research only if the gamete donors also have
given explicit consent for donation for research.
7. Those donating excess frozen embryos for
embryonic stem cell research must be adequate-
ly informed of the goals, anticipated benefits,
and potential hazards of the particular research.
Each potential donor is informed that she or he
is at liberty to decline participation in the
research and, until such a point when the tissues
are used or cell lines created, to withdraw con-
sent for research.
8. Other information must be included in informed
consent for donation of embryos for stem cell
research:
Acknowledgment that removal of the inner
cell mass will destroy the embryo
Statement that stem cell lines may continue
indefinitely and be shared with other
researchers
Discussion of potential ownership, patent,
and commercial uses of stem cell lines that
may be developed from the embryo
Information regarding whether any identifiers
will be preserved in the stem cell lines derived
9. For research or therapy involving somatic cell
nuclear transfer, oocyte donors and somatic cell
donors must give informed consent for use of
their eggs or somatic cells. In the rare circum-
stances in which IVF embryos are created for
research, the gamete donors should provide
informed consent for fertilization for research
purposes. In both cases, informed consent
should include points in guideline 8 and clearly
describe the researchers intention to deliber-
ately create a human embryo for research.
10. Special care must be taken to ensure that poten-
tial donors of oocytes for research understand
113 COMMITTEE OPINIONS 113
the procedure and its risks. To safeguard donors
as much as possible, medical and psychologic
screening should be required. Although com-
pensation for egg donors for research is accept-
able, as it is for donors for infertility treatment,
such compensation should be understood to be
compensation for the womans time, effort, risk,
and discomfort and not as payment for the eggs
that may be recovered. The level of compensa-
tion should be consistent with ASRM guidelines
to minimize the possibility of exploitation of
egg donors.
11. Techniques and research designed to clone
human beings raise a different set of ethical con-
cerns. The Committee on Ethics opposes repro-
ductive cloning.
Conclusion
The Committee on Ethics has offered a position that
supports embryo research but limits it according to
ethical guidelines. This position advocates treatment
of the embryo with respect but not the same level of
respect that is given to human persons. It is a posi-
tion that will not be acceptable to those who believe
that full rights should be extended to early-stage
embryos. In arriving at its position, the Committee
on Ethics considered scientific and clinical informa-
tion relevant to ethical analysis, although it recog-
nizes that such consideration necessarily involves
both scientific and ethical interpretation of what can-
not be simply incontrovertible facts.
The Committee on Ethics once again acknowl-
edges that no single position can encompass the
variety of opinions within the membership of
ACOG, and it affirms that no physician should be
required or expected to participate in embryo
research if he or she finds it morally objectionable.
Nonetheless, it is important to public discourse and
to the practice of responsible medicine that physi-
cians become aware of the medical and ethical
issues involved in the complex areas of embryo
research. To advance this discourse, it is helpful for
physicians to reflect on and share the basis of their
own views and to recognize and explore the ethical
perspectives of their patients and colleagues.
References
1. Definitions. 45 CFR 46.202 (2005).
2. U.S. Department of Health, Education, and Welfare. HEW
support of research involving human in vitro fertilization
and embryo transfer. Washington, DC: U.S. Government
Printing Office; 1979.
3. Ethical considerations of the new reproductive technolo-
gies. Ethics Committee of the American Fertility Society.
Fertil Steril 1986;46(suppl 1):1S94S.
4. Ethical considerations of the new reproductive technolo-
gies. Ethics Committee of The American Fertility
Society. Fertil Steril 1990;53(suppl 2):1S104S.
5. Ethical considerations of assisted reproductive technolo-
gies. Ethics Committee of the American Fertility Society.
Fertil Steril 1994;62(suppl 1):1S125S.
6. The Balanced Budget Downpayment Act, I, Pub. L. No
10499, 128, 110 Stat. 34 (1996).
7. National Bioethics Advisory Commission. Ethical issues
in human stem cell research. Rockville (MD): NBAC;
1999.
8. Radio address by the President to the nation. Available at:
http://www.whitehouse.gov/news/releases/2001/08/print/
20010811-1.html. Retrieved March 9, 2006.
9. 42 U.S.C. 289g-1 (2002).
10. Lyerly AD, Steinhauser K, Namey E, Tulsky JA, Cook-
Deegan R, Sugarman J, et al. Factors that affect infertility
patients decisions about frozen embryos. Fertil Steril
2006;85:162330.
11. McCormick RA. Who or what is the preembryo?
Kennedy Inst Ethics J 1991;1:115.
12. Grobstein C. Becoming an individual. In: Science and the
unborn. New York (NY): Basic Books; 1988. p. 2139.
13. Ford NM. When did I begin? Conception of the human
individual in history, philosophy, and science. New York
(NY): Cambridge University Press; 1988.
14. Report from the Select Committee on Stem Cell
Research. House of Lords HL 2002;83(i). Available
at: http://www.publications.parliament.uk/pa/ld200102/
ldselect/ldstem/83/8301.htm. Retrieved June 28, 2006.
15. King PA. Embryo research: the challenge for public pol-
icy. J Med Philos 1997;22:44155.
16. Kukla H. Embryonic stem cell research: an ethical justifi-
cation. Georgetown Law J 2002;90:50343.
17. Green RM. Benefiting from evil: an incipient problem
in human stem cell research. Bioethics 2002;16:54456.
18. Wilcox AJ, Weinberg CR, OConnor JF, Baird DD,
Schlatterer JP, Canfield RE, et al. Incidence of early loss
of pregnancy. N Engl J Med 1988;319:18994.
19. Weissman IL. Stem cellsscientific, medical, and politi-
cal issues. N Engl J Med 2002;346:15769.
20. Porada GA, Porada C, Zanjani ED. The fetal sheep: a
unique model system for assessing the full differentiative
potential of human stem cells. Yonsei Med J 2004;45:
714.
21. Kogler G, Sensken S, Airey JA, Trapp T, Muschen M,
Feldhahn N, et al. A new human somatic stem cell from
placental cord blood with intrinsic pluripotent differenti-
ation potential. J Exp Med 2004;200:12335.
22. The Presidents Council on Bioethics. Alternative sources
of human pluripotent stem cells. A white paper of the
Presidents Council on Bioethics. Washington, DC: The
Presidents Council on Bioethics; 2005. Available at:
ht t p: / / www. bi oet hi cs. gov/ report s/ whi t e_paper/
alternative_sources_white_paper.pdf. Retrieved June 28,
2006.
COMPENDIUM OF SELECTED PUBLICATIONS 114 114
23. Wagers AJ, Weissman IL. Plasticity of adult stem cells.
Cell 2004;116:63948.
24. National Research Council; Institute of Medicine.
Recruiting donors and banking hES cells. In: Guidelines
for human embryonic stem cell research. Washington,
DC: The Institute; 2005. p. 8196.
25. Financial incentives for oocyte donors. The Ethics
Committee of the American Society for Reproductive
Medicine. Fertil Steril 2000;74:21620.
26. Kalfoglou AL, Geller G. A follow-up study with oocyte
donors exploring their experiences, knowledge, and atti-
tudes about the use of their oocytes and the outcome of
the donation. Fertil Steril 2000;74:6607.
27. Klock SC, Sheinin S, Kazer RR. The disposition of
unused frozen embryos. N Engl J Med 2001;345:6970.
28. Lo B, Chou V, Cedars MI, Gates E, Taylor RN, Wagner
RM, et al. Informed consent in human oocyte, embryo,
and embryonic stem cell research. Fertil Steril 2004;82:
55963.
29. Donating spare embryos for embryonic stem-cell
research. Ethics Committee of the American Society for
Reproductive Medicine. Fertil Steril 2004;82(suppl 1):
S2247.
30. Ethics Committee of the American Society for Repro-
ductive Medicine. Disposition of abandoned embryos.
Fertil Steril 2004;82(suppl 1):S253.
31. Wolf SM, Kahn JP. Bioethics matures: the field faces the
future. Hastings Cent Rep 2005;35(4):224.
32. Hoffman DI, Zellman GL, Fair CC, Mayer JF, Zeitz JG,
Gibbons WE, et al. Cryopreserved embryos in the United
States and their availability for research. Society for
Assisted Reproduction Technology (SART) and RAND.
Fertil Steril 2003;79:10639.
33. Human Fertilisation & Embryology Authority. HFEA
grants the first therapeutic cloning licence for research.
Press release. London: HFEA; 2004. Available at:
http://www.hfea.gov.uk/PressOffice/Archive/109223388.
Retrieved June 28, 2006.
34. Edwards RG, Steptoe PC. A matter of life: the story of a
medical breakthrough. London: Hutchinson; 1980.
*Blastocyst: A preimplantation embryo of approximately
150 cells. The blastocyst consists of a sphere made up of an
outer layer of cells (the trophectoderm), a fluid-filled cavity
(the blastocoel), and a cluster of cells on the interior (the
inner cell mass).
Blastomere: The cells derived from the first and subsequent
cell divisions of the zygote.
*Embryo: In humans, the developing organism from the
time of fertilization until the end of the eighth week of ges-
tation, when it becomes known as a fetus. Other ACOG
guidelines address research involving postimplantation
embryos and fetuses (ie, research during pregnancy).
(American College of Obstetricians and Gynecologists.
Research involving women. In: Ethics in obstetrics and
gynecology. 2nd ed. Washington, DC: ACOG; 2004. p.
8691.)
*Embryonic stem cells: Primitive (undifferentiated) cells
from the embryo that have the potential to become a wide
variety of specialized cell types.
Fertilization: The process whereby male and female
gametes unite.
Gametes: Mature reproductive cells, usually having half the
adult chromosome number (ie, sperm or ovum).
Implantation: Attachment of the blastocyst to the endome-
trial lining of the uterus and subsequent embedding in the
endometrium. Implantation begins approximately 57 days
after fertilization and may be complete as early as 89 days
after fertilization.
*Inner cell mass: The cluster of cells inside the blastocyst.
These cells give rise to the embryonic disk of the later
embryo and, ultimately, the fetus.
Oocyte: An immature female reproductive cell, one that has
not completed the maturing process to form an ovum
(gamete).
Pluripotent: Able to differentiate into multiple cell and tis-
sue types.
Preimplantation embryo: In humans, the developing organ-
ism from the time of fertilization until implantation in the
uterus or other tissue (eg, ectopic pregnancy).
Primitive streak: The initial band of cells from which many
tissue systems, including the neural system of the embryo,
begin to develop, located at the caudal end of the embryonic
disc. The primitive streak is present approximately 15 days
after fertilization and marks the axis along which the spinal
cord develops.
Somatic cell nuclear transfer: The transfer of a cell nucle-
us from a somatic cell into an egg from which the nucleus
has been removed.
Stem cells: Undifferentiated multipotent precursor cells that
are capable of perpetuating themselves indefinitely and of
differentiating into specialized types of cells.
Totipotent: Able to differentiate into every cell and tissue
type; the capacity of a cell or group of cells to produce all of
the products of conception: the extra-embryonic membrane
and tissue, the embryo, and, subsequently, the fetus.
Zygote: The single cell formed by the union of the male and
female haploid gametes at syngamy.
*Definitions marked with an asterisk are adapted from the National
Institutes of Health glossary, available at: http://stemcells.nih.gov.
Glossary
115 COMMITTEE OPINIONS 115
Committee on
Ethics
Reaffirmed 2009
ACOG
Number 352, December 2006
Committee
Opinion
Copyright December 2006
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of this
publication may be reproduced,
stored in a retrieval system,
posted on the Internet, or trans-
mitted, in any form or by any
means, electronic, mechanical,
photocopying, recording, or
otherwise, without prior written
permission from the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Innovative practice: ethical guidelines.
ACOG Committee Opinion No. 352.
American College of Obstetricians
and Gynecologists. Obstet Gynecol
2006;108:158995.
Innovative Practice: Ethical
Guidelines
ABSTRACT: Innovations in medical practice are critical to the advancement
of medicine. Good clinicians constantly adapt and modify their clinical
approaches in ways they believe will benefit patients. Innovative practice
frequently is approached very differently from formal research, which is gov-
erned by distinct ethical and regulatory frameworks. Although opinions
differ on the distinction between research and innovative practice, the pro-
duction of generalizable knowledge is one defining characteristic of
research. Physicians considering innovative practice must disclose to
patients the purpose, benefits, and risks of the proposed treatment, including
risks not quantified but plausible. They should attempt an innovative proce-
dure only when familiar with and skilled in its basic components. A clinician
should share results, positive or negative, with colleagues and, when feasi-
ble, teach successful techniques and procedures to other physicians.
Practitioners should be wary of adopting innovative procedures or diagnos-
tic tests on the basis of promotions and marketing when the value of the
procedures or tests has not been proved. A practitioner should move an inno-
vative practice into formal research if the innovation represents a significant
departure from standard practice, if the innovation carries unknown or
potentially significant risks, or if the practitioners goal is to use data from
the innovation to produce generalizable knowledge. If there is any question
whether innovative practices should be formalized as research, clinicians
should seek advice from the relevant institutional review board.
Overview
In 21st-century medicine, the pace at which innovations are introduced into
clinical practice continues to increase. Many innovations differ considerably
from previous practices and may or may not have been subjected to formal
research protocols. In this context, the boundary between innovative practice
and medical research becomes blurred, making it difficult for physicians to
distinguish between them and to recognize the ethical issues that are
involved.
When innovative practices are introduced, they may become widely
accepted based on anecdotal reports of success. As a result, formal research
COMPENDIUM OF SELECTED PUBLICATIONS 116 116
may never be done that might show 1) that the inno-
vative practice carries higher risk than other treat-
ments or 2) that it is no more effective than standard
treatment. An inappropriate introduction of an inno-
vative practice, circumventing the formal study of
the new technique, leaves patients and practitioners
without the necessary data for appropriately assess-
ing an innovations risks and benefits, as well as its
long-term effects on health.
In this Committee Opinion, the Committee on
Ethics will review efforts to distinguish innovative
practice from research, identify ethical concerns
raised by innovative practice, and note current obsta-
cles to the conduct of formal research. Recommen-
dations will focus on two questions: 1) When does
the clinician have an obligation to subject an innov-
ative practice to formal research? 2) In situations
where innovative practice is not regulated as
research, what special ethical obligations might the
clinician haveto patients, to the community of
medical professionals, and to society at large?
Distinguishing Innovative Practice From
Research
In clinical practice, physicians aim to benefit their
patients by providing the best possible procedures
and treatments. The desire to improve currently
available practices has given an important impetus to
the development of new medical knowledge. The
notion of what is best or most appropriate evolves
with time, ongoing research, and changing individ-
ual and societal values. Good clinicians constantly
adapt and modify their clinical approaches in ways
they believe will benefit patients. The introduction of
such innovative interventions is guided primarily by
the judgment of the individual physician, although
professional organizations often advise and monitor.
Formal research, however, is highly regulated in
the United States. Research protocols involving
human participants must be described in detail and
submitted to an institutional review board (IRB) for
approval. Federal regulations mandate that IRBs
approve research protocols in order to ensure ade-
quate disclosure to potential participants, informed
consent from participants, appropriate riskbenefit
ratio, protection of participants privacy, and free-
dom of participants to withdraw from the study at
any time.
Innovative practice has elements in common
with research including, for example, the desire to
learn and to improve treatment. Yet, innovation in
practice frequently is approached very differently
from formal research, which is governed by distinct
ethical and regulatory frameworks. The federal
research regulations as expressed in the Common
Rule draw a sharp distinction between research, which
is regulated, and innovation, which is not, stressing the
production of generalizable knowledgeknowledge
that can be applied beyond the particular individuals
studiedas the defining characteristic of research
(1). However, the distinction is somewhat artificial
and is not always clearly delineated.
An innovative practice may later become the
subject of a formal research protocol, with the
results of this research then applied to guide evi-
dence-based practice. In some cases, however, inno-
vative practice that appears to be safe and effective
may become accepted practice, even if it has never
been subjected to formal research and an evidence
base has never been developed to support efficacy
and safety. When this happens, patients and practi-
tioners are left without the data they need to make
adequately informed decisions.
Background: History and Evolution of
Terminology
It often is difficult to draw a clear line between inno-
vative practice and research. The history of research
regulation illuminates the effort to clarify the dis-
tinction.
The National Commission for the Protection of
Human Subjects, established by federal statute in
1975, developed the Belmont Report in 1978 to
identify the basic ethical principles governing
human research (2). In defining research, the
National Commission first distinguished it from
the practice of accepted therapy. However, exam-
ples proposed to the National Commission led it to
recognize that much practice is experimental (a term
the American College of Obstetricians and
Gynecologists Committee on Ethics interprets as
congruent with the term innovative), even though it
is not formalized as research. Should all such exper-
imental practice be treated as research and governed
by the ethical and regulatory guidelines for
research? The National Commission decided
against taking this position and adopted a narrower
definition of research, concluding that research
occurs when the clinician or investigator intends the
work to result in generalizable knowledge (2).
117 COMMITTEE OPINIONS 117
According to the National Commission,
Research designates an activity designed to test a
hypothesis, permit conclusions to be drawn, and
thereby to contribute to generalizable knowledge
rather than being designed solely to enhance the
well-being of an individual patient or client (2).
The fact that activities designed to enhance patient
well-being may depart significantly from standard
or accepted practice does not of itself make them
research. However, the National Commission
strongly urged that radically new procedures be
tested by formal research at an early stage and that
medical practice committees insist that new tech-
niques and treatments be submitted to formal
hypothesis testing. The National Commission did
not, however, define radically new, leaving its
definition to the judgment of practitioners.
Federal research regulations in effect since 1981
incorporate these concepts to a limited degree, defin-
ing research as follows: Research means a system-
atic investigation, including research development,
testing and evaluation, designed to develop or con-
tribute to generalizable knowledge (3). The pream-
ble to the regulations as finalized in 1981 explicitly
states that the definition is restricted to generaliz-
able knowledge because the regulations were not
intended to encompass innovative therapy (4).
In March 2003, the Lasker Foundation, a chari-
table trust established to promote advances in medi-
cine, sponsored the invitational Lasker Forum on
Ethical Challenges in Biomedical Research and
Practice. The forum focused on the intersection of
research and practice and questioned the artificial
separation between what is called research and
therefore requires more regulatory oversight, and
what is called care and requires little or none (5).
The report on the Lasker Forum proposed that clini-
cal innovation involving a significant departure from
standard of care imposes particular moral duties on
the practitioner. In the view expressed at the forum,
a practitioner who attempts through innovation to
benefit an individual patient also is morally obligat-
ed to facilitate the development of knowledge useful
to other physicians and patients, thus suggesting an
obligation to conduct research on the innovative
practice.
The Lasker Forum report proposed criteria for
identifying the ethical threshold that mandates mov-
ing from innovative practice to formal research. In
this view, the most important criterion is the degree
of departure from standard practice, followed by the
potential for harm to the patient from the innovative
practice. Other criteria proposed for consideration
are the goal of the clinician investigator, the avail-
ability of organizational structures supportive of
research, and the presence of commercial interests
or conflict of interest (5). These considerations will
be discussed more fully after examination of specif-
ic ethical concerns related to the introduction of
innovative practices.
Ethical Concerns Regarding Innovative
Practice
A variety of problems may arise when innovative
practices are inappropriately introduced apart from
formal research protocols. These problems often have
ethical implications related to patient safety, patient
autonomy, and the patients right to effective therapy:
Premature adoption of innovative practices
without adequate supporting evidence may pro-
mote wide acceptance of therapies that are
ineffective. Examples of procedures that have
been proved ineffective include:
Bed rest or home uterine activity monitoring
for prevention of prematurity (6, 7)
Bone marrow transplant for breast cancer (8)
Diethylstilbestrol or paternal antigen sensiti-
zation for the prevention of recurrent miscar-
riage
From an ethical perspective, recommending
procedures that are not effective for the intend-
ed purpose is misleading to patients, incurs
increased unnecessary costs both financial and
personal, and violates the patients autonomy-
based right to consent to therapy after accurate
disclosure. In addition, an unproven innovative
treatment may carry additional risks or morbid-
ity in comparison with standard treatment, as in
the case of bone marrow transplant for breast
cancer.
Premature adoption of innovative practices
without formal scientific testing may compro-
mise the ability to determine effectiveness,
weigh risk against benefit, compare the practice
with other procedures, or develop alternative
approaches. When results of an innovative prac-
tice are publicized without adequate testing, it
may become increasingly difficult to recruit par-
ticipants for a clinical trial, particularly one that
COMPENDIUM OF SELECTED PUBLICATIONS 118 118
involves randomization. Such may have been
the case when techniques for maternalfetal
surgery, electronic fetal monitoring, and laparo-
scopic hysterectomy were first introduced as
innovative and only later systematically studied.
When innovative practices are widely adopted
without formal research testing, an incremental
risk over standard practice may not be recog-
nized, and relative effectiveness, safety, and
riskbenefit ratio may never be determined.
Such a situation may make it difficult or impos-
sible for physicians to know if they are fulfilling
their obligation to provide safe and efficacious
treatment to patients (9).
Long-term safety concerns may result when
innovative practices are widely adopted as stan-
dard practice without adequate scientific testing.
Examples in which careful, continued study
after a techniques introduction demonstrated
small but potentially important risks include:
Limb reductions associated with early chori-
onic villus sampling (10, 11)
Sex chromosome abnormalities associated
with intracytoplasmic sperm injection used in
assisted reproductive technology (ART) (12,
13)
Although innovations in obstetrics and ART
offer important benefits to prospective parents,
they also may carry long-term risks that are not
recognized unless formal research is carried out.
Because of their eagerness to become parents,
infertile couples may be willing to overlook risks
involved in the use of ART. It is the responsibil-
ity of practitioners to carry out the studies that
are needed to ensure that patients are offered
effective and safe procedures. Appropriately,
many ART centers and practitioners have partic-
ipated in the ongoing registries and collabora-
tions needed for this research.
Research Barriers to Be Overcome
Medicine cannot advance without innovation.
Recent examples of highly valuable innovations
include new efficient laparoscopic components that
may improve visualization and new laparoscopic
procedures, such as laparoscopic retroperitoneal
lymph node dissection, that may speed or otherwise
facilitate closed surgical procedures. This could
reduce the need for open procedures that may be
associated with longer or more complicated post-
operative recovery. At times, it may be appropriate to
introduce an innovative technique apart from a for-
mal research protocol. However, both the National
Commission for the Protection of Human Subjects
and the National Bioethics Advisory Commission
stipulate that innovations in clinical practice should
be studied under a research protocol as soon as it is
appropriate to study them systematically (2, 14).
A number of barriers to the conduct of formal
research exist, with some of them specific to partic-
ular subspecialties:
1. Lack of supportive structures. In many clinical
situations, the structures to facilitate research,
such as administrative support and an IRB, may
be lacking. Even if a particular innovation is ripe
for formalization as research, research may be
difficult to accomplish without the necessary
supportive structures. Bureaucratic obstacles
may be cited as an excuse for not conducting
research; however, such obstacles do not pro-
vide valid reasons for failure to conduct appro-
priate research under ethical guidelines. Rather,
clinicians ought to advocate changes in policy
and collaborative efforts that will provide neces-
sary support for research.
2. Absence of financial reimbursement. In addition
to the lack of supportive structures, financial
pressures may inhibit the pursuit of appropriate
research. Insurance coverage may be available
for treatment that is described as innovative
therapy, but not for formal research. This reim-
bursement situation played a role in the promo-
tion of the untested procedure of bone marrow
transplant for breast cancer, for example (15).
3. Lack of oversight for surgical innovation and
research. The absence of regulations that specif-
ically govern surgical innovation and research
has frequently been noted. Proposals have been
suggested to ensure oversight of surgical inno-
vation when formal research is not planned, for
example, submission of a written plan to the
department head for referral to an ad hoc com-
mittee. This committee would provide peer
review of medical and scientific plausibility,
the adequacy of patient safeguards, and the
legitimacy of [the] clinical rationale (16).
4. Prohibition of federal funding for ART and
embryo research. Because of the statutory pro-
119 COMMITTEE OPINIONS 119
hibition of federal funding for in vitro fertiliza-
tion and early embryo research, most research on
ART is privately funded and is conducted within
the practice of clinical infertility treatment.
Hence, it may be difficult to obtain funding for
some types of research on ART, particularly
basic research.
Clinical Decisions on Moving From
Innovation to Research
The field of medicine could neither progress nor be
practiced without innovative therapy. Given the
importance of formal research for evidence-based
medicine, however, the medical community must
determine when an innovative practice should be
subjected to formal research. If there is any question
whether an innovation should be formalized as
research, it is advisable that the protocol be submit-
ted to an IRB for review. From an ethical standpoint,
the following considerations offer guidance and cri-
teria to the clinician for a decision to move from
innovation to formal research (5):
The degree of departure from standard practice.
As recommended by the Lasker Forum, if inno-
vation constitutes a significant departure from
standard practice, the innovative procedure
should quickly be subjected to a formal research
protocol. Significant departure from standard
practice occurs, for example, in most
maternalfetal surgery and many new ART tech-
niques. However, minor modifications, such as a
change in a step during surgery, a different kind
of suture, or a new instrument similar to an old
one, clearly do not require formalization as
research.
The potential for harm to the patient. When an
innovation carries risks that are unknown or that
may be significant in proportion to expected
benefits, its safety should be assessed through a
formal research protocol with the oversight of
an IRB, one of whose primary purposes is to
protect the welfare of participants. In addition,
formal research is essential in order to identify
long-term risks that may affect the safety of
large numbers of patients in the future.
The intent of the physician. The original intent
in an innovation may be solely the welfare of the
individual patient. If the physician intends, how-
ever, to eventually use results of a trial of the
innovation to produce generalizable knowledge,
the trial should be formalized in a research pro-
tocol. Valid generalizable knowledge ordinarily
requires randomized clinical trials rather than
reliance on case series and unplanned observa-
tions (17).
Special Ethical Requirements for
Innovative Practice
Duties to Patients
When patients become participants in a formal
research project, they become protected by the fed-
eral regulations for research involving human partic-
ipants. Even when a particular project does not
strictly fall under federal regulations because it does
not involve federal funding or oversight by the U.S.
Food and Drug Administration, most institutions
still comply with federal standards. Also, reputable
journals require compliance with ethical guidelines
as a condition for publication. Access to results of
clinical trials, even trials with negative outcomes, is
protected by the clinical trials registration process
(1820). Many journals now require evidence that
trials were previously registered before accepting
reports for consideration for publication.
The same protections do not hold for a patient
who is offered innovative therapy. Although the
intent of such innovation is to provide the most ben-
eficial treatment possible for the patient, the patient
may not realize that a therapy is new or experimen-
tal. The practitioner has the obligation to disclose
information that would be material to the patients
decision, and in many cases, a patient would want to
know that a proposed therapy is innovative. As with
all therapies, the practitioner has the obligation to
disclose the purpose, benefits, and risks of the pro-
posed innovative treatment, including not quantified
but plausible risks. In addition, the practitioner has a
particular obligation to protect the patient from
potential harms that are not proportionate to expect-
ed benefits, a role that the IRB assumes with respect
to formal research protocols. To minimize risk,
physicians also need to consider their own knowl-
edge and skill levels and should attempt an innova-
tive procedure only when familiar with and skilled
in its basic components.
Patient protection requires transparent commu-
nication. In the words of the Lasker Forum report,
Where innovation is clearly present, the require-
COMPENDIUM OF SELECTED PUBLICATIONS 120 120
ments for disclosure are likely to become more
pressing (5). It may be important to the patient to
know how often this procedure has been done, what
this particular physicians experience with the proce-
dure is, and what is known and unknown about pos-
sible adverse events and long-term sequelae. Care
should be taken that a patient is not unduly influ-
enced to consent to an innovative procedure solely
out of deference to her physician. When the advan-
tages and disadvantages of a truly new approach are
explained to the patient, the assistance of an experi-
enced third-party communicator, such as a patient
representative or social worker, may be helpful (5).
Particular care is needed when discussing proposed
treatments with vulnerable or possibly desperate
patients because they may be eager to pursue innov-
ative but unproven procedures or treatments.
Duties to the Profession and to Society
Innovative practice, unlike research, is not directed
specifically toward the production of generalized
knowledge. Yet, it is expected that innovation would
lead to the improvement of practice in general, not
just the practice of an individual physician. This
expectation imposes two duties on the physician: 1)
to structure the process of innovation so as to learn
from it, even if it is not as successful as hoped, and
2) to share what is learned with the medical commu-
nity as a whole and, where appropriate, with society.
A clinician should share results, positive or negative,
with colleagues and, when feasible, cooperate in
teaching successful techniques and procedures to
other physicians.
Current focus on clinical trials, especially ran-
domized clinical trials, suggests that they ordinarily
provide the best opportunity for unbiased learning
within the practice of medicine. Consequently, inno-
vative practice should move toward clinical trials
whenever possible in order to provide evidence-
based knowledge to the medical community for the
welfare of patients.
Practitioners need to be careful not to adopt
innovative procedures or diagnostic tests on the
basis of promotional and marketing campaigns
when the value of such procedures and tests has not
yet been proved. For example, serum-based screen-
ing tests for ovarian cancer have been promoted
even though more research is needed to determine
whether they are effective (21, 22). Similar cautions
apply to off-label and unproven uses of pharmaceu-
ticals that may be suggested to physicians. In all
cases, physicians should rely on documented evi-
dence to guide clinical practice.
Summary
The introduction of innovative practices and tech-
niques is essential to medical progress. Ordinarily,
however, innovations should be subjected to system-
atic formal research as soon as feasible:
In the absence of formal research, innovative
practices may become widely accepted without
adequate data for assessing risks and benefits.
Without an adequate evidence base, practition-
ers cannot determine whether an innovative
technique is the most safe and effective method
for treating a patient.
Without adequate data on the risks and benefits
of new treatments, patients are unable to provide
a true informed consent.
A practitioner should move an innovative prac-
tice into formal research when one of these criteria
is satisfied:
The innovation represents a significant depar-
ture from standard practice.
The innovation carries risks that are unknown or
that may be significant in proportion to expect-
ed benefits.
The introduction of the innovation is expected
to result in generalizable knowledge, which de-
pends on results of formal clinical trials.
References
1. Protection of human subjects. 45 CFR 46 (2005).
2. National Commission for the Protection of Human
Subjects. Belmont report: ethical principles and guide-
lines for the protection of human subjects of research. Fed
Regist 1979;44:231927.
3. Definitions. 45 CFR 46.102 (2005).
4. Final regulations amending basic HHS policy for the
protection of human research subjects. U.S. Department
of Health and Human Services. Fed Regist 1981;46:
836691.
5. Lasker Foundation. The Lasker Forum on Ethical
Challenges in Biomedical Research and Practice, May
1416, 2003. New York (NY): Lasker Foundation; 2003.
Available at: http://www.laskerfoundation.org/ethics/ethics_
report.html. Retrieved June 28, 2006.
6. Sosa C, Althabe F, Belizn J, Bergel E. Bed rest in single-
ton pregnancies for preventing preterm birth. Cochrane
Database of Systematic Reviews 2004, Issue 1. Art. No.:
CD003581. DOI: 10.1002/14651858.CD003581.pub2.
121 COMMITTEE OPINIONS 121
7. Assessment of risk factors for preterm birth. ACOG
Practice Bulletin No. 31. American College of Obstetricians
and Gynecologists. Obstet Gynecol 2001;98:70916.
8. Farquhar C, Marjoribanks J, Basser R, Lethaby A. High
dose chemotherapy and autologous bone marrow or stem
cell transplantation versus conventional chemotherapy for
women with early poor prognosis breast cancer. Cochrane
Database of Systematic Reviews 2005, Issue 3. Art. No.:
CD003139. DOI: 10.1002/14651858.CD003139.pub2.
9. Mayer M. When clinical trials are compromised: a per-
spective from a patient advocate. PLoS Med 2005;
2(11):e358. Available at: http://medicine.plosjournals.
org/archive/1549-1676/2/11/pdf/10.1371_journal.pmed.
0020358-L.pdf. Retrieved June 28, 2006.
10. World Health Organization Regional Office for Europe
(WHO/EURO). Risk evaluation of chorionic villus sam-
pling (CVS): report on a meeting. Copenhagen: WHO/
EURO; 1992. (WHO/EURO document EUR/ICP/MCH
123).
11. Kuliev AM, Modell B, Jackson L, Simpson JL, Brambati
B, Froster U, et al. Risk evaluation of CVS. Prenat Diagn
1993;13:197209.
12. Rimm AA, Katayama AC, Diaz M, Katayama KP. A meta-
analysis of controlled studies comparing major malforma-
tion rates in IVF and ICSI infants with naturally conceived
children. J Assisted Reprod Genet 2004;21:43743.
13. Perinatal risks associated with assisted reproductive tech-
nology. ACOG Committee Opinion No. 324. American
College of Obstetricians and Gynecologists. Obstet
Gynecol 2005;106:11436.
14. National Bioethics Advisory Commission. Ethical and
policy issues in research involving human participants:
report and recommendations of the National Bioethics
Advisory Commission. Bethesda (MD): NBAC; 2001.
15. Mello MM, Brennan TA. The controversy over high-dose
chemotherapy with autologous bone marrow transplant
for breast cancer. Health Aff (Millwood) 2001;20:10117.
16. Jones JW, McCullough LB, Richman BW. The ethics of
innovative surgical approaches for well-established proce-
dures. J Vasc Surg 2004;40:199201.
17. Horton R. Surgical research or comic opera: questions,
but few answers [letter]. Lancet 1996;347:9845.
18. DeAngelis C, Drazen JM, Frizelle FA, Haug C, Horton R,
Kotzin S, et al. Clinical trial registration: a statement from
the International Committee of Medical Journal Editors.
International Committee of Medical Journal Editors [edi-
torial]. Lancet 2004;364:9112.
19. Mayor S. Drug companies agree to make clinical trial
results public [news]. BMJ 2005;330:109.
20. DeAngelis C, Drazen JM, Frizelle FA, Haug C, Hoey J,
Horton R, et al. Is this clinical trial fully registered? A
statement from the International Committee of Medical
Journal Editors. Ann Intern Med 2005;143:1468.
21. American College of Obstetricians and Gynecologists,
Committee on Gynecologic Practice. Position regarding
OvaCheck
TM
, February 25, 2005.
22. Petricoin EF, Ardekani AM, Hitt BA, Levine PJ, Fusaro
VA, Steinberg SM, et al. Use of proteomic patterns in
serum to identify ovarian cancer. Lancet 2002;359:5727.
COMPENDIUM OF SELECTED PUBLICATIONS 122 122
Professional Responsibilities in
ObstetricGynecologic Education*
ABSTRACT: Physicians must learn new skills in a manner consistent with their eth-
ical obligations to benefit the patient, to do no harm, and to respect a patients right to
make informed decisions. Patients should be given the opportunity to consent to or
refuse treatment by students. Students must hold in confidence any information they
learn about patients. The relationship between teacher and student involves an imbalance
of power and the risk of exploitation of a student for the benefit of the teacher. Students
should not be placed in situations where they must provide care or perform procedures
for which they are not qualified and not adequately supervised. Students have the oblig-
ation to be honest, conscientious, and respectful in their relationships with their teachers.
They should act in ways that preserve the dignity of patients and do not undermine rela-
tionships between patients and their physicians. If a student observes unethical behavior
or incompetent conduct by a teacher, the appropriate institutional authority should be
informed. Institutions have an obligation to provide a work environment that enhances
professional competence by ensuring that students and residents work reasonable hours,
helping them balance education and patient care responsibilities; providing adequate sup-
port services; and, in the case of residents, providing reasonable salaries and benefits.
With increasing numbers of women in education programs, special attention must be
given to the parallel demands of pregnancy and career goals.
Committee on Ethics
Number 358 January 2007
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Education of health care professionals is
essential to maintain standards of competent
and beneficial practice. Inherent in the edu-
cation of health professionals is the problem
of disparity in power and authority, includ-
ing the power of teachers over students and
the power of practitioners over patients
(1).
It is therefore important to clarify both the
professional responsibilities to those patients
whose care provides educational opportuni-
ties and the responsibilities of teachers and
students toward one another. Students in the
context of this Committee Opinion include
both medical students and residents. How-
ever, residents have a dual responsibility as
teacher and student and must be aware of
that in understanding their ethical responsi-
bilities to the students they teach and the
patients they care for.
Ethical Responsibilities Toward
Patients in Educational Settings
At the turn of the 20th century, some medical
educators were concerned about the needs of
*Update of ObstetricGynecologic Education, in Ethics
in Obstetrics and Gynecology, Second Edition, 2004.
Basic HHS policy for protection of human research subjects. 45 C.F.R. 46.101124 Subpart A (2006).
175 COMMITTEE OPINIONS 175
for comparison should be that of the general population
or that of the participant. Using the participants daily life
as the standard might make a higher level of risk accept-
able; therefore, the general population standard is advised
(10). Anything beyond minimal risk must be weighed
carefully against the potential benefits to the woman and
the fetus when the advisability of participation is consid-
ered. When a pregnancy has been exposed to risk in the
conduct of research, the woman should be strongly
encouraged to participate in follow-up evaluations to
assess the impact on her and her fetus or child.
It is appropriate for investigators and sponsors, with
the approval of the IRB, to require a negative pregnancy
test result as a criterion for participation in research when
the research may pose more than minimal risk to the
fetus. For an adolescent, the process of informed consent
should include a discussion about pregnancy testing and
the management of pregnancy test results, including
whether the results will be shared with her parents or
guardian.
Similarly, it is reasonable for investigators and
research sponsors, with the IRBs approval, to require the
use of effective birth control measures for women of
reproductive capacity as an inclusion criterion for partici-
pation in research that may entail more than minimal risk
to the fetus. Consultation with an obstetriciangynecolo-
gist or other knowledgeable professional is encouraged if
questions arise about efficacy and risk of contraceptive
measures.
Some study protocols mandate use of a specific con-
traceptive method, such as oral contraceptives or an
intrauterine device. These mandates are inappropriate
based on the principles of respect for autonomy, benefi-
cence, and justice. A woman should be allowed to choose
a birth control method, including abstinence, according
to her needs and values (16). Requiring birth control use
by women who are not sexually active violates a commit-
ment to respect them as persons. Hormonal contraceptive
methods that could interfere with study results may be
excluded on scientific grounds, but additional restrictions
are inappropriate.
After informed discussion about the research trial,
some women will decline to participate. Researchers
should respect this decision and not allow patient refusal
to affect subsequent clinical care. Reasonable compensa-
tion for a womans time, effort, and expense as a partici-
pant in a research study is both acceptable and desired,
but researchers should not offer inducements, financial or
otherwise, to influence participation in research beyond
reasonable compensation for the womans time, effort,
and expense.
Recommendations of the Committee
on Ethics
Federal and state laws and regulations governing research
involving women should be observed (2, 5, 11). In addi-
tion, the Committee on Ethics makes the following rec-
ommendations for research involving women:
1. Women should be presumed to be eligible for partic-
ipation in all clinical studies except for those address-
ing health concerns solely relevant to men.
2. Women should be included in research in sufficient
numbers to ensure that inferences from a clinical
trial apply validly to both sexes.
3. All research on women should be conducted in a man-
ner consistent with the following ethical principles:
Research should conform to general scientific stan-
dards for valid research.
Research may be conducted only with the informed
consent of the woman.
Researchers should not offer inducements, financial
or otherwise, to influence participation in research
beyond reasonable compensation for the womans
time, effort, and expense.
Conscientious efforts should be made to avoid
any conflicts between appropriate health care and
research objectives. Health care needs of the indi-
vidual woman should take precedence over research
interests in all situations affecting clinical man-
agement.
4. Research involving pregnant women should conform
to the following recommendations:
Research may be conducted only with the informed
consent of the woman. Pregnant women consider-
ing participation in a research study should deter-
mine the extent to which the father is to be
involved in the process of informed consent and
the decision.
Informed consent of the father must be obtained
when federal regulations require it for research that
has the prospect of direct benefit to the fetus alone.
Research protocols should be evaluated for their
potential impact on both the woman and the fetus,
and that evaluation should be made as part of the
process of informed consent.
In this Committee Opinion, an attempt has been
made to take into account protection of human partici-
pants, the eligibility of women to participate in research,
and the benefits that society could derive from participa-
tion of women in research. These potential benefits include
reduction in morbidity and mortality from sex-specific
disease processes, as well as reduction in fetal, infant, and
maternal morbidity and mortality.
References
1. National Institutes of Health. NIH policy and guidelines on
the inclusion of women and minorities as subjects in clini-
cal research Amended, October, 2001. Bethesda (MD):
NIH; 2001. Available at http://grants.nih.gov/grants/
funding/women_min/guidelines_amended_10_2001.htm.
Retrieved May 1, 2007.
COMPENDIUM OF SELECTED PUBLICATIONS 176 176
2. Protection of human subjects. 45 C.F.R. 46 (2006).
3. National Commission for the Protection of Human
Subjects of Biomedical and Behavioral Research (US). The
Belmont Report: ethical principles and guidelines for the
protection of human subjects of research. Washington, DC:
U.S. Government Printing Office; 1979. Available at:
http://www.hhs.gov/ohrp/humansubjects/guidance/
belmont.htm. Retrieved May 1, 2007.
4. World Medical Association. Declaration of Helsinki: Ethical
principles for medical research involving human subjects.
Ferney-Voltaire (France): WMA; 2004. Available at: http://
www.wma.net/e/policy/pdf/17c.pdf. Retrieved May 1, 2007.
5. Additional protections for pregnant women, human fetus-
es and neonates involved in research. 45 C.F.R. 46.201-
207 Subpart B (2006).
6. Research on transplantation of fetal tissue. Informed con-
sent of donor. 42 U.S.C. 289g-1(b) (2000).
7. Beauchamp TL. The intersection of research and practice.
In: Goldworth A, Silverman W, Stevenson DK, Young EW,
Rivers R. Ethics and perinatology. New York (NY): Oxford
University Press; 1995. p. 23144.
8. Innovative practice: ethical guidelines. ACOG Committee
Opinion No. 352. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2006;108:158995.
9. NIH Revitalization Act of 1993, Pub. L. No. 103-43 (1993).
10. National Bioethics Advisory Commission. Ethical and pol-
icy issues in research involving human participants.
Bethesda (MD): NBAC; 2001. Available at: http://www.
georgetown.edu/research/nrcbl/nbac/human/overvol1.pdf.
Retrieved May 1, 2007.
11. Additional protections for children involved as subjects in
research. 45 C.F.R. 46.401409 Subpart D (2006).
12. General requirements for informed consent. 45 CFR
46.116 (2006).
13. Institute of Medicine (US). Women and health research:
ethical and legal issues of including women in clinical stud-
ies. Vol. 1. Washington, DC: National Academy Press; 1994.
14. Appelbaum PS, Roth LH, Lidz CW, Benson P, Winslade W.
False hopes and best data: consent to research and the ther-
apeutic misconception. Hastings Cent Rep 1987;17(2):
204.
15. Definitions. 45 C.F.R. 46.102 (2006).
16. Anderson JR, Schonfeld TL, Kelso TK, Prentice ED. Women
in early phase trials: an IRBs deliberations. IRB 2003;25
(4):711.
Copyright September 2007 by the American College of Obstet-
ricians and Gynecologists, 409 12th Street, SW, PO Box 96920,
Washington, DC 20090-6920. All rights reserved. No part of this pub-
lication may be reproduced, stored in a retrieval system, posted on
the Internet, or transmitted, in any form or by any means, electronic,
mechanical, photocopying, recording, or otherwise, without prior writ-
ten permission from the publisher. Requests for authorization to make
photocopies should be directed to: Copyright Clearance Center, 222
Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
Research involving women. ACOG Committee Opinion No. 377.
American College of Obstetricians and Gynecologists. Obstet Gynecol
2007;110:7316.
ISSN 1074-861X
177 COMMITTEE OPINIONS 177
Committee on
Ethics
Number 385 November 2007
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
The Limits of Conscientious Refusal in
Reproductive Medicine
ABSTRACT: Health care providers occasionally may find that providing indicated,
even standard, care would present for them a personal moral problema conflict of con-
scienceparticularly in the field of reproductive medicine. Although respect for con-
science is important, conscientious refusals should be limited if they constitute an
imposition of religious or moral beliefs on patients, negatively affect a patients health,
are based on scientific misinformation, or create or reinforce racial or socioeconomic
inequalities. Conscientious refusals that conflict with patient well-being should be accom-
modated only if the primary duty to the patient can be fulfilled. All health care providers
must provide accurate and unbiased information so that patients can make informed deci-
sions. Where conscience implores physicians to deviate from standard practices, they
must provide potential patients with accurate and prior notice of their personal moral com-
mitments. Physicians and other health care providers have the duty to refer patients in a
timely manner to other providers if they do not feel that they can in conscience provide
the standard reproductive services that patients request. In resource-poor areas, access
to safe and legal reproductive services should be maintained. Providers with moral or reli-
gious objections should either practice in proximity to individuals who do not share their
views or ensure that referral processes are in place. In an emergency in which referral is
not possible or might negatively have an impact on a patients physical or mental health,
providers have an obligation to provide medically indicated and requested care.
Physicians and other providers may not
always agree with the decisions patients make
about their own health and health care. Such
differences are expectedand, indeed,
underlie the American model of informed
consent and respect for patient autonomy.
Occasionally, however, providers anticipate
that providing indicated, even standard, care
would present for them a personal moral
problema conflict of conscience. In such
cases, some providers claim a right to refuse
to provide certain services, refuse to refer
patients to another provider for these ser-
vices, or even decline to inform patients of
their existing options (1).
Conscientious refusals have been partic-
ularly widespread in the arena of reproduc-
tive medicine, in which there are deep
divisions regarding the moral acceptability of
pregnancy termination and contraception. In
Texas, for example, a pharmacist rejected a
rape victims prescription for emergency
contraception, arguing that dispensing the
medication was a violation of morals (2).
In Virginia, a 42-year-old mother of two was
refused a prescription for emergency contra-
ception, became pregnant, and ultimately
underwent an abortion she tried to prevent
by requesting emergency contraception (3).
In California, a physician refused to perform
intrauterine insemination for a lesbian cou-
ple, prompted by religious beliefs and disap-
proval of lesbians having children (4). In
Nebraska, a 19-year-old woman with a life-
threatening pulmonary embolism at 10 weeks
of gestation was refused a first-trimester preg-
nancy termination when admitted to a reli-
giously affiliated hospital and was ultimately
transferred by ambulance to another facility
to undergo the procedure (5). At the heart of
each of these examples of refusal is a claim of
consciencea claim that to provide certain
services would compromise the moral
integrity of a provider or institution.
ACOG COMMITTEE OPINION
COMPENDIUM OF SELECTED PUBLICATIONS 178 178
In this opinion, the American College of Obste-
tricians and Gynecologists (ACOG) Committee on Ethics
considers the issues raised by conscientious refusals in
reproductive medicine and outlines a framework for
defining the ethically appropriate limits of conscientious
refusal in reproductive health contexts. The committee
begins by offering a definition of conscience and describ-
ing what might constitute an authentic claim of con-
science. Next, it discusses the limits of conscientious
refusals, describing how claims of conscience should be
weighed in the context of other values critical to the eth-
ical provision of health care. It then outlines options for
public policy regarding conscientious refusals in repro-
ductive medicine. Finally, the committee proposes a series
of recommendations that maximize accommodation of
an individuals religious or moral beliefs while avoiding
imposition of these beliefs on others or interfering with
the safe, timely, and financially feasible access to repro-
ductive health care that all women deserve.
Defining Conscience
In this effort to reconcile the sometimes competing
demands of religious or moral freedom and reproductive
rights, it is important to characterize what is meant by
conscience. Conscience has been defined as the private,
constant, ethically attuned part of the human character. It
operates as an internal sanction that comes into play
through critical reflection about a certain action or inac-
tion (6). An appeal to conscience would express a senti-
ment such as If I were to do x, I could not live with
myself/I would hate myself/I wouldnt be able to sleep at
night. According to this definition, not to act in accor-
dance with ones conscience is to betray oneselfto risk
personal wholeness or identity. Thus, what is taken seri-
ously and is the specific focus of this document is not sim-
ply a broad claim to provider autonomy (7), but rather the
particular claim to a providers right to protect his or her
moral integrityto uphold the soundness, reliability,
wholeness and integration of [ones] moral character (8).
Personal conscience, so conceived, is not merely a
source of potential conflict. Rather, it has a critical and
useful place in the practice of medicine. In many cases, it
can foster thoughtful, effective, and humane care. Ethical
decision making in medicine often touches on individu-
als deepest identity-conferring beliefs about the nature
and meaning of creating and sustaining life (9). Yet, con-
science also may conflict with professional and ethical
standards and result in inefficiency, adverse outcomes,
violation of patients rights, and erosion of trust if, for
example, ones conscience limits the information or care
provided to a patient. Finding a balance between respect
for conscience and other important values is critical to
the ethical practice of medicine.
In some circumstances, respect for conscience must
be weighed against respect for particular social values.
Challenges to a health care professionals integrity may
occur when a practitioner feels that actions required by an
external authority violate the goals of medicine and his or
her fiduciary obligations to the patient. Established clini-
cal norms may come into conflict with guidelines imposed
by law, regulation, or public policy. For example, policies
that mandate physician reporting of undocumented
patients to immigration authorities conflict with norms
such as privacy and confidentiality and the primary prin-
ciple of nonmaleficence that govern the providerpatient
relationship (10). Such challenges to integrity can result in
considerable moral distress for providers and are best met
through organized advocacy on the part of professional
organizations (11, 12). When threats to patient well-being
and the health care professionals integrity are at issue,
some individual providers find a conscience-based refusal
to comply with policies and acceptance of any associated
professional and personal consequences to be the only
morally tenable course of action (10).
Claims of conscience are not always genuine. They
may mask distaste for certain procedures, discriminatory
attitudes, or other self-interested motives (13). Providers
who decide not to perform abortions primarily because
they find the procedure unpleasant or because they fear
criticism from those in society who advocate against it do
not have a genuine claim of conscience. Nor do providers
who refuse to provide care for individuals because of fear
of disease transmission to themselves or other patients.
Positions that are merely self-protective do not constitute
the basis for a genuine claim of conscience. Furthermore,
the logic of conscience, as a form of self-reflection on and
judgment about whether ones own acts are obligatory or
prohibited, means that it would be odd or absurd to say I
would have a guilty conscience if she did x. Although
some have raised concerns about complicity in the con-
text of referral to another provider for requested medical
care, the logic of conscience entails that to act in accor-
dance with conscience, the provider need not rebuke
other providers or obstruct them from performing an act
(8). Finally, referral to another provider need not be
conceptualized as a repudiation or compromise of ones
own values, but instead can be seen as an acknowledg-
ment of both the widespread and thoughtful disagree-
ment among physicians and society at large and the moral
sincerity of others with whom one disagrees (14).
The authenticity of conscience can be assessed
through inquiry into 1) the extent to which the underly-
ing values asserted constitute a core component of a
providers identity, 2) the depth of the providers reflec-
tion on the issue at hand, and 3) the likelihood that the
provider will experience guilt, shame, or loss of self-
respect by performing the act in question (9). It is the
genuine claim of conscience that is considered next, in the
context of the values that guide ethical health care.
Defining Limits for Conscientious
Refusal
Even when appeals to conscience are genuine, when a
providers moral integrity is truly at stake, there are clear-
179 COMMITTEE OPINIONS 179
ly limits to the degree to which appeals to conscience may
justifiably guide decision making. Although respect for
conscience is a value, it is only a prima facie value, which
means it can and should be overridden in the interest of
other moral obligations that outweigh it in a given cir-
cumstance. Professional ethics requires that health be
delivered in a way that is respectful of patient autonomy,
timely and effective, evidence based, and nondiscrimina-
tory. By virtue of entering the profession of medicine,
physicians accept a set of moral valuesand dutiesthat
are central to medical practice (15). Thus, with profes-
sional privileges come professional responsibilities to
patients, which must precede a providers personal inter-
ests (16). When conscientious refusals conflict with moral
obligations that are central to the ethical practice of med-
icine, ethical care requires either that the physician pro-
vide care despite reservations or that there be resources in
place to allow the patient to gain access to care in the pre-
sence of conscientious refusal. In the following sections,
four criteria are highlighted as important in determining
appropriate limits for conscientious refusal in reproduc-
tive health contexts.
1. Potential for Imposition
The first important consideration in defining limits for
conscientious refusal is the degree to which a refusal con-
stitutes an imposition on patients who do not share the
objectors beliefs. One of the guiding principles in the
practice of medicine is respect for patient autonomy,
a principle that holds that persons should be free to
choose and act without controlling constraints imposed
by others. To respect a patients autonomy is to respect her
capacities and perspectives, including her right to hold
certain views, make certain choices, and take certain
actions based on personal values and beliefs (17). Respect
involves acknowledging decision-making rights and act-
ing in a way that enables patients to make choices for
themselves. Respect for autonomy has particular impor-
tance in reproductive decision making, which involves
private, personal, often pivotal decisions about sexuality
and childbearing.
It is not uncommon for conscientious refusals to
result in imposition of religious or moral beliefs on a
patient who may not share these beliefs, which may
undermine respect for patient autonomy. Womens
informed requests for contraception or sterilization, for
example, are an important expression of autonomous
choice regarding reproductive decision making. Refusals
to dispense contraception may constitute a failure
to respect womens capacity to decide for themselves
whether and under what circumstances to become
pregnant.
Similar issues arise when patients are unable to
obtain medication that has been prescribed by a physi-
cian. Although pharmacist conduct is beyond the scope of
this document, refusals by other professionals can have an
important impact on a physicians efforts to provide
appropriate reproductive health care. Providing com-
plete, scientifically accurate information about options
for reproductive health, including contraception, steril-
ization, and abortion, is fundamental to respect for
patient autonomy and forms the basis of informed deci-
sion making in reproductive medicine. Providers refusing
to provide such information on the grounds of moral or
religious objection fail in their fundamental duty to
enable patients to make decisions for themselves. When
the potential for imposition and breach of autonomy is
high due either to controlling constraints on medication
or procedures or to the providers withholding of infor-
mation critical to reproductive decision making, consci-
entious refusal cannot be justified.
2. Effect on Patient Health
A second important consideration in evaluating consci-
entious refusal is the impact such a refusal might have on
well-being as the patient perceives itin particular, the
potential for harm. For the purpose of this discussion,
harm refers to significant bodily harm, such as pain, dis-
ability, or death or a patients conception of well-being.
Those who choose the profession of medicine (like those
who choose the profession of law or who are trustees) are
bound by special fiduciary duties, which oblige physicians
to act in good faith to protect patients healthparticu-
larly to the extent that patients health interests conflict
with physicians personal or self-interest (16). Although
conscientious refusals stem in part from the commitment
to first, do no harm, their result can be just the opposite.
For example, religiously based refusals to perform tubal
sterilization at the time of cesarean delivery can place a
woman in harms wayeither by putting her at risk for
an undesired or unsafe pregnancy or by necessitating an
additional, separate sterilization procedure with its atten-
dant and additional risks.
Some experts have argued that in the context of preg-
nancy, a moral obligation to promote fetal well-being also
should justifiably guide care. But even though views
about the moral status of the fetus and the obligations
that status confers differ widely, support of such moral
pluralism does not justify an erosion of clinicians basic
obligations to protect the safety of women who are, pri-
marily and unarguably, their patients. Indeed, in the vast
majority of cases, the interests of the pregnant woman
and fetus converge. For situations in which their interests
diverge, the pregnant womans autonomous decisions
should be respected (18). Furthermore, in situations in
which maternal competence for medical decision making
is impaired, health care providers should act in the best
interests of the woman first and her fetus second (19).
3. Scientific Integrity
The third criterion for evaluating authentic conscientious
refusal is the scientific integrity of the facts supporting the
objectors claim. Core to the practice of medicine is a
commitment to science and evidence-based practice.
COMPENDIUM OF SELECTED PUBLICATIONS 180 180
Patients rightly expect care guided by best evidence as
well as information based on rigorous science. When con-
scientious refusals reflect a misunderstanding or mistrust
of science, limits to conscientious refusal should be
defined, in part, by the strength or weakness of the science
on which refusals are based. In other words, claims of
conscientious refusal should be considered invalid when
the rationale for a refusal contradicts the body of scien-
tific evidence.
The broad debate about refusals to dispense emer-
gency contraception, for example, has been complicated
by misinformation and a prevalent belief that emergency
contraception acts primarily by preventing implantation
(20). However, a large body of published evidence sup-
ports a different primary mechanism of action, namely
the prevention of fertilization. A review of the literature
indicates that Plan B can interfere with sperm migration
and that preovulatory use of Plan B suppresses the
luteinizing hormone surge, which prevents ovulation or
leads to the release of ova that are resistant to fertilization.
Studies do not support a major postfertilization mecha-
nism of action (21). Although even a slight possibility of
postfertilization events may be relevant to some womens
decisions about whether to use contraception, provider
refusals to dispense emergency contraception based on
unsupported beliefs about its primary mechanism of
action should not be justified.
In the context of the morally difficult and highly con-
tentious debate about pregnancy termination, scientific
integrity is one of several important considerations. For
example, some have argued against providing access to
abortion based on claims that induced abortion is associ-
ated with an increase in breast cancer risk; however, a
2003 U.S. National Cancer Institute panel concluded that
there is well-established epidemiologic evidence that
induced abortion and breast cancer are not associated
(22). Refusals to provide abortion should not be justified
on the basis of unsubstantiated health risks to women.
Scientific integrity is particularly important at the
level of public policy, where unsound appeals to science
may have masked an agenda based on religious beliefs.
Delays in granting over-the-counter status for emergency
contraception are one such example. Critics of the U.S.
Food and Drug Administrations delay cited deep flaws in
the science and evidence used to justify the delay, flaws
these critics argued were indicative of unspoken and mis-
placed value judgments (23). Thus, the scientific integrity
of a claim of refusal is an important metric in determin-
ing the acceptability of conscience-based practices or
policies.
4. Potential for Discrimination
Finally, conscientious refusals should be evaluated on the
basis of their potential for discrimination. Justice is a
complex and important concept that requires medical
professionals and policy makers to treat individuals fairly
and to provide medical services in a nondiscriminatory
manner. One conception of justice, sometimes referred to
as the distributive paradigm, calls for fair allocation of
societys benefits and burdens. Persons intending consci-
entious refusal should consider the degree to which they
create or reinforce an unfair distribution of the benefits of
reproductive technology. For instance, refusal to dispense
contraception may place a disproportionate burden on
disenfranchised women in resource-poor areas. Whereas
a single, affluent professional might experience such a
refusal as inconvenient and seek out another physician, a
young mother of three depending on public transporta-
tion might find such a refusal to be an insurmountable
barrier to medication because other options are not real-
istically available to her. She thus may experience loss of
control of her reproductive fate and quality of life for her-
self and her children. Refusals that unduly burden the
most vulnerable of society violate the core commitment
to justice in the distribution of health resources.
Another conception of justice is concerned with
matters of oppression as well as distribution (24). Thus,
the impact of conscientious refusals on oppression of cer-
tain groups of people should guide limits for claims of
conscience as well. Consider, for instance, refusals to
provide infertility services to same-sex couples. It is likely
that such couples would be able to obtain infertility ser-
vices from another provider and would not have their
health jeopardized, per se. Nevertheless, allowing physi-
cians to discriminate on the basis of sexual orientation
would constitute a deeper insult, namely reinforcing the
scientifically unfounded idea that fitness to parent is
based on sexual orientation, and, thus, reinforcing the
oppressed status of same-sex couples. The concept of
oppression raises the implications of all conscientious
refusals for gender justice in general. Legitimizing refusals
in reproductive contexts may reinforce the tendency to
value women primarily with regard to their capacity for
reproduction while ignoring their interests and rights
as people more generally. As the place of conscience
in reproductive medicine is considered, the impact of
permissive policies toward conscientious refusals on the
status of women must be considered seriously as well.
Some might say that it is not the job of a physician to
fix social inequities. However, it is the responsibility,
whenever possible, of physicians as advocates for patients
needs and rights not to create or reinforce racial or socio-
economic inequalities in society. Thus, refusals that create
or reinforce such inequalities should raise significant
caution.
Institutional and Organizational
Responsibilities
Given these limits, individual practitioners may face diffi-
cult decisions about adherence to conscience in the con-
text of professional responsibilities. Some have offered,
however, that accepting a collective obligation does not
mean that all members of the profession are forced to vio-
late their own consciences (1). Rather, institutions and
181 COMMITTEE OPINIONS 181
professional organizations should work to create and
maintain organizational structures that ensure nondis-
criminatory access to all professional services and
minimize the need for individual practitioners to act in
opposition to their deeply held beliefs. This requires at the
very least that systems be in place for counseling and
referral, particularly in resource-poor areas where consci-
entious refusals have significant potential to limit patient
choice, and that individuals and institutions act affirma-
tively to protect patients from unexpected and disruptive
denials of service (13). Individuals and institutions
should support staffing that does not place practitioners
or facilities in situations in which the harms and thus
conflicts from conscientious refusals are likely to arise.
For example, those who feel it improper to prescribe
emergency contraception should not staff sites, such as
emergency rooms, in which such requests are likely to
arise, and prompt disposition of emergency contra-
ception is required and often integral to professional
practice. Similarly, institutions that uphold doctrinal
objections should not position themselves as primary
providers of emergency care for victims of sexual assault;
when such patients do present for care, they should be
given prophylaxis. Institutions should work toward struc-
tures that reduce the impact on patients of professionals
refusals to provide standard reproductive services.
Recommendations
Respect for conscience is one of many values important to
the ethical practice of reproductive medicine. Given this
framework for analysis, the ACOG Committee on Ethics
proposes the following recommendations, which it
believes maximize respect for health care professionals
consciences without compromising the health and well-
being of the women they serve.
1. In the provision of reproductive services, the
patients well-being must be paramount. Any consci-
entious refusal that conflicts with a patients well-
being should be accommodated only if the primary
duty to the patient can be fulfilled.
2. Health care providers must impart accurate and unbi-
ased information so that patients can make informed
decisions about their health care. They must disclose
scientifically accurate and professionally accepted
characterizations of reproductive health services.
3. Where conscience implores physicians to deviate
from standard practices, including abortion, steril-
ization, and provision of contraceptives, they must
provide potential patients with accurate and prior
notice of their personal moral commitments. In the
process of providing prior notice, physicians should
not use their professional authority to argue or advo-
cate these positions.
4. Physicians and other health care professionals have
the duty to refer patients in a timely manner to other
providers if they do not feel that they can in con-
science provide the standard reproductive services
that their patients request.
5. In an emergency in which referral is not possible or
might negatively affect a patients physical or mental
health, providers have an obligation to provide med-
ically indicated and requested care regardless of the
providers personal moral objections.
6. In resource-poor areas, access to safe and legal repro-
ductive services should be maintained. Conscien-
tious refusals that undermine access should raise
significant caution. Providers with moral or religious
objections should either practice in proximity to
individuals who do not share their views or ensure
that referral processes are in place so that patients
have access to the service that the physician does not
wish to provide. Rights to withdraw from caring for
an individual should not be a pretext for interfering
with patients rights to health care services.
7. Lawmakers should advance policies that balance pro-
tection of providers consciences with the critical
goal of ensuring timely, effective, evidence-based,
and safe access to all women seeking reproductive
services.
References
1. Charo RA. The celestial fire of consciencerefusing to
deliver medical care. N Engl J Med 2005;352:24713.
2. Denial of rape victims pills raises debate: moral, legal ques-
tions surround emergency contraception. New York (NY):
Associated Press; 2004. Available at: http://www.msnbc.
msn.com/id/4359430. Retrieved July 10, 2007.
3. L D. What happens when there is no plan B? Washington
Post; June 4, 2006. p. B1. Available at: http://www.
washingtonpost.com/wp-dyn/content/article/2006/06/02/
AR2006060201405.html. Retrieved July 10, 2007.
4. Weil E. Breeder reaction: does everyone now have a right
to bear children? Mother Jones 2006;31(4):337. Available
at: http://www.motherjones.com/news/feature/2006/07/
breeder_reaction.html. Retrieved July 10, 2007.
5. American Civil Liberties Union. Religious refusals and
reproductive rights: ACLU Reproductive Freedom Project.
New York (NY): ACLU; 2002. Available at: http://www.aclu.
org/FilesPDFs/ACF911.pdf. Retrieved July 10, 2007.
6. Childress JF. Appeals to conscience. Ethics 1979;89:31535.
7. Wicclair MR. Conscientious objection in medicine.
Bioethics 2000;14:20527.
8. Beauchamp TL, Childress JF. Principles of biomedical ethics.
5th ed. New York (NY): Oxford University Press; 2001.
9. Benjamin M. Conscience. In: Reich WT, editor. Encyclo-
pedia of bioethics. New York (NY): Simon & Schuster
Macmillan; 1995. p. 46973.
10. Ziv TA, Lo B. Denial of care to illegal immigrants.
Proposition 187 in California. N Engl J Med 1995;332:
10958.
11. American College of Obstetricians and Gynecologists. Code
of professional ethics of the American College of Obste-
COMPENDIUM OF SELECTED PUBLICATIONS 182 182
tricians and Gynecologists. Washington, DC: ACOG; 2004.
Available at: http://www.acog.org/from_home/acogcode.
pdf. Retrieved July 10, 2007.
12. American Medical Association. Principles of medical ethics.
In: Code of medical ethics of the American Medical
Association: current opinions with annotations. 20062007
ed. Chicago (IL): AMA; 2006. p. xv.
13. Dresser R. Professionals, conformity, and conscience.
Hastings Cent Rep 2005;35:910.
14. Blustein J. Doing what the patient orders: maintaining
integrity in the doctor-patient relationship. Bioethics
1993;7:290314.
15. Brody H, Miller FG. The internal morality of medicine:
explication and application to managed care. J Med Philos
1998;23:384410.
16. Dickens BM, Cook RJ. Conflict of interest: legal and ethical
aspects. Int J Gynaecol Obstet 2006;92:1927.
17. Faden RR, Beauchamp TL. A history and theory of
informed consent. New York (NY): Oxford University
Press; 1986.
18. Maternal decision making, ethics, and the law. ACOG
Committee Opinion No. 321. American College of
Obstetricians and Gynecologists. Obstet Gynecol 2005;106:
112737.
19. International Federation of Gynecology and Obstetrics.
Ethical guidelines regarding interventions for fetal well
being. In: Ethical issues in obstetrics and gynecology.
London (UK): FIGO; 2006. p. 567. Available at: http://
www.figo.org/docs/Ethics%20Guidelines.pdf. Retrieved
July 10, 2007.
20. Cantor J, Baum K. The limits of conscientious objection
may pharmacists refuse to fill prescriptions for emergency
contraception? N Engl J Med 2004;351:200812.
21. Davidoff F, Trussell J. Plan B and the politics of doubt.
JAMA 2006;296:17758.
22. Induced abortion and breast cancer risk. ACOG Committee
Opinion No. 285. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2003;102:4335.
23. Grimes DA. Emergency contraception: politics trumps sci-
ence at the U.S. Food and Drug Administration. Obstet
Gynecol 2004;104:2201.
24. Young IM. Justice and the politics of difference. Princeton
(NJ): Princeton University Press; 1990.
Copyright November 2007 by the American College of Obstet-
ricians and Gynecologists, 409 12th Street, SW, PO Box 96920,
Washington, DC 20090-6920. All rights reserved. No part of this pub-
lication may be reproduced, stored in a retrieval system, posted on
the Internet, or transmitted, in any form or by any means, electronic,
mechanical, photocopying, recording, or otherwise, without prior writ-
ten permission from the publisher. Requests for authorization to make
photocopies should be directed to: Copyright Clearance Center, 222
Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
The limits of conscientious refusal in reproductive medicine. ACOG
Committee Opinion No. 385. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2007;110:12038.
ISSN 1074-861X
183 COMMITTEE OPINIONS 183
Human Immunodeficiency Virus*
ABSTRACT: Because human immunodeficiency virus (HIV) infection often is detected
through prenatal and sexually transmitted disease testing, an obstetriciangynecologist
may be the first health professional to provide care for a woman infected with HIV.
Universal testing with patient notification and right of refusal (opt-out testing) is recom-
mended by most national organizations and federal agencies. Although opt-out and opt-
in testing (but not mandatory testing) are both ethically acceptable, the former approach
may identify more women who are eligible for therapy and may have public health advan-
tages. It is unethical for an obstetriciangynecologist to refuse to accept a patient or to
refuse to continue providing health care for a patient solely because she is, or is thought
to be, seropositive for HIV. Health care professionals who are infected with HIV should
adhere to the fundamental professional obligation to avoid harm to patients. Physicians
who believe that they have been at significant risk of being infected should be tested
voluntarily for HIV.
Committee on Ethics
Number 389 December 2007
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Between 1 million and 1.2 million individu-
als in the United States are estimated to be
living with human immunodeficiency virus
(HIV) or acquired immunodeficiency syn-
drome (AIDS) (1). Women represent the
fastest-growing group of individuals with
new HIV infections (2). Many women who
are infected with HIV are not aware of their
serostatus (3).
Human immunodeficiency virus often is
diagnosed in women during prenatal anti-
body screening or in conjunction with
screening for sexually transmitted diseases
(STDs). Because many women initially iden-
tified as infected with HIV are not aware that
they have been exposed to HIV and do not
consider themselves to be at risk, universal
testing with patient notification is more
effective than targeted, risk-based testing in
identifying those who are infected with HIV
(4). The tension between competing goals for
HIV testingtesting broadly in order to treat
the maximum number of women infected
with HIV and, if pregnant, to protect their
newborns, and counseling thoroughly in
order to maximally protect a womans auton-
omy and right to participate in decision mak-
inghas sparked considerable debate.
Because HIV infection often is detected
through prenatal and STD screening, it is
not uncommon for an obstetriciangynecol-
ogist to be the first health professional to
provide care for an infected woman. This
Committee Opinion is designed to provide
guidance to obstetriciangynecologists re-
garding ethical issues associated with HIV
testing, including the use of newly developed
rapid HIV tests and disclosure of positive
test results. It also outlines responsibilities
related to patient care for women who are
infected with HIV, access for affected couples
to assisted reproductive technology, and the
health care professional who is infected
with HIV.
Human Immunodeficiency
Virus Counseling and Testing
The major ethical principles that must be
considered when formulating policies for
HIV counseling and testing include respect
for autonomy, confidentiality, justice, protec-
tion of vulnerable individuals, and benefi-
cence to both the woman tested and, if she is
pregnant, to her newborn as well. Individuals
offering testing need to be mindful not only
of the benefits of testing but also its potential
risks because, if a womans test result is posi-
tive, she faces the possibility of being ostra-
*Update of Human Immunodeficiency Virus in Ethics
in Obstetrics and Gynecology, Second Edition, 2004.
ACOG COMMITTEE OPINION
COMPENDIUM OF SELECTED PUBLICATIONS 184 184
cized by her family, friends, and community or being
subjected to intimate partner violence. In addition,
although the overt stigma of HIV infection has been
reduced over the past 20 years, the potential for job dis-
crimination, loss of health insurance, and loss of housing
still exists.
Over time, three potential strategies for HIV testing
have been considered by public health and public policy
officials: 1) universal testing with patient notification and
right of refusal, also called opt-out testing; 2) voluntary
testing with pretest counseling regarding risks and bene-
fits, also called opt-in testing; and 3) mandatory testing
with no right of refusal. In order to understand their eth-
ical merits, each is considered briefly in the sections that
follow. Increasingly, national organizations and federal
agencies have recommended opt-out testing in preference
to other strategies.
Universal Testing With Patient Notification and
Right of RefusalOpt-Out Testing
Opt-out testing removes the requirement for pretest
counseling and detailed, testing-related informed con-
sent. Under the opt-out strategy, physicians must inform
patients that routine blood work will include HIV testing
and that they have the right to refuse this test. The goal of
this strategy is to make HIV testing less cumbersome and
more likely to be performed by incorporating it into the
routine battery of tests (eg, the first-trimester prenatal
panel or blood counts and cholesterol screening for
annual examinations). In theory, if testing barriers are
reduced, more physicians may offer testing, which may
lead to the identification and treatment of more women
who are infected with HIV and, if pregnant, to the pre-
vention of mother-to-infant transmission of HIV. This
testing strategy aims to balance competing ethical con-
siderations. On the one hand, personal freedom (auton-
omy) is diminished. On the other hand, there are medical
and social benefits for the woman and, if she is pregnant,
her newborn from identifying HIV infection. Although
many welcome the now widely endorsed opt-out testing
policy for the potential benefits it confers, others have
raised concerns about the possibility that the require-
ment for notification before testing will be ignored, par-
ticularly in todays busy practice environment. Indeed,
the opt-out strategy is an ethically acceptable testing
strategy only if the patient is given the option to refuse
testing. In the absence of that notification, this approach
is merely mandatory testing in disguise. If opt-out testing
is elected as a testing strategy, a clinician must notify the
patient that HIV testing is to be performed. Refusal of
testing should not have an adverse effect on the care the
patient receives or lead to denial of health care. This
guarantee of a right to refuse testing ensures that respect
for a womans autonomy is not completely abridged in
the quest to achieve a difficult-to-reach public health
goal.
Voluntary Testing With Pretest Counseling
Regarding Risks and BenefitsOpt-In Testing
Voluntary testing with counseling is the strategy most
consistent with respect for patient autonomy. Under this
option, physicians provide both pretest and posttest
counseling. Some physicians may perform such counsel-
ing themselves, whereas others may prefer to refer the
patient for counseling and testing. (Such specialized HIV
counseling was more widely available in previous years
but has become less available as more health care profes-
sionals have become more comfortable treating patients
with HIV and as the opt-out approach to testingan
approach that places less emphasis on pretest counsel-
inghas become more common.) In addition to medical
information, such counseling could include information
regarding potential uses of test information and legal
requirements pertaining to the release of information.
Patients should be told what information will be commu-
nicated and to whom and the possible implications of
reporting the information. This approach to testing
maintains HIVs status as being in a class by itself (sui
generis), even as many ethicists have acknowledged the
end to the exceptionalism that marked this disease in the
early years of the epidemic (5).
Mandatory Testing With No Right of Refusal
Mandatory testing strategies are problematic because they
abridge a womans autonomy. In addition, during preg-
nancy, the public health objective of this strategy, identifi-
cation of women who are infected with HIV who will ben-
efit from treatment, has been accomplished in certain
populations by other ethically sound testing strategies
noted previously (6). Some see mandatory testing as a
more efficient way of achieving universal testing.
Advocates support this strategy, believing it provides the
greatest good for the greatest number and that the poten-
tial benefit to the woman and, if pregnant, her newborn
justifies abridging a womans autonomy. However, because
of the limits it places on autonomy, the Committee on
Ethics believes that mandatory HIV screening without
informing those screened and offering them the option of
refusal is inappropriate. Mandatory prenatal testing is dif-
ficult to defend ethically and has few precedents in mod-
ern medicine, although HIV testing of newborns is now
required in New York, Connecticut, and Illinois (There are
provisions, however, that permit refusal in a few defined
circumstances.) (7, 8). Importantly, mandatory testing
may compromise the ability to form an effective physi-
cianpatient relationship at the very time when this rela-
tionship is critical to the success of treatment.
Selecting a Testing Strategy
Among these three strategies, the opt-out approach is
now recommended by most national organizations and
federal agencies. For prenatal HIV testing, universal test-
ing with patient notification and right of refusal was rec-
ommended by the Institute of Medicine to address
185 COMMITTEE OPINIONS 185
clinicians concerns that pretest counseling and informed
consent mandates for routine voluntary testing in preg-
nancy were too time consuming and, thus, reduced the
likelihood of testing being offered (9). The Centers for
Disease Control and Prevention, the American Academy
of Pediatrics, and the American College of Obstetricians
and Gynecologists (ACOG) endorse this approach (10,
11). Evidence suggests that this strategy may be accept-
able to many pregnant women (12, 13). To expand the
gains made in diagnosing HIV infection among pregnant
women, the Centers for Disease Control and Prevention
(14) has recently released, and ACOG (15) has adopted,
recommendations to make HIV testing a routine part of
medical care using a similar opt-out approach for all
women at the time of routine health care visits.
In recommending the opt-out approach for prenatal
HIV testing, ACOG encouraged Fellows to include coun-
seling as a routine part of care but not as a prerequisite
for, or barrier to, prenatal HIV testing (11). Similarly, the
American Medical Association, in recommending that
universal HIV testing of all pregnant women with patient
notification of the right of refusal be a routine compo-
nent of prenatal care, indicated that basic counseling on
HIV prevention and treatment also should be provided
to the patient, consistent with the principles of informed
consent (16). Accordingly, if adopting this option, physi-
cians should be prepared to provide both pretest and
posttest counseling. Broad implementation of an opt-out
strategy, however, will require changing laws in states that
require detailed and specific counseling and consent
before testing. Physicians should be aware of the laws in
their states that affect HIV testing. The National HIV/
AIDS Clinicians Consultation Center at the University of
CaliforniaSan Francisco maintains an online com-
pendium of state HIV testing laws that can be a useful
resource (see http://www.ucsf.edu/hivcntr/).
The benefits of identifying those with HIV infection
will be limited if necessary treatments are unavailable or
not covered by appropriate insurance. Where access to
HIV treatment is limited, Fellows should advocate for
changes in existing policies to broaden access.
Special Issues Involved With Rapid
Human Immunodeficiency Virus
Testing
Technologies have recently become available that allow
for testing with rapid results (eg, turnaround less than
1 hour). The advantage of these tools is that patients can
be informed of their results at the same visit at which the
testing occurs. In that manner, it is possible to lower the
rate of loss to follow-up associated with the traditional
two-stage testing and notification approach. Nothing
about rapid testing precludes the need for a patient to
opt-in or to be offered the opportunity to opt-out of test-
ing (depending on which strategy is adopted). Rapid test-
ing should not be implemented either as mandatory
testing or testing performed without informing the
patient that she will be tested.
In communities with a relatively low prevalence of
HIV, rapid testing can present certain logistic difficulties.
With the traditional approach, testing would occur dur-
ing an initial visit, and results would be provided during a
follow-up encounter. That would give the health care pro-
fessional an opportunity to arrange for an individual with
expertise in posttest counseling to be available in a cir-
cumstance in which the health care professional knew
that a patient was returning to receive a positive result. A
program of testing and notification at the same visit does
not allow the health care professional the luxury of noti-
fying a counselor before a patient who is infected with
HIV returns for a visit or of steering an individual who is
infected with HIV to a certain session at which the coun-
selor is routinely available. However, the obligation to
make sure that appropriate counseling and support ser-
vices are available still holds. Health care professionals
should develop links with individuals who can provide
those services on an emergent basis or train their own
staff to handle the initial encounter and thereafter transi-
tion infected individuals to professionals who can serve as
ongoing resources to them.
Human Immunodeficiency Virus
Reporting and Partner Notification
The clinician providing care for a woman who is infected
with HIV has important responsibilities concerning dis-
closure of the patients serostatus. Clinicians providing
health care should be aware of and respect legal require-
ments regarding confidentiality and disclosure of HIV-
related clinical information.
In considering disclosure, clinicians may have com-
peting obligations: protecting the patients confidentiality,
on the one hand, and disclosing test results to prevent
substantial harm to a third party, on the other. In some
jurisdictions, a breach of confidentiality may be required
by mandatory reporting regulations. Even absent legal
requirements, in some situations the need to protect
potentially exposed third parties may seem compelling. In
these situations, the clinician first should educate the
patient about her rights and responsibilities and encour-
age her to inform any third parties involved. If she remains
reluctant to voluntarily share information regarding her
infection, consultation with an institutional ethics com-
mittee, a medical ethics specialist, or an attorney may be
helpful in deciding whether to disclose her HIV status. In
general, a breach of confidentiality may be ethically justi-
fied for purposes of partner notification when all of the
following four conditions are met:
1. There is a high probability of harm to the partner.
2. The potential harm is serious.
3. The information communicated can be used to pre-
vent harm.
COMPENDIUM OF SELECTED PUBLICATIONS 186 186
4. Greater good will result from breaking confiden-
tiality rather than maintaining it.
Indeed, many if not all of these conditions are likely
met for intimate partners of women and men who are
infected with HIV. Nevertheless, when a breach of confi-
dence is contemplated, practitioners should weigh the
potential harm to the patient and to society at large.
Negative consequences of breaking confidentiality may
include the following situations:
Personal risks to the individual whose confidence is
breached, such as serious implications for the
patients relationship with family and friends, the
threat of discrimination in employment and hous-
ing, intimate partner violence, and the impact on
family members
Loss of patient trust, which may reduce the physicians
ability to communicate effectively and provide services
A ripple effect among cohorts of women that may
deter other women at risk from accepting testing and
have a serious negative impact on the educational
efforts that lie at the heart of attempts to reduce the
spread of disease
If, on balance, a breach of confidence is deemed nec-
essary, practitioners should work in advance to anticipate
and manage potentially negative consequences (ie, reac-
tions of intimate partners, family). As well, practitioners
should consider whether the goal of maintaining patient
privacy would be better served by personal communica-
tion with the individual placed at risk by the patients
seropositivity or by notification of local public health
authorities. In some areas, anonymous notification of
sexual contacts is possible through local or state depart-
ments of health. As a practical matter, because disclosure
is only possible when the index case freely identifies at-
risk partners, superseding an individuals refusal to dis-
close should be a rare occurrence.
Confidentiality should not be breached solely be-
cause of perceived risk to health care workers. Health care
workers should rely on strict observance of standard pre-
cautions rather than obtaining information about a
patients serostatus to minimize risk. Even in the setting of
an accidental needle-stick or other exposure, the patients
consent for release of serostatus (or for testing) should be
obtained. Efforts to protect patient confidentiality should
not prevent other health care professionals caring for the
patient from learning her serostatus, information they
need to ensure optimal medical management.
Health Care Professionals Obligation
to Provide Care
It is unethical for an obstetriciangynecologist to refuse
to accept a patient or to refuse to continue providing
health care for a patient solely because she is, or is thought
to be, seropositive for HIV. Refusing to provide care to
women who are infected with HIV for fear of contracting
HIV infection or simply as a practice preference is unrea-
sonable, unscientific, and unethical.
Epidemiologic studies have shown that the risk of
HIV transmission from patient to health care professional
is exceedingly low and is related to needle stick or intra-
operative injury or to potentially infectious fluid that
comes in contact with a mucous membrane (17). Most
contacts between health care professionals and women
who are infected with HIV occur, however, during rou-
tine obstetric and gynecologic care. Health care practi-
tioners should observe standard precautions with all
patients to minimize skin, mucous membrane, and per-
cutaneous exposure to blood and body fluids to protect
against a variety of pathogens, including HIV.
Health care professionals who fail to provide care to
women who are infected with HIV because of personal
practice preferences violate professional ethical stan-
dards. The public appropriately expects that health care
practitioners will not discriminate based on diagnosis,
provided that the patients care falls within their scope of
practice. Physicians should demonstrate integrity, com-
passion, honesty, and empathy. Failure to provide health
care to a woman solely because she is infected with HIV
violates these fundamental characteristics. As with any
other patient, it is acceptable, however, to refer women
who are infected with HIV for care that the physician is
not competent to provide or if care elsewhere would be
more convenient or associated with decreased financial
burden to the patient.
Assisted Reproductive Technology
There is an emerging consensus that indications for
assisted reproductive technology use should not vary
with HIV serostatus; therefore, assisted reproductive
technology should be offered to couples in which one or
both partners are infected with HIV. This approach is
consistent with the principles of respect for autonomy
and beneficence (18, 19). In addition, those who advocate
providing these services cite three clinical arguments to
support their position:
1. Therapeutic improvements in the management of
HIV infection have enhanced both quality and
length of life for individuals who are seropositive for
HIV.
2. Advances in prenatal therapy have substantially
reduced the risk of mother-to-infant HIV trans-
mission.
3. Current assisted reproductive technology methods
may reduce transmission of HIV from an infected
partner to an uninfected partner relative to natural
means of conception.
The Ethics Committee of the American Society for
Reproductive Medicine has said, Health care workers
who are willing to provide reproductive assistance to cou-
187 COMMITTEE OPINIONS 187
ples whose offspring are irreducibly at risk for a serious
genetic disease should find it ethically acceptable to treat
HIV-positive individuals or couples who are willing to
take reasonable steps to minimize the risks of transmis-
sion. (20).
Those who oppose offering these technologies to
couples who are infected with HIV cite two major objec-
tions:
1. Uncertain long-term parental prognosis
2. The continuing risk of mother-to-infant HIV trans-
mission
The ethical underpinning of this opposition is that it
is not felt to be in the best interest of the child to be born
to a parent who may not be available for continued child-
rearing. In addition, the risk of mother-to-infant transmis-
sion places the infant at risk of acquiring a highly debilitat-
ing illness. Yet as stated previously, HIV infection currently
is a manageable chronic illness with a life-expectancy
equivalent to that with many other chronic diseases for
which assisted reproductive technology is not routinely
precluded. Further, interventions, such as antiretroviral
therapy or cesarean delivery or both, reduce the absolute
risk of transmission to a level comparable, again, to risks
significantly lower than those tolerated among couples
choosing assisted reproductive technology (eg, parents
who are carriers of autosomal recessive conditions) or risks
often assumed as part of assisted reproductive technology
(eg, risks of prematurity from multiple pregnancies).
Health Care Professionals Who Are
Infected With Human
Immunodeficiency Virus
In making decisions about patient care, health care pro-
fessionals who are infected with HIV should adhere to the
fundamental professional obligation to avoid harm to
patients. Physicians who have reason to believe that they
have been at significant risk of being infected should be
tested voluntarily for HIV for the protection of their
patients as well as for their own benefit. The physician as
a patient is entitled to the same rights to privacy and con-
fidentiality as any other patient.
Although the risk of clinician-to-patient transmis-
sion is extremely low, all infected physicians must make a
decision as to which procedures they can continue to per-
form safely. This decision primarily will depend on the
particular surgical technique involved and also on the
physicians level of expertise and medical condition,
including mental status. The clinicians decision should
be made in consultation with a personal physician and
may possibly involve such other responsible individuals as
the chief of the department, the hospitals director of
infectious diseases, the chief of the medical staff, or a spe-
cialized advisory panel. If physicians avoid procedures
that place patients at risk of harm, they have no obligation
to inform the patient of their positive HIV serostatus.
Physicians who are infected with HIV should follow stan-
dard precautions, including the appropriate use of hand-
washing, protective barriers, and care in the use and
disposal of needles and other sharp instruments.
Recommendations
The Committee on Ethics makes the following recom-
mendations:
All women, pregnant or not, should have the oppor-
tunity to learn their HIV serostatus.
Women should, at a minimum, be told that they are
being tested and that they may refuse such tests.
Although opt-out and opt-in testing are both ethic-
ally acceptable, the former approach may identify
more women who are eligible for therapy and may
have public health advantages.
Rapid testing carries the same ethical responsibilities
as standard testing.
It is unethical for an obstetriciangynecologist to
refuse to accept a patient or to discontinue providing
health care for a patient solely because she is, or is
thought to be, seropositive for HIV.
Seropositivity for HIV per se should not be used as a
reason to refuse to provide assisted reproductive
technology to a family.
References
1. Epidemiology of HIV/AIDSUnited States, 19812005.
MMWR Morb Mortal Wkly Rep 2006;55:58992.
2. Chou R, Smits AK, Huffman LH, Fu R, Korthuis PT.
Prenatal screening for HIV: a review of the evidence for the
U.S. Preventive Services Task Force. U.S. Preventive Services
Task Force. Ann Intern Med 2005;143:3854.
3. Gwinn M, Wortley PM. Epidemiology of HIV infection in
women and newborns. Clin Obstet Gynecol 1996;39:
292304.
4. Revised recommendations for HIV screening of pregnant
women. MMWR Recomm Rep 2001;50(RR19):6385;
quiz CE119a2CE619a2.
5. Bayer R, Fairchild AL. Changing the paradigm for HIV test-
ingthe end of exceptionalism. N Engl J Med 2006;355:
6479.
6. Prenatal discussion of HIV testing and maternal HIV test-
ing14 states, 19961997. MMWR Morb Mortal Wkly Rep
1999;48:4014.
7. HIV testing among pregnant womenUnited States and
Canada, 19982001. MMWR Morb Mortal Wkly Rep 2002;
51:10136.
8. Perinatal HIV Prevention Act. 410 ILCS 335 (2006).
9. Institute of Medicine (US). Reducing the odds: preventing
perinatal transmission of HIV in the United States.
Washington, DC: National Academy Press; 1999.
10. Prenatal and perinatal human immunodeficiency virus
testing: expanded recommendations. ACOG Committee
COMPENDIUM OF SELECTED PUBLICATIONS 188 188
Opinion No. 304. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2004;104:111924.
11. American Academy of Pediatrics, American College of
Obstetricians and Gynecologists. Joint statement on human
immunodeficiency virus screening. Elk Grove Village
(IL): AAP; Washington, DC: ACOG; 2006. Available at:
http://www.acog.org/publications/policy_statements/
sop9905.cfm. Retrieved July 10, 2007.
12. Stringer EM, Stringer JS, Cliver SP, Goldenberg RL,
Goepfert AR. Evaluation of a new testing policy for human
immunodeficiency virus to improve screening rates. Obstet
Gynecol 2001;98:11048.
13. Jayaraman GC, Preiksaitis JK, Larke B. Mandatory report-
ing of HIV infection and opt-out prenatal screening for
HIV infection: effect on testing rates. CMAJ 2003;168:
67982.
14. Branson BM, Handsfield HH, Lampe MA, Janssen RS,
Taylor AW, Lyss SB, et al. Revised recommendations for HIV
testing of adults, adolescents, and pregnant women in
health-care settings. MMWR Recomm Rep 2006;55
(RR14):117; quiz CE14.
15. Primary and preventive care: periodic assessments. ACOG
Committee Opinion No. 357. American College of
Obstetricians and Gynecologists. Obstet Gynecol 2006;108:
161522.
16. American Medical Association. Universal, routine screening
of pregnant women for HIV infection. CSA Report I01.
Council on Scientific Affairs. Chicago (IL): AMA; 2001.
Available at: http://www.ama-assn.org/ama/pub/category/
13548.html. Retrieved July 10, 2007.
17. Updated U.S. Public Health Service guidelines for the man-
agement of occupational exposures to HBV, HCV, and HIV
and recommendations for postexposure prophylaxis.
MMWR Recomm Rep 2001;50(RR11):152.
18. Anderson DJ. Assisted reproduction for couples infected
with the human immunodeficiency virus type 1. Fertil
Steril 1999;72:5924.
19. Minkoff H, Santoro N. Ethical considerations in the treat-
ment of infertility in women with human immunodefi-
ciency virus infection. N Engl J Med 2000;342:174850.
20. Human immunodeficiency virus and infertility treatment.
Ethics Committee of the American Society for Reproduc-
tive Medicine. Fertil Steril 2002;77:21822.
Copyright December 2007 by the American College of Obste-
tricians and Gynecologists, 409 12th Street, SW, PO Box 96920,
Washington, DC 20090-6920. All rights reserved. No part of this pub-
lication may be reproduced, stored in a retrieval system, posted on
the Internet, or transmitted, in any form or by any means, electronic,
mechanical, photocopying, recording, or otherwise, without prior
written permission from the publisher. Requests for authorization to
make photocopies should be directed to: Copyright Clearance Center,
222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
Human immunodeficiency virus. ACOG Committee Opinion No. 389.
American College of Obstetricians and Gynecologists. Obstet Gynecol
2007;110:14738.
ISSN 1074-861X
189 COMMITTEE OPINIONS 189
Ethical Decision Making in Obstetrics and
Gynecology*
ABSTRACT: Physicians vary widely in their familiarity with ethical theories and meth-
ods and their sensitivity toward ethical issues. It is important for physicians to improve
their skills in addressing ethical questions. Obstetriciangynecologists who are familiar
with the concepts of medical ethics will be better able to approach complex ethical situ-
ations in a clear and structured way. By considering the ethical frameworks involving prin-
ciples, virtues, care and feminist perspectives, concern for community, and case
precedents, they can enhance their ability to make ethically justifiable clinical decisions.
Guidelines, consisting of several logical steps, are offered to aid the practitioner in ana-
lyzing and resolving ethical problems.
Committee on Ethics
Number 390 December 2007
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
The importance of ethics in the practice of
medicine was manifested at least 2,500 years
ago in the Hippocratic tradition, which
emphasized the virtues that were expected to
characterize and guide the behavior of physi-
cians. Over the past 50 years, medical tech-
nology expanded exponentially, so that
obstetriciangynecologists have had to face
complex ethical questions regarding assisted
reproductive technologies, prenatal diagnosis
and selective abortion, medical care at the
beginning and end of life, the use of genetic
information, and the like. Medical knowledge
alone is not sufficient to solve these prob-
lems. Instead, responsible decisions in these
areas depend on a thoughtful consideration
of the values, interests, goals, rights, and
obligations of those involved. All of these are
the concern of medical ethics. The formal
discipline of biomedical ethics and struc-
tured ethical analysis can help physicians
resolve ethical dilemmas.
Physicians vary widely in their familiar-
ity with ethical theories and methods and
their sensitivity toward ethical issues. It is
important for physicians to improve their
skills in addressing ethical questions through
formal undergraduate and graduate medical
education, organized continuing education,
or personal experience and reading as well as
discussion with others.
Ethical Frameworks and
Perspectives
Principle-Based Ethics
In recent decades, medical ethics has been
dominated by principle-based ethics (13).
In this approach, four principles offer a
systematic and relatively objective way to
identify, analyze, and address ethical issues,
problems, and dilemmas: 1) respect for patient
autonomy, 2) beneficence, 3) nonmaleficence,
and 4) justice. (These four principles will be
discussed in some detail in subsequent sec-
tions.) However, critics claim that a principle-
based approach cannot adequately resolve or
even helpfully evaluate many difficult clinical
problems. As a result, several other perspec-
tives and frameworks have emerged: virtue-
based ethics, an ethic of care, feminist ethics,
communitarian ethics, and case-based rea-
soning, all of which have merit as well as lim-
itations (28). As this discussion will stress,
these different perspectives and frameworks
are not necessarily mutually exclusive. They
often are complementary because each
emphasizes some important features of
moral reasoning, agents, situations, actions,
or relationships. Perspectives such as an ethic
of care or feminist ethics also may change the
lens through which to view both principles
*Update of Ethical Decision Making in Obstetrics and
Gynecology in Ethics in Obstetrics and Gynecology,
Second Edition, 2004.
ACOG COMMITTEE OPINION
COMPENDIUM OF SELECTED PUBLICATIONS 190 190
and particular situations in which decisions have to be
made.
Virtue Ethics
A virtue-based approach relies on qualities of character
that dispose health professionals to make choices and deci-
sions that achieve the well-being of patients, respect their
autonomous choices, and the like (8, 9). These qualities of
character include trustworthiness, prudence, fairness,
fortitude, temperance, integrity, self-effacement, and com-
passion. Virtues need not replace principles as a basis for
ethical decision making or conduct. Indeed, some virtues
correlate with principles and dispose people to act accord-
ing to those principlesfor instance, the virtue of benevo-
lence disposes agents to act beneficently. Virtues also can
complement and enhance the principles of medical ethics.
Interpreting the principles, applying them in concrete situ-
ations, and setting priorities among them require the judg-
ment of morally sensitive professionals with good moral
character and the relevant virtues. Furthermore, in deliber-
ating what to do, a physician may find helpful guidance by
asking, What would a good, that is, morally virtuous,
physician do in these circumstances? Ethical insight may
come from imagining which actions would be compatible
with, for instance, being a compassionate or honest or
trustworthy physician.
Care-Based Ethics
Care-based ethics, also called the ethic of care, directs
attention to dimensions of moral experience often exclud-
ed from or neglected by traditional ethical theories (10). It
is concerned primarily with responsibilities that arise from
attachment to others rather than with impartial principles
so emphasized in many ethical theories. The moral founda-
tions of an ethic of care are located not in rights and duties,
but rather in commitment, empathy, compassion, caring,
and love (11). This perspective also pays closer attention to
context and particularity than to abstract principles and
rules. It suggests that good ethical decisions both result
from personal caring in relationships, and should consider
the impact of different possible actions on those relation-
ships. An ethic of care overlaps with a virtue ethic, in
emphasizing the caregivers orientation and qualities. In
this ethical approach, care represents the fundamental ori-
entation of obstetrics and gynecology as well as much of
medicine and health care, and it indicates the direction and
rationale of the relationship between professionals and
those who seek their care. An ethic of care also joins case-
based approaches in focusing on particular contexts of
decision making.
Feminist Ethics
Feminist ethics uses the tools of feminist theory to exam-
ine ethical issues in at least three distinctive ways (12).
First, it indicates how conceptions of sex often distort peo-
ples view of the world and, more specifically, how gen-
dered conceptions constrain and restrict women. For
instance, feminist theory shows how human society tends
to be androcentric, or male centered, so that man
becomes the generic representative for what it means to
be human, and woman is viewed as different or deviant.
Thus, feminist ethics can expose forms of androcentric
reasoning in ethics of clinical care and public policy, call-
ing into question, for example, the rationale for exclud-
ing women from participation in clinical research.
Second, feminist ethics indicates how gendered thinking
has distorted the tools that philosophers and bioethicists
use to examine ethical issues. Historically entrenched
associations between man and reason, woman and emo-
tiondubious in and of themselveshave contributed
to the tendency in moral theory to view emotion as irrel-
evant or, at worst, distorting. Some, including many fem-
inist thinkers, however, have argued that appropriate
emotion (eg, empathy) is indispensable to moral reason-
ing in the ethical conduct of medical care. This position,
bolstered further by recent empirical research (13, 14), is
consistent with the perspective represented by the ethic
of care (see previous section). Third, in calling attention
to and attempting to redress the ways that gendered con-
cepts have produced constraints on women, feminism is
concerned with oppression as a pervasive and insidious
moral wrong (15, 16). The tools of feminist ethics can
help to identify and challenge dominance and oppression
not only of women, but also of other groups oppressed
because of race, class, or other characteristics. These tools
also can help to detect more subtle gender and other
biases and assist in addressing significant health dispari-
ties. Rather than rejecting such principles as respect for
autonomy and justice, feminist thinkers may interpret
and apply these principles to highlight and redress vari-
ous kinds of domination, oppression, and bias.
Communitarian Ethics
Communitarian ethics challenges the primacy often
attributed to personal autonomy in contemporary bio-
medical ethics (17). A communitarian ethic emphasizes a
communitys other shared values, ideals, and goals and
suggests that the needs of the larger community may take
precedence, in some cases, over the rights and desires of
individuals. If proponents of a communitarian ethic
accept the four principles of Beauchamp and Childress
(1), they will tend to interpret those principles through
the lens of community, stressing, for example, benefits
and harms to community and communities as well as the
need to override autonomy in some cases. Major exam-
ples arise in the context of public health. However, in
considering the proper framework for communitarian
ethics, questions arise in a pluralistic society about which
community is relevant. For instance, is the relevant
community one embodied in particular traditions (eg,
one religion) or is it the broader, pluralistic society? Even
though there is a broad consensus that communal values
and interests sometimes trump personal autonomy, dis-
putes persist about exactly when it is justifiable to over-
191 COMMITTEE OPINIONS 191
ride personal autonomy. To take one example, apart from
laws that specify which diseases are reportable, physicians
may have to balance a patients claims of privacy and con-
fidentiality against risks to others. Different judgments
about the appropriate balance often hinge on an assess-
ment of risks: How probable and serious must the harm
be to justify a breach of privacy and confidentiality?
Case-Based Reasoning
In a final approach, case-based reasoning (sometimes
called casuistry), ethical decision making builds on prece-
dents set in specific cases (18, 19). This is analogous to the
role of case law in jurisprudence in that an accumulated
body of influential cases and their interpretation provide
moral guidance. This approach analyzes current cases
requiring decisions in light of relevantly similar cases that
have already been settled or gained a rough consensus.
Case-based reasoning asserts the priority of practice over
both ethical theory and moral principles. It recognizes the
principles that emerge by a process of generalization from
the analysis of cases but views these principles as always
open to future revision. In considering a particular case,
someone taking this approach would seek to determine
whether there are any relevantly similar cases, either pos-
itive or negative, that enjoy an ethical consensus. If, for
example, a new research protocol is relevantly similar to
an earlier and widely condemned one (eg, the Tuskegee
Syphilis Study), that similarity is a reason for moral sus-
picion of the new protocol. A question for this approach
is how to identify relevant similarities and differences
among cases and whether ethical principles are some-
times useful in this process.
Ethics as Toolbox
An example of how the different ethical frameworks and
perspectives might address a particular case is shown in
the box. From this analysis of different approaches, it is
plausible to derive the following conclusion: enlightened
ethical decision making in clinical medicine cannot rely
exclusively on any single fundamental approach to bio-
medical ethics. The metaphor of toolbox or toolkit may
provide a useful way to think about these different
approaches to ethical decision making (20). Some ethical
tools may fit some contexts, situations, and cases better
than others, and more than oneor even all of them
usually are valuable.
It is helpful to have access to a variety of ethical tools
because clinical problems often are too complex to be
resolved by using simple rules or by rigidly applying eth-
ical principles. Indeed, virtues such as prudence, fairness,
and trustworthiness enable clinicians to apply ethical
principles sensitively and wisely in situations of conflict.
The specific virtues that are most important may vary
from one circumstance to another, but in womens health
care, there must be particular sensitivity to the needs of
women. Furthermore, in many, perhaps most, difficult
situations requiring ethical insight, tensions exist between
the well-being and interests of the individual patient and
the interest of the community, however that is defined.
Finally, current ethical decisions can be improved by
awareness of and guidance from existing precedents.
In short, even though a principle-based approach
may provide a reasonable starting point for ethical deci-
sion making, it is not adequate by itself and needs the
valuable contributions and insights of other approaches.
Principles often serve as initial points of reference in ethi-
cal decision making in obstetrics and gynecology, howev-
er, and the next section examines several ethical principles
in detail.
Ethical Principles
Clinicians and others often make decisions without
appealing to principles for guidance or justification. But
when they experience unclear situations, uncertainties, or
conflicts, principles often can be helpful. The major prin-
ciples that are commonly invoked as guides to profes-sion-
al action and for resolving conflicting obligations in health
care are respect for autonomy, beneficence and nonmalef-
icence, and justice (1). Other principles or rules, such as
fidelity, honesty, privacy, and confidentiality, also are
important, whether they are viewed as derived from the
four broad principles or as independent.
Respect for Autonomy
Autonomy, which derives from the Greek autos (self )
and nomos (rule or governance), literally means self-
rule. In medical practice, the principle of respect for
autonomy implies personal rule of the self that is free both
from controlling interferences by others and from person-
al limitations that prevent meaningful choice, such as
inadequate understanding (1). Respect for a patients
autonomy acknowledges an individuals right to hold
views, to make choices, and to take actions based on her
own personal values and beliefs. Respect for autonomy
provides a strong moral foundation for informed consent,
in which a patient, adequately informed about her medical
condition and the available therapies, freely chooses spe-
cific treatments or nontreatment. Respect for patient
autonomy, like all ethical principles, cannot be regarded as
absolute. At times it may conflict with other principles or
values and sometimes must yield to them.
Beneficence and Nonmaleficence
The principle of beneficence, which literally means doing
or producing good, expresses the obligation to promote
the well-being of others. It requires a physician to act in a
way that is likely to benefit the patient. Nonmaleficence is
the obligation not to harm or cause injury, and it is best
known in the maxim, primum non nocere (First, do no
harm.). Although there are some subtle distinctions
between nonmaleficence and beneficence, they often are
considered manifestations of a single principle. These two
principles taken together are operative in almost every
treatment decision because every medical or surgical pro-
COMPENDIUM OF SELECTED PUBLICATIONS 192 192
cedure has both benefits and risks, which must be balanced
knowledgeably and wisely. Beneficence, the obligation to
promote the patients well-being, may sometimes conflict
with the obligation to respect the patients autonomy. For
example, a patient may desire to deliver a fatally mal-
formed fetus by cesarean because she believes that this pro-
cedure will increase the newborns chance of surviving, if
only for a few hours. However, in the physicians best judg-
ment, the theoretical benefit to a nonviable infant may
not justify the risks of the surgical delivery to the woman.
In such a situation, the physicians task is further compli-
cated by the need to consider the patients psychologic,
physical, and spiritual well-being.
Justice
Justice is the principle of rendering to others what is due
to them. It is the most complex of the ethical principles to
be considered because it deals not only with the physi-
cians obligation to render to a patient what is owed but
also with the physicians role in the allocation of limited
medical resources in the broader community. In addition,
various criteria such as need, effort, contribution, and
merit are important in determining what is owed and to
whom it is owed. Justice is the obligation to treat equally
those who are alike or similar according to whatever cri-
teria are selected. Individuals should receive equal treat-
ment unless scientific and clinical evidence establishes
One Case Study: Five Approaches
Although the several approaches to ethical decision making
may all produce the same answer in a situation that requires
a decision, they focus on different, though related, aspects
of the situation and decision. Consider, for instance, how
they might address interventions for fetal well-being if a
pregnant woman rejects medical recommendations or
engages in actions that put the fetus at risk.*
A principle-based approach would seek to identify the
principles and rules pertinent to the case. These might
include beneficencenonmaleficence to both the pregnant
woman and her fetus, justice to both parties, and respect for
the pregnant womans autonomous choices. These princi-
ples cannot be applied mechanically. After all, it may be
unclear whether the pregnant woman is making an
autonomous decision, and there may be debates about the
balance of probable benefits and risks of interventions to all
the stakeholders as well as about which principle should
take priority in this conflict. Professional codes and com-
mentaries may offer some guidance about how to resolve
such conflicts.
A virtue-based approach would focus on the courses of
action to which different virtues would and should dispose
the obstetriciangynecologist. For instance, which course
of action would follow from compassion? From respectful-
ness? And so forth. In addition, the obstetriciangynecolo-
gist may find it helpful to ask more broadly: Which course
of action would best express the character of a good
physician?
An ethic of care would concentrate on the implications of
the virtue of caring in the obstetriciangynecologists spe-
cial relationship with the pregnant women and with the
fetus. In the process of deliberation, individuals using this
approach generally would resist viewing the relationship
between the pregnant woman and her fetus as adversarial,
acknowledging that most of the time women are paradig-
matically invested in their fetus well-being and that mater-
nal and fetal interests usually are aligned.* If, however, a
real conflict does exist, the obstetriciangynecologist
should resist feeling the need to take one side or the other.
Instead, he or she should seek a solution in identifying and
balancing his or her duties in these special relationships,
situating these duties in the context of a pregnant womans
values and concerns, instead of specifying and balancing
abstract principles or rights.
To take one example, in considering a case of a pregnant
woman in preterm labor who refuses admission to the hos-
pital for bed rest or tocolytics, Harris combines a care or
relational perspective with a feminist perspective to provide
a much wider gaze than a principle-based approach
might*:
The clinician would focus attention on important
social and family relationships, contexts or con-
straints that might come to bear on [a] pregnant
[womans] decision making, such as her need to care
for other children at home or to continue working to
support other family members, or whatever life pro-
ject occupied her, and attempt to provide relief in
those areas.[Often] fetal well-being is achieved
when maternal well-being is achieved.
As this example suggests, a feminist ethics approach
would attend to the social structures and factors that limit
and control the pregnant womans options and decisions in
this situation and would seek to alter any that can be
changed.* It also would consider the implications any inter-
vention might have for further control of womens choices
and actionsfor instance, by reducing a pregnant woman,
in extreme cases, to the status of fetal container or incu-
bator.
Finally, a case-based approach would consider whether
there are any relevantly similar cases that constitute prece-
dents for the current one. For instance, an obstetrician
gynecologist may wonder whether to seek a court order for
a cesarean delivery that he or she believes would increase
the chances of survival for the child-to-be but that the preg-
nant woman continues to reject. In considering what to do,
the physician may ask, as some courts have asked, whether
there is a helpful precedent in the settled consensus of not
subjecting a nonconsenting person to a surgical procedure
to benefit a third party, for instance, by removing an organ
for transplantation.
. Yet,
recent developments in the legal doctrine are few, and the
most serious current questions are ethical ones before
they become issues in the law. As the Presidents Commis-
sion reported in 1982, Although the informed consent
doctrine has substantial foundations in law, it is essential-
ly an ethical imperative (8). What above all bears review-
ing, then, is the ethical dimension of the meaning, basis,
and application of informed consent.
Although informed consent has both legal and ethi-
cal implications, its purpose is primarily ethical in nature.
As an ethical doctrine, informed consent is a process of
communication whereby a patient is enabled to make an
informed and voluntary decision about accepting or
declining medical care. There are important legal aspects
to informed consent that should not be overlooked. It is
critical for physicians to document the contents of this
conversation as part of the permanent medical record. A
signed consent document, however, does not ensure that
the process of informed consent has taken place in a
meaningful way or that the ethical requirements have
been met.
The Ethical Meaning of Informed
Consent
The ethical concept of informed consent contains two
major elements: 1) comprehension (or understanding)
and 2) free consent. Both of these elements together
constitute an important part of a patients self-determi-
nation (the taking hold of her own life and action,
determining the meaning and the possibility of what she
every year
Flexible sigmoidoscopy every 5 years
Fecal occult blood testing or fecal
immunochemical testing
) codes
(8670186703).
Although CDC and ACOG both recommend that
reproductive-aged women be tested at least once in their
lifetime, there is no consensus regarding how often
women should be retested. The American College of
Obstetricians and Gynecologist recommends that
obstetriciangynecologists annually review patients risk
factors for HIV and assess the need for retesting. Repeat
HIV testing should be offered at least annually to women
who:
Are injection drug users
Have sex partners who are injection drug users or are
infected with HIV
Exchange sex for drugs or money
Have received a diagnosis of another sexually trans-
mitted disease in the past year
Have had more than one sex partner since their most
recent HIV test
Obstetriciangynecologists also should encourage
women and their prospective sex partners to be tested
before initiating a new sexual relationship. In addition,
periodic retesting could be considered even in the absence
of risk factors depending on clinical judgment and the
patients wishes because patients may be concerned about
their status but not know about or want to disclose risk-
taking behavior to their physicians.
Although HIV-negative test results may be conveyed
without direct personal contact, HIV-positive test results
should be communicated confidentially and in person by
a physician, nurse, or other skilled staff member. Women
who are infected with HIV should receive or be referred
for appropriate clinical and supportive care.
Rapid test results usually will be available during the
same clinical visit that the specimen (eg, blood or oral
swab sample) is collected. Obstetriciangynecologists who
use these tests must be prepared to provide counseling to
women who receive positive rapid test results the same
day that the specimen is collected (ie, women with posi-
tive rapid test results should be counseled regarding the
meaning of these preliminarily positive test results and
the need for confirmatory testing) (4). Obstetrician
gynecologists should develop links with individuals who
can provide these counseling services on an emergent
basis or train their own staff to handle the initial
encounter and, thereafter, transition infected individuals
to professionals who can serve as ongoing resources to
them. Women whose confirmatory testing yields positive
results and, therefore, are infected with HIV should
receive or be referred to appropriate clinical and support-
ive care.
Resources
American College of Obstetricians and Gynecologists
409 12th Street SW, PO Box 96920
Washington, DC 20090-6920
202-638-5577
ACOG HIV resources: www.acog.org/goto/HIV
National HIV/AIDS Clinicians Consultation Center
UCSF Department of Family and Community Medicine at
San Francisco General Hospital
1001 Potrero Ave., Bldg. 20, Ward 22
San Francisco, CA 94110
415-206-8700
National HIV Telephone Consultation Service:
1-800-933-3413 (MF, 8 AM8 PM [EST])
www.nccc.ucsf.edu
American Academy of HIV Medicine, American Medical
Association. Coding guidelines for routine HIV testing in
health care settings. Washington, DC: AAHIVM; Chicago (IL):
AMA; 2008. Available at: http://aahivm.org/images/stories/
pdfs/brochure_reimburse_guide_routinehivtest.pdf. Retrieved
May 6, 2008.
References
1. Branson BM, Handsfield HH, Lampe MA, Janssen RS,
Taylor AW, Lyss SB, et al. Revised recommendations for HIV
testing of adults, adolescents, and pregnant women in
health-care settings. Centers for Disease Control and
Prevention (CDC). MMWR Recomm Rep 2006;55(RR-
14):117; quiz CE14.
2. Palella FJ Jr, Deloria-Knoll M, Chmiel JS, Moorman AC,
Wood KC, Greenberg AE, et al. Survival benefit of initiating
antiretroviral therapy in HIV-infected persons in different
CD4+ cell strata. HIV Outpatient Study Investigators. Ann
Intern Med 2003;138:6206.
3. U.S. Public Health Service Task Force. Recommendations
for use of antiretroviral drugs in pregnant HIV-infected
women for maternal health and interventions to reduce
perinatal HIV transmission in the United States. Rockville
(MD): USPHSTF; 2007. Available at: http://www.aidsinfo.
nih.gov/contentfiles/PerinatalGL.pdf. Retrieved March 7,
2008.
4. Human immunodeficiency virus. ACOG Committee
Opinion No. 389. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2007;110:14738.
*Current Procedural Terminology (CPT)
. The AMA
assumes no liability for the data contained herein. CPT
is a trademark
of the American Medical Association.
COMPENDIUM OF SELECTED PUBLICATIONS 374 374
5. Jamieson DJ, Cohen MH, Maupin R, Nesheim S, Danner
SP, Lampe MA, et al. Rapid human immunodeficiency
virus-1 testing on labor and delivery in 17 US hospitals: the
MIRIAD experience. Am J Obstet Gynecol 2007;197(suppl
1):S72S82.
Copyright August 2008 by the American College of Obstetricians
and Gynecologists, 409 12th Street, SW, PO Box 96920, Washington,
DC 20090-6920. All rights reserved. No part of this publication may be
reproduced, stored in a retrieval system, posted on the Internet, or
transmitted, in any form or by any means, electronic, mechanical,
photocopying, recording, or otherwise, without prior written permis-
sion from the publisher. Requests for authorization to make photo-
copies should be directed to: Copyright Clearance Center, 222
Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
Routine human immunodeficiency virus screening. ACOG Committee
Opinion No. 411. American College of Obstetricians and Gynecolo-
gists. Obstet Gynecol 2008;112:4013.
ISSN 1074-861X
375 COMMITTEE OPINIONS 375
Aromatase Inhibitors in Gynecologic
Practice
ABSTRACT: Aromatase inhibitors appear to be effective as an adjuvant treatment
for early-stage and late-stage breast cancer. Their role in chemoprevention of breast can-
cer in high-risk patients remains to be defined. Side effects of aromatase inhibitors in
postmenopausal women are due to estrogen-lowering action at the target tissues and
include hot flushes, vaginal dryness, arthralgias, and decreased bone mineral density. In
reproductive-aged women, aromatase inhibitors stimulate gonadotropin secretion and
increase ovarian follicular activity. The role of aromatase inhibitors in the treatment of
endometriosis and in ovulation induction is still being investigated.
Committee on
Gynecologic
Practice
This document reflects
emerging clinical and sci-
entific advances as of the
date issued and is subject
to change. The informa-
tion should not be con-
strued as dictating an
exclusive course of treat-
ment or procedure to be
followed.
Number 412 August 2008
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
The pharmacologic manipulation of hor-
mone levels has been very successful in the
treatment of estrogen-dependent disease
processes such as breast cancer, endometrio-
sis, and uterine leiomyomas. As part of this
approach, aromatase inhibitors have been
introduced for the treatment of breast cancer
and, more recently, endometriosis. Aromatase
inhibitors also have been used as ovulation
induction agents.
The aromatase enzyme is a cytochrome
P-450 complex encoded by a single gene, and
it is widely expressed in tissues, such as brain,
breast, placenta, ovary, testes, endometrium,
skin, bone, and fat. Within these tissues, aro-
matase mediates the conversion of andros-
tenedione to estrone and testosterone to
estradiol in situ. Thus, for tissues that express
this enzyme, conversion of circulating andro-
gens from an adrenal or ovarian source will
significantly increase the in situ estrogen
concentrations and provide these tissues with
a proliferative advantage.
Three aromatase inhibitors are currently
available in the United States. Exemestane is a
steroid-derived aromatase inhibitor that
binds irreversibly to aromatase and perma-
nently inactivates the available enzyme.
Letrozole and anastrozole are reversible
inhibitors of aromatase that compete with
androgens for aromatase binding sites. All
three aromatase inhibitors appear to have
similar clinical efficacy despite these differ-
ences in pharmacologic properties.
In postmenopausal women, aromatase
inhibitors were first introduced for the treat-
ment of advanced breast cancer. Although
these compounds did not increase overall
survival, they appeared to be similar or better
than megestrol when objective responses
were the endpoint (1). The early success of
these studies led to clinical trials of aromatase
inhibitors in breast cancer patients with
resectable, estrogen receptor-positive tumors.
The largest of these trials compared anastro-
zole with tamoxifen, alone or in combina-
tion, as adjuvant treatment in women with
early breast cancer following surgical resec-
tion. The study results demonstrated a small
but significantly improved 3-year disease-
free survival in postmenopausal women with
invasive, operable breast cancer who received
anastrazole alone compared with tamoxifen
(89.4% versus 87.4%, hazard ratio 0.83 [95%
confidence interval, 0.710.96]) (2). Subse-
quent trials have been initiated to examine
the effectiveness of aromatase inhibitors in
other breast cancer clinical scenarios, includ-
ing the use of aromatase inhibitors as a
sequential therapy following tamoxifen, aro-
matase inhibitors for the treatment of ductal
carcinoma in situ, and aromatase inhibitors
for the prevention of breast cancer in high-
risk patients (3). Although data from these
ACOG COMMITTEE OPINION
COMPENDIUM OF SELECTED PUBLICATIONS 376 376
trials are not complete, it appears that aromatase
inhibitors will play a significant role in therapy for estro-
gen receptor-positive breast cancer.
The short-term and long-term adverse effects of aro-
matase inhibitors in postmenopausal women are related
to lack of estrogen action at aromatase-targeted tissue
sites. These side effects include hot flushes, vaginal dry-
ness, arthralgias, decreased bone mineral density, and an
increased fracture rate (4). The American Society of
Clinical Oncologists recommends that bone mineral
density screening be repeated annually in all patients
receiving aromatase inhibitor adjuvant therapy, and
bisphosphonate therapy should be initiated when T
scores are 2.5 or lower (5). To reduce the risk of osteo-
porosis in high-risk patients, bisphosphonates may be co-
administered to patients during long-term treatment
with aromatase inhibitors.
In contrast to tamoxifen, aromatase inhibitors are
associated with a reduced incidence of thrombosis (6)
and endometrial cancer (7), and a reduction in vaginal
bleeding. Although the results of early studies suggest that
aromatase inhibitors have adverse effects on the cardio-
vascular system and lipid profiles compared with tamox-
ifen, these effects are milder or have not been seen when
comparing aromatase inhibitors with placebo. This sug-
gests that aromatase inhibitors lack the protective effects
found with tamoxifen rather than exhibit true toxicity
(8). Increased cardiovascular morbidity or mortality
through poor lipid profiles or other mechanisms has not
been clearly established in patients treated with aro-
matase inhibitors compared with tamoxifen or placebo
(9). More rigorous study is required in this area because
most of the trials were not designed to address cardiac
disease.
Aromatase inhibitors also have been used as treat-
ment for premenopausal women with early breast cancer
who have chemotherapy-induced amenorrhea. This off-
label use should be prescribed with caution because case
series have described the resumption of ovarian function
following initiation of an aromatase inhibitor regimen
(10, 11). Serial monitoring of estradiol and gonadotropin
levels to identify women who experience a return of ovar-
ian function may be indicated (10).
In premenopausal women, aromatase inhibitors
reduce hypothalamicpituitary estrogen feedback that
leads to increased gonadotropin-releasing hormone
(GnRH) secretion, concomitant elevations in luteini-
zing hormone and follicle-stimulating hormone, and
increased ovarian follicular development. The gonado-
tropin-stimulating action of letrozole has been used
off-label in the treatment of patients with ovulatory
dysfunction, such as polycystic ovary syndrome, and for
increasing the number of ovarian follicles recruited for
ovulation in women who are already ovulatory (12, 13).
In a meta-analysis of four published trials, including 662
women with polycystic ovary syndrome, pregnancy rates
were similar between women treated with clomiphene
and women treated with letrozole (relative risk, 1.02; 95%
confidence interval, 0.831.26) (14). Some have raised
concerns about this off-label use because letrozole may
disrupt the normal aromatase activity in tissues during
early fetal development and can be potentially teratogenic
if administered inadvertently during early pregnancy.
However, a large study of 911 newborns conceived using
letrozole for ovulation induction showed no difference in
rates of congenital malformations (15). In addition, the
half-life of letrozole (approximately 3060 hours) is
shorter than that of clomiphene citrate (57 days) and,
thus, should be effectively cleared from the body by the
time of embryo implantation, likely preventing a terato-
genic effect when used in ovulation induction (14).
Possible advantages of letrozole over clomiphene citrate
include reduced multiple pregnancies, lower estradiol lev-
els, and an absence of antiestrogenic adverse effects on the
endometrium. However, there is no evidence that letro-
zole is more effective than clomiphene for ovulation
induction. Letrozole may have a role in the treatment of
clomiphene-resistant patients (16).
The recent demonstration that aromatase is
expressed at higher levels in endometriosis implants than
in normal endometrium has led to pilot studies using
anastrozole co-administered with progestins in patients
with endometriosis resistant to conventional medical and
surgical therapies (17). These small studies suggest that
aromatase inhibitors could reduce endometriosis-associ-
ated pelvic pain, whereas the progestin could effectively
suppress gonadotropins and reduce ovarian activity.
Results of subsequent trials have shown similar efficacy
for relief of pelvic pain when aromatase inhibitors were
combined with combination oral contraceptives (18), or
when aromatase inhibitors were given concomitantly
with a GnRH agonist (19). There are no randomized con-
trolled trials comparing aromatase inhibitors with tradi-
tional medical treatment for endometriosis. Side effect
profiles of aromatase inhibitor regimens (including a
progestin or oral contraceptive as add-back therapy) are
favorable compared with regimens containing GnRH
agonists or danazol. These aromatase inhibitor regimens
with add-back progestin or oral contraceptives do not
appear to be associated with significant bone loss after 6
months of treatment and may be suitable for long-term
use (20). Randomized controlled trials are needed to
establish the efficacy and side effects of these regimens.
Aromatase inhibitors appear to be effective as an
adjuvant treatment for early-stage and late-stage breast
cancer. Their role in chemoprevention of breast cancer in
high-risk patients remains to be defined. Side effects of
aromatase inhibitors in postmenopausal women are due
to estrogen-lowering action at the target tissues and
include hot flushes, vaginal dryness, arthralgias, and
decreased bone mineral density. Although there are no
long-term data with regard to side effects and complica-
tions associated with the use of aromatase inhibitors in
breast cancer patients, the overall safety profile of aro-
377 COMMITTEE OPINIONS 377
matase inhibitors is good, with less endometrial and
thromboembolic toxicity than tamoxifen. In reproduc-
tive-aged women, aromatase inhibitors stimulate
gonadotropin secretion and increase ovarian follicular
activity. The role of aromatase inhibitors in the treatment
of endometriosis and in ovulation induction is still being
investigated.
References
1. Buzdar AU, Jonat W, Howell A, Jones SE, Blomqvist CP,
Vogel CL, et al. Anastrozole versus megestrol acetate in the
treatment of postmenopausal women with advanced breast
carcinoma: results of a survival update based on a com-
bined analysis of data from two mature phase III trials.
Arimidex Study Group. Cancer 1998;83:114252.
2. Baum M, Budzar AU, Cuzick J, Forbes J, Houghton JH,
Klijn JG, et al. Anastrozole alone or in combination with
tamoxifen versus tamoxifen alone for adjuvant treatment of
postmenopausal women with early breast cancer: first
results of the ATAC randomised trial. Lancet 2002;359:
21319.
3. Bickenbach KA, Jaskowiak N. Aromatase inhibitors: an
overview for surgeons. J Am Coll Surg 2006;203:37689.
4. Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes
JF, et al. Results of the ATAC (Arimidex, Tamoxifen, Alone
or in Combination) trial after completion of 5 years adju-
vant treatment for breast cancer. Lancet 2005;365:602.
5. Hillner BE, Ingle JN, Chlebowski RT, Gralow J, Yee GC,
Janjan NA, et al. American Society of Clinical Oncology 2003
update on the role of bisphosphonates and bone health
issues in women with breast cancer. J Clin Oncol 2003;21:
404257.
6. Coombes RC, Hall E, Gibson LJ, Paridaens R, Jassem J,
Delozier T, et al. A randomized trial of exemestane after two
to three years of tamoxifen therapy in postmenopausal
women with primary breast cancer. N Engl J Med 2004;
350:108192.
7. Jakesz R, Jonat W, Gnant M, Mittlboeck M, Greil R, Tausch
C, et al. Switching of postmenopausal women with
endocrine-responsive early breast cancer to anastrozole
after 2 years adjuvant tamoxifen: combined results of
ABCSG trial 8 and ARNO 95 trial. Lancet 2005;366:45562.
8. Conte P, Frassoldati A. Aromatase inhibitors in the adjuvant
treatment of postmenopausal women with early breast can-
cer: Putting safety issues into perspective. Breast J 2007;
13:2835.
9. Gandhi S, Verma S. Aromatase inhibitors and cardiac toxic-
ity: getting to the heart of the matter. Breast Cancer Res
Treat 2007;106:19.
10. Smith IE, Dowsett M, Yap YS, Walsh G, Lonning PE, Santen
RJ, et al. Adjuvant aromatase inhibitors for early breast can-
cer after chemotherapy-induced amenorrhoea: caution and
suggested guidelines. J Clin Oncol 2006;24:24447.
11. Burstein HJ, Mayer E, Patridge AH, OKane H, Litsas G,
Come SE, et al. Inadvertent use of aromatase inhibitors in
patients with breast cancer with residual ovarian function:
cases and lessons. Clin Breast Cancer 2006;7:15861.
12. Fisher SA, Reid RL, Van Vugt DA, Casper RF. A randomized
double-blind comparison of the effects of clomiphene cit-
rate and the aromatase inhibitor letrozole on ovulatory
function in normal women. Fertil Steril 2002;78:2805.
13. Bedaiwy MA, Forman R, Mousa NA, Al Inany HG, Casper
RF. Cost-effectiveness of aromatase inhibitor co-treatment
for controlled ovarian stimulation. Hum Reprod 2006;
21:283844.
14. Casper RF. Letrozole versus clomiphene citrate: which is
better for ovulation induction? Fertil Steril 2007 June 21.
DOI: 10.1016/j.fertnstert.2007.03.094.
15. Tulandi T, Martin J, Al-Fadhli R, Kabli N, Forman R, Hitkari
J, et al. Congenital malformations among 911 newborns
conceived after infertility treatment with letrozole or
clomiphene citrate. Fertil Steril 2006;85:17615.
16. Badawy A, Abdel Aal I, Abulatta M. Clomiphene citrate or
letrozole for ovulation induction in women with polycystic
ovarian syndrome: a prospective randomized trial. Fertil
Steril 2007 Jun 18. DOI: 10.1016/j.fertnstert.2007.02.062.
17. Ailawadi RK, Jobanputra S, Kataria M, Gurates B, Bulun SE.
Treatment of endometriosis and chronic pelvic pain with
letrozole and norethindrone acetate: a pilot study. Fertil
Steril 2004;81:2906.
18. Amsterdam LL, Gentry W, Jobanputra S, Wolf M, Rubin
SD, Bulun SE. Anastrazole and oral contraceptives: a novel
treatment for endometriosis. Fertil Steril 2005;84:3004.
19. Soysal S, Soysal ME, Ozer S, Gul N, Gezgin T. The effects of
post-surgical administration of goserelin plus anastrozole
compared to goserelin alone in patients with severe
endometriosis: a prospective randomized trial. Hum
Reprod 2004;19:1607.
20. Attar E, Bulun SE. Aromatase inhibitors: the next genera-
tion of therapeutics for endometriosis? Fertil Steril 2006;85:
130718.
Copyright August 2008 by the American College of Obstetricians
and Gynecologists, 409 12th Street, SW, PO Box 96920, Washington,
DC 20090-6920. All rights reserved. No part of this publication may be
reproduced, stored in a retrieval system, posted on the Internet, or
transmitted, in any form or by any means, electronic, mechanical,
photocopying, recording, or otherwise, without prior written permis-
sion from the publisher. Requests for authorization to make photo-
copies should be directed to: Copyright Clearance Center, 222
Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
Aromatase inhibitors in gynecologic practice. ACOG Committee
Opinion No. 412. American College of Obstetricians and Gynecolo-
gists. Obstet Gynecol 2008;112:4057.
ISSN 1074-861X
COMPENDIUM OF SELECTED PUBLICATIONS 378 378
Age-Related Fertility Decline
ABSTRACT: Age is a significant factor influencing a womans ability to conceive.
Social trends have led to deferred childbearing, and an increasing number of women are
experiencing age-related infertility and pregnancy loss. Women older than 35 years
should receive expedited evaluation and treatment after 6 months of failed attempts to
conceive, or earlier if clinically indicated.
Committee on
Gynecologic
Practice
This document reflects
emerging clinical and sci-
entific advances as of the
date issued and is subject
to change. The informa-
tion should not be con-
strued as dictating an
exclusive course of treat-
ment or procedure to be
followed.
Number 413 August 2008
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
The number of oocytes in the ovaries
declines naturally and progressively through
the process of atresia. The maximum com-
plement of oocytes is 67 million and exists
at 20 weeks of gestation in the female fetus.
The number of oocytes decreases to approx-
imately 12 million oocytes at birth;
300,000500,000 at puberty; 25,000 at age
37 years; and 1,000 at age 51 years, the aver-
age age of menopause in the United States
(13). Fecundity declines gradually but sig-
nificantly beginning approximately at age 32
years, and decreases more rapidly after age 37
years, reflecting primarily a decrease in egg
quality in association with a gradual increase
in the circulating level of follicle-stimulating
hormone (3). The mechanisms involved are
poorly understood, but appear to include
multiple factors encoded by genes on both
the X chromosome and the autosomes (4).
Age alone has an impact on fertility.
Historical data suggest that among popula-
tions that do not use contraception, fertility
rates decrease with increasing age of women
(Fig. 1). Because sexual activity also declines
with age, it is difficult to separate out the
effects of sexual behavior from age. However,
a classic French study was able to separate
behavioral and age effects by studying nor-
mal women with azoospermic husbands
undergoing donor insemination. The study
found that pregnancy rates decreased pro-
gressively with increasing age of the recipient
female (5). The cumulative pregnancy rate
observed across up to 12 insemination cycles
was 74% for women younger than 31 years
and decreased to 62% for women aged 3135
years and to 54% for women older than 35
years (5). A similar trend has been observed
in analyses of data derived from in vitro fer-
tilization (IVF) embryo transfer programs in
the United States. For the year 2006, the per-
centage of embryo transfers resulting in live
births decreased progressively from 44.9% in
women younger than 35 years to 37.3% for
women aged 3537 years, 26.6% for women
aged 3840 years, 15.2% for women aged 41
42 years, and 6.7% for women aged 4344
years (6). By contrast, in cycles using eggs
obtained from healthy, young donors, 54% of
transfers resulted in a live birth, regardless of
the age of the recipient (6). As age increases,
the risks of other disorders that may adversely
affect fertility, such as fibroids, tubal disease,
and endometriosis, also increase. Women
with a history of prior ovarian surgery,
chemotherapy, radiation therapy, severe
endometriosis, smoking, pelvic infection, or
a strong family history of early menopause
may be at increased risk for having a prema-
ture decline in the size of their follicular pool
and their fertility.
The age-related decline in fertility is
accompanied by a significant increase in the
rates of aneuploidy and spontaneous abor-
tion (7). Autosomal trisomy is the most fre-
quent finding and is related, at least in part,
to changes in the meiotic spindle (8) that
predispose to nondisjunction (9). Even for
morphologically normal embryos selected
for transfer in IVF cycles, the prevalence of
aneuploidy is high in women of advanced
maternal age (10). The fetal loss rate also is
significantly higher, even after fetal heart rate
motion is detected by transvaginal ultra-
sonography (11). Whereas 9.9% of women
American Society for
Reproductive
Medicine
ACOG COMMITTEE OPINION
379 COMMITTEE OPINIONS 379
600
500
400
300
200
100
0
younger than 33 years who conceive during IVF with a
fresh embryo transfer experience a pregnancy loss after
fetal heart activity is observed, the rate of miscarriage
progressively increases to 11.4% for women aged 3334
years, 13.7% for women aged 3537 years, 19.8% for
women aged 3840 years, 29.9% for women aged 4142
years, and 36.6% for women older than age 42 years (11).
Therefore, given the anticipated age-related decline in fer-
tility, the increased incidence of disorders that impair fer-
tility, and the higher risk of pregnancy loss, women older
than 35 years should receive expedited evaluation and
treatment after 6 months of failed attempts to conceive,
or earlier if clinically indicated.
In conclusion, fertility in women is closely related to
reproductive age and becomes significantly compromised
before the onset of perimenopausal menstrual irregulari-
ty. Education and enhanced awareness of the impact of
age on fertility is essential in counseling the patient who
desires pregnancy. Women older than 35 years should
receive expedited evaluation and treatment after 6
months of failed attempts to conceive, or earlier if clini-
cally indicated.
References
1. Baker TG. A quantitative and cytological study of germ cells
in human ovaries. Proc R Soc Lond B Biol Sci 1963;158:
41733.
2. Block E. Quantitative morphological investigations of the
follicular system in women; variations at different ages. Acta
Anat (Basel) 1952;14:10823.
3. Faddy MJ, Gosden RG, Gougeon A, Richardson SJ, Nelson
JF. Accelerated disappearance of ovarian follicles in mid-
life: implications for forecasting menopause. Hum Reprod
1992;7:13426.
4. Simpson JL. Genetic programming in ovarian development
and oogenesis. In: Lobo RA, Kelsey J, Marcus R, editors.
Menopause: biology and pathobiology. San Diego (CA):
Academic Press; 2000. p. 7794.
5. Schwartz D, Mayaux MJ. Female fecundity as a function of
age: results of artificial insemination in 2193 nulliparous
women with azoospermic husbands. Federation CECOS.
N Engl J Med 1982;306:4046.
6. Society for Assisted Reproductive Technology. Clinic sum-
mary report: all SART member clinics. Birmingham (AL):
SART; 2007. Available at: https://www.sartcorsonline.com/
rptCSR_PublicMultYear.aspx?ClinicPKID=0. Retrieved
March 18, 2008.
Fig.1. Marital fertility rates by 5-year age groups. The ten populations (in descending order at
age 2024 years) are Hutterites, marriages from 192130 (); Geneva bourgeoisie, husbands
born in 160049 (); Canada, marriages 170030 (); Normandy, marriages 176090 ( );
Hutterites, marriages before 1921 ( ); Tunis, marriages of Europeans 184059 ( );
Normandy, marriages 16741742 (); Norway, marriages 187476 ( ); Iran, village mar-
riages, 194050 (); Geneva bourgeoisie, husbands born before 1600 ( ). From Menken J,
Trussel J, Larsen U. Age and infertility. Science 1986;233:138994. Reprinted with permission
from AAAS.
20 25 30 35 40 45 50
R
a
t
e
p
e
r
1
,
0
0
0
w
i
v
e
s
Age of wife
COMPENDIUM OF SELECTED PUBLICATIONS 380 380
7. Newcomb WW, Rodriguez M, Johnson JW. Reproduction
in the older gravida. A literature review. J Reprod Med
1991;36:83945.
8. Battaglia DE, Goodwin P, Klein NA, Soules MR. Influence
of maternal age on meiotic spindle assembly in oocytes
from naturally cycling women. Hum Reprod 1996;11:
221722.
9. Pellestor F, Andreo B, Arnal F, Humeau C, Demaille J.
Maternal aging and chromosomal abnormalities: new data
drawn from in vitro unfertilized human oocytes. Hum
Genet 2003;112:195203.
10. Munne S, Alikani M, Tomkin G, Grifo J, Cohen J. Embryo
morphology, developmental rates, and maternal age are
correlated with chromosome abnormalities. Fertil Steril
1995;64:38291.
11. Farr SL, Schieve LA, Jamieson DJ. Pregnancy loss among
pregnancies conceived through assisted reproductive tech-
nology, United States, 1999-2002. Am J Epidemiol 2007;165:
13808.
Copyright August 2008 by the American College of Obstetricians
and Gynecologists, 409 12th Street, SW, PO Box 96920, Washington,
DC 20090-6920. All rights reserved. No part of this publication may be
reproduced, stored in a retrieval system, posted on the Internet, or
transmitted, in any form or by any means, electronic, mechanical,
photocopying, recording, or otherwise, without prior written permis-
sion from the publisher. Requests for authorization to make photo-
copies should be directed to: Copyright Clearance Center, 222
Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
Age-related fertility decline. ACOG Committee Opinion No. 413.
American College of Obstetricians and Gynecologists. Obstet
Gynecol 2008;112:40911.
ISSN 1074-861X
381 COMMITTEE OPINIONS 381
ACOG COMMITTEE OPINION
Hormone Therapy and Heart Disease
ABSTRACT: The effect of menopausal hormone therapy on coronary heart disease
has been the subject of much concern. The Heart and Estrogen/Progestin Replacement
Study (HERS) and Womens Health Initiative studies found an increased risk of cardiovas-
cular events with conjugated equine estrogen and medroxyprogesterone acetate use.
However, recent evidence suggests that women in early menopause who are in good
cardiovascular health are at low risk of adverse cardiovascular outcomes and as such
should be considered candidates for the use of conjugated equine estrogen or conjugat-
ed equine estrogen and medroxyprogesterone acetate for relief of menopausal vasomo-
tor symptoms. Hormone therapy use should be limited to the treatment of menopausal
symptoms at the lowest effective dosage over the shortest duration possible, and con-
tinued use should be reevaluated on a periodic basis.
Committee on
Gynecologic
Practice
This document reflects
emerging clinical and sci-
entific advances as of the
date issued and is subject
to change. The informa-
tion should not be con-
strued as dictating an
exclusive course of treat-
ment or procedure to be
followed.
Number 420 November 2008
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
More than two decades of accumulated evi-
dence suggested that women taking estrogen
plus progesterone hormone therapy (HT)
and estrogen therapy (ET) alone gained pro-
tection against coronary heart disease
(CHD). Notably criticized, these largely
observational studies were confounded by
superior cardiovascular health profiles
among participants electing to use HT or ET.
To assess fully the role of HT and ET for
CHD protection among menopausal
women, large-scale randomized, controlled
clinical trials were begun. Recent evidence
suggesting cardioprotective effects of HT
and ET has sparked debate regarding the
possibility of a timing hypothesis (ie,
women who recently experienced meno-
pause may be more likely to benefit from HT
than women who have been menopausal for
a longer period) (1, 2).
Among menopausal women with
known CHD, the Heart and Estrogen/Pro-
gestin Replacement Study (HERS) examined
whether conjugated equine estrogen and
medroxyprogesterone acetate altered CHD
risk (3). After 4 years of follow-up, the study
did not demonstrate an overall reduction
in CHD risk. Those receiving conjugated
equine estrogen and medroxyprogesterone
acetate exhibited a 52% increase in CHD and
a 34-fold increase in venous thromboem-
bolic events during the first and second years
of use.
In 2002, the Womens Health Initiative
(WHI), a CHD prevention trial among pre-
dominantly healthy menopausal women,
published its initial results after 5.2 years of
follow-up (4). The study was prematurely ter-
minated because of reports of adverse cardio-
vascular effects and a worsened global index.
Not only did conjugated equine estrogen and
medroxyprogesterone acetate not provide
protection against CHD, but its use also
imparted a 29% increase in CHD-related
events (37 versus 30 per 10,000 woman-years)
that developed soon after randomization.
Notably, most CHD events attributed to con-
jugated equine estrogen and medroxyproges-
terone acetate use were nonfatal myocardial
infarctions, and there were no significant dif-
ferences in overall CHD deaths (hazard ratio
(HR): 1.18; 95% CI, 0.701.97). Unlike prior
randomized studies (5, 6), WHI associated
conjugated equine estrogen and medroxy-
progesterone acetate use with a 41%
increased stroke risk, mostly nonfatal events
(29 versus 21 per 10,000 woman-years) that
became apparent between the first and sec-
ond year of use. Consistent with the HERS
trial, WHI provided further evidence that
conjugated equine estrogen and medroxy-
progesterone acetate increased venous throm-
COMPENDIUM OF SELECTED PUBLICATIONS 382 382
boembolism and pulmonary embolism risks twofold
(venous thromboembolism: 34 versus 16 per 10,000
woman-years; pulmonary embolism: 16 versus 8 per
10,000 woman-years). Time-trend analyses suggested that
the risk of CHD and pulmonary embolism began to
occur immediately following the initiation of HT. Similar
to HERS, the conjugated equine estrogen and medroxy-
progesterone acetate arm of the WHI indicated that there
was a 26% increase in invasive breast cancer (38 versus 30
per 10,000 woman-years). Benefits associated with conju-
gated equine estrogen and medroxyprogesterone acetate
use in the WHI trial included a 37% reduction in colorec-
tal carcinoma rates (10 versus 16 per 10,000 woman-
years) and reduced incidence of hip (10 versus 15 per
10,000 woman-years) and vertebral fractures (9 versus 15
per 10,000 woman-years).
Nearly 2 years later, the conjugated equine estrogen
alone study of the WHI was published after a mean of 6.8
years of follow-up, in advance of its designed observation
period because of a lack of improvement in CHD risk
(the primary outcome) and an increased rate of stroke
(7). This conjugated equine estrogen alone trial revealed
several notable differences from the initial WHI study
publications. No differences in CHD incidence were
observed among those receiving conjugated equine estro-
gen compared with placebo. Although not statistically sig-
nificant, another notable finding was that invasive breast
cancer occurred 23% less frequently in the conjugated
equine estrogen alone group compared with the control
group (HR=0.77; 95% CI, 0.591.01; P=.06). Moreover,
no differences were seen in colorectal carcinoma rates. In
line with the conjugated equine estrogen and medroxy-
progesterone acetate arm of the WHI trial, conjugated
equine estrogen alone increased stroke rates by 39% and
reduced both hip and vertebral fractures. Although deep
vein thrombosis risk was increased (21 versus 15 per
10,000 woman-years), increases in venous thromboem-
bolism and pulmonary embolism risk failed to reach sta-
tistical significance. Time-trend analyses demonstrated
an increased stroke risk immediately after randomization,
but no risk differences could be elucidated for pulmonary
embolism or CHD.
Subsequent to the aforementioned studies, the WHI
investigators have published several follow-up studies.
Consistent with previous reports, analysis directed at
extricating the HT effect on CHD risk found superior
lipid, insulin, and glucose profiles with conjugated equine
estrogen and medroxyprogesterone acetate (8). Subse-
quent data from the conjugated equine estrogen alone
arm suggested an attenuation of venous thromboem-
bolism risk by the exclusion of progestin, yet venous
thromboembolism risks were increased with HT use in
both the conjugated equine estrogen and conjugated
equine estrogen and medroxyprogesterone acetate arms
of the study after a longer mean follow-up period (conju-
gated equine estrogen: 7.1 years; conjugated equine estro-
gen and medroxyprogesterone acetate: 5.6 years) (9, 10).
Likewise, HT increased the risk of ischemic stroke in both
the conjugated equine estrogen and conjugated equine
estrogen and medroxyprogesterone acetate arms (11, 12).
Overall, the risks associated with long-term primary pre-
ventive therapy appeared to outweigh the beneficial
effects.
The mean participant age of the WHI trial exceeded
60 years and it has been suggested that the results may not
apply to women who recently experienced menopause
and for whom treatment would likely be initiated. In an
attempt to delineate the impact of age on CHD risk with
HT use, WHI data was stratified according to participant
age and duration of menopause (13). This study found
that the effects of either conjugated equine estrogen or
conjugated equine estrogen and medroxyprogesterone
acetate on CHD risk might depend, in part, on age at the
start of treatment. When analyzed according to treatment
type, a trend toward reduced total mortality with conju-
gated equine estrogen or conjugated equine estrogen and
medroxyprogesterone acetate use was noted among those
women aged 5059 years (see Table 1). When individual
treatment type data were pooled, total mortality decreased
by 30% with conjugated equine estrogen or conjugated
equine estrogen and medroxyprogesterone acetate use
(95% CI, 0.510.96). Whether conjugated equine estrogen
or conjugated equine estrogen and medroxyprogesterone
acetate administration improves the cardiovascular health
of women who recently experienced menopause remains
to be determined. Presently, there is insufficient evidence
to suggest that long-term conjugated equine estrogen or
conjugated equine estrogen and medroxyprogesterone
acetate use improves cardiovascular outcomes (1).
Nevertheless, recent evidence suggests that women in
early menopause who are in good cardiovascular health
are at low risk of adverse cardiovascular outcomes and as
such should be considered candidates for the use of con-
jugated equine estrogen or conjugated equine estrogen
and medroxyprogesterone acetate for relief of
menopausal vasomotor symptoms (2). Ongoing studies,
including the Kronos Early Estrogen Prevention Study
(KEEPS) are evaluating alterations in surrogate CHD risk
markers, including carotid intimal thickness and the
accrual of coronary calcium deposition induced by HT, in
this case conjugated equine estrogen or transdermal
estradiol patches combined with cyclic oral, micronized
progesterone.
The WHI Coronary-Artery Calcium Study (WHI-
CACS) recently evaluated 1,064 women aged 5059 years
who were previously enrolled in the conjugated equine
estrogen arm of WHI (14). Because coronary atheroscle-
rotic plaques have been associated with future CHD risk,
the investigators used computed tomography heart imag-
ing to determine the degree of coronary-artery calcium
burden. The study results indicated that the overall distri-
bution of coronary-artery calcification scores were lower
among those receiving conjugated equine estrogen com-
pared with those receiving placebo (P=.03). Furthermore,
383 COMMITTEE OPINIONS 383
Table 1. Cardiovascular and Global Index Events by Age at Baseline
for those who adhered to the study medication regimen
(80% medication adherence for 5 or more years), conju-
gated equine estrogen use was associated with a signifi-
cant reduction in the coronary-artery calcification
(OR=0.64; 95% CI, 0.46-0.91; P=.01). This preliminary
evidence, using surrogate outcome markers, needs confir-
mation of its clinical significance and correlation with
clinical outcomes. Nevertheless, it suggests that conjugat-
ed equine estrogen therapy may reduce CHD risk factors
and may provide cardiovascular protection for select
populations of women who experienced menopause
recently.
Conclusion
Menopausal HT should not be used for the primary or
secondary prevention of CHD at the present. Recent
analyses suggest that HT may not increase CHD risk for
select populations of women who have experienced
menopause recently. Hormone therapy use should be
limited to the treatment of menopausal symptoms at the
lowest effective dosage over the shortest duration possible
and continued use should be reevaluated on a periodic
basis. Some women may require extended therapy
because of persistent symptoms.
Abbreviations: CEE, conjugated equine estrogens; CHD, coronary heart disease; CI, confidence interval; HR, hazard ratio; MPA, medroxyprogesterone acetate.
*Cox regression models stratified according to prior cardiovascular disease and randomization status in the Dietary Modification Trial.
Test for trend (interaction) using age as continuous (linear) form of categorical coded values. Cox regression models stratified according to active vs placebo and trial,
including terms for age and the interaction between trials and age.
Defined as CHD death, nonfatal myocardial infarction, or definite silent myocardial infarction (Novacode 5.1 or 5.2).
Defined as CHD, stroke, pulmonary embolism, breast cancer, colorectal cancer, endometrial cancer for CEE plus MPA trial only, hip fracture, or death from other causes.
Rossouw JE, Prentice RL, Manson JE, Wu L, Barad D, Barnabei VM, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since
menopause. JAMA 2007;297:146577. April 4. Copyright 2007 American Medical Association. All rights reserved.
COMPENDIUM OF SELECTED PUBLICATIONS 384 384
References
1. Barrett-Connor E. Hormones and heart disease in women:
the timing hypothesis. Am J Epidemiol 2007;166:50610.
2. Manson JE, Bassuk SS. Invited commentary: hormone ther-
apy and risk of coronary heart disease why renew the focus
on the early years of menopause? Am J Epidemiol
2007;166:5117.
3. Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs
B, et al. Randomized trial of estrogen plus progestin for sec-
ondary prevention of coronary heart disease in post-
menopausal women. Heart and Estrogen/progestin
Replacement Study (HERS) Research Group. JAMA 1998;
280(7):60513.
4. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ,
Kooperberg C, Stefanick ML, et al. Risks and benefits of
estrogen plus progestin in healthy postmenopausal women:
principal results From the Womens Health Initiative ran-
domized controlled trial. Writing Group for Womens
Health Initiative Investigators. JAMA 2002;288(3):32133.
5. Simon JA, Hsia J, Cauley JA, Richards C, Harris F, Fong J,
et al. Postmenopausal hormone therapy and risk of stroke:
The Heart and Estrogen-progestin Replacement Study
(HERS). Circulation 2001;103:63842.
6. Grady D, Herrington D, Bittner V, Blumenthal R, Davidson
M, Hlatky M, et al. Cardiovascular disease outcomes during
6.8 years of hormone therapy: Heart and Estrogen/prog-
estin Replacement Study follow-up (HERS II). HERS
Research Group. JAMA 2002;288:4957.
7. Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford
SA, Black H, et al. Effects of conjugated equine estrogen in
postmenopausal women with hysterectomy: the Womens
Health Initiative randomized controlled trial. Womens
Health Initiative Steering Committee. JAMA 2004;291:
170112.
8. Manson JE, Hsia J, Johnson KC, Rossouw JE, Assaf AR,
Lasser NL, et al. Estrogen plus progestin and the risk of
coronary heart disease. Womens Health Initiative
Investigators. N Engl J Med 2003;349:52334.
9. Curb JD, Prentice RL, Bray PF, Langer RD, Van Horn L,
Barnabei VM, et al. Venous thrombosis and conjugated
equine estrogen in women without a uterus. Arch Intern
Med 2006;166:77280.
10. Cushman M, Kuller LH, Prentice R, Rodabough RJ, Psaty
BM, Stafford RS, et al. Estrogen plus progestin and risk of
venous thrombosis. Womens Health Initiative Investiga-
tors. JAMA 2004;292:157380.
11. Wassertheil-Smoller S, Hendrix SL, Limacher M, Heiss G,
Kooperberg C, Baird A, et al. Effect of estrogen plus prog-
estin on stroke in postmenopausal women: the Womens
Health Initiative: a randomized trial. WHI Investigators.
JAMA 2003 May;289:267384.
12. Hendrix SL, Wassertheil-Smoller S, Johnson KC, Howard
BV, Kooperberg C, Rossouw JE, et al. Effects of conjugated
equine estrogen on stroke in the Womens Health Initiative.
WHI Investigators. Circulation 2006;113:242534.
13. Rossouw JE, Prentice RL, Manson JE, Wu L, Barad D,
Barnabei VM, et al. Postmenopausal hormone therapy and
risk of cardiovascular disease by age and years since
menopause. JAMA 2007;297:146577.
14. Manson JE, Allison MA, Rossouw JE, Carr JJ, Langer RD,
Hsia J, et al. Estrogen therapy and coronary-artery calcifica-
tion. WHI and WHI-CACS Investigators. N Engl J Med
2007;356:2591602.
Copyright November 2008 by the American College of Obstetricians
and Gynecologists, 409 12th Street, SW, PO Box 96920, Washington,
DC 20090-6920. All rights reserved. No part of this publication may be
reproduced, stored in a retrieval system, posted on the Internet, or
transmitted, in any form or by any means, electronic, mechanical,
photocopying, recording, or otherwise, without prior written permis-
sion from the publisher. Requests for authorization to make photo-
copies should be directed to: Copyright Clearance Center, 222
Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
Hormone therapy and heart disease. ACOG Committee Opinion No.
420. American College of Obstetricians and Gynecologists. Obstet
Gynecol 2008;112:118992.
ISSN 1074-861X
385 COMMITTEE OPINIONS 385
ACOG COMMITTEE OPINION
Number 434 June 2009 (Replaces No. 285, August 2003)
Induced Abortion and Breast Cancer Risk
Abstract: The relationship between induced abortion and the subsequent develop-
ment of breast cancer has been the subject of a substantial amount of epidemiologic
study. Early studies of the relationship between prior induced abortion and breast cancer
risk were methodologically flawed. More rigorous recent studies demonstrate no causal
relationship between induced abortion and a subsequent increase in breast cancer risk.
Committee on
Gynecologic
Practice
This document reflects
emerging clinical and sci-
entific advances as of the
date issued and is subject
to change. The informa-
tion should not be con-
strued as dictating an
exclusive course of treat-
ment or procedure to be
followed.
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
The relationship between induced abortion
and the subsequent development of breast
cancer has been the subject of a substantial
amount of epidemiologic study. Early case
control studies that reported an association
between induced abortion and subsequent
development of breast cancer had significant
methodological problems, most notably
reliance on retrospective reporting of abor-
tion history. A key methodological consider-
ation in interpreting the evidence for any
relationship between abortion and breast
cancer risk is the sensitive nature of abortion,
which could affect the accuracy in retrospec-
tive studies that rely on participant reports of
having had an abortion.
In contrast to retrospective studies,
prospective studies conclude there is no asso-
ciation between induced abortion and breast
cancer. A world-wide meta-analysis of 83,000
women examined the relationship between
induced abortion and breast cancer and
found a significant difference between the
overall estimate of relative risk (RR) from
studies that had recorded information on
induced abortion prospectively (RR, 0.93;
95% confidence interval, 0.890.96) and the
overall estimate of RR from studies that had
recorded such information retrospectively
(RR, 1.11; 95% confidence interval, 1.091.14),
suggesting that reporting bias was probably
present in studies using retrospective report-
ing of abortion history (1).
In 2003, the National Cancer Institute
convened the Early Reproductive Events and
Breast Cancer Workshop to evaluate the cur-
rent strength of evidence of epidemiologic,
clinical, and animal studies addressing the
association between reproductive events and
the risk of breast cancer (2). The workshop
participants concluded that induced abor-
tion is not associated with an increase in
breast cancer risk. Studies published since
2003 continue to support this conclusion
(37).
Early studies of the relationship between
prior induced abortion and breast cancer risk
were methodologically flawed. More rigorous
recent studies demonstrate no causal rela-
tionship between induced abortion and a
subsequent increase in breast cancer risk.
References
1. Beral V, Bull D, Doll R, Peto R, Reeves G.
Breast cancer and abortion: collaborative
reanalysis of data from 53 epidemiological
studies, including 83,000 women with breast
cancer from 16 countries. Collaborative
Group on Hormonal Factors in Breast Cancer.
Lancet 2004;363:100716.
2. National Cancer Institute. Summary report:
early reproductive events and breast cancer
workshop. Bethesda (MD): NCI; 2003. Avail-
able at: http://www.cancer.gov/cancertopics/
ere-workshop-report. Retrieved November 6,
2008.
3. Rosenblatt KA, Gao DL, Ray RM, Rowland
MR, Nelson ZC, Wernli KJ, et al. Induced
abortions and the risk of all cancers com-
bined and site-specific cancers in Shanghai.
Cancer Causes Control 2006;17:127580.
4. Reeves GK, Kan SW, Key T, Tjonneland A,
Olsen A, Overvad K, et al. Breast cancer risk in
relation to abortion: results from the EPIC
study. Int J Cancer 2006;119:17415.
5. Michels KB, Xue F, Colditz GA, Willett WC.
Induced and spontaneous abortion and inci-
COMPENDIUM OF SELECTED PUBLICATIONS 386 386
dence of breast cancer among young women: a prospective
cohort study. Arch Intern Med 2007;167:81420.
6. Lash TL, Fink AK. Null association between pregnancy ter-
mination and breast cancer in a registry-based study of
parous women. Int J Cancer 2004;110:4438.
7. Henderson KD, Sullivan-Halley J, Reynolds P, Horn-Ross
PL, Clarke CA, Chang ET, et al. Incomplete pregnancy is not
associated with breast cancer risk: the California Teachers
Study. Contraception 2008;77:3916.
Copyright June 2009 by the American College of Obstetricians and
Gynecologists, 409 12th Street, SW, PO Box 96920, Washington, DC
20090-6920. All rights reserved. No part of this publication may be
reproduced, stored in a retrieval system, posted on the Internet, or
transmitted, in any form or by any means, electronic, mechanical,
photocopying, recording, or otherwise, without prior written permis-
sion from the publisher. Requests for authorization to make photo-
copies should be directed to: Copyright Clearance Center, 222
Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
ISSN 1074-861X
Induced abortion and breast cancer risk. ACOG Committee Opinion
No. 434. American College of Obstetricians and Gynecologists. Obstet
Gynecol 2009;113:14178.
387 COMMITTEE OPINIONS 387
ACOG COMMITTEE OPINION
Number 440 August 2009
The Role of Transvaginal Ultrasonography in
the Evaluation of Postmenopausal Bleeding
ABSTRACT: The clinical approach to postmenopausal bleeding requires prompt and
efficient evaluation to exclude or diagnose carcinoma. Women with postmenopausal
bleeding may be assessed initially with either endometrial biopsy or transvaginal ultra-
sonography; this initial evaluation does not require performance of both tests.
Transvaginal ultrasonography can be useful in the triage of patients in whom endo-
metrial sampling was performed but tissue was insufficient for diagnosis. When trans-
vaginal ultrasonography is performed for patients with postmenopausal bleeding and an
endometrial thickness of less than or equal to 4 mm is found, endometrial sampling is
not required. Meaningful assessment of the endometrium by ultrasonography is not pos-
sible in all patients. In such cases, alternative assessment should be completed. When
bleeding persists despite negative initial evaluations, additional assessment usually is
indicated.
Committee on
Gynecologic
Practice
This document reflects
emerging clinical and sci-
entific advances as of the
date issued and is subject
to change. The informa-
tion should not be con-
strued as dictating an
exclusive course of treat-
ment or procedure to be
followed.
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Cancer of the endometrium is the most com-
mon type of gynecologic cancer in the
United States. In 2008, an estimated 40,100
cases of cancer of the endometrium will
occur and an estimated 7,470 deaths (1).
Vaginal bleeding is the presenting sign in
more than 90% of postmenopausal patients
with endometrial carcinoma (2). The major-
ity of patients with postmenopausal vaginal
bleeding experience bleeding secondary to
atrophic changes of the vagina or endometri-
um. However, depending on age and risk fac-
tors, 114% will have endometrial cancer
(36). Thus, the clinical approach to post-
menopausal bleeding requires prompt and
efficient evaluation to exclude or diagnose
carcinoma.
Transvaginal Ultrasonography
Transvaginal ultrasonography has been
explored as an alternative technique to indi-
rectly visualize the endometrium. Endome-
trial thickness is measured as the maximum
anteriorposterior thickness of the endome-
trial echo on a long-axis transvaginal view of
the uterus. The earliest reports comparing
transvaginal ultrasonography with endome-
trial sampling consistently found that an
endometrial thickness of less than or equal to
45 mm in patients with postmenopausal
bleeding reliably excluded endometrial cancer
(79). Since that time, a number of confirma-
tory multicenter trials have been completed
(see Table 1). Because transvaginal ultra-
sonography in postmenopausal patients with
bleeding has an extremely high negative pre-
dictive value, it is a reasonable first approach.
An endometrial thickness of greater than
4 mm is not diagnostic of any particular
pathology and cannot be relied on to exclude
disease.
Biopsy Findings of Tissue
Insufficient for Diagnosis
Endometrial tissue sampling resulting in
findings insufficient for diagnosis is com-
mon. In a study of 97 consecutive patients
with postmenopausal bleeding evaluated by
transvaginal ultrasonography and endome-
trial biopsy, in only 82% of the patients with
an endometrial thickness of less than 5 mm
(n=45) was a Pipelle biopsy able to be per-
formed (10). Of these patients, a sample ade-
quate for diagnosis was obtained in only
27%. There was no correlation with parity or
cavity length. In other studies of patients
COMPENDIUM OF SELECTED PUBLICATIONS 388 388
Table 1. Endometrial Thickness and Cancer Findings in Postmenopausal Women With Bleeding
Endometrial Number of Number of Negative
Reference Thickness* Women Cases of Cancer Predictive Value
Karlsson 1995
4 mm 1,168 0 100%
Ferrazzi 1996
4 mm 930 2 99.8%
5 mm 4 99.6%
Gull 2000
4 mm 163 1 99.4%
Epstein 2001
||
5 mm 97 0 100%
Gull 2003
4 mm 394 0 100%
*Determined by transvaginal ultrasonography
Karlsson B, Granberg S, Wikland M, Ylostalo P, Torvid K, Marsal K, et al. Transvaginal ultrasonography of the endometrium in women with post-
menopausal bleedinga Nordic multicenter study. Am J Obstet Gynecol 1995;172:148894.
Ferrazzi E, Torri V, Trio D, Zannoni E, Filiberto S, Dordoni D. Sonographic endometrial thickness: a useful test to predict atrophy in patients with post-
menopausal bleeding. An Italian multicenter study. Ultrasound Obstet Gynecol 1996;7:31521.
Gull B, Carlsson S, Karlsson B, Ylostalo P, Milsom I, Granberg S. Transvaginal ultrasonography of the endometrium in women with postmenopausal
bleeding: is it always necessary to perform an endometrial biopsy? Am J Obstet Gynecol 2000;182:50915.
||
Epstein E, Valentin L. Rebleeding and endometrial growth in women with postmenopausal bleeding and endometrial thickness < 5 mm managed by
dilatation and curettage or ultrasound follow-up: a randomized controlled study. Ultrasound Obstet Gynecol 2001;18:499504.
Gull B, Karlsson B, Milsom I, Granberg S. Can ultrasound replace dilation and curettage? A longitudinal evaluation of postmenopausal bleeding and
transvaginal sonographic measurement of the endometrium as predictors of endometrial cancer. Am J Obstet Gynecol 2003;188:4018.
with postmenopausal bleeding, the range of sampling
failure (ie, inadequate sample or inability to perform the
biopsy) with Pipelle biopsy was 054% (11).
Transvaginal ultrasonography can be useful in the
triage of patients in whom endometrial sampling was
performed but tissue was insufficient for diagnosis (12).
No further evaluation is necessary following an insuffi-
cient endometrial biopsy if subsequent transvaginal
ultrasonography demonstrates an endometrial thickness
of less than or equal to 4 mm in a woman with post-
menopausal bleeding because the incidence of malig-
nancy is rare in these cases (Table 1). However, if
bleeding recurs or persists, additional evaluation usually
is indicated.
Postmenopausal Patients Without
Bleeding
Whereas several studies have evaluated transvaginal ultra-
sonography in postmenopausal women with bleeding,
there are fewer data on transvaginal ultrasonography
endometrial findings in patients without bleeding. In
1,750 postmenopausal women without bleeding being
screened for a selective estrogen receptor modulator study,
an endometrial thickness of less than or equal to 6 mm
had a negative predictive value of 99.94% for excluding
malignancy (only 1 case of cancer in 1,750 women) and a
99.77% negative predictive value for complex hyperplasia
(only 4 cases in 1,750 women) (13). Among 42 patients
with endometrial thickness of greater than 6 mm, there
was 1 case of adenocarcinoma and no cases of hyperplasia
(positive predictive value = 2.4%).
In another study, 82 asymptomatic postmenopausal
women had an incidental ultrasonographic finding suspect-
ed to be an intrauterine polyp (14). All underwent operative
hysteroscopy. Of these patients, a benign polyp was found in
68, submucosal myoma in 7, atrophic endometrium in 6,
and proliferative endometrium in 1. One polyp contained
simple hyperplasia. There were no cases of endometrial car-
cinoma or complex hyperplasia. The total complication rate
was 3.6% (two perforations, one difficult intubation).
The significance of an endometrial measurement
greater than 4 mm incidentally discovered in a post-
menopausal patient without bleeding has not been estab-
lished. This finding need not routinely trigger evaluation,
although an individualized assessment based on patient
characteristics and risk factors is appropriate. Transvagi-
nal ultrasonography is not an appropriate screening tool
for cancer in postmenopausal women without bleeding.
Limitations
It is not possible to complete a meaningful transvaginal
ultrasound examination with a reliable measurement of
endometrial thickness in all patients (15). An axial uterus,
marked obesity, coexisting myomas, or previous uterine
surgery all can contribute to difficulty in obtaining reli-
able transvaginal ultrasound assessment of endometrial
thickness and texture. Failure to adequately identify a
thin, distinct endometrial thickness in a postmenopausal
patient with bleeding should trigger some alternative
method of evaluation. In addition, when endometrial
fluid is present, it should not be included in measuring
endometrial thickness.
389 COMMITTEE OPINIONS 389
Recommendations
Any vaginal bleeding in a postmenopausal woman
requires assessment to exclude malignancy.
Women with postmenopausal uterine bleeding may
be assessed initially with either endometrial biopsy
or transvaginal ultrasonography; this initial evalua-
tion does not require performance of both tests.
When endometrial biopsy is performed and tissue is
reported as insufficient for diagnosis, some further
investigation is necessary and transvaginal ultra-
sonography may be performed.
When transvaginal ultrasonography is performed for
patients with postmenopausal bleeding and an
endometrial thickness of less than or equal to 4 mm
is found, endometrial sampling is not required.
Endometrial thickness of greater than 4 mm in a
patient with postmenopausal bleeding should trigger
alternative evaluation (such as sonohysterography,
office hysteroscopy, or endometrial biopsy), as
should an inability to adequately visualize thickness.
Meaningful assessment of the endometrium by
ultrasonography is not possible in all patients. In such
cases, alternative assessment should be completed.
When bleeding persists despite negative initial evalu-
ations, additional assessment usually is indicated.
The significance of an endometrial thickness of
greater than 4 mm in an asymptomatic, postmeno-
pausal patient has not been established, and this
finding need not routinely trigger evaluation.
References
1. American Cancer Society. Cancer facts and figures 2008.
Atlanta (GA): ACS; 2008. Available at: http://www.cancer.
org/downloads/STT/2008CAFFfinalsecured.pdf. Retrieved
June 20, 2008.
2. Goldstein RB, Bree RL, Benson CB, Benacerraf BR, Bloss JD,
Carlos R, et al. Evaluation of the woman with postmen-
opausal bleeding: Society of Radiologists in Ultrasound-
Sponsored Consensus Conference statement. J Ultrasound
Med 2001;20:102536.
3. Smith-Bindman R, Kerlikowske K, Feldstein VA, Subak L,
Scheidler J, Segal M, et al. Endovaginal ultrasound to
exclude endometrial cancer and other endometrial abnor-
malities. JAMA 1998;280:15107.
4. Tabor A, Watt HC, Wald NJ. Endometrial thickness as a test
for endometrial cancer in women with postmenopausal
vaginal bleeding. Obstet Gynecol 2002;99:66370.
5. Gupta JK, Chien PF, Voit D, Clark TJ, Khan KS.
Ultrasonographic endometrial thickness for diagnosing
endometrial pathology in women with postmenopausal
bleeding: a meta-analysis. Acta Obstet Gynecol Scand 2002;
81:799816.
6. Smith-Bindman R, Weiss E, Feldstein V. How thick is too
thick? When endometrial thickness should prompt biopsy
in postmenopausal women without vaginal bleeding.
Ultrasound Obstet Gynecol 2004;24:55865.
7. Goldstein SR, Nachtigall M, Snyder JR, Nachtigall L.
Endometrial assessment by vaginal ultrasonography before
endometrial sampling in patients with postmenopausal
bleeding. Am J Obstet Gynecol 1990;163:11923.
8. Varner RE, Sparks JM, Cameron CD, Roberts LL, Soong SJ.
Transvaginal sonography of the endometrium in post-
menopausal women. Obstet Gynecol 1991;78:1959.
9. Granberg S, Wikland M, Karlsson B, Norstrom A, Friberg
LG. Endometrial thickness as measured by endovaginal
ultrasonography for identifying endometrial abnormality.
Am J Obstet Gynecol 1991;164:4752.
10. Elsandabesee D, Greenwood P. The performance of Pipelle
endometrial sampling in a dedicated postmenopausal
bleeding clinic. J Obstet Gynaecol 2005;25:324.
11. Dijkhuizen FP, Mol BW, Brolmann HA, Heintz AP. The
accuracy of endometrial sampling in the diagnosis of
patients with endometrial carcinoma and hyperplasia: a
meta-analysis. Cancer 2000;89:176572.
12. Bakour SH, Khan KS, Gupta JK. Controlled analysis of fac-
tors associated with insufficient sample on outpatient
endometrial biopsy. BJOG 2000;107:13124.
13. Fleischer AC, Wheeler JE, Lindsay I, Hendrix SL, Grabill S,
Kravitz B, et al. An assessment of the value of ultrasono-
graphic screening for endometrial disease in post-
menopausal women without symptoms. Am J Obstet
Gynecol 2001;184:705.
14. Lev-Sagie A, Hamani Y, Imbar T, Hurwitz A, Lavy Y. The sig-
nificance of intrauterine lesions detected by ultrasound in
asymptomatic postmenopausal patients. BJOG 2005;112:
37981.
15. Sit AS, Modugno F, Hill LM, Martin J, Weissfeld JL.
Transvaginal ultrasound measurement of endometrial
thickness as a biomarker for estrogen exposure. Cancer
Epidemiol Biomarkers Prev 2004;13:145965.
Copyright August 2009 by the American College of Obstetricians
and Gynecologists, 409 12th Street, SW, PO Box 96920, Washington,
DC 20090-6920. All rights reserved. No part of this publication may be
reproduced, stored in a retrieval system, posted on the Internet, or
transmitted, in any form or by any means, electronic, mechanical,
photocopying, recording, or otherwise, without prior written permis-
sion from the publisher. Requests for authorization to make photo-
copies should be directed to: Copyright Clearance Center, 222
Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
ISSN 1074-861X
The role of transvaginal ultrasonography in the evaluation of post-
menopausal bleeding. ACOG Committee Opinion No. 440. American
College of Obstetricians and Gynecologists. Obstet Gynecol 2009;
114:40911.
COMPENDIUM OF SELECTED PUBLICATIONS 390 390
ACOG COMMITTEE OPINION
Number 444 November 2009
Choosing the Route of Hysterectomy for
Benign Disease
Abstract: Hysterectomies are performed vaginally, abdominally, or with laparoscopic
or robotic assistance. When choosing the route and method of hysterectomy, the physi-
cian should take into consideration how the procedure may be performed most safely
and cost-effectively to fulfill the medical needs of the patient. Evidence demonstrates
that, in general, vaginal hysterectomy is associated with better outcomes and fewer
complications than laparoscopic or abdominal hysterectomy. When it is not feasible to
perform a vaginal hysterectomy, the surgeon must choose between laparoscopic hys-
terectomy, robot-assisted hysterectomy, or abdominal hysterectomy. Experience with
robot-assisted hysterectomy is limited at this time; more data are necessary to determine
its role in the performance of hysterectomy. The decision to electively perform a salpin-
goophorectomy should not be influenced by the chosen route of hysterectomy and is not
a contraindication to performing a vaginal hysterectomy.
Committee on
Gynecologic
Practice
This document reflects
emerging clinical and sci-
entific advances as of the
date issued and is subject
to change. The informa-
tion should not be con-
strued as dictating an
exclusive course of treat-
ment or procedure to be
followed.
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Hysterectomy is one of the most frequently
performed surgical procedures in the United
States. During 20002004, approximately
3.1 million hysterectomies were performed
(approximately 600,000 per year). The most
common indications for hysterectomy are
symptomatic uterine leiomyomas (40.7%),
endometriosis (17.7%), and prolapse (14.5%)
(1).
Hysterectomies are performed vaginally,
abdominally, or with laparoscopic or robotic
assistance. When choosing the route and
method of hysterectomy, the physician should
take into consideration how the procedure
may be performed most safely and cost-effec-
tively to fulfill the medical needs of the
patient. Most literature supports the opinion
that, when feasible, vaginal hysterectomy is the
safest and most cost-effective route by which
to remove the uterus (2). However, analysis of
U.S. surgical data shows that abdominal
hysterectomy is performed in 66% of cases,
vaginal hysterectomy in 22% of cases, and
laparoscopic hysterectomy in 12% of cases (3).
Factors That Influence the
Route of Hysterectomy
Factors that may influence the route of hys-
terectomy for benign causes include the size
and shape of the vagina and uterus; accessi-
bility to the uterus; extent of extrauterine dis-
ease; the need for concurrent procedures;
surgeon training and experience; available
hospital technology, devices, and support;
emergency or scheduled cases; and prefer-
ence of the informed patient.
A narrow pubic arch (less than 90
degrees), a narrow vagina, an undescended
immobile uterus, nulliparity, prior cesarean
delivery, and enlarged uterus have been pro-
posed by some authors as contraindications
for vaginal hysterectomy. However, many
nulliparous women and women who have
not given birth vaginally have adequate vagi-
nal caliber to allow successful completion of
the vaginal hysterectomy (4). If the vagina
will allow access to divide the uterosacral and
cardinal ligaments, uterine mobility usually is
improved enough to allow vaginal hyster-
ectomy, even in cases where there is minimal
uterine descent (5). When the uterus is
enlarged, vaginal hysterectomy often can be
accomplished safely by using uterine size
reduction techniques such as wedge morcella-
tion, uterine bisection, and intramyometrial
coring.
Guidelines incorporating uterine size,
mobility, accessibility, and pathology con-
391 COMMITTEE OPINIONS 391
fined to the uterus (no adnexal pathology or known or
suspected adhesions) have been proposed as selection cri-
teria for vaginal hysterectomy (6). In a randomized trial,
when residents followed specific guidelines for selection
and performance of hysterectomy, the percentage of vagi-
nal hysterectomies for benign conditions was more than
90%. Uterine morcellation and other uterine size reduc-
tion techniques were only necessary in 11% of cases (7).
Extrauterine disease such as adnexal pathology,
severe endometriosis, or adhesions may preclude vaginal
hysterectomy. However, in these cases, it may be prudent
to visualize the pelvis with a laparoscope before deciding
on the route of hysterectomy.
The decision to electively perform a salpin-
goophorectomy should not be influenced by the chosen
route of hysterectomy and is not a contraindication to
performing a vaginal hysterectomy. The success of remov-
ing the ovaries vaginally varies greatly and is reported to
range from 6597.5% (810). In a randomized trial that
compared vaginal hysterectomy with bilateral salpin-
goophorectomy to laparoscopically assisted vaginal hys-
terectomy with bilateral salpingoophorectomy, there were
more complications and increased operating time with
the laparoscopic approach (11).
Outcomes and Complication Rates
Evidence demonstrates that, in general, vaginal hysterec-
tomy is associated with better outcomes and fewer com-
plications. A Cochrane review of 34 randomized trials of
abdominal hysterectomy, laparoscopic hysterectomy, and
vaginal hysterectomy, including 4,495 patients, concluded
that vaginal hysterectomy has the best outcomes of these
three routes. The review also found that when a vaginal
hysterectomy is not possible, laparoscopic hysterectomy
has advantages (including faster return to normal activ-
ity, shorter duration of hospital stays, lower intraoperative
blood loss, and fewer wound infections) over abdominal
hysterectomy; however, laparoscopic surgery also is asso-
ciated with longer operating time and higher rates of uri-
nary tract injury (2) (see Box 1).
The authors of one study compared vaginal and
abdominal hysterectomy and found that abdominal hys-
terectomy was associated with 1.7 times more complica-
tions, 1.9 times more febrile morbidity, and 2.1 times
more blood transfusions than vaginal hysterectomy (12).
In another study, when women with enlarged uteri (200
1,300 gm) were randomly assigned surgery by the vag-
inal or abdominal route, the vaginal procedure resulted in
decreased operative time, less febrile morbidity, reduced
postoperative narcotic use, and shorter hospital stay (13).
When it is not feasible to perform a vaginal hysterec-
tomy, the surgeon must choose between laparoscopic hys-
terectomy, robot-assisted hysterectomy, or abdominal
hysterectomy. Experience with robot-assisted hysterectomy
for benign conditions is currently limited (14). Abdom-
inal hysterectomy is also an important surgical procedure,
especially when the vaginal or laparoscopic approach is
not appropriate to manage the patients clinical situation
or when facilities cannot support a specific procedure.
Other Considerations
Cost analysis has consistently demonstrated that vaginal
hysterectomy is the most cost-effective route (15, 16).
Patient preference may influence the route by which the
hysterectomy is performed (17). For example, despite the
evidence that there is no significant difference in outcome
between a supracervical hysterectomy and a total hys-
terectomy (18), some patients may choose a supracervical
hysterectomy. In these cases, a laparoscopic or open
abdominal approach is most appropriate.
Conclusions
Listed as follows are the conclusions of the ACOG Com-
mittee on Gynecologic Practice:
Vaginal hysterectomy is the approach of choice
whenever feasible, based on its well-documented
advantages and lower complication rates.
The choice of when to perform prophylactic ooph-
orectomy at the time of hysterectomy is based on the
patients age, risk factors, and informed wishes, but
not on the route of hysterectomy.
Box 1. Comparison of Different
Approaches to Hysterectomy
Vaginal Hysterectomy Compared With Abdominal
Hysterectomy
Shorter duration of hospital stay
Faster return to normal activity
Fewer febrile episodes or unspecified infections
Vaginal Hysterectomy Compared With Laparoscopic
Hysterectomy
Shorter operating time
Laparoscopic Hysterectomy Compared With Abdominal
Hysterectomy
Faster return to normal activity
Shorter duration of hospital stay
Smaller drop in hemoglobin
Lower intraoperative blood loss
Fewer wound or abdominal wall infections
Longer operating time
Higher rate of lower urinary tract (bladder and ureter)
injuries
Data from Nieboer TE, Johnson N, Lethaby A, Tavender E, Curr E,
Garry R, et al. Surgical approach to hysterectomy for benign
gynaecological disease. Cochrane Database of Systematic
Reviews 2009, Issue 3. Art. No.: CD003677. DOI: 10.1002/14651858.
CD003677.pub4.
COMPENDIUM OF SELECTED PUBLICATIONS 392 392
Laparoscopic hysterectomy is an alternative to abdom-
inal hysterectomy for those patients in whom a vagi-
nal hysterectomy is not indicated or feasible.
Experience with robot-assisted hysterectomy is limited
at this time; more data are necessary to determine its
role in the performance of hysterectomy.
References
1. Whiteman MK, Hillis SD, Jamieson DJ, Morrow B,
Podgornik MN, Brett KM, et al. Inpatient hysterectomy
surveillance in the United States, 2000-2004. Am J Obstet
Gynecol 2008;198:34.e134.e7.
2. Nieboer TE, Johnson N, Lethaby A, Tavender E, Curr E,
Garry R, et al. Surgical approach to hysterectomy for benign
gynaecological disease. Cochrane Database of Systematic
Reviews 2009, Issue 3. Art. No.: CD003677. DOI: 10.1002/
14651858.CD003677.pub4.
3. Wu JM, Wechter ME, Geller EJ, Nguyen TV, Visco AG.
Hysterectomy rates in the United States, 2003. Obstet
Gynecol 2007;110:10915.
4. Tohic AL, Dhainaut C, Yazbeck C, Hallais C, Levin I,
Madelenat P. Hysterectomy for benign uterine pathology
among women without previous vaginal delivery. Obstet
Gynecol 2008;111:82937.
5. Doucette RC, Sharp HT, Alder SC. Challenging generally
accepted contraindications to vaginal hysterectomy.
Am J Obstet Gynecol 2001;184:13869; discussion 13901.
6. Kovac SR. Decision-directed hysterectomy: a possible
approach to improve medical and economic outcomes. Int
J Gynaecol Obstet 2000;71:15969.
7. Kovac SR, Barhan S, Lister M, Tucker L, Bishop M, Das A.
Guidelines for the selection of the route of hysterectomy:
application in a resident clinic population. Am J Obstet
Gynecol 2002;187:15217.
8. Ballard LA, Walters MD. Transvaginal mobilization and
removal of ovaries and fallopian tubes after vaginal hys-
terectomy. Obstet Gynecol 1996;87:359.
9. Davies A, OConnor H, Magos AL. A prospective study to
evaluate oophorectomy at the time of vaginal hysterectomy.
Br J Obstet Gynaecol 1996;103:91520.
10. Sheth SS. The place of oophorectomy at vaginal hysterec-
tomy. Br J Obstet Gynaecol 1991;98:6626.
11. Agostini A, Vejux N, Bretelle F, Collette E, De Lapparent T,
Cravello L, et al. Value of laparoscopic assistance for vaginal
hysterectomy with prophylactic bilateral oophorectomy.
Am J Obstet Gynecol 2006;194:3514.
12. Dicker RC, Greenspan JR, Strauss LT, Cowart MR, Scally MJ,
Peterson HB, et al. Complications of abdominal and vaginal
hysterectomy among women of reproductive age in the
United States. The Collaborative Review of Sterilization.
Am J Obstet Gynecol 1982;144:8418.
13. Benassi L, Rossi T, Kaihura CT, Ricci L, Bedocchi L, Galanti B,
et al. Abdominal or vaginal hysterectomy for enlarged uteri:
a randomized clinical trial. Am J Obstet Gynecol 2002;187:
15615.
14. ACOG Technology Assessment: Robot-Assisted Surgery (in
publication for November 2009)
15. Dorsey JH, Holtz PM, Griffiths RI, McGrath MM, Steinberg EP.
Costs and charges associated with three alternative tech-
niques of hysterectomy. N Engl J Med 1996;335:47682.
16. Sculpher M, Manca A, Abbott J, Fountain J, Mason S, Garry R.
Cost effectiveness analysis of laparoscopic hysterectomy
compared with standard hysterectomy: results from a ran-
domised trial. BMJ 2004;328:134.
17. Surgery and patient choice. ACOG Committee Opinion
No. 395. American College of Obstetricians and Gynecolo-
gists. Obstet Gynecol 2008;111:2437.
18. Supracervical hysterectomy. ACOG Committee Opinion
No. 388. American College of Obstetricians and Gynecol-
ogists. Obstet Gynecol 2007;110:12157.
Copyright November 2009 by the American College of Obstetricians
and Gynecologists, 409 12th Street, SW, PO Box 96920, Washington,
DC 20090-6920. All rights reserved. No part of this publication may be
reproduced, stored in a retrieval system, posted on the Internet, or
transmitted, in any form or by any means, electronic, mechanical,
photocopying, recording, or otherwise, without prior written permis-
sion from the publisher. Requests for authorization to make photo-
copies should be directed to: Copyright Clearance Center, 222
Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
ISSN 1074-861X
Choosing the route of hysterectomy for benign disease. ACOG
Committee Opinion No. 444. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2009;114:11568.
393 COMMITTEE OPINIONS 393
ACOG COMMITTEE OPINION
Number 450 December 2009
Increasing Use of Contraceptive Implants
and Intrauterine Devices To Reduce
Unintended Pregnancy
ABSTRACT: High unintended pregnancy rates in the United States may in part be
the result of relatively low use of long-acting reversible contraceptive (LARC) methods,
specifically the contraceptive implant and intrauterine devices. Top-tier reversible meth-
ods share the characteristic of requiring a single act of motivation for long-term use, elim-
inating adherence and user-dependence from the effectiveness equation. According to
the World Health Organizations evidence-based Medical Eligibility Criteria for contracep-
tive use, LARC methods have few contraindications, and almost all women are eligible
for implants and intrauterine devices. Because of these advantages and the potential to
reduce unintended pregnancy rates, LARC methods should be offered as first-line con-
traceptive methods and encouraged as options for most women. To increase use of
LARC methods, barriers such as lack of health care provider knowledge or skills, low
patient awareness, and high upfront costs must be addressed.
Committee on
Gynecologic
Practice
Long-Acting
Reversible
Contraception
Working Group
This document reflects
emerging clinical and sci-
entific advances as of the
date issued and is subject
to change. The informa-
tion should not be con-
strued as dictating an
exclusive course of treat-
ment or procedure to be
followed.
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Unintended pregnancy persists as a major
public health problem in the United States.
Over the past 20 years, overall rates in the
United States have not changed and remain
unacceptably high at approximately 50% of
all pregnancies (1). Although the rate for
unintended pregnancy has decreased some-
what for higher income women, rates have
increased for lower income women (1).
Unwanted births to women aged 1524 years
nearly doubled between 1995 and 2002 (2).
Many factors, including contraceptive
method choice and continuation patterns,
contribute to the lack of progress in reducing
unintended pregnancies. Combined oral con-
traceptives and condoms, the predominant
reversible contraceptive methods used in the
United States, are user dependent, have rela-
tively low continuation rates, and have rela-
tively high failure rates with typical use pat-
terns (3). Interventions such as enhanced
counseling and same day start have not con-
sistently improved contraceptive use pat-
terns, continuation rates, or unintended
pregnancy rates (46). Further, the predicted
effect of emergency contraception to reduce
unintended pregnancy has not been achieved
(7). The United States has higher unintended
pregnancy rates than other countries (8).
Long-Acting Reversible
Contraception and
Unintended Pregnancy
In part, high-unintended pregnancy rates in
the United States may be the result of relative-
ly low use of long-acting reversible contracep-
tive (LARC) methods, specifically the contra-
ceptive implant and intrauterine devices
(IUDs). Use of LARC methods is much less
common in the United States than in coun-
tries such as France, where unintended preg-
nancy rates are much lower (7). According to
the most recent cycle of the National Survey of
Family Growth, fewer than 5% of women in
the United States reported ever using
intrauterine contraception or an implant (9).
Increasing use of LARC methods in the
United States could lower unintended preg-
nancy rates (7), and expanding access to
LARC for young women has been declared a
national priority (10).
Emerging evidence indicates that increas-
ing the use of contraceptive implants and IUDs
COMPENDIUM OF SELECTED PUBLICATIONS 394 394
also could reduce repeat pregnancy among adolescent
mothers and repeat abortions among women seeking
induced abortion. In a U.S. study of adolescent mothers,
the factor most strongly associated with repeat pregnancy
prevention in the first 2 postpartum years was initiation
of the six-rod contraceptive implant (11). Other studies
have concluded that immediate postabortion initiation of
LARC methods is associated with reduced repeat abor-
tion rates. In a retrospective cohort study conducted in
the United States, women who received immediate
postabortion IUDs for contraception had a significantly
lower rate of repeat abortions than women who chose
other non-IUD postabortion contraception (34.6 versus
91.3 abortions per 1,000 woman-years of follow-up) (12).
Similarly, in a prospective cohort study from Northern
Europe, 1,269 women undergoing early medical abortion
were monitored for 49 months. Women who chose
immediate IUD insertion had the lowest repeat abortion
risk, as compared with those who chose other methods or
postponed starting a contraceptive method (13).
Long-Acting Reversible Contraceptive
Methods
The World Health Organization family planning counsel-
ing guide lists all methods in tiers of effectiveness (see
Fig. 1). The top-tier reversible methods all share the char-
acteristic of requiring a single act of motivation for
long-term use, essentially eliminating adherence and user-
dependence from the effectiveness equation. These top-
tier methods also share the highest continuation rates of
all contraceptive methods, one of the most important fac-
tors in contraceptive success (3).
Currently, three LARC methods are available in the
United States. The single-rod etonogestrel implant was
approved by the U.S. Food and Drug Administration in
July 2007 for use up to 3 years. Two IUDs are available, the
Copper T380A for use up to 10 years, and the levonor-
gestrel intrauterine system for use up to 5 years. Accord-
ing to the World Health Organizations evidence-based
Medical Eligibility Criteria for contraceptive use, LARC
methods have few contraindications, and almost all women
are eligible for implants and IUDs (14, 15).
Despite high up-front costs and the need for office
visits for insertion and removal, LARC methods share the
following advantages over other methods:
Are independent from coitus and user motivation
and adherence
Have the highest effectiveness, continuation rates,
and user satisfaction
Do not require frequent visits for resupply
Require no additional funding for consistent use
once they have been placed
Are highly cost-effective
Are reversible, with a rapid return to fertility after
removal
Because of these advantages and the potential to reduce
unintended pregnancy rates, LARC methods should be
offered as first-line contraceptive methods and encour-
aged as options for most women.
Barriers to Long-Acting Reversible
Contraception
To increase use of LARC methods, barriers such as lack of
health care provider knowledge or skills, low patient
awareness, and high upfront costs should be addressed.
Increasing familiarity with changes in practice guide-
lines and improvements associated with the newer LARC
devices may address some health care provider reluctance
to encourage LARC use. Although health care providers
generally have favorable attitudes about IUDs, they may
use overly restrictive criteria to identify IUD candidates
(16). For example, IUDs may be safely used by nullipar-
ous women and by adolescents (17, 18). Although there is
a slight increased risk of infection in the first 20 days after
IUD insertion, evidence indicates there is no increased
risk of pelvic inflammatory disease or infertility in IUD
users (18).
Immediate postpartum and postabortal insertion of
an IUD is safe and effective (19, 20). Although expulsion
rates may be higher, the convenience of postpartum or
postabortal placement may outweigh this disadvantage and
increase access and use of effective contraception (19, 20).
The single-rod contraceptive implant is relatively new
and many physicians may be unaware of its advantages,
including its ease of removal as compared with the older
six-rod system. In one study, mean removal time for the sin-
gle-rod implant was 3.5 minutes (21). In order to procure
the single-rod contraceptive implant, health care providers
are required by the U.S. Food and Drug Administration to
participate in manufacturer-sponsored training.
Lack of experience or comfort with implant or IUD
insertion may result in physician reluctance to recom-
mend LARC methods, and overly cumbersome insertion
protocols, multiple visits, and unnecessary testing could
discourage patient use. The American College of Obstet-
ricians and Gynecologists supports efforts to increase
educational and hands-on training opportunities for clini-
cians in implant and IUD insertion.
Patient barriers include a general lack of awareness of
LARC methods and their safety and effectiveness. Women
describe the ideal contraceptive as reversible and not
needing frequent thought (22). Yet, two recent surveys
found that most young women had not heard of the IUD
(23, 24). However, young women were likely to report a
positive attitude about intrauterine contraception after a
brief, 3-minute educational intervention (23).
Cost may present a barrier to LARC method use for
many women. Implants and IUDs have high up-front
costs that often are not fully covered by insurance.
Instead, less effective but initially less expensive methods
such as oral contraceptives are more often covered.
However, both the implant and IUDs are highly cost-
395 COMMITTEE OPINIONS 395
Fig. 1. Abbreviations: IUD, intrauterine device; LAM, lactational amenorrhea method.
effective even with relatively short-term (1224 months)
use (2527).
Recommendations
Although lowering unintended pregnancy rates requires
multiple approaches, individual obstetriciangynecolo-
gists may contribute by increasing access to LARC meth-
ods for their patients. The following strategies can reduce
barriers and increase use of implants and IUDs:
Provide counseling on all contraceptive options,
including implants and IUDs, even if the patient ini-
tially states a preference for a specific contraceptive
method.
Encourage implants and IUDs for all appropriate can-
didates, including nulliparous women and adolescents.
Adopt same-day insertion protocols. Screening for
chlamydia, gonorrhea, and cervical cancer should not
be required before implant or IUD insertion but may
be obtained on the day of insertion, if indicated.
Avoid unnecessary delays, such as waiting to initiate
a method until after a postabortion or miscarriage
follow-up visit or to time insertion with menses.
Support efforts to lower the up-front costs of LARC
methods.
Advocate for coverage of all contraceptive methods
by all insurance plans, both private and public.
Become familiar with and support local, state, feder-
al (including Medicaid), and private programs that
improve affordability of all contraceptive methods,
including implants and IUDs.
COMPENDIUM OF SELECTED PUBLICATIONS 396 396
Resources
American College of Obstetricians and Gynecologists
Long-Acting Reversible Contraception Program
409 12th Street, SW, PO Box 96920
Washington, DC 20090-6920
800-673-8444 or 202-638-5577
http://www.acog.org/goto/larc
American College of Obstetricians and Gynecologists
Patient Education Pamphlet AP014 (2007)
The intrauterine device
Available at: http://www.acog.org/publications/patient_
education/bp014.cfm
Spanish language version (pamphlet SP014) available at:
http://www.acog.org/publications/patient_education/
sp014.cfm
American College of Obstetricians and Gynecologists
Patient Education Pamphlet AP159 (2007)
Hormonal contraceptionInjections, implants, rings,
and patches.
Available at: http://www.acog.org/publications/patient_
education/bp159.cfm
Spanish language version (pamphlet SP159) available at:
http://www.acog.org/publications/patient_education/
sp159.cfm
World Health Organization
Promoting family planning
Available at: http://www.who.int/reproductivehealth/
topics/family_planning/en/index.html
References
1. Finer LB, Henshaw SK. Disparities in rates of unintended
pregnancy In the United States, 1994 and 2001. Perspect Sex
Reprod Health 2006;38(2):906.
2. Kissin DM, Anderson JE, Kraft JM, Warner L, Jamieson DJ.
Is there a trend of increased unwanted childbearing among
young women in the United States? J Adolesc Health 2008;
43:36471.
3. Hatcher RA, Trussell J, Nelson AL, Cates W Jr, Stewart F,
Kowal D, editors. Contraceptive technology. 19th rev. ed.
New York (NY): Ardent Media, Inc.; 2007.
4. Halpern V, Grimes DA, Lopez LM, Gallo MF. Strategies to
improve adherence and acceptability of hormonal methods
of contraception. Cochrane Database of Systematic Reviews
2006, Issue 1. Art. No.: CD004317. DOI: 10.1002/14651858.
CD004317.pub2.
5. Moos MK, Bartholomew NE, Lohr KN. Counseling in the
clinical setting to prevent unintended pregnancy: an evi-
dence-based research agenda. Contraception 2003;67:
11532.
6. Lopez LM, Newmann SJ, Grimes DA, Nanda K, Schulz KF.
Immediate start of hormonal contraceptives for contracep-
tion. Cochrane Database of Systematic Reviews 2008, Issue
2. Art. No.: CD006260. DOI: 10.1002/14651858.CD006260.
pub2.
7. Trussell J, Schwarz EB, Guthrie K, Raymond E. No such
thing as an easy (or EC) fix. Contraception 2008;78:3514.
8. Trussell J, Wynn LL. Reducing unintended pregnancy in the
United States. Contraception 2008;77:15.
9. Chandra A, Martinez GM, Mosher WD, Abma JC, Jones J.
Fertility, family planning, and reproductive health of U.S.
women: data from the 2002 National Survey of Family
Growth. Vital Health Stat 23 2005;(25):1160.
10. Institute of Medicine (US). Initial national priorities for
comparative effectiveness research. Washington, DC:
National Academies Press; 2009.
11. Stevens-Simon C, Kelly L, Kulick R. A village would be nice
but...it takes a long-acting contraceptive to prevent repeat
adolescent pregnancies. Am J Prev Med 2001;21:605.
12. Goodman S, Hendlish SK, Reeves MF, Foster-Rosales A.
Impact of immediate postabortal insertion of intrauterine
contraception on repeat abortion. Contraception 2008;78:
1438.
13. Heikinheimo O, Gissler M, Suhonen S. Age, parity, history
of abortion and contraceptive choices affect the risk of
repeat abortion. Contraception 2008;78:14954.
14. World Health Organization. Medical eligibility criteria for
contraceptive use. 3rd ed. Geneva: WHO; 2004. Available at:
http://whqlibdoc.who.int/publications/2004/9241562668.p
df. Retrieved August 13, 2009.
15. World Health Organization. Medical eligibility criteria for
contraceptive use: 2008 update. Geneva: WHO; 2008.
Available at: http://whqlibdoc.who.int/hq/2008/WHO_
RHR_08.19_eng.pdf. Retrieved August 13, 2009.
16. Harper CC, Blum M, de Bocanegra HT, Darney PD, Speidel
JJ, Policar M, et al. Challenges in translating evidence to
practice: the provision of intrauterine contraception. Obstet
Gynecol 2008;111:135969.
17. Intrauterine device and adolescents. ACOG Committee
Opinion No. 392. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2007;110:14935.
18. Intrauterine device. ACOG Practice Bulletin No. 59.
American College of Obstetricians and Gynecologists.
Obstet Gynecol 2005;105:22332.
19. Grimes DA, Lopez LM, Schulz KF, Stanwood NL.
Immediate postabortal insertion of intrauterine devices.
Cochrane Database of Systematic Reviews 2004, Issue 4.
Art. No.: CD001777. DOI: 10.1002/14651858.CD001777.
pub2.
20. Grimes DA, Schulz KF, Van Vliet HH, Stanwood NL, Lopez
LM. Immediate post-partum insertion of intrauterine
devices. Cochrane Database of Systematic Reviews 2001,
Issue 2. Art. No.: CD003036. DOI: 10.1002/14651858.
CD003036.
21. Funk S, Miller MM, Mishell DR Jr, Archer DF, Poindexter A,
Schmidt J, et al. Safety and efficacy of Implanon, a single-
rod implantable contraceptive containing etonogestrel. The
Implanon US Study Group. Contraception 2005;71:31926.
22. Cwiak C, Gellasch T, Zieman M. Peripartum contraceptive
attitudes and practices. Contraception 2004;70:3836.
23. Whitaker AK, Johnson LM, Harwood B, Chiappetta L,
Creinin MD, Gold MA. Adolescent and young adult
womens knowledge of and attitudes toward the intrauter-
ine device. Contraception 2008;78:2117.
397 COMMITTEE OPINIONS 397
24. Stanwood NL, Bradley KA. Young pregnant womens
knowledge of modern intrauterine devices. Obstet Gynecol
2006;108:141722.
25. Trussell J, Lalla AM, Doan QV, Reyes E, Pinto L, Gricar J.
Cost effectiveness of contraceptives in the United States.
Contraception 2009;79:514.
26. Foster DG, Rostovtseva DP, Brindis CD, Biggs MA, Hulett
D, Darney PD. Cost savings from the provision of specific
methods of contraception in a publicly funded program.
Am J Public Health 2009;99:44651.
27. Chiou CF, Trussell J, Reyes E, Knight K, Wallace J, Udani J,
et al. Economic analysis of contraceptives for women.
Contraception 2003;68:310.
Copyright December 2009 by the American College of Obstetricians
and Gynecologists, 409 12th Street, SW, PO Box 96920, Washington,
DC 20090-6920. All rights reserved. No part of this publication may be
reproduced, stored in a retrieval system, posted on the Internet, or
transmitted, in any form or by any means, electronic, mechanical,
photocopying, recording, or otherwise, without prior written permis-
sion from the publisher. Requests for authorization to make photo-
copies should be directed to: Copyright Clearance Center, 222
Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
ISSN 1074-861X
Increasing use of contraceptive implants and intrauterine devices to
reduce unintended pregnancy. ACOG Committee Opinion No. 450.
American College of Obstetricians and Gynecologists. Obstet Gynecol
2009;114:14348.
COMPENDIUM OF SELECTED PUBLICATIONS 398 398
ACOG COMMITTEE OPINION
Number 452 December 2009 (Replaces No. 357, December 2006)
Primary and Preventive Care: Periodic
Assessments
ABSTRACT: Periodic assessments offer an excellent opportunity for obstetricians
and gynecologists to provide preventive screening, evaluation, and counseling. The
American College of Obstetricians and Gynecologists Committee on Gynecologic
Practice recommends routine assessments in primary and preventive care for women
based on age and risk factors.
Committee on
Gynecologic
Practice
This document reflects
emerging clinical and sci-
entific advances as of the
date issued and is subject
to change. The informa-
tion should not be con-
strued as dictating an
exclusive course of treat-
ment or procedure to be
followed.
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
The following charts are updated versions of
those previously published by the American
College of Obstetricians and Gynecologists
(ACOG) in Committee Opinion No. 357 and
Guidelines for Womens Health Care, Third
Edition. This version replaces the previous
versions. The policies and recommendations
of ACOG committees regarding specific
aspects of the health care of women have
been incorporated; they may differ from the
recommendations of other groups.
The American College of Obstetricians
and Gynecologists recommends that the first
visit to the obstetriciangynecologist for
screening and the provision of preventive
health care services and guidance take place
between the ages 13 years and 15 years. This
visit will provide health guidance, screening,
and preventive health care services and pro-
vide an excellent opportunity for the obstetri-
ciangynecologist to start a physicianpatient
relationship. This visit does not necessarily
include an internal pelvic examination.
Periodic assessments provide an excellent
opportunity to counsel patients about preven-
tive care. These assessments, yearly or as
appropriate, should include screening, evalua-
tion and counseling, and immunizations
based on age and risk factors. Personal behav-
ioral characteristics are important aspects of a
womans health. Positive behaviors, such as
exercise, should be reinforced, and negative
ones, such as smoking, should be discouraged.
The following guidelines indicate routine
assessments for nonpregnant women based on
age groups and risk factors (see Table 1) and
list leading causes of death for each age group.
The American College of Obstetricians and
Gynecologists generally adopts the immuniza-
tion recommendations of the Centers for
Disease Control and Prevention. The current
adolescent and adult immunization schedules
are available atwww.cdc.gov/vaccines/recs/
schedules.
The recommendations included in this
document serve as a framework for care,
which may be provided by a single physician
or a team of health care professionals. The
scope of services provided by obstetrician
gynecologists in the ambulatory setting will
vary from practice to practice. The list should
serve as a guide for the obstetriciangynecol-
ogist and others providing health care for
women and should be adapted as necessary
to meet patients needs. For example, certain
risk factors may influence additional assess-
ments and interventions. Physicians should
be alert to high-risk factors (indicated by an
asterisk and further elucidated in Table 1).
During evaluation, the patient should be
made aware of high-risk conditions that
require targeted screening or treatment.
399 COMMITTEE OPINIONS 399
Screening
History
Reason for visit
Health status: medical, menstrual,
surgical, family
Dietary/nutrition assessment
Physical activity
Use of complementary and alternative
medicine
Tobacco, alcohol, other drug use
Abuse/neglect
Sexual practices
Physical Examination
Height
Weight
Body mass index (BMI)
Blood pressure
Secondary sexual characteristics
(Tanner staging)
Pelvic examination (when indicated by
the medical history)
Skin*
Laboratory Testing
Periodic
Chlamydia and gonorrhea testing
(if sexually active)
High-Risk Groups*
Colorectal cancer screening
Urine-based sexually transmitted disease screening is an efficient means for accomplishing such screening without a speculum examination.
Physicians should be aware of and follow their states HIV screening requirements. For a more detailed discussion of HIV screening, see Branson BM, Handsfield HH, Lampe
MA, Janssen RS, Taylor AW, Lyss SB, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. Centers for Disease
Control and Prevention (CDC). MMWR Recomm Rep 2006;55(RR-14):117; quiz CE14. See also Routine human immunodeficiency virus screening. ACOG Committee Opinion
No. 411. American College of Obstetricians and Gynecologists. Obstet Gynecol 2008;112:4013.
Only for those with a family history of familial adenomatous polyposis or 8 years after the start of pancolitis. For a more detailed discussion of colorectal cancer screening,
see Levin B, Lieberman DA, McFarland B, Smith RA, Brooks D, Andrews KS, et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous
polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. American
Cancer Society Colorectal Cancer Advisory Group; US Multi-Society Task Force; American College of Radiology Colon Cancer Committee. CA Cancer J Clin 2008;58:13060.
||
For more information on the use of Td and Tdap, see Broder KR, Cortese MM, Iskander JK, Kretsinger K, Slade BA, Brown KH, et al. Preventing tetanus, diphtheria, and
pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the Advisory Committee on Immunization
Practices (ACIP). Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2006;55(RR-3):134.
Leading causes of mortality are provided by the Mortality Statistics Branch at the National Center for Health Statistics. Data are from 2004, the most recent year for which
final data are available. The causes are ranked.
Evaluation and Counseling
Sexuality
Development
High-risk behaviors
Preventing unwanted/unintended
pregnancy
Postponing sexual involvement
Contraceptive options, including
emergency contraception
Sexually transmitted diseases
Partner selection
Barrier protection
Fitness and Nutrition
Exercise: discussion of program
Dietary/nutrition assessment
(including eating disorders)
Folic acid supplementation
Calcium intake
Psychosocial Evaluation
Suicide: depressive symptoms
Interpersonal/family relationships
Sexual orientation and gender identity
Personal goal development
Behavioral/learning disorders
Abuse/neglect
Satisfactory school experience
Peer relationships
Date rape prevention
Cardiovascular Risk Factors
Family history
Hypertension
Dyslipidemia
Obesity
Diabetes mellitus
Health/Risk Behaviors
Hygiene (including dental), fluoride
supplementation*
Injury prevention
Exercise and sports involvement
Firearms
Hearing
Occupational hazards
Recreational hazards
Safe driving practices
Helmet use
Periodic Assessment
Ages 1318 Years
COMPENDIUM OF SELECTED PUBLICATIONS 400 400
Periodic Assessment
Ages 1939 Years
Screening
History
Reason for visit
Health status: medical, surgical, family
Dietary/nutrition assessment
Physical activity
Use of complementary and alternative
medicine
Tobacco, alcohol, other drug use
Abuse/neglect
Sexual practices
Urinary and fecal incontinence
Physical Examination
Height
Weight
Body mass index (BMI)
Blood pressure
Neck: adenopathy, thyroid
Breasts
Abdomen
Pelvic examination: for ages 1920 years,
when indicated by the medical history;
age 21 or older, periodic pelvic
examination
Skin*
Laboratory Testing
Periodic
Cervical cytology
:
Age 21 years: screen every 2 years
Age 30 years or older:
Option 1: may screen every 3 years
after three consecutive negative
test results with no history of
cervical intraepithelial neoplasia
2 or 3, immunosuppression, human
immunodeficiency virus (HIV)
infection, or diethylstilbestrol
exposure in utero; or
Option 2: screen every 3 years after
negative human papillomavirus
DNA test and negative cervical
cytology
Chlamydia and gonorrhea testing (if
aged 25 years or younger and sexually
active)
Human immunodeficiency virus (HIV)
testing
High-Risk Groups*
Bone mineral density screening
Colorectal cancer screening
*See Table 1.
For a more detailed discussion of cervical cytology screening, including the use of human papillomavirus DNA testing and screening after hysterectomy, see Cervical cytology
screening. ACOG Practice Bulletin No. 109. American College of Obstetricians and Gynecologists. Obstet Gynecol 2009:114;140920.
Physicians should be aware of and follow their states HIV screening requirements. For a more detailed discussion of HIV screening, see Branson BM, Handsfield HH, Lampe
MA, Janssen RS, Taylor AW, Lyss SB, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. Centers for Disease
Control and Prevention (CDC). MMWR Recomm Rep 2006;55(RR-14):117; quiz CE14. See also Routine human immunodeficiency virus screening. ACOG Committee Opinion
No. 411. American College of Obstetricians and Gynecologists. Obstet Gynecol 2008;112:4013.
For a more detailed discussion of the reproductive health plan, see The importance of preconception care in the continuum of womens health care. ACOG Committee Opinion
No. 313. American College of Obstetricians and Gynecologists. Obstet Gynecol 2005;106:6656.
||
Despite a lack of definitive data for or against breast self-examination, breast self-examination has the potential to detect palpable breast cancer and can be recommended.
For a more detailed discussion of risk assessment and chemoprevention therapy, see Selective estrogen receptor modulators. ACOG Practice Bulletin No. 39. American College
of Obstetricians and Gynecologists. Obstet Gynecol 2002;100:83543.
#
For more information on the use of Td and Tdap, see Kretsinger K, Broder KR, Cortese MM, Joyce MP, Ortega-Sanchez I, Lee GM, et al. Preventing tetanus, diphtheria, and
pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine recommendations of the Advisory Committee on Immunization Practices
(ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among health-care personnel. Centers
for Disease Control and Prevention; Advisory Committee on Immunization Practices; Healthcare Infection Control Practices Advisory Committee. MMWR Recomm Rep
2006;55(RR-17):137.
**Leading causes of mortality are provided by the Mortality Statistics Branch at the National Center for Health Statistics. Data are from 2004, the most recent year for which
final data are available. The causes are ranked.
Hygiene (including dental)
Injury prevention
Exercise and sports involvement
Firearms
Hearing
Occupational hazards
Recreational hazards
Safety belts and helmets
Skin exposure to ultraviolet rays
Suicide: depressive symptoms
Tobacco, alcohol, other drug use
Immunizations
Periodic
Diphtheria and reduced tetanus
toxoids and acellular pertussis vaccine
(substitute one-time dose of Tdap for
Td booster; then boost with Td every
10 years)
#
Human papillomavirus vaccine (one
series for those aged 26 years or less
and not previously immunized)
Varicella vaccine (one series for those
without evidence of immunity)
High-Risk Groups*
Hepatitis A vaccine (consider
combination vaccine for those at risk
for hepatitis A and B)
Hepatitis B vaccine (consider
combination vaccine for those at risk
for hepatitis A and B)
Influenza vaccine
Measlesmumpsrubella vaccine
Meningococcal vaccine
Pneumococcal vaccine
Leading Causes of Death**
1. Malignant neoplasms
2. Accidents (unintentional injuries)
3. Diseases of the heart
4. Intentional self harm (suicide)
5. Human immunodeficiency virus
(HIV) disease
6. Assault (homicide)
7. Cerebrovascular diseases
8. Diabetes mellitus
9. Chronic liver diseases and cirrhosis
10. Chronic lower respiratory diseases
Fasting glucose testing
Genetic testing/counseling
Hemoglobin level assessment
Hepatitis C virus testing
Lipid profile assessment
Mammography
Rubella titer assessment
Sexually transmitted disease testing
Thyroid-stimulating hormone testing
Tuberculosis skin testing
Evaluation and Counseling
Sexuality and Reproductive
Planning
Contraceptive options for prevention of
unwanted pregnancy, including
emergency contraception
Discussion of a reproductive health plan
High-risk behaviors
Preconception and genetic counseling
Sexual function
Sexually transmitted diseases
Partner selection
Barrier protection
Fitness and Nutrition
Exercise: discussion of program
Dietary/nutrition assessment
Folic acid supplementation
Calcium intake
Psychosocial Evaluation
Interpersonal/family relationships
Intimate partner violence
Date rape prevention
Work satisfaction
Lifestyle/stress
Sleep disorders
Cardiovascular Risk Factors
Family history
Hypertension
Dyslipidemia
Obesity
Diabetes mellitus
Lifestyle
Health/Risk Behaviors
Breast self-examination
||
Chemoprophylaxis for breast cancer (for
high-risk women aged 35 years or older)
Periodic Assessment
Ages 1939 Years
401 COMMITTEE OPINIONS 401
*See Table 1.
For a more detailed discussion of cervical cytology screening, including the use of human papillomavirus DNA testing and screening after hysterectomy, see Cervical cytology
screening. ACOG Practice Bulletin No. 109. American College of Obstetricians and Gynecologists. Obstet Gynecol 2009:114;140920.
Other methods include: 1) fecal occult blood testing or fecal immunochemical test, annual patient-collected (fecal occult blood testing and fecal immunochemical testing require
two or three samples of stool collected by the patient at home and returned for analysis. A single stool sample obtained by digital rectal examination is not adequate for the
detection of colorectal cancer.); 2) flexible sigmoidoscopy every 5 years; 3) double contrast barium enema every 5 years; 4) computed tomography colonography every 5 years; and
5) stool DNA. The American College of Gastroenterology recommends that African Americans begin screening at age 45 years with colonoscopy because of increased incidence
and earlier age of onset of colorectal cancer. (Agrawal S, Bhupinderjit A, Bhutani MS, Boardman L, Nguyen C, Romero Y, et al. Colorectal cancer in African Americans. Committee
of Minority Affairs and Cultural Diversity, American College of Gastroenterology [published erratum appears in Am J Gastroenterol 2005;100:1432]. Am J Gastroenterol
2005;100:515,523; discussion 514.)
Physicians should be aware of and follow their states HIV screening requirements. For a more detailed discussion of HIV screening, see Branson BM, Handsfield HH, Lampe MA,
Janssen RS, Taylor AW, Lyss SB, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. Centers for Disease Control
and Prevention (CDC). MMWR Recomm Rep 2006;55(RR-14):117; quiz CE14. See also Routine human immunodeficiency virus screening. ACOG Committee Opinion No. 411.
American College of Obstetricians and Gynecologists. Obstet Gynecol 2008;112:4013.
||
Preconception and genetic counseling is appropriate for certain women in this age group.
The recommendation for aspirin prophylaxis must weigh the benefits of stroke prevention against the harm of gastrointestinal bleeding. See Aspirin for the prevention of
cardiovascular disease: U.S. Preventive Services Task Force recommendation statement. U.S. Preventive Services Task Force. Ann Intern Med 2009;150:396404.
#
Despite a lack of definitive data for or against breast self-examination, breast self-examination has the potential to detect palpable breast cancer and can be recommended.
**For a more detailed discussion of risk assessment and chemoprevention therapy, see Selective estrogen receptor modulators. ACOG Practice Bulletin No. 39. American College
of Obstetricians and Gynecologists. Obstet Gynecol 2002;100:83543.
If Tdap not previously given, give one time, then Td every 10 years thereafter. If Tdap previously given, give Td every 10 years. For more information on the use of Td and Tdap,
see Kretsinger K, Broder KR, Cortese MM, Joyce MP, Ortega-Sanchez I, Lee GM, et al. Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced
diphtheria toxoid and acellular pertussis vaccine recommendations of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the
Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among health-care personnel. Centers for Disease Control and Prevention; Advisory Committee
on Immunization Practices; Healthcare Infection Control Practices Advisory Committee. MMWR Recomm Rep 2006;55(RR-17):137.
Leading causes of mortality are provided by the Mortality Statistics Branch at the National Center for Health Statistics. Data are from 2004, the most recent year for which final
data are available. The causes are ranked.
Periodic Assessment
Ages 4064 Years
Screening
History
Reason for visit
Health status: medical, surgical, family
Dietary/nutrition assessment
Physical activity
Use of complementary and alternative
medicine
Tobacco, alcohol, other drug use
Pelvic prolapse
Menopausal symptoms
Abuse/neglect
Sexual practices
Urinary and fecal incontinence
Physical Examination
Height
Weight
Body mass index (BMI)
Blood pressure
Oral cavity
Neck: adenopathy, thyroid
Breasts, axillae
Abdomen
Pelvic examination
Skin*
Laboratory Testing
Periodic
Cervical cytology (may screen every
3 years after three consecutive negative
test results if no history of cervical intra-
epithelial neoplasia 2 or 3, immuno-
suppression, human immunodeficiency
virus infection (HIV), or diethylstilbes-
trol exposure in utero, or every 3 years
after negative human papillomavirus
DNA test and negative cervical cytology)
: colonoscopy every 10
years [preferred])
Fasting glucose testing (every 3 years
after age 45 years)
Human immunodeficiency virus (HIV)
testing
Breast self-examination
#
Chemoprophylaxis for breast cancer
(for high-risk women)**
Hormone therapy
Hygiene (including dental)
Injury prevention
Exercise and sports involvement
Firearms
Hearing
Occupational hazards
Recreational hazards
Safety belts and helmets
Skin exposure to ultraviolet rays
Suicide: depressive symptoms
Tobacco, alcohol, other drug use
Immunizations
Periodic
Diphtheria and reduced tetanus
toxoids and acellular pertussis vaccine
booster (substitute one-time dose of
Tdap for Td booster; then boost with
Td every 10 years)
1. Malignant neoplasms
2. Diseases of the heart
3. Accidents (unintentional injuries)
4. Chronic lower respiratory diseases
5. Cerebrovascular diseases
6. Diabetes mellitus
7. Chronic liver disease and cirrhosis
8. Septicemia
9. Intentional self harm (suicide)
10. Human immunodeficiency virus
(HIV) disease
Periodic Assessment
Ages 4064 Years
COMPENDIUM OF SELECTED PUBLICATIONS 402 402
Periodic Assessment
Ages 65 Years and Older
Screening
History
Reason for visit
Health status: medical, surgical, family
Dietary/nutrition assessment
Physical activity
Pelvic prolapse
Menopausal symptoms
Use of complementary and alternative
medicine
Tobacco, alcohol, other drug use, and
concurrent medication use
Abuse/neglect
Sexual practices
Urinary and fecal incontinence
Physical Examination
Height
Weight
Body mass index (BMI)
Blood pressure
Oral cavity
Neck: adenopathy, thyroid
Breasts, axillae
Abdomen
Pelvic examination*
Skin
Laboratory Testing
Periodic
Bone mineral density screening (In the
absence of new risk factors, screen no
more frequently than every 2 years.)
Cervical cytology: consider discontinuing
at age 65 years or 70 years if patient
has had three or more normal results in
a row, no abnormal results in 10 years,
no history of cervical cancer, no history
of diethylstilbestrol exposure in utero, is
human immunodeficiency virus (HIV)
negative, is not immunosuppressed; if
cervical cytology has been discontinued,
annual review of risk factors to evaluate
need for reinitiation of screening. If
cervical cytology is needed: may screen
every 3 years after three consecutive
negative test results if no history of
cervical intraepithelial neoplasia 2 or 3,
immunosuppression, HIV infection, or
diethylstilbestrol exposure in utero or
every 3 years after negative human
papillomavirus DNA test and negative
cervical cytology.
:
colonoscopy every 10 years (preferred)
Fasting glucose testing (every 3 years)
Lipid profile assessment (every 5
years)
Mammography
Thyroid-stimulating hormone testing
(every 5 years)
Urinalysis
High-Risk Groups
See Table 1.
For a more detailed discussion of cervical cytology screening, including the use of human papillomavirus DNA testing and screening after hysterectomy,
see Cervical cytology screening. ACOG Practice Bulletin No. 109. American College of Obstetricians and Gynecologists. Obstet Gynecol 2009:114;140920.
Other methods include: 1) fecal occult blood testing or fecal immunochemical test, annual patient-collected (fecal occult blood testing and fecal
immunochemical testing require two or three samples of stool collected by the patient at home and returned for analysis. A single stool sample obtained
by digital rectal examination is not adequate for the detection of colorectal cancer.); 2) flexible sigmoidoscopy every 5 years; 3) double contrast barium
enema every 5 years; 4) computed tomography colonography every 5 years; and 5) stool DNA. More frequent testing is recommended for those with other
risk factors.
||
The recommendation for aspirin prophylaxis must weigh the benefits of stroke prevention against the harm of gastrointestinal bleeding. See Aspirin for the
prevention of cardiovascular disease: U.S. Preventive Services Task Force recommendation statement. U.S. Preventive Services Task Force. Ann Intern Med
2009;150:396404.
Despite a lack of definitive data for or against breast self-examination, breast self-examination has the potential to detect palpable breast cancer and can
be recommended.
#
For a more detailed discussion of risk assessment and chemoprevention therapy, see Selective estrogen receptor modulators. ACOG Practice Bulletin No. 39.
American College of Obstetricians and Gynecologists. Obstet Gynecol 2002;100:83543.
**Leading causes of mortality are provided by the Mortality Statistics Branch at the National Center for Health Statistics. Data are from 2004, the most
recent year for which final data are available. The causes are ranked.
Leading Causes of Death**
1. Diseases of the heart
2. Malignant neoplasms
3. Cerebrovascular diseases
4. Chronic lower respiratory diseases
5. Alzheimers disease
6. Influenza and pneumonia
7. Diabetes mellitus
8. Nephritis, nephrotic syndrome, and
nephrosis
9. Accidents (unintentional injuries)
10. Septicemia
Periodic Assessment
Ages 65 Years and Older
403 COMMITTEE OPINIONS 403
(continued)
Table 1. High-Risk Factors
Intervention High-Risk Factors
Bone mineral density screening* Postmenopausal women younger than age 65 years: history of prior fracture as an adult; family history of
osteoporosis; Caucasian; dementia; poor nutrition; smoking; low weight and BMI; estrogen deficiency
caused by early (age younger than 45 years) menopause, bilateral oophorectomy, or prolonged (longer than
1 year) premenopausal amenorrhea; low lifelong calcium intake; alcoholism; impaired eyesight despite ade-
quate correction; history of falls; inadequate physical activity
All women: certain diseases or medical conditions and certain drugs associated with an increased risk of
osteoporosis
Colorectal cancer screening
Colorectal cancer or adenomatous polyps in first-degree relative younger than age 60 years or in two or
more first-degree relatives of any ages; family history of familial adenomatous polyposis or hereditary non-
polyposis colon cancer; history of colorectal cancer, adenomatous polyps, inflammatory bowel disease,
chronic ulcerative colitis, or Crohns disease
Diphtheria and reduced tetanus Adults who have or who anticipate having close contact with an infant aged less than 12 months and
toxoids and acellular pertussis health care providers. When possible, women should receive Tdap before becoming pregnant.
vaccine
Overweight (BMI greater than or equal to 25); first-degree relative with diabetes mellitus; habitual physical
inactivity; high-risk race or ethnicity (eg, African American, Latina, Native American, Asian American,
Pacific Islander); have given birth to a newborn weighing more than 9 lb or have a history of gestational
diabetes mellitus; hypertension; high-density lipoprotein cholesterol level less than 35 mg/dL; triglyceride
level greater than 250 mg/dL; history of impaired glucose tolerance or impaired fasting glucose; polycystic
ovary syndrome; history of vascular disease; other clinical conditions associated with insulin resistance
Fluoride supplementation Live in area with inadequate water fluoridation (less than 0.7 ppm)
Genetic testing/counseling Considering pregnancy and: patient, partner, or family member with history of genetic disorder or birth
defect; exposure to teratogens; or African, Cajun, Caucasian, European, Eastern European (Ashkenazi)
Jewish, French Canadian, Mediterranean, or Southeast Asian ancestry
Hemoglobin level assessment Caribbean, Latin American, Asian, Mediterranean, or African ancestry; history of excessive menstrual flow
HAV vaccination Chronic liver disease, clotting factor disorders, illegal drug user, individuals who work with HAV-infected
nonhuman primates or with HAV in a research laboratory setting, individuals traveling to or working in
countries that have high or intermediate endemicity of hepatitis A
HBV vaccination Hemodialysis patients; patients who receive clotting factor concentrates; health care workers and public safety
workers who have exposure to blood in the workplace; individuals in training in schools of medicine, dentistry,
nursing, laboratory technology, and other allied health professions; injecting drug users; individuals with more
than one sexual partner in the previous 6 months; individuals with a recently acquired STD; all clients in STD
clinics; household contacts and sexual partners of individuals with chronic HBV infection; clients and staff of
institutions for the developmentally disabled; international travelers who will be in countries with high or
intermediate prevalence of chronic HBV infection for more than 6 months; inmates of correctional facilities
HCV testing History of injecting illegal drugs, recipients of clotting factor concentrates before 1987, chronic (long-term)
hemodialysis, persistently abnormal alanine aminotransferase levels, recipients of blood from donors who
later tested positive for HCV infection, recipients of blood or blood-component transfusion or organ trans-
plant before July 1992, occupational percutaneous or mucosal exposure to HCV-positive blood
HIV testing More than one sexual partner since most recent HIV test or a sexual partner with more than one sexual
partner since most recent HIV test, have received a diagnosis of another STD in the past year, drug use by
injection, history of prostitution, past or present sexual partner who is HIV positive or injects drugs, long-
term residence or birth in an area with high prevalence of HIV infection, history of transfusion from 1978 to
1985, invasive cervical cancer, sexually active adolescent younger than age 19 years, adolescent entering
detention facilities. Recommend to women seeking preconception evaluation.
COMPENDIUM OF SELECTED PUBLICATIONS 404 404
Table 1. High-Risk Factors (continued)
Intervention High-Risk Factors
Influenza vaccination Anyone who wishes to reduce the chance of becoming ill with influenza; anyone who wants to reduce the
risk of transmitting it to others; chronic cardiovascular or pulmonary disorders, except hypertension, includ-
ing asthma; chronic metabolic diseases, including diabetes mellitus, renal dysfunction, hemoglobinopathies,
and immunosuppression (including immunosuppression caused by medications or by HIV); hepatic disorders;
residents and employees of nursing homes and other long-term care facilities; individuals likely to transmit
influenza to high-risk individuals (eg, household members and caregivers of the elderly, children aged from
birth to 59 months, and adults with high-risk conditions); those with any condition (eg, cognitive dysfunc-
tion, spinal cord injury, seizure or other neuromuscular disorder) that compromises respiratory function or
the handling of respiratory secretions, or that increases the risk of aspiration; health care workers; preg-
nancy during the influenza season; adults older than age 50 years; adolescents who are receiving long-
term aspirin therapy who therefore might be at risk for experiencing Reye syndrome after influenza virus
infection
Lipid profile assessment Family history suggestive of familial hyperlipidemia; family history of premature cardiovascular disease (age
younger than 50 years for men, age younger than 60 years for women); previous personal history of coro-
nary heart disease or noncoronary atherosclerosis (eg, abdominal aortic aneurysm, peripheral artery dis-
ease, carotid artery stenosis); obesity (BMI greater than 30); personal and/or family history of peripheral
vascular disease; diabetes mellitus; multiple coronary heart disease risk factors (eg, tobacco use, hyper-ten-
sion)
Mammography Women who have had breast cancer or who have a first-degree relative (ie, mother, sister, or daughter) or
multiple other relatives who have a history of premenopausal breast or breast and ovarian cancers
Meningococcal vaccination Adults with anatomic or functional asplenia or terminal complement component deficiencies, first-year
college students living in dormitories, microbiologists routinely exposed to Neisseria meningitides isolates,
military recruits, travel to hyperendemic or epidemic areas
MMR vaccination Adults born in 1957 or later should be offered vaccination (one dose of MMR) if there is no proof of immu-
nity or documentation of a dose given after first birthday; individuals vaccinated in 19631967 should be
offered revaccination (two doses); health care workers, students entering college, international travelers,
and rubella-negative postpartum patients should be offered a second dose.
Pneumococcal vaccination Chronic illness, such as cardiovascular disease, pulmonary disease, diabetes mellitus, alcoholism, chronic
liver disease, cerebrospinal fluid leaks, Hodgkin disease, lymphoma, leukemia, kidney failure, multiple
myeloma, nephrotic syndrome, functional asplenia (eg, sickle cell disease) or splenectomy; exposure to
an environment where pneumococcal outbreaks have occurred; immunocompromised patients (eg, HIV
infection, hematologic or solid malignancies, chemotherapy, steroid therapy); Alaskan Natives and certain
Native American populations. Revaccination after 5 years may be appropriate for certain high-risk groups.
Rubella titer assessment Childbearing age and no evidence of immunity
STD testing History of multiple sexual partners or a sexual partner with multiple contacts; sexual contact with individuals
with culture-proven STD; history of repeated episodes of STDs; attendance at clinics for STDs; women with
developmental disabilities; annual screening for chlamydial infection for all sexually active women aged
25 years or younger; other asymptomatic women at high risk for infection and women older than age 25 years
with risk factors (new sexual partner or multiple sexual partners); annual screening for gonorrheal infection
for all sexually active adolescents and other asymptomatic women at high risk for infection; testing for
syphilis for sexually active adolescents who exchange sex for drugs or money, use intravenous drugs, are
entering a detention facility, or live in a high prevalence area
Skin examination Increased recreational or occupational exposure to sunlight; family or personal history of skin cancer;
clinical evidence of precursor lesions; fair skin, freckling; light hair; immune suppression; age; xeroderma
pigmentosum
405 COMMITTEE OPINIONS
Copyright December 2009 by the American College of Obstetricians and Gynecologists, 409 12th Street, SW, PO Box 96920, Washington, DC
20090-6920. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, posted on the Internet, or transmit-
ted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior written permission from the pub-
lisher. Requests for authorization to make photocopies should be directed to: Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA
01923, (978) 750-8400.
ISSN 1074-861X
Primary and preventive care: periodic assessments. ACOG Committee Opinion No. 452. American College of Obstetricians and Gynecologists.
Obstet Gynecol 2009;114:144451.
Table 1. High-Risk Factors (continued)
Intervention High-Risk Factors
Thyroid-stimulating hormone Strong family history of thyroid disease; autoimmune disease (evidence of subclinical hypothyroidism may
testing be related to unfavorable lipid profiles)
Tuberculosis skin testing HIV infection; close contact with individuals known or suspected to have tuberculosis; medical risk factors
known to increase risk of disease if infected; born in country with high tuberculosis prevalence; medically
underserved; low income; alcoholism; intravenous drug use; resident of long-term care facility (eg, correc-
tional institutions, mental institutions, nursing homes and facilities); health professional working in high-
risk health care facilities; recent tuberculin skin test converter (individuals with baseline testing results who
have an increase of 10 mm or more in the size of the tuberculin skin test reaction within a 2-year period);
radiographic evidence of prior healed tuberculosis
Varicella vaccination Adults and adolescents aged 13 years or older; all adolescents and adults without evidence of immunity;
students in all grade levels, and persons attending college or other postsecondary educational institutions;
susceptible persons who have close contact with persons at high risk for serious complications, including
health care workers; household contacts of immunocompromised individuals; teachers; daycare workers;
residents and staff of institutional settings, colleges, prisons, or military installations; adolescents and
adults living in households with children; international travelers; nonpregnant women of childbearing age
Abbreviations: BMI, body mass index; HAV, hepatitis A virus; HBV, hepatitis B virus; HCV, hepatitis C virus; HIV, human immunodeficiency virus; MMR, measlesmumps
rubella; STD, sexually transmitted disease; Tdap, diptheria and reduced tetanus toxoids and acellular pertussis vaccine.
*For a more detailed discussion of bone mineral density screening, see Osteoporosis. ACOG Practice Bulletin No. 50. American College of Obstetricians and Gynecologists.
Obstet Gynecol 2004;103:20316.
For a more detailed discussion of colorectal cancer screening, see Levin B, Lieberman DA, McFarland B, Smith RA, Brooks D, Andrews KS, et al. Screening and surveillance
for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal
Cancer, and the American College of Radiology. American Cancer Society Colorectal Cancer Advisory Group; US Multi-Society Task Force; American College of Radiology
Colon Cancer Committee. CA Cancer J Clin 2008;58:13060.
For more information, see Broder KR, Cortese MM, Iskander JK, Kretsinger K, Slade BA, Brown KH, et al. Preventing tetanus, diphtheria, and pertussis among adolescents:
use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the Advisory Committee on Immunization Practices (ACIP). Advisory
Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2006;55(RR-3):134.; Kretsinger K, Broder KR, Cortese MM, Joyce MP, Ortega-Sanchez I, Lee GM, et al.
Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine recommendations of the Advisory
Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of
Tdap among health-care personnel. Centers for Disease Control and Prevention; Advisory Committee on Immunization Practices; Healthcare Infection Control Practices
Advisory Committee. MMWR Recomm Rep 2006;55(RR-17):137.
For more information, see Postpartum screening for abnormal glucose tolerance in women who had gestational diabetes mellitus. ACOG Committee Opinion No. 435.
American College of Obstetricians and Gynecologists. Obstet Gynecol 2009;113:141921.
COMPENDIUM OF SELECTED PUBLICATIONS 406
Hysteroscopy
ABSTRACT: Hysteroscopy is an effective, minimally invasive procedure for
the diagnosis and treatment of intrauterine pathology. Selection of a dis-
tending medium requires consideration of the advantages, disadvantages,
and risks associated with various media as well as their compatibility with
electrosurgical or laser energy. Preoperative discussions with patients
should address risks and benefits of the procedure, comorbidities, analgesia
or anesthesia, and possible preoperative cervical dilation. Pregnancy, gen-
ital tract infection, and uterine carcinoma are contraindications to hys-
teroscopy. Possible complications include hemorrhage, fluid overload, per-
foration, visceral injury, infection, and embolization.
Hysteroscopy is performed to view and treat pathology within the uterine
cavity. Diagnostic hysteroscopy allows visualization of the endocervical
canal, endometrial cavity, and fallopian tube ostia. Common abnormal find-
ings include polyps, leiomyomata, intrauterine adhesions, and mllerian
anomalies. Operative hysteroscopy incorporates the use of mechanical,
electrosurgical, or laser instruments to treat intracavitary disease.
INSTRUMENTATION
Hysteroscopes are available in both flexible and rigid models, all of which
contain a telescope consisting of light bundles. Flexible hysteroscopes range
in diameter from 2.7 mm to 5 mm and have a bendable tip that can be
deflected in two directions ranging from 120 degrees to 160 degrees. Most
also contain an operating channel for tubal catheterization or endometrial
biopsy. Rigid hysteroscopes may consist of two or three pieces and range
from 1 mm to 5 mm in diameter. Their tips have varying viewing angles (0,
12, 15, 30, and 70 degrees). An outer sheath fits over the telescope to allow
inflow of a distending medium into the intrauterine cavity. This system
allows fluid to return on the outside of the outer sheath passively from the
intrauterine cavity through the cervix.
Continuous flow hysteroscopes consist of two channels to allow fluid to
flow into the intrauterine cavity while debris and cloudy intrauterine fluid
exit through perforations in the outer sheath to the outflow port. Fluid exit-
ing the outflow port can be collected through tubing and returned to a device
for the accurate measurement of fluid volume.
ACOG
I N OBSTE TRI CS AND GYNE COLOGY
TECHNOLOGY ASSESSMENT
This Technology Assessment was
developed by the ACOG Com-
mittee on Gynecologic Practice.
This document reflects emerging
clinical and scientific advances
as of the date issued and is sub-
ject to change. The information
should not be construed as dic-
tating an exclusive course of
treatment or procedure to be fol-
lowed. Variations in practice
may be warranted based on the
needs of the individual patient,
resources, and limitations unique
to the institution or type of
practice.
Reaffirmed 2007
NUMBER 4, AUGUST 2005
THE AMERICAN COLLEGE
OF OBSTETRICIANS
AND GYNECOLOGISTS
WOMEN S HEALTH CARE PHYSI CI ANS
407 COMMITTEE OPINIONS
Operative hysteroscopes typically range from 8
mm to 10 mm in diameter and contain a working
element. These hysteroscopes contain a retractable
hand piece wherein electrosurgical tips (eg, roller-
balls, loops, and vaporizing tips), lasers, or mechan-
ical instruments (eg, scissors) can be attached.
DISTENDING MEDIA
The uterine cavity requires distension for adequate
visualization. Several distending media are avail-
able, and each has inherent advantages and disad-
vantages. It is critically important to understand
which media are compatible with electrosurgical
and laser energy. Furthermore, the risks associated
with various media should be understood.
Carbon Dioxide Gas
Carbon dioxide (CO
2
), a colorless gas, is used in
outpatient settings for diagnostic purposes. The
advantages include the ease of cleaning and main-
taining equipment and a clear view of the cavity in
the absence of active bleeding or bubbles. To mini-
mize the risk of gas embolization, the flow of CO
2
should be limited to 100 mL/min with intrauterine
pressures less than 100 mm Hg. Insufflators
designed for use in laparoscopy must not be used for
hysteroscopy.
Fluid Media
Fluid media have historically been divided into elec-
trolyte and nonelectrolyte media, based on compati-
bility with electrosurgical procedures. However, it is
now possible to use electrolyte media with bipolar
electrosurgical systems. It also is important to under-
stand which media are hypoosmolar. Media also are
categorized by viscosity.
Low-Viscosity, Electrolyte-Poor Fluid. Low-vis-
cosity, electrolyte-poor fluids include glycine, 1.5%,
sorbitol, 3%, and mannitol, 5%. These fluids have
been widely used for operative hysteroscopy. They
are compatible with radiofrequency energy, which
cuts, desiccates, and fulgurates intrauterine tissue.
Monopolar devices require electrolyte-poor fluids. If
electrolyte-containing fluid is used, the electrical
current will dissipate away from the electrode, ren-
dering it ineffective. Glycine, 1.5%, and sorbitol,
3%, are hypoosmolar. The use of these fluids can
cause hyponatremia and decreased serum osmolal-
ity, with the potential for cerebral edema and death.
Some clinicians have recommended mannitol, 5%,
which is isoosmolar and acts as its own diuretic. It
may cause hyponatremia but not decreased serum
osmolality (1).
Low-Viscosity Electrolyte Fluid. Normal saline
and lactated Ringers solution are electrolyte fluids.
The use of these fluids is advantageous because they
are readily available and are isotonic. These solu-
tions are the distending media of choice during diag-
nostic hysteroscopy and in operative cases where
mechanical, laser, or bipolar energy is used.
Although the risk of hyponatremia and decreased
serum osmolality can be reduced by using these
media, pulmonary edema can still occur, and careful
attention should be paid to fluid input and output.
High-Viscosity Fluid. Dextran 70 is a colorless, vis-
cous, polysaccharide liquid. The advantage of using
this liquid is that it is immiscible with blood and,
therefore, provides excellent visibility, especially in
the presence of blood in the endometrial cavity. The
major disadvantage of using dextran 70 is that it is
sticky and, when dry, tends to harden and crystallize
onto the equipment. It also can be a powerful plas-
ma expander, and the volume usually is limited to
300 mL and must not exceed 500 mL. For every 100
mL absorbed, the plasma volume may expand by
an additional 860 mL (2). Other concerns include
anaphylaxis and disseminated intravascular coag-
ulation. Beet sugar allergy is an absolute contra-
indication.
PREOPERATIVE CONSIDERATIONS
A preoperative consultation allows the patient and
physician to discuss the hysteroscopic procedure,
weigh its inherent risks and benefits, and review the
patients medical history for any comorbid condi-
tions. Appropriate analgesia or anesthesia should
also be considered depending on the venue (ie,
office versus operating room). Preoperative place-
ment of laminar or osmotic dilators or pretreatment
with misoprostol for cervical ripening may facilitate
cervical dilation and decrease operative time (3).
CONTRAINDICATIONS
Known viable pregnancy, known genital tract infec-
tions, and known uterine carcinomas are contraindi-
cations to hysteroscopy. Theoretically, hysteroscopy
may cause reflux of neoplastic cells into the peri-
toneal cavity, although it is unclear if this adversely
affects the prognosis (4, 5). However, hysteroscopy
is acceptable as part of the evaluation of abnormal
uterine bleeding.
COMPENDIUM OF SELECTED PUBLICATIONS 408
PREVENTION AND MANAGEMENT OF
COMPLICATIONS
The most common perioperative complications
associated with operative hysteroscopy are hemor-
rhage (2.4%), fluid overload (1.5%) (6), and cervical
laceration (111%) (7). Other complications include
uterine perforation, visceral injury, infection, CO
2
and air embolism, and, rarely, death. Late com-
plications may include intrauterine adhesions and
infertility.
Hemorrhage
Hemorrhage may occur during hysteroscopic resec-
tion of the endometrium, myomata, uterine septa, or
synechia. For cases in which there is continued
bleeding, electrosurgical coagulation can be used
(8). Alternative strategies such as injection of vaso-
pressin at the bleeding site, Foley catheter balloon
tamponade (9), or irrigation of the uterine cavity
with epsilon aminocaproic acid can be attempted. In
extreme cases, uterine artery embolization or hys-
terectomy may be necessary.
Fluid Overload
Complications from fluid overload may best be
avoided by limiting excess fluid absorption, recog-
nizing and treating fluid overload promptly, and
selecting a distending medium that minimizes risk.
The best way to limit excess fluid intravasation
is to monitor the fluid deficit closely and frequently
throughout the procedure. Newer methods of fluid
monitoring based on measurement of fluid weight
have made this more accurate; however, some of
these systems can be expensive and may not be
available in all settings. One difficulty in estimating
fluid input and output is that commercially pur-
chased 3-liter bags may be overfilled by up to
150300 mL (10). Dilutional hyponatremia can be
rapidly evaluated by serum sodium analysis.
Guidelines for fluid monitoring and the limits
of fluid excess have been published (1) and adapted
by the American College of Obstetricians and
Gynecologists Committee on Gynecologic Practice
as follows:
Hydration of patients undergoing hysteroscopy
should be closely monitored preoperatively and
intraoperatively.
With low-viscosity, electrolyte-poor fluids, a
deficit of 750 mL implies excessive intravasation,
and the fluid deficit should be monitored at an
extremely close interval. In elderly patients,
patients with comorbid conditions, and patients
with cardiovascular compromise, consideration
should be given to terminating the procedure
immediately.
Depending on patient size and other factors, if
fluid deficit reaches 1,0001,500 mL of a non-
electrolyte solution or 2,500 mL of an electrolyte
solution, further infusion should be stopped and
the procedure should be promptly concluded.
Electrolytes should be assessed, administration of
diuretics considered, and further diagnostic and
therapeutic intervention begun as indicated.
In an outpatient setting with limited acute care
and laboratory services, consideration should be
given to discontinuing procedures at a lower fluid
deficit threshold.
An automated fluid monitoring system facilitates
early recognition of excessive deficit in real-time
totals.
In the absence of automated monitoring, an indi-
vidual should be designated to frequently mea-
sure intake and outflow and report the deficit to
the operative team.
The treatment of fluid overload from hypotonic
agents may require consultation and possibly trans-
fer to an acute care facility. Whereas most women
recover, seizures, permanent brain damage, and
death have been reported with serum sodium levels
of 116 2 mmol/L (11). Although the rate at which
severe hyponatremia should be corrected is contro-
versial, most authors agree that if acute hyponatre-
mia has existed for less than 24 hours, there are few
long-term complications from rapid correction.
Therapy is most often provided in the form of hyper-
tonic saline in conjunction with loop-acting diuret-
ics. Serum sodium levels should be increased by 12
mEq/L/h but by no more than 12 mEq/L in the first
24 hours (12). When patients present with hypona-
tremia of greater than 48 hours postoperatively,
rapid correction should not be undertaken because it
can lead to neurologic compromise, seizures, and
death. Consultation is strongly encouraged in these
situations and often requires slower correction in an
intensive care setting.
Perforation
Prior to performing hysteroscopy, a pelvic examina-
tion should be performed to determine uterine posi-
tion. If resistance is encountered during insertion of
the hysteroscope, the cervix may need further dila-
tion. Midline uterine perforation rarely leads to sig-
nificant morbidity unless a laser or electrosurgical
409 COMMITTEE OPINIONS
device is used. Lateral uterine or cervical perfora-
tions can result in significant bleeding. Laparoscopy
may be useful to determine the extent of damage,
including the existence of bowel or bladder injury.
Embolization
Air and CO
2
emboli are rare complications of hys-
teroscopy and may result in circulatory collapse. For
such emboli to occur, there must be both vascular
access and a pressure gradient between the site of
access and the right side of the heart. In the con-
scious patient, chest pain and dyspnea may be noted.
Other findings can include decreased oxygen satura-
tion, the presence of a mill wheel heart murmur,
hypotension, bradycardia, or tachycardia. In the
anesthetized patient, cardiopulmonary status shows
signs of collapse with sudden hypotension, decrease
in oxygenation and/or in end-tidal CO
2
, or cardiac
dysrhythmias (13).
Management of this emergency consists of plac-
ing the patient in a left lateral decubitus position
with the head tilted downward 5 degrees. This
maneuver favors the movement of air in the right
ventricle and right ventricular outflow tract toward
the apex of the right ventricle (14). The air may be
aspirated by passing a catheter down the jugular vein
into the right ventricle, or possibly by performing
cardiocentesis.
SUMMARY
Hysteroscopy is an effective procedure for the diag-
nosis and treatment of intrauterine pathology. It is
minimally invasive and can be used with a high
degree of safety. Knowledge of potential dangers
relating to distending media and intraoperative com-
plications will enhance its safety.
REFERENCES
1. Loffer FD, Bradley LD, Brill AI, Brooks PG, Cooper JM.
Hysteroscopic fluid monitoring guidelines. The ad hoc
committee on hysteroscopic training guidelines of the
American Association of Gynecologic Laparoscopists. J
Am Assoc Gyn Laparosc 2000;7:1678.
2. Lukacsko P. Noncardiogenic pulmonary edema secondary
to intrauterine instillation of 32% dextran 70. Fertil Steril
1985;44:5601.
3. Thomas JA, Leyland N, Durand N, Windrim RC. The use
of oral misoprostol as a cervical ripening agent in operative
hysteroscopy: a double-blind, placebo-controlled trial. Am
J Obstet Gynecol 2002;186:8769.
4. Obermair A, Geramou M, Gucer F, Denison U, Graf AH,
Kapshammer E, et al. Does hysteroscopy facilitate tumor
cell dissemination? Incidence of peritoneal cytology from
patients with early stage endometrial carcinoma following
dilatation and curettage (D&C) versus hysteroscopy and
D&C. Cancer 2000;88:13943.
5. Arikan G, Reich O, Weiss U, Hahn T, Reinisch S,
Tamussino K, et al. Are endometrial carcinoma cells dis-
seminated at hysteroscopy functionally viable? Gynecol
Oncol 2001;83:2216.
6. Overton C, Hargreaves J, Maresh M. A national survey of
the complications of endometrial destruction for men-
strual disorders: the MISTLETOE study. Minimally
Invasive Surgical TechniquesLaser, EndoThermal or
Endoresection. Br J Obstet Gynaecol 1997;104:13519.
7. Preutthipan S, Herabutya Y. Vaginal misoprostol for cervi-
cal priming before operative hysteroscopy: a randomized
control trial. Obstet Gynecol 2000;96:8904.
8. Loffer FD. Complications of hysteroscopytheir cause,
prevention, and correction. J Am Assoc Gynecol Laparosc
1995;3:1126.
9. Goldrath MH. Uterine tamponade for the control of acute
uterine bleeding. Am J Obstet Gynecol 1983;147:86972.
10. Vulgaropulos SP, Haley LC, Hulka JF. Intrauterine pres-
sure and fluid absorption during continuous flow hys-
teroscopy. Am J Obstet Gynecol 1992;167:386390; dis-
cussion 3901.
11. Arieff AI. Management of hyponatraemia. BMJ 1993;
307:3058.
12. Witz CA, Silverberg CM, Burns WN, Schenken RS, Olive
DL. Complications associated with the absorption of hys-
teroscopic fluid media. Fertil Steril 1993;60:74556.
13. Stoloff DR, Isenberg RA, Brill AI. Venous air and gas
emboli in operative hysteroscopy. J Am Assoc Gynecol
Laparosc 2001;8:18192.
14. deWet C, Harrison L, Jacobsohn E. Air embolism. In: Atlee
JL, editor. Complications in anesthesia. Philadelphia
(PA):WB Saunders;1999. p. 3235.
Copyright August 2005 by the American College of Obste-
tricians and Gynecologists. All rights reserved. No part of this
publication may be reproduced, stored in a retrieval system, or
transmitted, in any form or by any means, electronic, mechan-
ical, photocopying, recording, or otherwise, without prior writ-
ten permission from the publisher.
Requests for authorization to make photocopies should be
directed to Copyright Clearance Center, 222 Rosewood Drive,
Danvers, MA 01923, (978) 750-8400.
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Hysteroscopy. ACOG Technology Assessment in Obstetrics
and Gynecology No. 4. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2005;106:43942.
COMPENDIUM OF SELECTED PUBLICATIONS 410
ACOG
I N OBSTE TRI CS AND GYNE COLOGY
TECHNOLOGY ASSESSMENT
NUMBER 5, DECEMBER 2008
(Replaces Technology Assessment No. 3, September 2003)
This Technology Assessment was
developed by the ACOG Com-
mittee on Gynecologic Practice
with the assistance of Daniel
Breitkopf, MD, John W. Seeds,
MD, and Steven R. Goldstein,
MD. This document reflects
emerging clinical and scientific
advances as of the date issued and
is subject to change. The informa-
tion should not be construed as
dictating an exclusive course of
treatment or procedure to be
followed. Variations in practice
may be warranted based on the
needs of the individual patient,
resources, and limitations unique
to the institution or type of
practice.
Sonohysterography
ABSTRACT: The goal of sonohysterography is to visualize the endometrial
cavity in more detail than is possible with routine transvaginal ultrasound.
The procedure consists of the manual injection of sterile fluid under
real-time ultrasonographic imaging. The most common indication for sono-
hysterography is abnormal uterine bleeding. The procedure should not be
performed in a woman who is pregnant or who could be pregnant, or who
has a pelvic infection or unexplained pelvic tenderness. Physicians who per-
form or supervise diagnostic sonohysterography should be skilled in vagi-
nal ultrasonography and transcervical placement of catheters; should have
training, experience, and demonstrated competence in gynecologic ultra-
sonography and sonohysterography; and should keep careful records.
Portions of this document were developed jointly with the American College
of Radiology and the American Institute of Ultrasound in Medicine.
Sonohysterography can provide information about the uterus and endome-
trial cavity. Additional studies may be necessary for a complete diagnosis.
Adherence to the following recommendations serves to maximize the diag-
nostic benefits and safety of sonohysterography.
The clinical aspects of this document include sections addressing indi-
cations and contraindications, specifications of the examination, and equip-
ment specifications that were developed collaboratively by the American
College of Radiology, the American Institute of Ultrasound in Medicine,
and the American College of Obstetricians and Gynecologists and adapted
by the American College of Obstetricians and Gynecologists Committee on
Gynecologic Practice. Sections of the document addressing physician qual-
ifications and responsibilities, documentation, quality control, performance
improvement, safety, infection control, and patient education are recom-
mendations of the American College of Obstetricians and Gynecologists
Committee on Gynecologic Practice.
Most clinical experience and medical literature to date have focused on
the ultrasonographic imaging of the uterus, and specifically the endometri-
al cavity, using the transcervical injection of sterile fluid. Thus, terms such
as saline infusion sonohysterography or simply sonohysterography have
been used to describe this technique. The goal of sonohysterography is to
visualize the endometrial cavity in more detail than is possible with routine
transvaginal ultrasound.
Studies are underway to evaluate fluids other than saline for use in
sonohysterography to determine tubal patency, but their use is currently
THE AMERICAN COLLEGE
OF OBSTETRICIANS
AND GYNECOLOGISTS
WOMEN S HEALTH CARE PHYSI CI ANS
411 COMMITTEE OPINIONS
investigational because this application of sonohys-
terography has not yet been validated.
INDICATIONS AND CONTRAINDICATIONS
The indications for sonohysterography include, but
are not limited to, evaluation of
abnormal uterine bleeding in premenopausal and
postmenopausal women
infertility and habitual abortion
congenital abnormalities of the uterine cavity
suspected uterine myomas, polyps, and synechiae
abnormalities detected on transvaginal ultra-
sonography, including focal or diffuse endometrial
or intracavitary abnormalities
suboptimally imaged endometrium by transvagi-
nal ultrasonography
The most common indication for sonohysterog-
raphy is as an adjunct to transvaginal ultrasound in
the evaluation of abnormal uterine bleeding in both
premenopausal and postmenopausal women.
Sonohysterography should not be performed in
a woman who is pregnant or who could be pregnant.
This usually is avoided by scheduling the examina-
tion in the follicular phase of the menstrual cycle,
after the menstrual flow has essentially ceased, but
before the patient has ovulated. In a patient with reg-
ular menstrual cycles, sonohysterography should, in
most cases, be performed by the 10th day of the
menstrual cycle. Sonohysterography should not be
performed in patients with a pelvic infection or
unexplained pelvic tenderness, which could be due
to pelvic inflammatory disease. Active vaginal
bleeding is not an absolute contraindication to the
procedure but may make the interpretation more
challenging.
PHYSICIAN QUALIFICATIONS AND
RESPONSIBILITIES
Physicians who perform or supervise diagnostic
sonohysterography should be skilled in vaginal
ultrasonography and transcervical placement of
catheters. They should understand the indications,
limitations, and possible complications of the proce-
dure. Physicians should have training, experience,
and demonstrated competence in gynecologic ultra-
sonography and sonohysterography. Physicians are
responsible for the documentation of the examina-
tion, quality control, and patient safety.
SPECIFICATIONS OF THE EXAMINATION
Patient Preparation
The sonohysterography procedure should be fully
explained to the patient in advance. Transvaginal
ultrasonography is a specialized form of a pelvic
examination. Therefore, policies applied locally
regarding chaperone or patient privacy issues during a
pelvic examination also should be applied during a
transvaginal ultrasound examination. Pelvic organ
tenderness should be assessed during a preliminary
transvaginal ultrasound examination. If adnexal ten-
derness or pain suspicious for active pelvic infection is
found prior to fluid infusion, the examination should
be deferred until after an appropriate course of treat-
ment. Although routine use of antibiotic prophylaxis is
not recommended, consideration should be given to
administering antibiotics based on individual risk fac-
tors (eg, in the presence of nontender hydrosalpinges).
A pregnancy test is advised when clinically indicated.
Procedure
Preliminary routine transvaginal ultrasonography
with measurements of the endometrium and evalua-
tion of the uterus and ovaries should be performed
before sonohysterography. A speculum is used to
allow visualization of the cervix. The presence of
unusual pain, lesions, or purulent vaginal or cervical
discharge may require rescheduling the procedure
pending further evaluation. After the external os is
cleansed, a catheter should be inserted into the cervi-
cal canal or uterine cavity or both using aseptic tech-
nique. Appropriate sterile fluid should be instilled
slowly by means of manual injection under real-time
ultrasonographic imaging. Imaging should include
real-time scanning of the endometrium and cervical
canal.
Images
Appropriate images, in at least two planes, using a
high-frequency transvaginal ultrasound probe should
be produced and recorded to demonstrate normal and
abnormal findings. Precatheterization images should
be obtained, including the thickest bilayer endome-
trial measurement on a sagittal image.
Once the uterine cavity is filled with fluid, rep-
resentative images with a complete survey of the
uterine cavity are obtained as necessary for diagnos-
tic evaluation. If a balloon catheter is used for the
examination, images should be obtained at the end
of the procedure with the balloon deflated to fully
evaluate the endometrial cavity, particularly the cer-
vical canal and lower uterine segment.
COMPENDIUM OF SELECTED PUBLICATIONS 412
Documentation
Appropriate documentation of a sonohysterography
examination is essential for clinical care and quality
assessment and improvement. An adequate written
report should include patient identification, proce-
dural technique, measurements, morphologic
descriptions, and interpretation. Images of key find-
ings and written reports from ultrasound examina-
tions are considered part of the medical record and
should be documented and stored appropriately. (In
Current Procedural Terminology [CPT], sonohys-
terography is referred to as hysterosonography.)
Equipment Specifications
Sonohysterography usually is conducted with a
transvaginal transducer. If a patient has an enlarged
uterus, additional transabdominal images during
infusion may be required to fully evaluate the
endometrium. The transducer should be adjusted to
operate at the highest clinically appropriate fre-
quency under the ALARA (as low as reasonably
achievable) principle.
Quality and Infection Control
Quality control is accomplished through careful
record keeping, reliable archiving of reports and
images, and clinical correlation with outcomes. Tran-
svaginal transducers always should be covered with a
single-use disposable latex or nonlatex cover. How-
ever, because no such disposable protective cover is
without risk of rupture or defect, transvaginal trans-
ducers should undergo appropriate antimicrobial and
antiviral reprocessing between patient use.
BIBLIOGRAPHY
Becker E Jr, Lev-Toaff AS, Kaufman EP, Halpern EJ, Edel-
weiss MI, Kurtz AB. The added value of transvaginal sonohys-
terography over transvaginal sonography alone in women with
known or suspected leiomyoma. J Ultrasound Med 2002;
21:23747.
Benacerraf BR, Shipp TD, Bromley B. Improving the efficien-
cy of gynecologic sonography with 3-dimensional volumes: a
pilot study. J Ultrasound Med 2006;25:16571.
Bree RL, Bowerman RA, Bohm-Velez M, Benson CB,
Doubilet PM, DeDreu S, et al. US evaluation of the uterus in
patients with postmenopausal bleeding: a positive effect on
diagnostic decision making. Radiology 2000;216:2604.
Breitkopf DM, Frederickson RA, Snyder RR. Detection of
benign endometrial masses by endometrial stripe measurement
in premenopausal women. Obstet Gynecol 2004;104:1205.
Doubilet PM. Society of Radiologists in Ultrasound Consensus
Conference statement on postmenopausal bleeding. J Ultra-
sound Med 2001;20:103742.
Dubinsky TJ, Stroehlein K, Abu-Ghazzeh Y, Parvey HR, Mak-
lad N. Prediction of benign and malignant endometrial disease:
hysterosonographic-pathologic correlation. Radiology 1999;
210:3937.
Goldstein RB, Bree RL, Benson CB, Benacerraf BR, Bloss JD,
Carlos R, et al. Evaluation of the woman with postmenopausal
bleeding: Society of Radiologists in Ultrasound-Sponsored
Consensus Conference statement. J Ultrasound Med 2001;20:
102536.
Goldstein SR. Use of ultrasonohysterography for triage of per-
imenopausal patients with unexplained uterine bleeding. Am J
Obstet Gynecol 1994;170:56570.
Hann LE, Gretz EM, Bach AM, Francis SM. Sonohysterogra-
phy for evaluation of the endometrium in women treated with
tamoxifen. AJR Am J Roentgenol 2001;177:33742.
Laifer-Narin S, Ragavendra N, Parmenter EK, Grant EG.
False-normal appearance of the endometrium on conventional
transvaginal sonography: comparison with saline hys-
terosonography. AJR Am J Roentgenol 2002;178:12933.
Laifer-Narin SL, Ragavendra N, Lu DS, Sayre J, Perrella RR,
Grant EG. Transvaginal saline hysterosonography: characteris-
tics distinguishing malignant and various benign conditions.
AJR Am J Roentgenol 1999;172:151320.
Lev-Toaff AS, Toaff ME, Liu JB, Merton DA, Goldberg BB.
Value of sonohysterography in the diagnosis and management
of abnormal uterine bleeding. Radiology 1996;201:17984.
Lindheim SR, Sprague C, Winter TC 3rd. Hysterosalpingogra-
phy and sonohysterography: lessons in technique. AJR Am J
Roentgenol 2006;186:249.
Mihm LM, Quick VA, Brumfield JA, Connors AF Jr, Finnerty
JJ. The accuracy of endometrial biopsy and saline sonohys-
terography in the determination of the cause of abnormal uter-
ine bleeding. Am J Obstet Gynecol 2002;186:85860.
Parsons AK, Lense JJ. Sonohysterography for endometrial
abnormalities: preliminary results. J Clin Ultrasound 1993;
21:8795.
Schwartz LB, Snyder J, Horan C, Porges RF, Nachtigall LE,
Goldstein SR. The use of transvaginal ultrasound and saline
infusion sonohysterography for the evaluation of asymptomatic
postmenopausal breast cancer patients on tamoxifen. Ultra-
sound Obstet Gynecol 1998;11:4853.
Copyright December 2008 by the American College of
Obstetricians and Gynecologists. All rights reserved. No part
of this publication may be reproduced, stored in a retrieval
system, or transmitted, in any form or by any means, electron-
ic, mechanical, photocopying, recording, or otherwise, without
prior written permission from the publisher.
Requests for authorization to make photocopies should be
directed to Copyright Clearance Center, 222 Rosewood Drive,
Danvers, MA 01923, (978) 750-8400.
The American College of Obstetricians and Gynecologists
409 12th Street, SW, PO Box 96920
Washington, DC 20090-6920
Sonohysterography. ACOG Technology Assessment No. 5.
American College of Obstetricians and Gynecologists. Obstet
Gynecol 2008;112:14679.
413 COMMITTEE OPINIONS
ACOG
TECHNOLOGY ASSESSMENT
NUMBER 6, NOVEMBER 2009
Robot-Assisted Surgery
ABSTRACT: The field of robotic surgery is developing rapidly, but experi-
ence with this technology is currently limited. In response to increasing
interest in robotics technology, the Committee on Gynecologic Practices
Technology Assessment was developed to describe the robotic surgical sys-
tem, potential advantages and disadvantages, gynecologic applications, and
the current state of the evidence. Randomized trials comparing robot-assisted
surgery with traditional laparoscopic, vaginal, or abdominal surgery are
needed to evaluate long-term clinical outcomes and cost-effectiveness, as
well as to identify the best applications of this technology.
Robot-assisted surgery evolved from the on-site needs of battlefield medicine and
from the technical limitations of traditional laparoscopy (1). Although a number
of precursors existed, the da Vinci Surgical System, introduced in 1999, is the only
commercially available system approved by the U.S. Food and Drug
Administration (FDA) for gynecologic surgery. Initial applications included radi-
cal retropubic prostatectomy and cardiac surgery. Use in gynecologic surgery was
approved by the FDA in 2005. In response to increasing interest in robotics tech-
nology, the Committee on Gynecologic Practices Technology Assessment was
developed to describe the robotic surgical system, potential advantages and disad-
vantages, gynecologic applications, and the current state of the evidence.
DESCRIPTION OF ROBOTIC INSTRUMENTATION
The current robotic surgical system consists of four components: 1) a console
where the surgeon sits, views the screen, and controls the robotic instruments and
camera via finger graspers and foot pedals; 2) a robotic cart with three or four
interactive arms that hold instruments through trocars attached to the patient; 3) a
camera and vision system that allows for a three-dimensional image of the pelvis
using image synchronizers and illuminators; and 4) wristed instruments with com-
puter interfaces that translate the mechanical movements of the surgeons hands
into computer algorithms directing the instrument use within the patient (2).
During robotic surgery, the primary surgeon sits unscrubbed at the console, and at
some distance from the patient, with fingers through graspers controlling the
instruments. Foot pedals and a clutch are used for camera control, activation of
energy sources, focusing, and robotic arm switching. Three or four robotic arms
are docked to trocars inserted through the patients abdomen. A 12-mm, three-
dimensional endoscope is placed at the midline and two or three instruments are
This Technology Assessment
was developed by the ACOG
Committee on Gynecologic
Practice. This document reflects
emerging clinical and scientific
advances as of the date issued
and is subject to change. The
information should not be con-
strued as dictating an exclusive
course of treatment or proce-
dure to be followed. Variations
in practice may be warranted
based on the needs of the indi-
vidual patient, resources, and
limitations unique to the insti-
tution or type of practice.
THE AMERI CAN COLLEGE
OF OBSTETRI CI ANS
AND GYNECOLOGI STS
WOMEN S HEALTH CARE PHYSI CI ANS
I N OBSTE TRI CS AND GYNE COLOGY
COMPENDIUM OF SELECTED PUBLICATIONS 414
passed through the lateral ports. Assistant surgical team
members pass robotic instruments and sutures through
these ports for use by the primary surgeon and also pro-
vide suction, irrigation, and countertraction. Instruments
for suturing, clamping, endosurgery, and tissue manipu-
lation are used with the robotic arms.
POTENTIAL ADVANTAGES AND
DISADVANTAGES
Potential advantages over traditional laparoscopic
surgery include 1) three-dimensional visualization with
improved depth perception, 2) improved dexterity and
instrument articulation secondary to increased freedom
of movement and elimination of tremor and counterintu-
itive motions, and 3) the potential for use in telesurgery.
The improved visualization and dexterity may offer
some advantages over conventional laparoscopy for
complex procedures such as those required for gyneco-
logic malignancy or invasive endometriosis (3, 4). Shorter
hospital stays and decreased blood loss also may be
advantages over laparotomy (5, 6).
Disadvantages of robotic surgery include 1) the high
costs associated with the technology (more than $1 million
for the initial system, with additional costs of yearly ser-
vice contracts and disposable instrumentation), 2) the
increased operating time associated with equipment
setup and docking, 3) the lack of tactile feedback and sen-
sation (haptics), 4) the inability to reposition the patient
once the robotic arms are attached, and 5) the bulkiness
of the current robotic system making it difficult for assis-
tants to maneuver around it (eg, when applying uterine
manipulation for hysterectomy).
Robotic surgery has the potential to be a useful edu-
cational tool in resident and physician training. A current
concern is that its use may adversely affect surgical
training by decreasing residents overall surgical experi-
ence because only one surgeon can sit at the console.
Newer models that allow two surgeons to operate with
dual consoles are now available.
GYNECOLOGIC APPLICATIONS
The field of robotic surgery is developing rapidly, but
experience with the technology is limited at this time.
Limited data, mostly from heterogeneous small retro-
spective case series and a few small nonrandomized,
mostly retrospective comparative studies (2, 3, 511)
have shown the safety and feasibility of robot-assisted
surgery for numerous procedures, including tubal
reanastomosis, hysterectomy, nodal sampling, and pro-
lapse suspension procedures. However, the comparative
studies frequently use historical controls, with different
surgeons, patient selection criteria, or settings (8). Large
prospective comparative studies evaluating long-term
clinical outcomes and costs are lacking. Few data exist on
how surgeon experience relates to overall complication
rates, operative time, or costs. Similarly, data are insuffi-
cient to demonstrate the specific patients or indications
where robot-assisted procedures might be advantageous
over vaginal surgery, laparotomy, or conventional lapar-
oscopy. Although randomized controlled trials comparing
robotic-assisted surgery to conventional approaches are
ongoing (7), results are currently unavailable. Additional
information on ongoing clinical trials is available at
ClinicalTrials.gov.
CREDENTIALING
When surgeons adopt a new surgical technique, they
should be supervised or assisted by a more experienced
colleague, whenever feasible, until satisfactory compe-
tency has been demonstrated (12). Credentialing for
robotic-assisted surgery within and across specialties is
based on training, experience, and documented current
competency.
CONCLUSION
The field of robotic surgery is developing rapidly, but
experience with this technology is currently limited.
Randomized trials comparing robot-assisted surgery with
traditional laparoscopic, vaginal, or abdominal surgery are
needed to evaluate long-term clinical outcomes and cost-
effectiveness, as well as to identify the best applications of
this technology.
REFERENCES
1. Falcone T, Goldberg JM. Robotics in gynecology. Surg
Clin North Am 2003;83:14839, xii.
2. Visco AG, Advincula AP. Robotic gynecologic surgery.
Obstet Gynecol 2008;112:136984.
3. Veljovich DS, Paley PJ, Drescher CW, Everett EN, Shah C,
Peters WA 3rd. Robotic surgery in gynecologic oncology:
program initiation and outcomes after the first year with
comparison with laparotomy for endometrial cancer stag-
ing. Am J Obstet Gynecol 2008;198:679.e19; discussion
679.e910.
4. Advincula AP, Reynolds RK. The use of robot-assisted
laparoscopic hysterectomy in the patient with a scarred or
obliterated anterior cul-de-sac. JSLS 2005;9:28791.
5. Geller EJ, Siddiqui NY, Wu JM, Visco AG. Short-term out-
comes of robotic sacrocolpopexy compared with abdomi-
nal sacrocolpopexy. Obstet Gynecol 2008;112:12016.
6. Magrina JF, Kho RM, Weaver AL, Montero RP, Magtibay PM.
Robotic radical hysterectomy: comparison with lap-
415 COMMITTEE OPINIONS
aroscopy and laparotomy. Gynecol Oncol 2008;109:86
91.
7. Obermair A, Gebski V, Frumovitz M, Soliman PT,
Schmeler KM, Levenback C, et al. A phase III randomized
clinical trial comparing laparoscopic or robotic radical hys-
terectomy with abdominal radical hysterectomy in patients
with early stage cervical cancer. J Minim Invasive Gynecol
2008;15:5848.
8. Belgian Health Care Knowledge Center (KCE). Robot-
assisted surgery: health technology assessment. KCE reports
104C. Brussels: KCE; 2009. Available at: http://www.kce.
fgov.be/Download.aspx?ID=1462. Retrieved June 29, 2009.
9. Persson J, Reynisson P, Borgfeldt C, Kannisto P, Lindahl B,
Bossmar T. Robot assisted laparoscopic radical hysterectomy
and pelvic lymphadenectomy with short and long term
morbidity data. Gynecol Oncol 2009;113:18590.
10. Seamon LG, Cohn DE, Henretta MS, Kim KH, Carlson MJ,
Phillips GS, et al. Minimally invasive comprehensive sur-
gical staging for endometrial cancer: robotics or
laparoscopy? Gynecol Oncol 2009;113:3641.
11. Dharia Patel SP, Steinkampf MP, Whitten SJ, Malizia BA.
Robotic tubal anastomosis: surgical technique and cost
effectiveness. Fertil Steril 2008;90:11759.
12. Patient safety in the surgical environment. ACOG
Committee Opinion No. 328. American College of
Obstetricians and Gynecologists. Obstet Gynecol
2006;107:42933.
Copyright November 2009 by the American College of
Obstetricians and Gynecologists. All rights reserved. No part
of this publication may be reproduced, stored in a retrieval
system, or transmitted, in any form or by any means, electronic,
mechanical, photocopying, recording, or otherwise, without
prior written permission from the publisher.
Requests for authorization to make photocopies should be
directed to Copyright Clearance Center, 222 Rosewood Drive,
Danvers, MA 01923, (978) 750-8400.
The American College of Obstetricians and Gynecologists
409 12th Street, SW, PO Box 96920
Washington, DC 20090-6920
Robot-assisted surgery. ACOG Technology Assessment in
Obstetrics and Gynecology No. 6. American College of
Obstetricians and Gynecologists. Obstet Gynecol 2009;114:
11535.
417 COMMITTEE OPINIONS
COMMITTEE OPINIONS
COMMITTEE ON HEALTH CARE FOR
UNDERSERVED WOMEN
COMMITTEE OPINIONS
COMMITTEE ON HEALTH CARE FOR
UNDERSERVED WOMEN
419
Committee on
Health Care for
Underserved Women
Reaffirmed 2008
ACOG
Number 307, December 2004
Committee
Opinion
The information should not be
construed as dictating an exclu-
sive course of treatment or proce-
dure to be followed.
The Committee wishes to thank
Kurt Barnhart, MD, MSCE;
Jeffrey Ecker, MD; and Carol
Tauer, PhD; for their assistance in
the development of this document.
Copyright December 2004
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of this
publication may be reproduced,
stored in a retrieval system, or
transmitted, in any form or by any
means, electronic, mechanical,
photocopying, recording, or other-
wise, without prior written per-
mission from the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Partner Consent for Participation in
Womens Reproductive Health
Research
ABSTRACT: Recent advances in reproductive medicine include treatment of
subfertility as well as investigation of agents that may serve as both contra-
ceptives and potential prophylaxis against sexually transmitted diseases,
including potential protection from human immunodeficiency virus (HIV).
Although there is no doubt regarding the need for informed consent by women
participating in trials evaluating the safety and effectiveness of these novel
agents and treatments, there has been some debate regarding the necessity
and propriety of requiring consent from the partners of women involved in
certain types of clinical trials involving reproductive health. Issues of partner
consent are unique to research surrounding womens reproductive health as
opposed to research pertaining to womens health, in general. This is due, in
part, to a valid concern about a potential effect of the research on the part-
ner. There are, therefore, legitimate reasons to obtain partner consent for a
womans participation in a clinical trial. In the absence of such reason, part-
ner consent should not be mandated.
Background
A large number of clinical trials are currently being conducted in nearly every
therapeutic area, including womens health. Women may be motivated to par-
ticipate in clinical trials by altruism to further the care of women, by the abil-
ity to receive novel and state-of-the-art medical care, or by the benefits of
highly supervised medical monitoring of treatment. Often women without
health insurance choose to participate in these trials because such trials may
provide enhanced access to care, the care provided is often rendered without
cost, and there is reimbursement for time and travel. The American College
of Obstetricians and Gynecologists supports the development of new devices
and medications to advance womens health and reproductive options. The
American College of Obstetricians and Gynecologists also endorses the high-
est ethical and moral conduct of clinical research. All women, regardless of
socioeconomic status and race, should have access to enrollment in clinical
trials. The decision to enter a clinical trial should be autonomous, without
Partner consent for participation in
womens reproductive health research.
ACOG Committee Opinion No. 307.
American College of Obstetricians and
Gynecologists. Obstet Gynecol 2004;
104:14679.
COMPENDIUM OF SELECTED PUBLICATIONS 420 420
coercion, and after informed consent. Informed con-
sent is the ability to understand the risks and benefits
of ones participation in a research activity and to
authorize ones participation in this activity freely (1).
A research subject is defined as An individual
who participates in a clinical trial, either as a recipi-
ent of the investigational product(s) or as a control.
(2). In research on womens reproductive health,
sometimes both the woman and her partner will be
the subjects. For example, in a study designed to
identify any risk or harm to a partner of a new con-
traceptive method, both the woman and her partner
may be research subjects. If a partner is a subject in
the research, informed consent for both participants
is required. This Committee Opinion primarily
addresses the need for partner consent in research
for which the woman, and not a partner, is the
research subject. The respect for the autonomy of
research subjects to consent to participation is one of
the pillars of The Belmont Report, promulgated by
The National Commission for the Protection of
Human Subjects of Biomedical and Behavioral
Research in 1979 (3). The decision to reproduce or
use contraceptives should remain autonomous for a
woman even when enrolled in a clinical trial.
It also is important to note that the discussion
and recommendations that follow do not pertain to
research involving pregnant women. There are spe-
cific regulations that apply to federally funded
research involving this population (4).
Partner Consent Requirement
Inconsistencies
Recent advances in reproductive medicine include
treatment of subfertility as well as investigation of
agents that may serve as both contraceptives and
potential prophylaxis against sexually transmitted
diseases, including potential protection from human
immunodeficiency virus (HIV). Although there is no
doubt regarding the need for informed consent by
women participating in trials evaluating the safety
and effectiveness of these novel agents and treat-
ments, there has been some debate regarding the
necessity and propriety of requiring consent from the
partners of women involved in certain types of clinical
trials involving reproductive health. Some local insti-
tutional review boards (IRB) have requested consent
of a womans partner and at other times a trial spon-
sor or an individual investigator has made the deci-
sion unilaterally. Because of the lack of guidance on
this issue, there is great inconsistency regarding
requirements for partner consent and the manner in
which partner consent is obtained (see box
Methods of Obtaining Partner Consent).
When Is Partner Consent Needed?
Issues of partner consent are unique to research sur-
rounding womens reproductive health as opposed
to research pertaining to womens health, in general.
This is partly due to a valid concern about a poten-
tial impact of the research on the partner. Therefore,
there are legitimate reasons to obtain partner consent
for a womans participation in a clinical trial. In the
absence of such reason, partner consent should not
be mandated. Partner consent should be obtained if:
A sexual partner is a subject in the same clinical
trial as the woman.
A partner will be exposed to a novel agent and
there is a potential for more than minimal risks
*
of exposure to the investigational agent.
Data will be collected regarding a partners
acceptance of the investigational agent, or the
impact of partners acceptance of the agent on
the female participant.
Inclusion or exclusion criteria directly relate to
a partner, for example, if testing of a partner is
required for a woman to enroll in the trial (eg,
semen analysis or testing for a sexually trans-
mitted disease).
If, after careful consideration, it is determined that
none of the previous conditions apply, partner con-
sent is not warranted because it should not need-
lessly:
Impose a barrier to participation for a woman
Interfere with a womans choice of reproduc-
tive options
Interfere with a womans right to make inde-
pendent decisions about her reproductive health
care due to an IRBs or regulatory agencys
paternalistic reasons for partner consent
*According to applicable federal regulations, Minimal risk
means that the probability and magnitude of harm or discom-
fort anticipated in the research are not greater in and of them-
selves than those ordinarily encountered in daily life or during
the performance of routine physical or psychological examina-
tions or tests. (45 C.F.R 46.102[I]).
421 COMMITTEE OPINIONS 421
Recommendations
Recognizing the complexities of the conduct and
consent requirements for trials in womens repro-
ductive health, the following recommendations are
made:
The partner consent requirements of each clini-
cal trial need to be individually evaluated and
based on the best available scientific and med-
ical evidence and ethical principles.
When partner consent is required, efforts
should be undertaken to decrease the likelihood
that receipt of such consent will be a barrier for
participation of a woman interested in enrolling
in such a trial. The addition of consent adds
complexity to all trials, often resulting in addi-
tional visits for the participant and partner.
This can result in fewer women enrolling and a
decrease in compliance.
Whenever possible, the choice of a woman to
enroll in a clinical trial regarding her reproduc-
tive function and health should be hers alone
when it does not also include a partner as a
research subject. In these instances, the woman,
not the IRB or the researcher(s), considering
the research study should determine the extent
to which a partner is to be involved in the
process of informed consent and the decision to
participate. For example:
In the case of the study of a microbicide or
barrier contraception efficacy, the risk to a
partner is likely negligible (compared with
the female partner) because of minimal con-
tact time. If potential irritation to a male part-
ner is suspected, it should be ruled out in the
early stages of clinical investigation.
In contraceptive research where the partici-
pant may face an unintended pregnancy, a
partner may be a potential father with the
resultant legal and moral responsibilities for
the child. However, the principle of autono-
my, allowing a woman to make a choice to
enter a trial regarding her reproductive
rights, should take precedence (5). The
American College of Obstetricians and
Gynecologists does not support recognition
of distinct paternal rights before the birth of a
child (6).
Regardless of the requirement for partner con-
sent, communication with a partner about
reproductive health and contraception use
should be encouraged.
References
1. American College of Obstetricians and Gynecologists.
Informed consent. In: Ethics in obstetrics and gynecology.
2nd ed. Washington (DC): ACOG; 2004. p. 917.
2. International Conference On Harmonisation. Guideline for
good clinical practice. ICH Harmonised Tripartite Guideline
E6. London: ICH; 1997. Available at: http://www.proclinica.fr/
GCPICH.pdf. Retrieved August 26, 2004.
3. The National Commission for the Protection of Human
Subjects of Biomedical and Behavioral Research. The
Belmont report: ethical principles and guidelines for the
protection of human subjects of research. Washington,
DC: U.S Department of Health and Human Services;
1979. Available at: http://www.hhs.gov/ohrp/humansub
jects/guidance/belmont.htm. Retrieved August 26, 2004.
4. Protection of human subjects. 45 C.F.R 46 (2003). Available
at: http://www.access.gpo.gov/nara/cfr/waisidx_03/45cfr46
_03.html. Retrieved August 27, 2004.
5. Holder AR. Contraceptive research: do sex partners have
rights? IRB 1982;4(2):67.
6. American College of Obstetricians and Gynecologists.
Research involving women. In: Ethics in obstetrics and
gynecology. 2nd ed. Washington (DC): ACOG; 2004.
p. 8691.
Methods of Obtaining Partner Consent
Several methods exist that may be used to obtain partner
consent regarding a womans participation in a clinical
trial. The suitability of these methods depends on the
particular research study. Some ways of obtaining part-
ner consent include:
Having a partner attend the screening visit and sign
the consent at that time
Giving a copy of the consent to the participant and
having a partner come in for a separate visit to con-
sent
Mailing the consent and having it mailed back
Performing the informed consent process over the
telephone
Obtaining a single informed consent that is signed by
the woman and partner
COMPENDIUM OF SELECTED PUBLICATIONS 422 422
ACOG Committee on
Health Care for
Underserved Women
ACOG
Number 312, August 2005
Committee
Opinion
This information should not be
construed as dictating an exclu-
sive course of treatment or proce-
dure to be followed.
The Committee wishes to thank
Gene Burkett, MD; Ronald Chez,
MD; and Eve Espey, MD, for
their assistance in the develop-
ment of this document.
Copyright August 2005
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of this
publication may be reproduced,
stored in a retrieval system, or
transmitted, in any form or by any
means, electronic, mechanical,
photocopying, recording, or other-
wise, without prior written per-
mission from the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Health Care for Homeless Women.
ACOG Committee Opinion No. 312.
American College of Obstetricians and
Gynecologists. Obstet Gynecol
2005;106:42934.
Health Care for Homeless Women
Abstract: Homelessness is a considerable social and health problem in the
United States with far-reaching effects on the health of homeless women.
Homeless women are at higher risk for injury and illness and are less likely
to obtain needed health care than women who are not homeless. It is critical
to undertake efforts to prevent homelessness. Until this can be accomplished,
community-based services targeted specifically to this population that pro-
vide both health care and support services are essential. Health care
providers can help address the needs of the homeless by identifying their own
patients who may be homeless, treating their health problems, offering pre-
ventive care, and working with the community to improve the full range of
resources available to these individuals.
Approximately 3.5 million Americans are currently homeless (1), and as
many as 14% of the U.S. population have been homeless at some time (2)
(see box Definition of Homelessness). Women make up nearly one third of
the homeless population and are one of the fastest growing groups (3). In the
population of homeless individuals in families, 84% are women (4). Sixty
percent of homeless women have children younger than 18 years, but many
do not have custody of their children. There also are children who are home-
less in their own right. This group includes runaways (5). Many homeless
adolescents left home because of conflicts with parents over their sexual ori-
entation (6). Most homeless adolescents are white and come from suburban
and rural areas. They are more likely than other populations to experience
depression and substance abuse, to have previously attempted suicide, and to
have a history of sexual and physical abuse (7).
Extreme poverty is a universal characteristic of homeless individuals, but
not all impoverished individuals become homeless. The shortage of low-
income housing is a major precipitating factor to homelessness. It can render
homeless even individuals who are not extremely poor. Unemployment or job
loss, personal or family crisis, an increase in rent disproportionate to income,
or reduction in public health benefits increase the likelihood of loss of a home
among those at risk (4). For women, an additional risk factor is early moth-
erhood (8).
Many homeless individuals lack education and money. Thirty-eight per-
cent of homeless individuals did not graduate from high school and another
34% finished only high school. Slightly more than one quarter of homeless
individuals have any education beyond high school. The average monthly
423 COMMITTEE OPINIONS 423
income for a homeless family is $475 (46% of the
federal poverty level for a family of three at the time
of the study), and for a single homeless individual is
$348 (51% of the federal poverty level for one per-
son) (4). Other risk factors include lack of job skills,
inadequate social support, problems with alcohol or
illicit drugs, mental illness, experiences of violence
and victimization, and previous incarceration.
Impact of Homelessness on Women
Homelessness may be difficult to recognize. How-
ever, certain circumstances, many of which affect
the individuals health, are seen more frequently in
this population (see box Common Characteristics
of Homelessness). Being homeless creates an in-
creased risk for illness and injury resulting in high
levels of morbidity and mortality (9). Homeless ado-
lescent and adult women often participate in survival
sex, which refers to the selling of sex to meet subsis-
tence needs (10, 11). Approximately 26% of young
homeless females reported having participated in
survival sex (10). More than two thirds of homeless
mothers have a diagnosis of mental illness. Cases of
posttraumatic stress disorder, substance abuse disor-
ders, and major depression are disproportionately higher
among homeless women compared with other popula-
tions (12).
Violence
Violence is common among homeless populations.
Homeless individuals are at risk because they lack
personal security when living outdoors or in a shel-
ter. Twenty-two percent report having been physically
assaulted or beaten up at least once while home-
less (4). One study reported that 13% of homeless
women, particularly those with mental illness, were
sexually assaulted or raped in the past year, com-
pared with 2.7% of the general population (13).
Twenty-two percent of homeless adolescents report
prior child abuse and 13% report sexual abuse (1, 4).
Gynecologic Health
Among homeless women interviewed in Los
Angeles, 66% used no method of contraception even
though most had intercourse at least once per week.
Fewer than 10% of homeless women report regular
condom use although they are at high risk for sexu-
ally transmitted diseases (STDs) and human im-
munodeficiency virus (HIV) infection (14, 15), which
are especially problematic in the homeless adoles-
cent population (11). Pelvic inflammatory disease
occurred in approximately 28% of homeless wo-
men, and 60% had a history of a least one STD (1).
Obstetric Health
Pregnancy and recent birth are highly correlated with
becoming homeless in the newly homeless popula-
tion. At the time they requested emergency shelter,
35% of homeless women were pregnant and 26%
Definition of Homelessness
An individual is considered homeless if he or she lacks a
fixed, regular, and adequate nighttime residence, or an
individual who has a primary nighttime residence that is:
a) a supervised publicly or privately operated shelter
designed to provide temporary living accommoda-
tions (including welfare hotels, congregate shel-
ters, and transitional housing for the mentally ill);
b) a public or private place that provides a temporary
residence for individuals intended to be institution-
alized; or
c) a public or private place not designed for, or ordi-
narily used as, regular sleeping accommodations
for human beings.
Interagency Council on the Homeless. Homelessness: programs
and the people they serve. Findings of the National Survey of
Homeless Assistance Providers and Clients. Washington, DC:
U.S. Department of Housing and Urban Development, Office of
Policy Development and Research; 1999.
Common Characteristics of Homelessness
Appearance: unkempt, disheveled, dirty, aggressive,
hostile
Chronic recurrent diseases, including respiratory
infections, hepatitis, asthma, arthritis, or tuberculosis
Multiple STDs or HIV
Substance abuse (alcohol and other substances)
Chronic mental illness with or without comorbidity,
suicide attempts, posttraumatic stress disorders,
stresses associated with sexual identity and
orientation
Repetitive, nonspecific complaints for which a diagno-
sis cannot be found
Underweight with history of subnutrition or poor
nutritional state
Domestic violence, including sexual abuse and
victimization
No fixed address or multiple addresses in a short
period
Lack of adherence with physician directives and
orders
COMPENDIUM OF SELECTED PUBLICATIONS 424 424
had given birth in the past year. Only 6% of women
in the study who were not homeless were pregnant
and only 11% had given birth in the past year (8).
Homeless women often have little choice in the tim-
ing, the place, the partner, and the circumstances
surrounding conception. Factors associated with un-
intended pregnancy were victimization, survival sex,
lack of contraception, uncertain fertility status, desire
for intimacy, and lack of hope for the future (16).
Women younger than 21 years living on the streets
are at much greater risk of having ever been pregnant
than are young women living in households (5).
Adverse birth outcomes are substantially higher
in homeless women than in the general population
(17). In a study conducted in 1997, 17% of babies
born to homeless women were low birth weight
compared with 11% among those residing in low-
income housing (17). The rate of low birth weight at
the time of that study was 7.5% for all women (18).
Similarly, 19% of births in the homeless population
were preterm compared with 11% nationally (17,
18). Homeless women are less likely to receive pre-
natal care (19, 20). The more severe the homeless-
ness (defined by whether or not the woman was
homeless during the first trimester of her pregnancy,
the number of times she had been homeless, and the
percentage of her life during which she had been
homeless), the less likely a woman is to receive pre-
natal care and the more likely an adverse pregnancy
outcome will occur. Older homeless women and
those who abuse drugs also are less likely to receive
prenatal care. Other predictors of adverse pregnancy
outcomes among homeless women include history
of preterm birth, antenatal complications, and birth
complications; STDs; low income; nulliparity; and
being African American (17).
Adverse birth outcomes are higher in African-
American homeless women than in homeless
women of other races. In the homeless population,
22% of infants born to African-American women
were low birth weight, whereas only 16% of
Hispanic infants and 5% of non-Hispanic white
infants were low birth weight. African-American
homeless women are more likely to experience
preterm birth. Homeless Native American women
also appear to have a large proportion of preterm
births and babies with low birth weight (17).
Homeless women may forgo meals in favor of
alcohol and other drugs (20). Day-to-day survival
stresses are superimposed on emotional distress,
which may lead to new or increased substance abuse
(20). Homeless pregnant women are prone to uri-
nary tract infections and vaginal infections (20).
Children of homeless women are more likely to
be separated from their mothers by social service
providers. Forty-four percent of homeless mothers,
compared with 8% of mothers receiving public
assistance who are not homeless, were separated
from their children. Homelessness was the major
risk factor in such separation, although substance
abuse, domestic violence, and maternal institution-
alization also were risk factors. A substantial minor-
ity of these children are placed in foster care. (21).
This separation from children may lead to emo-
tional strain, anxiety, loss of control, instability,
guilt, and insecurity among homeless mothers.
Preventive Health
Homeless women receive breast examinations,
mammograms, and Pap tests at lower rates than the
general population (2224). Although no studies
have specifically examined cervical dysplasia and
cancer in this population, homeless women have
many risk factors for inadequate diagnosis, incom-
plete follow-up, and incomplete treatment because
of the competing survival needs.
Use of Health Care
Most homeless people seek care in hospital emer-
gency rooms; only 27% go to an established ambula-
tory care provider. The younger homeless population
is even more likely to receive care in the emergency
room. Nearly three quarters of homeless individuals
who are hospitalized have conditions that were pre-
ventable and could have been treated before admis-
sion compared with 41% of low-income individuals
who are not homeless (25). Recurrent admission for
the same diagnosis is common and occurs in approx-
imately 40% of homeless adults, which imposes a
financial burden on hospitals (1).
Barriers to Health Care
Approximately 57% of homeless individuals lack a
regular source of care compared with 24% of the
poor and 19% of the general population (26). Nearly
25% of homeless individuals who reported a need
for medical attention in the previous year were
unable to obtain care. The following factors con-
tribute to this situation (1, 4, 27, 28):
Cost and lack of health insurance (55% of
homeless individuals report that they have no
medical insurance) and inability to purchase or
acquire medications
425 COMMITTEE OPINIONS 425
Lack of transportation to and from medical
facilities
Competing needs for survival (food, clothing,
shelter)
Mental illness and substance abuse
Unstable lifestyle interfering with continuity of
care and adherence with treatment
Because an exhibition of toughness is necessary
to survive on the streets, homeless individuals
may at times deny that they have health prob-
lems. They also may have a fear of authority fig-
ures, including medical providers.
Lack of availability of shelters and treatment
facilities for the homeless
Medical providers, including physicians, may
prefer not to care for homeless individuals in
their offices
Inadequate inpatient discharge planning and fol-
low-up care because of failure to recognize
homelessness
Lack of health care professionals knowledge
and information on services available within the
community for homeless individuals
Recommendations to Improve the Health
of Homeless Women
Health care services for a homeless woman should
be a part of a multifaceted approach tailored to her
needs, perspectives, and values. Acceptance of the
individual is critical to the provision of services.
Accomplishing these goals is a major challenge to
the obstetriciangynecologist or any other health
care provider. Often the resources required, includ-
ing the necessary professionals and support services,
are either not available in the community or difficult
for the private provider to obtain. Even though indi-
vidual obstetriciangynecologists can and do pro-
vide services to homeless patients in their practices,
it may be more beneficial for communities to de-
velop organized services targeted specifically to this
population that can better provide both health care
and support services. Organized services can better
implement both the preventive care and the obstetric
and gynecologic care recommended in the guide-
lines of the American College of Obstetricians and
Gynecologists (30). Prenatal care that coordinates
with social services, rehabilitation programs, and
housing programs to shelter homeless women dur-
ing pregnancy should be the goal.
Health care professionals also can contribute to
improved health care for homeless women by partic-
ipating in the following activities:
Care for homeless women in individual prac-
tices without bias.
Volunteer or form volunteer groups to provide
health care services at homeless shelters and
soup kitchens. Adherence to treatment is en-
hanced when medical care is coupled with ser-
vices to meet the survival needs of patients. Care
should not be withheld because of concerns
about lack of adherence.
Seek donations of medications from pharma-
ceutical companies for use in homeless clinics
and shelters.
Implement health care programs for the home-
less with local hospitals and clinics (see box
J.C. Lewis Health Center: An Example of
Success).
J.C. Lewis Health Center: An Example of Success
An example of a successful health care program for
homeless women is the J.C. Lewis Health Center. This
center is a 32-bed primary and respite care clinic in
Savannah, Georgia, that has saved area hospitals $10.3
million in uncompensated care for the homeless. The
center allows homeless individuals to gain access to pri-
mary care providers who manage acute and episodic
health needs and diagnose, control, and monitor chronic
health problems such as HIV, hypertension, and dia-
betes. The operation includes the staffing of four shelter-
based primary care clinics across the city where health
promotion and primary care divert homeless people
from emergency rooms. Wellness care for the homeless
includes physical examinations, screening for disease,
and patient education. Respite care allows the hospital
to release patients too sick to stay in shelters, but not
sick enough to stay in the hospital. These individuals
would otherwise have remained hospitalized. The health
center also coordinates its services with housing and
social services to help the individuals obtain permanent
housing. Ninety-five percent of the respite care patients
ended their homelessness after leaving the program.
Program funding is provided by hospitals (each con-
tribute $250,000 to the program), public support
through government grants ($244,000), philanthropic
organizations ($164,000), and private citizens ($19,000).
In addition, volunteers from the community, including
doctors, nurses, and educators, donate their time to the
health center, and the center receives in-kind contribu-
tions of pharmaceuticals and supplies.
The J.C. Lewis Health Center. Available at:
http://www.unionmission.org. Retrieved June 6, 2005.
COMPENDIUM OF SELECTED PUBLICATIONS 426 426
Work with medical schools and residency pro-
grams to encourage modification of the educa-
tional curriculum to increase awareness of the
problems associated with homelessness and to
involve medical students and residents in care
for homeless individuals as part of their training.
Assess current community programs for home-
less individuals and advocate for improved coor-
dination of services between these programs and
other special programs such as prenatal care,
immunization, tuberculosis treatment, STD clin-
ics, mental health care, and housing and legal aid.
Advocate for professional liability protections
for physicians who volunteer their services to
the homeless.
Encourage federal, state, and local governments
to provide adequate funding for the provision of
comprehensive health care services, including
mental health treatment for all homeless indi-
viduals. (See box Health Care for the Home-
less Federal Program.)
The Prevention of Homelessness
Although it is critical to undertake efforts to improve
the health of homeless women, it is even more
important to undertake efforts to prevent homeless-
ness. Increased federal, state, and local govern-
ment support and provision of adequate funding for
comprehensive programs for the prevention of
homelessness, including increased availability of
affordable, usually subsidized, housing are essential
to this goal. Numerous studies indicate that afford-
able housing prevents homelessness more effective-
ly than anything else. This applies to all groups of
poor people, including those with persistent and
severe mental illness or those with substance abuse
problems (29). Additional research is needed to deter-
mine other efforts that would be effective at reducing
this problem and thereby improve womens health
and the overall health of society.
References
1. Gelberg L, Arangua L. Homeless persons. In: Anderson
RM, Rice TH, Kominski GF, editors. Changing the U.S.
health care system: key issues in health services, policy,
and management. San Francisco (CA): Jossey-Bass;
2001. p.33286.
2. Link BG, Susser E, Stueve A, Phelan J, Moore RE,
Struening E. Lifetime and five-year prevalence of home-
lessness in the United States. Am J Public Health 1994;
84:190712.
3. Hodnicki DR, Horner SD, Boyle JS. Womens perspectives
on homelessness. Public Health Nurs 1992;9:25762.
4. Interagency Council on the Homeless. Homelessness:
programs and the people they serve. Findings of the
National Survey of Homeless Assistance Providers and
Clients. Washington, DC: U.S. Department of Housing
and Urban Development, Office of Policy Development
and Research; 1999.
5. Greene JM, Ringwalt CL. Pregnancy among three nation-
al samples of runaway and homeless youth. J Adolesc
Health 1998;23:370 7.
6. Farrow JA, Deisher RW, Brown R, Kulig JW, Kipke MD.
Health and health needs of homeless and runaway youth.
A position paper of the Society for Adolescent Medicine.
J Adolesc Health 1992;13:71726.
7. Pennbridge J, Mackenzie RG, Swofford A. Risk profile of
homeless pregnant adolescents and youth. J Adolesc
Health 1991;12:5348.
8. Weitzman BC. Pregnancy and childbirth: risk factors for
homelessness? Fam Plann Perspect 1989;21:1758.
9. Hwang SW. Is homelessness hazardous to your health?
Obstacles to the demonstration of a causal relationship.
Can J Public Health 2002;93:40710.
10. Greene JM, Ennett ST, Ringwalt CL. Prevalence and cor-
relates of survival sex among runaway and homeless
youth. Am J Public Health 1999;89:14069.
11. Bailey SL, Camlin CS, Ennett ST. Substance use and risky
sexual behavior among homeless and runaway youth.
J Adolesc Health 1998;23:37888.
Health Care for the Homeless Federal Program
The Health Care for the Homeless program is the only
federal program with the sole responsibility of address-
ing the primary health care needs of homeless individ-
uals. The Health Care for the Homeless program pro-
vides primary health care and substance abuse services
at locations accessible to individuals who are homeless,
emergency care with referrals to hospitals for inpatient
care services or other needed services, outreach ser-
vices to assist difficult-to-reach homeless individuals in
gaining access to care, and assistance in establishing eli-
gibility for entitlement programs and housing.
To increase access to services and resources for peo-
ple who are homeless, the grantees of the Health Care
for the Homeless program are encouraged to develop,
or actively participate in, local coalitions of health care
providers and social service agencies. These collabora-
tions help ensure the adequate and appropriate delivery
of services to the clients of the Health Care for the
Homeless program. Each individual program determines
which service delivery system or combination of sys-
tems is appropriate for the people it serves. Programs
provide services in a variety of different settings, includ-
ing traditional clinic sites, shelter-based clinics, and
mobile units. In addition, they take health care services
to locations where homeless individuals are found, such
as streets, parks, and soup kitchens.
Bureau of Primary Health Care. Health Care for the Homeless
Information Resource Center. 2004-2005 Health Care for the
Homeless Grantee profiles. Available at:
http://www.bphc.hrsa.gov/hchirc/directory/text_directory.htm.
Retrieved June 6, 2005.
427 COMMITTEE OPINIONS 427
12. Bassuk EL, Buckner JC, Perloff JN, Bassuk SS.
Prevalence of mental health and substance use disorders
among homeless and low-income housed mothers. Am J
Psychiatry 1998;155:15614.
13. Wenzel SL, Leake BD, Gelberg L. Health of homeless
women with recent experience of rape. J Gen Intern Med
2000;15:2658.
14. Shuler PA, Gelberg L, Davis JE. Characteristics associat-
ed with the risk of unintended pregnancy among urban
homeless women: use of the Shuler Nurse Practitioner
Practice Model in research. J Am Acad Nurse Pract
1995;7:1322.
15. Gelberg L, Leake BD, Lu MC, Andersen RM, Wenzel SL,
Morgenstern H, et al. Use of contraceptive methods
among homeless women for protection against unwanted
pregnancies and sexually transmitted diseases: prior use
and willingness to use in the future. Contraception 2001;
63:27781.
16. Killion CM. Poverty and procreation among women. An
anthropologic study with implications for health care
providers. J Nurse Midwifery 1998;43:2739.
17. Stein JA, Lu MC, Gelberg L. Severity of homelessness
and adverse birth outcomes. Health Psychol 2000;19:
52434.
18. Ventura SJ, Martin JA, Curtin SC, Mathews TJ. Births:
final data for 1997. Natl Vital Stat Rep 1999;47(18):196.
19. Chavkin W, Kristal A, Seabron C, Guigli PE. The repro-
ductive experience of women living in hotels for the
homeless in New York City. NY State J Med 1987; 87:
103.
20. Killion CM. Special health care needs of homeless preg-
nant women. ANS Adv Nurs Sci 1995;18:4456.
21. Cowal K, Shinn M, Weitzman BC, Stojanovic D, Labay L.
Mother-child separations among homeless and housed
families receiving public assistance in New York City. Am
J Community Psychol 2002;30:71130.
22. Chau S, Chin M, Chang J, Luecha A, Cheng E,
Schlesinger J, et al. Cancer risk behaviors and screening
rates among homeless adults in Los Angeles County.
Cancer Epidemiol Biomarkers Prev 2002;11:4318.
23. Long HL, Tulsky JP, Chambers DB, Alpers LS, Robertson
MJ, Moss AR, et al. Cancer screening in homeless
women: attitudes and behaviors. J Health Care Poor
Underserved 1998;9:27692.
24. Weinreb L, Goldberg R, Perloff J. Health characteristics
and medical service use patterns of sheltered homeless
and low-income housed mothers. J Gen Intern Med 1998;
13:38997.
25. Salit SA, Kuhn EM, Hartz AJ, Vu JM, Mosso AL.
Hospitalization costs associated with homelessness in
New York City. N Engl J Med 1998;338:173440.
26. Gallagher TC, Andersen RM, Koegel P, Gelberg L.
Determinants of regular source of care among homeless
adults in Los Angeles. Med Care 1997;35:81430.
27. Lim YW, Andersen R, Leake B, Cunningham W, Gelberg
L. How accessible is medical care for homeless women?
Med Care 2002;40:51020.
28. Kushel MB, Vittinghoff E, Haas JS. Factors associated
with the health care utilization of homeless persons.
JAMA 2001;285:2006.
29. U.S. Department of Housing and Urban Development,
U.S. Department of Health and Human Services. Practical
lessons: the 1998 National Symposium on Homelessness
Research. Available at: http://aspe.hhs.gov/progsys/home
less/symposium/toc.htm. Retrieved April 12, 2005.
30. Primary and preventive care: periodic assessments.
ACOG Committee Opinion No. 292. American College of
Obstetricians and Gynecologists. Obstet Gynecol 2003;
102:111724.
COMPENDIUM OF SELECTED PUBLICATIONS 428 428
Committee
Opinion
Committee on
Health Care for
Underserved Women
Committee on
Obstetric Practice
ACOG
(Replaces Educational Bulletin 260,
Number 316, October 2005 September 2000)
This document reflects emerging
clinical and scientific advances as
of the date issued and is subject to
change. The information should
not be construed as dictating an
exclusive course of treatment or
procedure to be followed.
The Committees would like to
thank Kelli Mudd Miller, MD,
and Kirsten Smith, MD, for their
assistance in the development of
this bulletin.
Copyright October 2005
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of this
publication may be reproduced,
stored in a retrieval system, or
transmitted, in any form or by any
means, electronic, mechanical,
photocopying, recording, or other-
wise, without prior written per-
mission from the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Smoking cessation during pregnancy.
ACOG Committee Opinion No. 316.
American College of Obstetricians
and Gynecologists. Obstet Gynecol
2005;106:8838.
Smoking Cessation During Pregnancy
ABSTRACT: Smoking is one of the most important modifiable causes of poor
pregnancy outcomes in the United States. An office-based protocol that sys-
tematically identifies pregnant women who smoke and offers treatment has
been proved to increase quit rates. For pregnant women who are light to mod-
erate smokers, a short counseling session with pregnancy-specific educa-
tional materials often is an effective intervention for smoking cessation. The
5 As is an office-based intervention developed for use by trained practi-
tioners. Techniques for smoking reduction, pharmacotherapy, and health
care support systems can help smokers quit.
Epidemiology
Increased public education measures and public health campaigns in the
United States have led to a decline in smoking during pregnancy (1).
Pregnancy appears to motivate women to make lifestyle changes; approxi-
mately 46% of prepregnancy smokers quit during pregnancy (1). From 1990
to 2003, the rate of smoking reported by pregnant women decreased from
18.4% (2) to 11% (3). The smoking rate during pregnancy in 2002 for
women ages 18 and 19 years was 18%, higher than that for pregnant women
of any other age (4).
Consequences of Maternal Smoking
The biologic evidence that maternal smoking has a detrimental effect on the
fetus includes fetal hypoxia from increased carboxyhemoglobin; reduced
blood flow to the uterus, placenta, and fetus; and direct effects of nicotine
and other compounds in tobacco smoke on the placenta and fetus (5). Health
risks associated with smoking during pregnancy include intrauterine growth
restriction, placenta previa, and abruptio placentae (5). Adverse pregnancy
outcomes include premature rupture of membranes (6, 7), low birth weight,
and perinatal mortality (5). Evidence also suggests that smoking is associat-
ed with an increase in ectopic pregnancies (5). It is estimated that eliminat-
ing smoking during pregnancy would reduce infant deaths by 5% (8) and
reduce the incidence of singleton low-birth-weight infants by 10.4% (9).
429 COMMITTEE OPINIONS 429
There is a strong association between smoking dur-
ing pregnancy and sudden infant death syndrome
(SIDS) (5). Children born to mothers who smoke
during pregnancy are at increased risk for asthma
(10), infantile colic (11), and childhood obesity (12).
Successful smoking cessation before the third
trimester eliminates much of the reduced birth
weight caused by maternal smoking (5). Women
who continue to smoke during pregnancy must
achieve very low levels of tobacco use to see
improvements in infant birth weight, and they must
quit entirely if their infants are to have birth weights
similar to those of women who do not smoke (13).
Intervention
Both cessation of tobacco use and prevention of
relapse to smoking are key clinical intervention
strategies during pregnancy. Techniques for helping
patients to stop smoking have included counseling,
cognitive and behavioral therapy, hypnosis, acupunc-
ture, and pharmacologic therapy. A 515-minute
counseling session performed by appropriately
trained health care providers is most effective with
pregnant women who smoke fewer than 20 cigarettes
per day (14). This intervention, known as the 5 As, is
appropriate for use during routine prenatal office vis-
its and includes the following five steps: Ask, Advise,
Assess, Assist, and Arrange. The intervention is
adapted from the U.S. Public Health Service clinical
practice guideline, Treating Tobacco Use and
Dependence (14). Its effectiveness can be enhanced
for those who smoke any amount by referring the
patient to a pregnancy-specific smokers quitline.
The approach described in the box and outlined as
follows guides the provider through the interaction
and in documentation of the treatment (14).
1. Ask about smoking status. Providers should ask
the patient at the first prenatal visit to choose a
statement that best describes her smoking status
from a list of statements on smoking behavior
(see the box). Using this multiple-choice method
is more likely to elicit an accurate response than
asking a question that elicits a simple yes or
no answer. A smoking cessation chart, a to-
bacco use sticker, or a vital signs stamp that
includes smoking status may be useful in the
medical record to remind providers to ask
patients about smoking status at follow-up visits
(see resource box).
2. Advise patients who smoke to stop by providing
clear, strong advice to quit with personalized
messages about the benefits of quitting and the
impact of continued smoking on the woman,
fetus, and newborn. Congratulate patients who
report having stopped smoking and affirm their
efforts with a statement about the benefits of
quitting.
3. Assess the patients willingness to attempt to
quit smoking within the next 30 days. One
approach to this assessment is to say, Quitting
smoking is one of the most important things you
can do for your health and your babys health. If
we can give you some help, are you willing to
try? If the patient is willing, the provider can
move to the next step. If the patient is unwilling
to try, providers may consider having a brief dis-
cussion with the patient to educate and reassure
her about quitting (14). Quitting advice, assess-
ment, and assistance should be offered at subse-
quent prenatal care visits.
4. Assist patients who are interested in quitting by
providing pregnancy-specific, self-help smok-
ing cessation materials (see resource box).
Enhance the patients problem-solving skills by
asking when and where she typically smokes
and suggesting how she might avoid these situ-
ations that trigger the desire to smoke. Offer
support on the importance of 1) having a smoke-
free space at home, 2) seeking out a quitting
buddy such as a former smoker or nonsmoker
both at work and at home, and 3) understanding
nicotine withdrawal, such as irritability and
cravings. Communicate caring and concern and
encourage the patient to talk about the process
of quitting.
The provider also may refer the patient to a
smokers quitline. Telephone quitlines offer
information, direct support, and ongoing coun-
seling and have been very successful in helping
pregnant smokers quit and remain smoke free
(15). Great Start (1-866-66-START) is a nation-
al pregnancy-specific smokers quitline operated
by the American Legacy Foundation. Some
states also have proactive direct fax referral
capability for providers to connect pregnant
smokers directly to their state quitline. By dial-
ing the national quitline network (1-800-QUIT
NOW), callers are routed immediately to their
state smokers quitline.
COMPENDIUM OF SELECTED PUBLICATIONS 430 430
5. Arrange follow-up visits to track the progress of
the patients attempt to quit smoking. For current
and former smokers, smoking status should be
monitored throughout pregnancy, providing
opportunities to congratulate and support suc-
cess, reinforce steps taken toward quitting, and
advise those still considering a cessation attempt.
Although counseling and pregnancy-specific
materials are effective cessation aids for many preg-
nant women, some women continue to smoke.
These women often are heavily addicted to nicotine
and should be Asked and Advised and Assessed
about smoking at follow-up visits. Women who con-
tinue to smoke may benefit from screening for alco-
hol use and other drug use (16). If the alcohol or
drug use screen result is positive, information about
the risks associated with alcohol and drug use dur-
ing pregnancy should be added to the Advise step,
and specific strategies for abstaining from alcohol
and drugs should be discussed in the Assist step.
Clinicians also may consider referring patients for
additional psychosocial treatment (14).
Although quitting smoking early in pregnancy
yields the greatest benefits for the pregnant woman
and fetus, quitting at any point can be beneficial
(14). The benefits of cutting down are difficult to
measure or verify. The effort of women who cut
down should be reinforced, but these women also
should be reminded that quitting entirely brings the
best results for their health, the health of the fetus,
and that of their babies (17).
Approximately 6080% of women who quit
smoking during pregnancy return to smoking within
a year postpartum (1). Former smokers should be
counseled in the third trimester and at the postpar-
tum visit and subsequent gynecology visits concern-
ing relapse to smoking (18).
Pharmacotherapy
The use of nicotine replacement products or other
pharmaceuticals for smoking cessation aids during
pregnancy and lactation have not been sufficiently
evaluated to determine their efficacy or safety.
Nicotine gum, lozenges, patches, inhalers, and spe-
cial-dose antidepressants that reduce withdrawal
symptoms, such as bupropion, should be consid-
ered for use during pregnancy and lactation only
when nonpharmacologic treatments (eg, counsel-
ing) have failed. If the increased likelihood of
Smoking Cessation Intervention
for Pregnant Patients
Ask1 minute
Ask the patient to choose the statement that best
describes her smoking status:
A. I have NEVER smoked or have smoked FEWER
THAN 100 cigarettes in my lifetime.
B. I stopped smoking BEFORE I found out I was preg-
nant, and I am not smoking now.
C. I stopped smoking AFTER I found out I was preg-
nant, and I am not smoking now.
D. I smoke some now, but I have cut down on the
number of cigarettes I smoke SINCE I found out I
was pregnant.
E. I smoke regularly now, about the same as BEFORE I
found out I was pregnant.
If the patient stopped smoking before or after she found
out she was pregnant (B or C), reinforce her decision to
quit, congratulate her on success in quitting, and encour-
age her to stay smoke free throughout pregnancy and
postpartum.
If the patient is still smoking (D or E), document smok-
ing status in her medical record, and proceed to Advise,
Assess, Assist, and Arrange.
Advise1 minute
Provide clear, strong advice to quit with personalized
messages about the benefits of quitting and the
impact of smoking and quitting on the woman, fetus,
and newborn.
Assess1 minute
Assess the willingness of the patient to attempt to quit
within 30 days.
If the patient is ready to quit, proceed to Assist.
If the patient is not ready, provide information to moti-
vate the patient to quit and proceed to Arrange.
Assist3 minutes
Suggest and encourage the use of problem-solving
methods and skills for smoking cessation (eg, identify
situations that trigger the desire to smoke).
Provide social support as part of the treatment (eg,
We can help you quit).
Arrange social support in the smokers environment
(eg, identify a quit buddy and smoke-free space).
Provide pregnancy-specific, self-help smoking cessa-
tion materials.
Arrange1 minute or more
Assess smoking status at subsequent prenatal visits
and, if patient continues to smoke, encourage cessation.
Adapted from Melvin CL, Dolan-Mullen P, Windsor RA Jr,
Whiteside HP, Goldenberg RL. Recommended cessation coun-
selling for pregnant women who smoke: a review of the evi-
dence. Tob Control 2000;9(suppl 3):III804. Reproduced with
permission from the BMJ Publishing Group.
431 COMMITTEE OPINIONS 431
Resources for Smoking Cessation
The American College of Obstetricians and
Gynecologists Resources for the Clinician
American College of Obstetricians and Gynecologists.
Smoking cessation during pregnancy: a clinicians guide
to helping pregnant women quit smoking. Washington,
DC: ACOG; 2002. Contains guidelines, a tool kit for the
clinician, lecture guide, and CD-ROM. Request a copy by
e-mail to: smoking@acog.org. Lecture guide is available
online. Go to www.acog.org/goto/smoking.
Dartmouth Medical School. Smoking cessation for pregnan-
cy and beyond: learn proven strategies to help your patients
quit. Hanover (NH): Dartmouth Medical School; 2004.
Available for purchase from the ACOG Distribution Center
(800-762-2264, sales.acog.org): Item No. AA423; price: $25.
American College of Obstetricians and Gynecologists.
Smoking and womens health. In: Special issues in womens
health. Washington, DC: ACOG; 2005. p. 15167. Available
for purchase from the ACOG Distribution Center (800-762-
2264, sales.acog.org): Item No. AA451; price: $59; ACOG
members: $45. Available online to members. Go to
www.acog.org/goto/underserved.
American College of Obstetricians and Gynecologists Ask
about tobacco use chart stickers. Washington, DC: ACOG.
Available for purchase from the ACOG Distribution Center
(800-762-2264, sales.acog.org): Item No. AA268; price:
$19/260 stickers; ACOG members: $15/260 stickers.
Other Resources for the Clinician
The following resources are for information purposes only.
Referral to these sources and web sites does not imply the
endorsement of ACOG. This list is not meant to be com-
prehensive. The exclusion of a source or web site does not
reflect the quality of that source or web site. Please note
that web sites are subject to change without notice.
Many states offer free or low-cost smoking cessation
counseling services consisting of telephone quitlines,
group or individual counseling programs, and materials to
help the smoker quit and prevent relapse. Check with the
state or local public health office or tobacco control pro-
gram to access these resources.
Helping pregnant women quit smoking: progress and future
directions. Nicotine Tob Res 2004; 6(suppl 2): S95277.
National Partnership to Help Pregnant Smokers Quit: has
tools on helping patients quit, assessing smokers quit-
lines, and obtaining Medicaid reimbursement for smoking
cessation services. Posters are also available.
Web: www.helppregnantsmokersquit.org.
E-mail: info@helppregnantsmokersquit.org.
British Medical Association. Smoking and reproductive life:
the impact of smoking on sexual, reproductive and child
health. London (UK): BMA; 2004. Available at:
www.bma.org.uk/ap.nsf/Content/smokingreproductivelife/
$file/smoking.pdf. Retrieved June 22, 2005.
Treating tobacco use and dependence: clinicians packet.
A how-to guide for implementing the Public Health Service
Clinical Practice Guidelines. Washington, DC: U.S. Public
Health Service; 2003. Available at: www.surgeongeneral.
gov/tobacco/clincpack.html. Retrieved June 22, 2005.
Web Sites
American Cancer Society
www.cancer.org
The American Heart Association
www.americanheart.org
The Centers for Disease Control and Prevention: Tobacco
Information and Prevention Source (TIPS).
www.cdc.gov/tobacco
TIPS contains documents for health providers to implement
tobacco control programs
The National Cancer Institute
www.cancer.gov
National Partnership to Help Pregnant Smokers Quit
www.helppregnantsmokersquit.org/quit/toll_free.asp
The partnership has a listing of states with pregnancy-
specific quitlines.
Smoke-Free Families
www.smokefreefamilies.org
Smokefree.gov
www.smokefree.gov
Web site has multiple cessation strategies and information
for smokers.
Resources for Patients
American College of Obstetricians and Gynecologists, Smoke-
Free Families. Need help putting out that cigarette?
Washington, DC: ACOG; Chapel Hill (NC): Smoke-Free
Families; 2001. Available in English and Spanish for purchase
from the ACOG Distribution Center (800-762-2264,
sales.acog.org): Item Nos. AA424 and AA4245; price:
$10/10 booklets.
You can quit smoking: support and advice from your prenatal
care provider. Available at: www.surgeongeneral.gov/tobacco/
prenatal.pdf. Retrieved June 22, 2005. Available for multiple
orders from AHRQ (PO Box 8547, Silver Spring MD 20907-
8547, 800-358-9295): Item No. AHRQ 00-0052.
Recomendaciones y apoyo de su mdico de cuidados, Spanish
language. Available at: www.surgeongeneral.gov/tobacco/
prenatalsp.pdf. Retrieved June 22, 2005. Available for multiple
orders from AHRQ (PO Box 8547, Silver Spring MD 20907-
8547, 800-358-9295): Item No. AHRQ 00-0065.
American Legacy Foundation. Great start quitline. Available at:
www.americanlegacy.org/greatstart/html/quitline.html.
Retrieved: June 22, 2005. 866-66-START for toll free help
MondayFriday 8:00 AM8:00 PM (Eastern Time) and Saturday
9:00 AM4:00 PM. Counseling in English or Spanish.
COMPENDIUM OF SELECTED PUBLICATIONS 432 432
smoking cessation, with its potential benefits, out-
weighs the unknown risk of nicotine replacement
and potential concomitant smoking, nicotine
replacement products or other pharmaceuticals may
be considered (14). Because potential benefits seem
to outweigh potential risks, research to determine
the safety and efficacy of pharmacotherapy is
underway. Some tobacco control experts have
reported that if nicotine replacement therapy is
used during pregnancy, products with intermittent
dosages, such as the gum or inhaler, should be tried
first (19). If the nicotine patch is used, it can be
removed at night to reduce fetal nicotine exposure
(20). Nicotine replacement therapy also may be
considered during lactation. Optimally, smokers
can be treated with these pharmacotherapies before
conception.
Support Systems
The Agency for Healthcare Research and Quality
has recommended systems changes to help health
care providers identify and treat tobacco users (14).
These changes require the partnership of health care
administrators and insurers, and include the follow-
ing strategies: 1) provide education, resources, and
feedback to promote provider involvement in smok-
ing cessation; 2) promote hospital policies that sup-
port and provide smoking cessation services; 3)
include effective smoking cessation treatments as
paid or covered services in all health benefits pack-
ages; and 4) reimburse clinicians and specialists for
delivery of effective tobacco dependence treatments
and include these interventions among the defined
duties of the clinicians (14).
Coding
Office visits specifically addressing smoking cessa-
tion may be coded using International Classification
of Diseases, Ninth Revision, Clinical Modification
(ICD-9-CM) code 305.1 (tobacco use disorder,
tobacco dependence from the Mental Health sec-
tion) with Current Procedural Terminology* (CPT
)
code 99401 or 99211:
CPT code 99401 (preventive medicine counsel-
ing lasting approximately 15 minutes): If coun-
seling is done by the physician at the time of a
regular antepartum visit, use modifier 25 on
code 99401. If counseling is done by the physi-
cian at another encounter, separate from the
antepartum visit, no modifier is needed with
code 99401.
CPT code 99211: If a nurse counsels the patient,
and if nurses are recognized by the insurance
company as qualified providers of the service,
code 99211 would be used instead of code
99401. If the nurse is not recognized as a care-
giver, the services will not be covered unless
provided by the physician.
Note that not all payers reimburse for counseling
outside of the global package and some do not cover
preventive services at all.
Many private and public insurers are changing
policy to provide coverage for smoking cessation
counseling for pregnant women. Although coverage
for such counseling may have been denied previous-
ly, it may be prudent for the clinician to continue to
submit for reimbursement for these services.
References
1. Colman GJ, Joyce T. Trends in smoking before, during,
and after pregnancy in ten states. Am J Prev Med
2003;24:2935.
2. Smoking during pregnancyUnited States19902002.
Centers for Disease Control and Prevention. MMWR
Morb Mortal Wkly Rep 2004;53:9115.
3. Hamilton BE, Martin JA, Sutton PD. Births: preliminary
data for 2003. Centers for Disease Control and Prevention,
National Center for Health Statistics. Natl Vital Stat Rep
2004;53(a):117.
4. National Center for Health Statistics. Health, United
States, 2004: with chartbook on trends in the health of
Americans. Hyattsville (MD): NCHS; 2004. Available at:
http://www.cdc.gov/nchs/data/hus/hus04.pdf. Retrieved June
20, 2005.
5. U.S. Department of Health and Human Services. The
health consequences of smoking: a report of the Surgeon
General. Washington, DC: HHS; 2004. Available at: www.
cdc.gov/tobacco/sgr/sgr_2004/chapters.htm. Retrieved
June 20, 2005.
6. Castles A, Adams EK, Melvin CL, Kelsch C, Boulton
ML. Effects of smoking during pregnancy. Five meta-
analyses. Am J Prev Med 1999;16:20815.
7. Spinillo A, Nicola S, Piazzi G, Ghazal K, Colonna L,
Baltaro F. Epidemiological correlates of preterm prema-
ture rupture of membranes. Int J Gynaecol Obstet 1994;
47:715.
*Current Procedural Terminology (CPT) is copyright 2004
American Medical Association. All rights reserved. No fee
schedules, basic units, relative values or related listings are
included in CPT. The AMA assumes no liability for the data
contained herein. CPT
*If onset of labor or rupture of amniotic membranes occurs at <37 weeks of gestation and there is a significant risk for preterm delivery (as
assessed by the clinician), follow the suggested algorithm for GBS prophylaxis as indicated by the CDC.
If amnionitis is suspected, broad-spectrum antibiotic therapy that includes an agent known to be active against GBS should replace GBS pro-
phylaxis.
Schrag S, Gorwitz R, Fultz-Butts K, Schuchat A. Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC. MMWR
Recomm Rep 2002;51(RR-11):122.
Intrapartum prophylaxis not indicated
Previous pregnancy with a positive GBS
screening culture (unless a culture was also
positive during the current pregnancy)
Planned cesarean delivery performed in the
absence of labor or membrane rupture
(regardless of maternal GBS culture status)
Negative vaginal and rectal GBS screening
culture in late gestation during the current
pregnancy, regardless of intrapartum risk
factors
511 COMMITTEE OPINIONS 511
Procedures for collecting and processing clinical specimens for group B streptococcal culture
and performing susceptibility testing to clindamycin and erythromycin
cAMP, cyclic adenosine monophosphate; CNA, Columbia colistinnalidixic acid; LIM broth, Todd-Hewitt with CNA.
*Before inoculation step, some laboratories may choose to roll swab(s) on a single sheep blood agar plate or CNA sheep blood agar plate.
This should be done only in addition to, and not instead of, inoculation into selective broth. The plate should be streaked for isolation, incu-
bated at 3537C in ambient air or 5% CO
2
for 1824 hours and inspected for organisms suggestive of GBS as described above. If suspect-
ed colonies are confirmed as GBS, the broth can be discarded, thus shortening the time to obtain culture results.
Source: Fenton, LJ, Harper MH. Evaluation of colistin and nalidixic acid in Todd-Hewitt broth for selective isolation of group B streptococci. J
Clin Microbiol 1979;9:1679. Although Trans-Vag medium is often available without sheep blood, direct comparison of medium with and
without sheep blood has shown higher yield when blood is added. LIM broth also may benefit from the addition of sheep blood, although the
improvement in yield is smaller and sufficient data are not yet available to support a recommendation.
Source: NCCLS. Performance standard for antimicrobial susceptibility testing. M100-S12, Table 2H, Wayne Pa.: NCCLS, 2002. NCCLS recom-
mends disk diffusion (M-2) or broth microdilution testing (M-7) for susceptibility testing of GBS. Commercial systems that have been cleared
or approved for testing of streptococci other than S pneumoniae may also be used. Penicillin susceptibility testing is not routinely recom-
mended for GBS because penicillin-resistant isolates have not been confirmed to date.
Schrag S, Gorwitz R, Fultz-Butts K, Schuchat A. Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC. MMWR
Recomm Rep 2002;51(RR-11):122.
Procedure for collecting clinical specimens for culture
of group B streptococcus at 3537 weeks of gestation
Swab the lower vagina (vaginal introitus), followed by
the rectum (ie, insert swab through the anal sphincter)
using the same swab or two different swabs. Cultures
should be collected in the outpatient setting by the
health care provider or the patient herself, with appro-
priate instruction. Cervical cultures are not recom-
mended and a speculum should not be used for culture
collection.
Place the swab(s) into a nonnutritive transport medi-
um. Appropriate transport systems (eg, Amies or
Stuart without charcoal) are commercially available. If
vaginal and rectal swabs were collected separately,
both swabs can be placed into the same container of
medium. Transport media will maintain GBS viability
for up to 4 days at room temperature or under refrig-
eration.
Specimen labels should clearly identify that specimens
are for group B streptococcal culture. If susceptibility
testing is ordered for penicillin-allergic women, speci-
men labels should also identify the patient as penicillin
allergic and should specify that susceptibility testing for
clindamycin and erythromycin should be performed if
GBS is isolated.
Procedure for processing clinical specimens for culture
of group B streptococcus
Remove swab(s) from transport medium.* Inoculate
swab(s) into a recommended selective broth medium,
such as Todd-Hewitt broth supplemented with either
gentamicin (8 g/mL) and nalidixic acid (15 g/mL), or
with colistin (10 g/mL) and nalidixic acid (15 g/mL).
Examples of appropriate commercially available options
include Trans-Vag broth supplemented with 5% defibri-
nated sheep blood or LIM broth.
clindamycin: 19 mm = sus-
ceptible, 1618 = intermediate, 15 = resistant; ery-
thromycin: 21 mm = susceptible, 1620 = intermedi-
ate, 15 = resistant).
COMPENDIUM OF SELECTED PUBLICATIONS 512 512
communicate culture results to the obstetric
provider, the anticipated site of delivery if possible,
and the patient so that intrapartum antibiotic prophy-
laxis can be given to all GBS-positive women. For
women who have GBS bacteriuria in any concentra-
tion during the current pregnancy or who have pre-
viously given birth to an infant with early-onset
GBS disease, GBS cultures are not required. Those
women should automatically receive intrapartum
prophylaxis. Urine specimens should be labeled to
indicate they were obtained from a pregnant woman
so laboratories can report any presence of GBS bac-
teriuria in specimens obtained from pregnant
women. If, at anytime during pregnancy, GBS is pre-
sent in urine in concentrations equal to or greater
than 10
5
, antibiotics for asymptomatic bacteriuria or
a symptomatic urinary tract infection should be
administered, as it would be for any other organism
in significant concentration (42, 43). Women who
had GBS colonization during a previous pregnancy
may no longer be colonized during subsequent preg-
nancies and require GBS culture evaluation with
each pregnancy.
Penicillin remains the agent of choice for intra-
partum prophylaxis. Ampicillin is an acceptable
alternative, but penicillin is preferred. However, data
also show that GBS isolates are increasingly resis-
tant to second-line therapies. Up to 15% of GBS
isolates are resistant to clindamycin and 725% of
isolates are resistant to erythromycin (44). This pat-
tern of resistance has led to a change in the recom-
mendations for second-line therapies (see Table 1).
Intravenous administration is the only route recom-
mended for intrapartum GBS prophylaxis because
of the higher intraamniotic concentrations achieved
with this route. Of note, erythromycin does not cross
the placenta.
The benefit of GBS prevention must be weighed
against the risk to the woman and her fetus of mater-
nal allergic reactions to antibiotics during labor.
Although the risk of fatal anaphylaxis has been esti-
mated at 1 per 100,000 (45, 46), the risk of less
severe anaphylactic or allergic reactions is impor-
tant. In the recent CDC surveillance project of more
than 5,000 live births, there was a single, nonfatal
anaphylactic reaction (13, 47). The Committee
agrees with the CDC that local health agencies
should establish surveillance systems to monitor the
incidence of early-onset neonatal GBS disease, the
emergence of infection in women and their new-
borns that is caused by resistant organisms, and
other complications of widespread maternal antibi-
otic administration such as severe allergic reactions.
The Committee believes that when culture
results are not available, intrapartum prophylaxis
should be offered only on the basis of the presence
Table 1. Recommended Regimens for Intrapartum
Antimicrobial Prophylaxis for Perinatal Group B
Streptococcal Disease Prevention*
Regimens Antimicrobial
Recommended Penicillin G, 5 million units IV
initial dose, then 2.5 million
units IV every 4 hours until
delivery
Alternative Ampicillin, 2 g IV initial dose,
then 1 g IV every 4 hours until
delivery
If penicillin allergic
OR
Erythromycin, 500 mg IV every
6 hours until delivery
GBS resistant to Vancomycin,
||
1 g IV every
clindamycin or 12 hours until delivery
erythromycin or
susceptibility
unknown
GBS, group B streptococci; IV, intravenously.
*Broader-spectrum agents, including an agent active against GBS, may
be necessary for treatment of chorioamnionitis.
IAP
||
at delivery
No GBS
prophylaxis
No growth
at 48 hrs
Obtain vaginal
and rectal GBS
culture and
initiate IV penicillin
Penicillin IV
for 48 hrs
(during tocolysis)
GBS+
*If a hospital chooses to give antibiotics to prolong the latent period, a GBS culture should be obtained before initiating therapy and the
results used to guide intrapartum management.
Penicillin should be continued for a total of at least 48 hours, unless delivery occurs sooner. At the physicians discretion, antibiotic prophy-
laxis may be continued beyond 48 hours in a GBS culture-positive woman if delivery has not yet occurred. For women who are GBS culture
positive, antibiotic prophylaxis should be reinitiated when labor likely to proceed to delivery occurs or recurs.
If antibiotics are used to prolong the latent period, GBS cultures should be obtained prior to initiating therapy and the results used to guide
intrapartum management.
If delivery has not occurred within 4 weeks, a vaginal and rectal GBS screening culture should be repeated and the patient should be man-
aged as described, based on the result of the repeat culture.
||
Intrapartum antibiotic prophylaxis.
Adapted from Schrag S, Gorwitz R, Fultz-Butts K, Schuchat A. Prevention of perinatal group B streptococcal disease. Revised guidelines from
CDC. MMWR Recomm Rep 2002;51(RR-11):122.
No GBS culture GBS GBS+
COMPENDIUM OF SELECTED PUBLICATIONS 514 514
the timing of administration of antibiotics and the
timing of incision should be individualized (49).
The Committee has insufficient data to support
or discourage the use of scalp electrodes or fetal
scalp/blood pH determinations in women known to
be GBS colonized. Furthermore, the risks of mem-
brane stripping in GBS-colonized women have not
been investigated in well-designed prospective stud-
ies. Therefore, data are insufficient to encourage or
discourage this practice in women known to be GBS
colonized.
Current rapid tests for the detection of GBS
colonization at the time of labor or rupture of
membranes do not have sufficient sensitivity and
specificity to eliminate the need for culture-based
prenatal screening (50, 51).
The Committee on Obstetric Practice recog-
nizes that compliance with the culture-based
approach will require the implementation of
several steps. Patient and professional materials are
available from ACOG (sales.acog.org and
www.acog.org) and the CDC (www.cdc.gov.nci-
dod/dbmd/gbs). Success of the culture-based
approach will require the following:
Obtaining accurate culture data
Appropriate processing of the culture by labora-
tories
Timely reporting of results to obstetric providers
Administering intrapartum prophylaxis to cul-
ture-positive women
It is important to acknowledge that complete imple-
mentation of this complex strategy still will not
eliminate all cases of early-onset GBS.
References
1. Schrag SJ, Zywicki S, Farley MM, Reingold AL, Harrison
LH, Lefkowitz LB, et al. Group B streptococcal disease in
the era of intrapartum antibiotic prophylaxis. N Engl J
Med 2000;342:1520.
2. Early-onset group B streptococcal diseaseUnited
States, 1998-1999. Centers for Disease Control and
Prevention. MMWR Morb Mortal Wkly Rep 2000;49:
7936.
3. Anthony BF, Okada DM, Hobel CJ. Epidemiology of
group B Streptococcus: longitudinal observations during
pregnancy. J Infect Dis 1978;137:52430.
4. Regan JA, Klebanoff MA, Nugent RP. The epidemiology
of group B streptococcal colonization in pregnancy.
Vaginal Infections and Prematurity Study Group. Obstet
Gynecol 1991;77:60410.
5. Dillon HC Jr, Gray E, Pass MA, Gray BM. Anorectal and
vaginal carriage of group B streptococci during preg-
nancy. J Infect Dis 1982;145:7949.
6. Boyer KM, Gadzala CA, Kelly PD, Burd LI, Gotoff SP.
Selective intrapartum chemoprophylaxis of neonatal
group B streptococcal early-onset disease. II. Predictive
value of prenatal cultures. J Infect Dis 1983;148:8029.
7. Pass MA, Gray BM, Dillon HC Jr. Puerperal and perina-
tal infections with group B streptococci. Am J Obstet
Gynecol 1982;143:14752.
8. Bobitt JR, Ledger WJ. Amniotic fluid analysis. Its role in
maternal neonatal infection. Obstet Gynecol 1978;51:5662.
9. Braun TI, Pinover W, Sih P. Group B streptococcal menin-
gitis in a pregnant woman before the onset of labor. Clin
Infect Dis 1995;21:10423.
10. Yancey MK, Duff P, Clark P, Kurtzer T, Frentzen BH,
Kubilis P. Peripartum infection associated with vaginal
group B streptococcal colonization. Obstet Gynecol
1994;84:8169.
11. Fox BC. Delayed-onset postpartum meningitis due to
group B streptococcus. Clin Infect Dis 1994;19:350.
12. Aharoni A, Potasman I, Levitan Z, Golan D, Sharf M.
Postpartum maternal group B streptococcal meningitis.
Rev Infect Dis 1990;12:2736.
13. Schrag S, Gorwitz R, Fultz-Butts K, Schuchat A.
Prevention of perinatal group B streptococcal disease.
Revised guidelines from CDC. MMWR Recomm Rep
2002;51(RR-11):122.
14. Boyer KM, Gotoff SP. Strategies for chemoprophylaxis of
GBS early-onset infections. Antibiot Chemother 1985;
35:26780.
15. Zangwill KM, Schuchat A, Wenger JD. Group B strepto-
coccal disease in the United States, 1990: report from a
multistate active surveillance system. Mor Mortal Wkly
Rep CDC Surveill Summ 1992;41(6):2532.
16. Schuchat A, Oxtoby M, Cochi S, Sikes RK, Hightower A,
Plikaytis B, et al. Population-based risk factors for neona-
tal group B streptococcal disease: results of a cohort study
in metropolitan Atlanta. J Infect Dis 1990;162:6727.
17. Schuchat A, Deaver-Robinson K, Plikaytis BD, Zangwill
KM, Mohle-Boetani J, Wenger JD. Multistate case-con-
trol study of maternal risk factors for neonatal group B
streptococcal disease. The Active Surveillance Study
Group. Pediatr Infect Dis J 1994;13:6239.
18. Carstensen H, Christensen KK, Grennert L, Persson K,
Polberger S. Early-onset neonatal group B streptococcal
septicaemia in siblings. J Infect 1988;17:2014.
19. Faxelius G, Bremme K, Kvist-Christensen K, Christensen
P, Ringertz S. Neonatal septicemia due to group B strep-
tococci-perinatal risk factors and outcome of subsequent
pregnancies. J Perinat Med 1988;16:42330.
20. Christensen KK, Dahlander K, Linden V, Svenningsen N,
Christensen P. Obstetrical care in future pregnancies after
fetal loss in group B streptococcal septicemia. A preven-
tion program based on bacteriological and immunological
follow-up. Eur J Obstet Gynecol Reprod Biol 1981;12:
14350.
21. Pass MA, Gray BM, Khare S, Dillon HC Jr. Prospective
studies of group B streptococcal infections in infants. J
Pediatr 1979;95:43743.
22. Wood EG, Dillon HC Jr. A prospective study of group B
streptococcal bacteriuria in pregnancy. Am J Obstet
Gynecol 1981;140:51520.
23. Moller M, Thomsen AC, Borch K, Dinesen K, Zdravkovic
M. Rupture of fetal membranes and premature delivery
515 COMMITTEE OPINIONS 515
associated with group B streptococci in urine of pregnant
women. Lancet 1984;2(8394):6970.
24. Liston TE, Harris RE, Foshee S, Null DM Jr. Relationship
of neonatal pneumonia to maternal urinary and neonatal
isolates of group B streptococci. South Med J 1979;72:
14102.
25. Persson K, Christensen KK, Christensen P, Forsgren A,
Jorgensen C, Persson PH. Asymptomatic bacteriuria dur-
ing pregnancy with special reference to group B strepto-
cocci. Scand J Infect Dis 1985;17:1959.
26. Baker CJ, Kasper DL. Correlation of maternal antibody
deficiency with susceptibility to neonatal group B strepto-
coccal infection. N Engl J Med 1976;294:7536.
27. Schuchat A, Hilger T, Zell E, Farley M, Reingold A,
Harrison L, et al. Active bacterial core surveillance of the
emerging infections program network. Emerging Infect
Dis 2001;7:929.
28. Jeffery HE, Moses Lahra M. Eight-year outcome of uni-
versal screening and intrapartum antibiotics for maternal
group B streptococcal carriers. Pediatrics 1998;101:E2.
29. Isaacs D, Royle JA. Intrapartum antibiotics and early
onset neonatal sepsis caused by group B streptococcus
and by other organisms in Australia. Australasian Study
Group for Neonatal Infections. Pediatr Infect Dis J
1999;18:5248.
30. Davies HD, Adair CE, Schuchat A, Low DE, Sauve RS,
McGeer A. Physicians prevention practices and incidence
of neonatal group B streptococcal disease in 2 Canadian
regions. CMAJ 2001;164:47985.
31. Prevention of perinatal group B streptococcal disease: a
public health perspective. Centers for Disease Control and
Prevention. MMWR Recomm Rep1996;45:124.
32. Schrag SJ, Zell ER, Lynfield R, Roome A, Arnold KE,
Craig AS, et al. A population-based comparison of strate-
gies to prevent early-onset group B streptococcal disease
in neonates. N Engl J Med 2002;347:2339.
33. Hafner E, Sterniste W, Rosen A, Schuchter K, Plattner M,
Asboth F, et al. Group B streptococci during pregnancy: a
comparison of two screening and treatment protocols. Am
J Obstet Gynecol 1998;179:67781.
34. Lieu TA, Mohle-Boetani JC, Ray GT, Ackerson LM,
Walton DL. Neonatal group B streptococcal infection in a
managed care population. Perinatal Group B Strepto-
coccal Infection Study Group. Obstet Gynecol 1998;92:
217.
35. Factor SH, Levine OS, Nasser A, Potter J, Fajardo A,
OSullivan MJ, et al. Impact of a risk-based prevention
policy on neonatal group B streptococcal disease. Am J
Obstet Gynecol 1998;179:156871.
36. Cheon-Lee E, Amstey MS. Compliance with the Centers
for Disease Control and Prevention antenatal culture pro-
tocol for preventing group B streptococcal neonatal sep-
sis. Am J Obstet Gynecol 1998;179:779.
37. Katz VL, Moos MK, Cefalo RC, Thorp JM Jr, Bowes WA
Jr, Wells SD. Group B streptococci: results of a protocol
of antepartum screening and intrapartum treatment. Am J
Obstet Gynecol 1994;170:5216.
38. Gilson GJ, Christensen F, Romero H, Bekes K, Silva L,
Qualls CR. Prevention of group B streptococcus early-
onset neonatal sepsis: comparison of the Center for
Disease Control and Prevention screening-based protocol
to a risk-based protocol in infants at greater than 37
weeks gestation. J Perinatol 2000;20:4915.
39. Brozanski BS, Jones JG, Krohn MA, Sweet RL. Effect of
a screening-based prevention policy on prevalence of
early-onset group B streptococcal sepsis. Obstet Gynecol
2000;95:496501.
40. Bromberger P, Lawrence JM, Braun D, Saunders B,
Contreras R, Petitti DB. The influence of intrapartum
antibiotics on the clinical spectrum of early-onset group B
streptococcal infection in term infants. Pediatrics 2000;
106:24450.
41. Rosenstein NE, Schuchat A. Opportunities for prevention
of perinatal group B streptococcal disease: a multistate
surveillance analysis. The Neonatal Group B Strepto-
coccal Disease Study Group. Obstet Gynecol 1997;90:
9016.
42. Persson K, Bjerre B, Elfstrom L, Polberger S, Forsgren A.
Group B streptococci at delivery: high count in urine
increases risk for neonatal colonization. Scand J Infect
Dis 1986;18:52531.
43. Persson K, Bjerre B, Elfstrom L, Forsgren A. Longi-
tudinal study of group B streptococcal carriage during late
pregnancy. Scand J Infect Dis 1987;19:3259.
44. Pearlman MD, Pierson CL, Faix RG. Frequent resistance
of clinical group B streptococci isolates to clindamycin
and erythromycin. Obstet Gynecol 1998;92:25861.
45. Schwartz B, Schuchat A, Oxtoby MJ, Cochi SL,
Hightower A, Broome CV. Invasive group B streptococcal
disease in adults. A population-based study in metropoli-
tan Atlanta. JAMA 1991;266:11124.
46. Hardman JG, Limbird LE, Molinoff PB, Ruddon RW,
Gilman AG, editors. Goodman and Gilmans the pharma-
cological basis of therapeutics. 9th ed. New York:
McGraw-Hill; 1996.
47. Dunn AB, Blomquist J, Khouzami V. Anaphylaxis in labor
secondary to prophylaxis against group B Streptococcus:
a case report. J Reprod Med 1999;44:3814.
48. Ramus RM, McIntire DD, Wendel GD Jr. Antibiotic
chemoprophylaxis for group B strep is not necessary with
elective cesarean section at term [abstract]. Am J Obstet
Gynecol 1999;180:S85.
49. Hager WD, Schuchat A, Gibbs R, Sweet R, Mead P,
Larsen JW. Prevention of perinatal group B streptococcal
infection: current controversies. Obstet Gynecol 2000;96:
1415.
50. Yancey MK, Armer T, Clark P, Duff P. Assessment of
rapid identification tests for genital carriage of group B
streptococci. Obstet Gynecol 1992;80:103847.
51. Walker CK, Crombleholme WR, Ohm-Smith MJ, Sweet
RL. Comparison of rapid tests for detection of group B
streptococcal colonization. Am J Perinatol 1992;9:
3048.
COMPENDIUM OF SELECTED PUBLICATIONS 516
Number 281, December 2002
Committee
Opinion
Rubella Vaccination
ABSTRACT: The incidence of rubella decreased from 0.45 per 100,000 in
1990 to 0.1 per 100,000 in 1999. Although there is a nationwide shortage of
rubella vaccine, women who are rubella susceptible during pregnancy should
receive MMR (measlesmumpsrubella) vaccination postpartum. In October
2001, the federal Centers for Disease Control and Prevention changed the
recommendations concerning the pregnancy interval after receiving rubella
vaccine. This interval has been reduced from 3 months to 1 month.
The incidence of rubella decreased from 0.45 per 100,000 in 1990 to 0.1 per
100,000 in 1999 (1). There have been cluster outbreaks, especially among
persons born outside of the United States. Although there is a nationwide
shortage of rubella vaccine, women who are rubella susceptible during
pregnancy should receive MMR (measlesmumpsrubella) vaccination post-
partum. The appropriate test for assessing rubella immunity is the
immunoglobulin G serology. There is no contraindication to giving MMR
vaccination while breastfeeding. Receipt of rubella vaccination in a new
mother does not pose a risk of transmission of the virus to the newborn or to
other children in her household. Receipt of rubella vaccination during preg-
nancy is not an indication for interruption of that pregnancy.
In October 2001, the federal Centers for Disease Control and Prevention
changed the recommendations concerning the pregnancy interval after receiv-
ing rubella vaccine. This interval has been reduced from 3 months to 1 month
(2). The safe interval for measles and mumps vaccination was already 1
month.
References
1. Reef SE, Frey TK, Theall K, Abernathy E, Burnett CL, Icenogle J, et al. The changing
epidemiology of rubella in the 1990s: on the verge of elimination and new challenges
for control and prevention. JAMA 2002;287:464-72.
2. Revised ACIP recommendation for avoiding pregnancy after receiving a rubella-con-
taining vaccine. MMWR Morb Mortal Wkly Rep 2001;50:1117.
ACOG
This document reflects emerg-
ing clinical and scientific ad-
vances as of the date issued and
is subject to change. The infor-
mation should not be construed
as dictating an exclusive course
of treatment or procedure to be
followed.
Copyright December 2002
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of
this publication may be repro-
duced, stored in a retrieval sys-
tem, or transmitted, in any form
or by any means, electronic,
mechanical, photocopying,
recording, or otherwise, without
prior written permission from
the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Rubella vaccination. ACOG
Committee Opinion No. 281.
American College of Obstetricians
and Gynecologists. Obstet Gynecol
2002;100:1417.
Committee on
Obstetric Practice
Reaffirmed 2008
516
517 COMMITTEE OPINIONS 517
Committee on
Obstetric Practice
Reaffirmed 2006
ACOG
Number 284, August 2003
Committee
Opinion
This document reflects emerg-
ing clinical and scientific ad-
vances as of the date issued and
is subject to change. The infor-
mation should not be construed
as dictating an exclusive course
of treatment or procedure to be
followed.
Copyright August 2003
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of
this publication may be repro-
duced, stored in a retrieval sys-
tem, or transmitted, in any form
or by any means, electronic,
mechanical, photocopying,
recording, or otherwise, without
prior written permission from
the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Nonobstetric surgery in pregnancy.
ACOG Committee Opinion No. 284.
American College of Obstetricians
and Gynecologists. Obstet Gynecol
2003;102:431.
Nonobstetric Surgery in Pregnancy
ABSTRACT: Although there are no data to support specific recommendations
regarding nonobstetric surgery and anesthesia in pregnancy, it is important
for nonobstetric physicians to obtain obstetric consultation before perform-
ing nonobstetric surgery. The decision to use fetal monitoring should be indi-
vidualized, and each case warrants a team approach for optimal safety of the
woman and her baby.
The American College of Obstetricians and Gynecologists Committee on
Obstetric Practice acknowledges that the issue of nonobstetric surgery and
anesthesia in pregnancy is an important concern for physicians who care for
women; however, there are no data to allow us to make specific recommen-
dations. It is important for physicians to obtain obstetric consultation before
performing nonobstetric surgery because obstetricians are uniquely qualified
to discuss aspects of maternal physiology and anatomy that may affect
intraoperative maternalfetal well-being. The decision to use fetal monitoring
should be individualized, and, if used, may be based on gestational age, type
of surgery, and facilities available. Ultimately, each case warrants a team
approach (anesthesia, obstetrics, surgery) for optimal safety of the woman
and her baby.
COMPENDIUM OF SELECTED PUBLICATIONS 518 518
ACOG
Number 295, July 2004 (Replaces No. 231, February 2000)
Committee
Opinion
This document reflects emerg-
ing clinical and scientific ad-
vances as of the date issued and
is subject to change. The infor-
mation should not be construed
as dictating an exclusive course
of treatment or procedure to be
followed.
Copyright July 2004
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of
this publication may be repro-
duced, stored in a retrieval sys-
tem, or transmitted, in any form
or by any means, electronic,
mechanical, photocopying,
recording, or otherwise, without
prior written permission from
the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Pain relief during labor. ACOG
Committee Opinion No. 295.
American College of Obstetricians
and Gynecologists. Obstet Gynecol
2004;104:213.
Pain Relief During Labor
ABSTRACT: Pain management should be provided whenever medically indi-
cated. The American Society of Anesthesiologists (ASA) and the American
College of Obstetricians and Gynecologists (ACOG) believe that women
requesting epidural analgesia during labor should not be deprived of this ser-
vice based on their insurance or inadequate nursing participation in the man-
agement of regional analgesic modalities. Furthermore, in an effort to allow
the maximum number of patients to benefit from neuraxial analgesia, ASA
and ACOG believe that labor nurses should not be restricted from participat-
ing in the management of pain relief during labor.
Labor causes severe pain for many women. There is no other circumstance
where it is considered acceptable for an individual to experience untreated
severe pain, amenable to safe intervention, while under a physicians care. In
the absence of a medical contraindication, maternal request is a sufficient
medical indication for pain relief during labor. Pain management should be
provided whenever medically indicated.
Of the various pharmacologic methods used for pain relief during labor
and delivery, neuraxial analgesia techniques (epidural, spinal, and combined
spinalepidural) are the most flexible, effective, and least depressing to the
central nervous system, allowing for an alert participating woman and an alert
neonate. The American Society of Anesthesiologists (ASA) and the American
College of Obstetricians and Gynecologists (ACOG) believe that women
requesting epidural analgesia during labor should not be deprived of this ser-
vice based on their insurance or inadequate nursing participation in the man-
agement of regional analgesic modalities. In addition, third-party payers who
provide reimbursement for obstetric services should not deny reimbursement
for labor analgesia because of an absence of other medical indications.
Although the availability of various methods of labor analgesia will vary from
hospital to hospital, within an institution the methods available should not be
based on a patients ability to pay. Furthermore, in an effort to allow the max-
imum number of patients to benefit from neuraxial analgesia, ASA and
ACOG believe that labor nurses should not be restricted from participating in
the management of pain relief during labor. Under appropriate physician
supervision, labor and delivery nursing personnel who have been properly
educated and have demonstrated current competence should be able to partic-
ipate in the management of epidural infusions, including adjusting dosage
and discontinuing infusions.
Committee on
Obstetric Practice
Reaffirmed 2008
American Society of
Anesthesiologists
519 COMMITTEE OPINIONS 519
Committee on
Obstetric Practice
Reaffirmed 2009
ACOG
Number 299, September 2004 (Replaces No. 158, September 1995)
Committee
Opinion
This document reflects emerg-
ing clinical and scientific ad-
vances as of the date issued and
is subject to change. The infor-
mation should not be construed
as dictating an exclusive course
of treatment or procedure to be
followed.
Copyright September 2004
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of
this publication may be repro-
duced, stored in a retrieval sys-
tem, or transmitted, in any form
or by any means, electronic,
mechanical, photocopying,
recording, or otherwise, without
prior written permission from
the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Guidelines for diagnostic imaging
during pregnancy. ACOG Committee
Opinion No. 299. American College
of Obstetricians and Gynecologists.
Obstet Gynecol 2004;104:64751.
Guidelines for Diagnostic Imaging
During Pregnancy
ABSTRACT: Undergoing a single diagnostic X-ray procedure does not result
in radiation exposure adequate to threaten the well-being of the developing
preembryo, embryo, or fetus and is not an indication for therapeutic abortion.
When multiple diagnostic X-rays are anticipated during pregnancy, imaging
procedures not associated with ionizing radiation, such as ultrasonography
and magnetic resonance imaging, should be considered. Additionally, it may
be helpful to consult an expert in dosimetry calculation to determine estimat-
ed fetal dose. The use of radioactive isotopes of iodine is contraindicated for
therapeutic use during pregnancy. Other radiopaque and paramagnetic con-
trast agents have not been studied in humans, but animal studies suggest that
these agents are unlikely to cause harm to the developing human fetus.
Although imaging techniques requiring these agents may be diagnostically
beneficial, these techniques should be used during pregnancy only if potential
benefits justify potential risks to the fetus.
Various imaging modalities are available for diagnostic use during preg-
nancy. These include X-ray, ultrasonography, magnetic resonance imaging
(MRI), and nuclear medicine studies. Of these, diagnostic X-ray is the most
frequent cause of anxiety for obstetricians and patients. Much of this anxiety
is secondary to a general belief that any radiation exposure is harmful and
will result in an anomalous fetus. This anxiety could lead to inappropriate
therapeutic abortion and litigation. Actually, most diagnostic radiologic pro-
cedures are associated with little, if any, known significant fetal risks.
Moreover, according to the American College of Radiology, no single diag-
nostic X-ray procedure results in radiation exposure to a degree that would
threaten the well-being of the developing preembryo, embryo, or fetus (1).
Thus, exposure to a single X-ray during pregnancy is not an indication for
therapeutic abortion (2, 3).
Some women are exposed to X-rays before the diagnosis of pregnancy.
Occasionally, X-ray procedures will be indicated during pregnancy for signif-
icant medical problems or trauma. To enable physicians to counsel patients
appropriately, the following information is provided about the potential risks
and measures that can reduce diagnostic X-ray exposure.
COMPENDIUM OF SELECTED PUBLICATIONS 520 520
X-Ray Exposure
Ionizing radiation can result in the following 3 harm-
ful effects: 1) cell death and teratogenic effects, 2)
carcinogenesis, and 3) genetic effects or mutations
in germ cells (2, 3). There is little or no information
to estimate either the frequency or magnitude of
adverse genetic effects on future generations.
Units traditionally used to measure the effects of
X-ray include the rad and roentgen equivalents man
(rem). Modern units include the gray (Gy) and siev-
ert (Sv). The definitions of these units of measure
are summarized in Table 1.
The estimated fetal exposure from some com-
mon radiologic procedures is summarized in Table
2. A plain X-ray generally exposes the fetus to very
small amounts of radiation. Commonly during preg-
nancy, the uterus is shielded for nonpelvic proce-
dures. With the exception of barium enema or small
bowel series, most fluoroscopic examinations result
in fetal exposure of millirads. Radiation exposure
from computed tomography (CT) varies depending
on the number and spacing of adjacent image sec-
tions. Although CT pelvimetry can result in fetal
exposures as high as 1.5 rad, exposure can be
reduced to approximately 250 mrad (including fetal
gonad exposure) by using a low-exposure technique
(4).
Spiral (or helical) CT allows continuous scan-
ning of the patient as the couch is moved through the
scanner, providing superior speed and image quality.
Radiation exposure is affected by slice thickness, the
number of cuts obtained, and the pitch, a ratio
defined as the distance the couch travels during one
360-degree rotation divided by the section thickness.
The patient dose is proportional to 1 per pitch.
Under typical use with a pitch of 1 or greater, the
radiation exposure to the fetus from spiral CT is
comparable to conventional CT (5).
Cell Death and Teratogenic Effects
Data from an animal study suggest that exposure to
high-dose ionizing radiation (ie, much greater than
that used in diagnostic procedures) before implanta-
tion will most likely be lethal to the embryo (2). In
other words, cell death is most likely an all or
none phenomenon in early embryonic develop-
ment.
Myriad teratogenic effects have developed in
animals exposed to large doses of radiation (ie,
100200 rad). However, in humans, growth restric-
tion, microcephaly, and mental retardation are the
most common adverse effects from high-dose radia-
tion (3, 6, 7). Based on data from atomic bomb sur-
vivors, it appears that the risk of central nervous
system effects is greatest with exposure at 815
weeks of gestation, with no proven risk at less than
8 weeks of gestation or at greater than 25 weeks of
gestation (3, 8). Thus, at 815 weeks of gestation,
the fetus is at greatest risk for radiation-induced
mental retardation, and the risk appears to be a non-
threshold linear function of dose at doses of at least
20 rad (3, 6, 8, 9). For example, the risk of severe
mental retardation in fetuses exposed to ionizing
radiation is approximately 40% at 100 rad of expo-
sure and as high as 60% at 150 rad of exposure (3,
8). It has been suggested that a threshold for this
adverse effect may exist in the range of 2040 rad
(7, 8). Even multiple diagnostic X-ray procedures
rarely result in ionizing radiation exposure to this
degree. Fetal risks of anomalies, growth restriction,
or abortions are not increased with radiation expo-
sure of less than 5 rad, a level above the range of
exposure for diagnostic procedures (2).
Carcinogenesis
The risk of carcinogenesis as a result of in utero
exposure to ionizing radiation is unclear but is prob-
Table 1. Some Measures of Ionizing Radiation
Measure Definition Unit Unit
Exposure Number of ions produced by X-rays per kilogram of air Roentgen (R) Roentgen (R)
Dose Amount of energy deposited per kilogram of tissue Rad (rad)* Gray (Gy)
1 Gy = 100 rad
Relative Amount of energy deposited per kilogram of tissue Roentgen Sievert (Sv)
effective normalized for biological effectiveness equivalents 1 Sv = 100 rem
dose man (rem)*
*For diagnostic X-rays, 1 rad = 1 rem
Cunningham FG, Gant NF, Leveno KJ, Gilstrap LC 3rd, Hauth JC, Wenstrom KD. General considerations and maternal evaluation. In: Williams obstet-
rics. 21st ed. New York (NY): McGraw-Hill; 2001. p. 114358. Reproduced with permission of The McGraw-Hill Companies.
521 COMMITTEE OPINIONS 521
ably very small. It is estimated that a 12 rad fetal
exposure may increase the risk of leukemia by a fac-
tor of 1.52.0 over natural incidence and that an
estimated 1 in 2,000 children exposed to ionizing
radiation in utero will develop childhood leukemia.
This is increased from a background rate of approxi-
mately 1 in 3,000 (2, 10). If elective abortion were
chosen in every instance of fetal exposure to radia-
tion, 1,999 exposed, normal fetuses would be aborted
for each case of leukemia prevented (2, 11). It has
been estimated that the risk of radiation-induced car-
cinogenesis may indeed be higher in children com-
pared with adults, but such risks are not likely to
exceed 1 in 1,000 children per rad (12). Thus, abor-
tion should not be recommended solely on the basis
of exposure to diagnostic radiation.
Ultrasonography
Ultrasonography involves the use of sound waves and
is not a form of ionizing radiation. There have been no
reports of documented adverse fetal effects for diag-
nostic ultrasound procedures, including duplex
Doppler imaging. Energy exposure from ultrasonog-
raphy has been arbitrarily limited to 94 mW/cm
2
by
the U.S. Food and Drug Administration. There are no
contraindications to ultrasound procedures during
pregnancy, and this modality has largely replaced X-
ray as the primary method of fetal imaging during
pregnancy.
Magnetic Resonance Imaging
With MRI, magnets that alter the energy state of
hydrogen protons are used instead of ionizing radia-
tion (13). This technique could prove especially
useful for diagnosis and evaluation of fetal central
nervous system anomalies and placental abnormali-
ties (eg, accreta, previa).
Nuclear Medicine
Nuclear studies such as pulmonary ventilationper-
fusion, thyroid, bone, and renal scans are performed
by tagging a chemical agent with a radioisotope.
The fetal exposure depends on the physical and bio-
chemical properties of the radioisotope (6).
Technetium Tc 99m is one of the most common-
ly used isotopes and is used for brain, bone, renal,
and cardiovascular scans. In general, these latter
procedures result in a uterus, embryo, or fetal expo-
sure of less than 0.5 rad (6, 12).
One of the more common nuclear medicine
studies performed during pregnancy is the ventila-
tionperfusion scan for suspected pulmonary
embolism. Macroaggregated albumin labeled with
Technetium Tc 99m is used for the perfusion por-
tion, and inhaled xenon gas (
127
Xe or
133
Xe) is used
for the ventilation portion. The amount of radiation
to which the fetus is exposed is extremely small
(approximately 50 mrad) (14).
In a 2002 study, investigators calculated the
mean fetal radiation exposure resulting from heli-
cal (spiral) CT in healthy pregnant women and
compared it with reported fetal radiation doses
for ventilationperfusion lung scanning (approxi-
mately 100370 Gy) (15). Although the exposure
from ventilationperfusion is relatively low, the
study found that the mean fetal doses associated
with helical CT were lower. Although exposure
varied with gestational age (3.320.2 Gy for
the first trimester, 7.976.7 Gy for the second
trimester, and 51.3130.8 Gy for the third
trimester), 20 of 23 study patients exhibited a
mean fetal dose of less than 60 Gy for all 3
trimesters.
Radioactive iodine readily crosses the placenta
and can adversely affect the fetal thyroid, especially
if used after 1012 weeks of gestation. Radioactive
isotopes of iodine used for treatment of hyperthy-
roidism are contraindicated during pregnancy, and
such therapy should be delayed until after delivery.
If a diagnostic scan of the thyroid is essential,
Table 2. Estimated Fetal Exposure From Some Common
Radiologic Procedures
Procedure Fetal Exposure
Chest X-ray (2 views) 0.020.07 mrad
Abdominal film (single view) 100 mrad
Intravenous pyelography 1 rad*
Hip film (single view) 200 mrad
Mammography 720 mrad
Barium enema or small bowel series 24 rad
CT
1 g intravenously
Allergic to penicillin or ampicillin* Cefazolin or ceftriaxone
1 g intravenously
or clindamycin
600 mg intravenously
Oral Amoxicillin 2 g
*Cephalosporins should not be used in patients with a significant sensitivity to penicillins.
This regimen does not cover enterococcus. Vancomycin can be used if enterococcus is of concern.
577 COMMITTEE OPINIONS 577
Number 433 May 2009 (Replaces No. 256, May 2001)
ACOG COMMITTEE OPINION
Optimal Goals for Anesthesia Care in
Obstetrics
ABSTRACT: A joint statement from the American Society of Anesthesiologists and
the American College of Obstetricians and Gynecologists was developed to address
issues of concern to both specialties. Good obstetric care requires the availability of qual-
ified personnel and equipment to administer general or regional anesthesia both elective-
ly and emergently. The extent and degree to which anesthesia services are available
varies widely among hospitals. However, for hospitals providing obstetric care, certain
optimal anesthesia goals should be sought.
Committee on
Obstetric Practice
This document reflects
emerging clinical and sci-
entific advances as of the
date issued and is subject
to change. The informa-
tion should not be con-
strued as dictating an
exclusive course of treat-
ment or procedure to be
followed.
This joint statement from the American
Society of Anesthesiologists and the American
College of Obstetricians and Gynecologists
has been designed to address issues of con-
cern to both specialties. Good obstetric care
requires the availability of qualified person-
nel and equipment to administer general or
regional anesthesia both electively and emer-
gently. The extent and degree to which anes-
thesia services are available varies widely
among hospitals. However, for any hospital
providing obstetric care, certain optimal
anesthesia goals should be sought as follows:
I. Availability of a licensed practitioner who
is credentialed to administer an appro-
priate anesthetic whenever necessary.
For many women, regional anesthesia
(epidural, spinal, or combined spinal
epidural) will be the most appropriate
anesthetic.
II. Availability of a licensed practitioner
who is credentialed to maintain support
of vital functions in any obstetric emer-
gency.
III. Availability of anesthesia and surgical
personnel to permit the start of a cesa-
rean delivery within 30 minutes of the
decision to perform the procedure.
IV. Immediate availability of appropriate
facilities and personnel, including obstet-
ric anesthesia, nursing personnel, and a
physician capable of monitoring labor
and performing cesarean delivery, in-
cluding an emergency cesarean delivery
in cases of vaginal birth after cesarean
delivery (1). The definition of immedi-
ately available personnel and facilities
remains a local decision based on each
institutions available resources and geo-
graphic location.
V. Appointment of a qualified anesthesiol-
ogist to be responsible for all anesthetics
administered. There are many obstetric
units where obstetricians or obstetrician-
supervised nurse anesthetists administer
labor anesthetics. The administration of
general or regional anesthesia requires
both medical judgment and technical
skills. Thus, a physician with privileges
in anesthesiology should be readily
available.
Persons administering or supervising
obstetric anesthesia should be qualified to
manage the infrequent but occasional life-
threatening complications of major regional
anesthesia such as respiratory and cardiovas-
cular failure, toxic local anesthetic convul-
sions, or vomiting and aspiration. Mastering
and retaining the skills and knowledge
necessary to manage these complications
require adequate training and frequent appli-
cation.
To ensure the safest and most effective
anesthesia for obstetric patients, the director
of anesthesia services, with the approval of
the medical staff, should develop and enforce
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
COMPENDIUM OF SELECTED PUBLICATIONS 578 578
written policies regarding provision of obstetric anesthe-
sia as follows:
I. A qualified physician with obstetric privileges to per-
form operative vaginal or cesarean delivery should be
readily available during administration of anesthesia.
Readily available should be defined by each institu-
tion within the context of its resources and geo-
graphic location. Regional or general anesthesia or
both should not be administered until the patient has
been examined and the fetal status and progress of
labor evaluated by a qualified individual. A physician
with obstetric privileges who concurs with the
patients management and has knowledge of the
maternal and fetal status and the progress of labor
should be readily available to handle any obstetric
complications that may arise. A physician with
obstetric privileges should be responsible for mid-
wifery back up in hospital settings that utilize certi-
fied nursemidwives and certified midwives as
obstetric providers.
II. Availability of equipment, facilities, and support per-
sonnel equal to that provided in the surgical suite.
This should include the availability of a properly
equipped and staffed recovery room capable of
receiving and caring for all patients recovering from
major regional or general anesthesia. Birthing facili-
ties, when used for analgesia or anesthesia, must be
appropriately equipped to provide safe anesthetic
care during labor and delivery or postanesthesia
recovery care.
III. Personnel other than the surgical team should be
immediately available to assume responsibility for
resuscitation of the depressed newborn. The surgeon
and anesthesiologist are responsible for the mother
and may not be able to leave her to care for the new-
born even when a regional anesthetic is functioning
adequately. Individuals qualified to perform neonatal
resuscitation should demonstrate:
A. Proficiency in rapid and accurate evaluation of the
newborn condition, including Apgar scoring
B. Knowledge of the pathogenesis of a depressed
newborn (acidosis, drugs, hypovolemia, trauma,
anomalies, and infection), as well as specific indi-
cations for resuscitation
C. Proficiency in newborn airway management,
laryngoscopy, endotracheal intubations, suction-
ing of airways, artificial ventilation, cardiac mas-
sage, and maintenance of thermal stability
In larger maternity units and those functioning as
high-risk centers, 24-hour in-house anesthesia, obstetric,
and neonatal specialists usually are necessary. Preferably,
the obstetric anesthesia services should be directed by an
anesthesiologist with special training or experience in
obstetric anesthesia. These units also will frequently
require the availability of more sophisticated monitoring
equipment and specially trained nursing personnel.
A survey jointly sponsored by the American Society
of Anesthesiologists and The American College of
Obstetricians and Gynecologists found that many hospi-
tals in the United States have not yet achieved the goals
mentioned previously. Deficiencies were most evident in
smaller delivery units. Some small delivery units are nec-
essary because of geographic considerations. Currently,
approximately 34% of hospitals providing obstetric care
have fewer than 500 deliveries per year (2). Providing
comprehensive care for obstetric patients in these small
units is extremely inefficient, not cost-effective, and fre-
quently impossible. Thus, the following recommenda-
tions are made:
1. Whenever possible, small units should consolidate.
2. When geographic factors require the existence of
smaller units, these units should be part of a well-
established regional perinatal system.
The availability of the appropriate personnel to assist
in the management of a variety of obstetric problems is a
necessary feature of good obstetric care. The presence of
a pediatrician or other trained physician at a high-risk
cesarean delivery to care for the newborn, or the availabil-
ity of an anesthesiologist during active labor and
delivery when vaginal birth after cesarean delivery is
attempted and at a breech or multifetal delivery are
examples. Frequently, these physicians spend a consider-
able amount of time standing by for the possibility that
their services may be needed emergently but may ulti-
mately not be required to perform the tasks for which
they are present. Reasonable compensation for these
standby services is justifiable and necessary.
A variety of other mechanisms have been suggested to
increase the availability and quality of anesthesia ser-
vices in obstetrics. Improved hospital design, which places
labor and delivery suites closer to the operating rooms,
would allow for more efficient supervision of nurseanes-
thetists. Anesthesia equipment in the labor and delivery
area must be comparable to that in the operating room.
Finally, good interpersonal relations between obste-
tricians and anesthesiologists are important. Joint meet-
ings between the two departments should be encouraged.
Anesthesiologists should recognize the special needs and
concerns of obstetricians and obstetricians should recog-
nize anesthesiologists as consultants in the management
of pain and life-support measures. Both should recognize
the need to provide high-quality care for all patients.
References
1. Vaginal birth after previous cesarean delivery. ACOG
Practice Bulletin No. 54. American College of Obstetricians
and Gynecologists. Obstet Gynecol 2004;104:20312.
2. Bucklin BA, Hawkins JL, Anderson JR, Ullrich FA. Obstetric
anesthesia workforce survey: twenty-year update. Anesthe-
siology 2005;103:64553.
579 COMMITTEE OPINIONS 579
Copyright May 2009 by the American College of Obstetricians and
Gynecologists and the American Society of Anesthesiologists.
All rights reserved. No part of this publication may be reproduced,
stored in a retrieval system, posted on the Internet, or transmitted, in
any form or by any means, electronic, mechanical, photocopying,
recording, or otherwise, without prior written permission from the
publisher. Requests for authorization to make photocopies should be
directed to: Copyright Clearance Center, 222 Rosewood Drive,
Danvers, MA 01923, (978) 750-8400.
ISSN 1074-861X
Optimal goals for anesthesia care in obstetrics. ACOG Committee
Opinion No. 433. American College of Obstetricians and Gynecolo-
gists and American Society of Anesthesiologists. Obstet Gynecol
2009;113:11979.
COMPENDIUM OF SELECTED PUBLICATIONS 580 580
Number 435 June 2009
ACOG COMMITTEE OPINION
Postpartum Screening for Abnormal
Glucose Tolerance in Women Who Had
Gestational Diabetes Mellitus
ABSTRACT: Establishing the diagnosis of gestational diabetes mellitus offers an
opportunity not only to improve pregnancy outcome, but also to decrease risk factors
associated with the subsequent development of type 2 diabetes. The American College
of Obstetricians and Gynecologists Committee on Obstetric Practice recommends that
all women with gestational diabetes mellitus be screened at 612 weeks postpartum and
managed appropriately.
Committee on
Obstetric Practice
This document reflects
emerging clinical and sci-
entific advances as of the
date issued and is subject
to change. The informa-
tion should not be con-
strued as dictating an
exclusive course of treat-
ment or procedure to be
followed.
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Gestational diabetes mellitus (GDM),
defined as carbohydrate intolerance leading
to hyperglycemia with onset or first recogni-
tion during pregnancy, affects 210% of
pregnancies in the United States depending
on the characteristics of the population stud-
ied (1). Gestational diabetes mellitus is char-
acterized by insulin resistance that is specific
to pregnancy. This Committee Opinion aug-
ments ACOG Practice Bulletin No. 30:
Gestational Diabetes (2) by highlighting
recent thinking about the risk for diabetes
mellitus among women whose pregnancies
were affected by GDM, and presents recom-
mendations for screening and management
for these women.
Although the carbohydrate intolerance
of GDM frequently resolves after delivery (3,
4), up to one third of affected women will
have diabetes or impaired glucose metabo-
lism at postpartum screening, and it has been
estimated that 1550% will develop diabetes
in the decades following the affected preg-
nancy (512). The original cutoff points for
performing an abnormal glucose tolerance
test in pregnancy were chosen for their abil-
ity to predict the subsequent onset of type 2
diabetes mellitus (13). Postpartum screening
at 612 weeks has been recommended for
women who had GDM to identify women
with diabetes mellitus, or impaired fasting
glucose level, or impaired glucose tolerance
(14, 19). The latter two may respond to life-
style modification and pharmacologic inter-
ventions to decrease incident diabetes.
However, there is marked variability in the
proportion of women with GDM who are
screened postpartum as well as in the type of
screening used (67, 9, 1520).
Either a fasting plasma glucose test or
the 75-g, 2-hour oral glucose tolerance test
are appropriate for diagnosing diabetes. Al-
though the fasting plasma glucose test is
easier to perform, it lacks sensitivity for detect-
ing other forms of abnormal glucose metabo-
lism; results of the oral glucose tolerance test
can confirm an impaired fasting glucose level
and impaired glucose tolerance (see Table 1).
In light of this, the Fifth International Work-
shop on GDM recommended that women
with GDM undergo a 75-g oral glucose toler-
ance test 612 weeks postpartum (21).
Establishing the diagnosis of GDM offers
an opportunity not only to improve preg-
nancy outcome, but also to affect risk factors
associated with the subsequent development
of type 2 diabetes. The American College of
Obstetricians and Gynecologists Committee
on Obstetric Practice recommends that all
women with GDM be screened at 612 weeks
postpartum and managed appropriately (see
Fig. 1). The American Diabetes Association
recommends repeat testing at least every 3
years for women who had a pregnancy affect-
ed by GDM and normal results of postpar-
tum screening (14). For women who may
581 COMMITTEE OPINIONS 581
Fig. 1. Management of postpartum screening results. Abbreviations: FPG, fasting plasma glucose; OGTT, oral glucose
tolerance test; IGT, impaired glucose tolerance.
Gestational diabetes
FPG or 75-g 2 hr OGTT at 612 weeks postpartum
Impaired fasting glucose or IGT or both
Consider referral for management
Weight loss and physical activity
counseling as needed
Consider metformin if combined
impaired fasting glucose and IGT
Medical nutrition therapy
Yearly assessment of glycemic status
Refer for diabetes management
Assess glycemic status every
3 years
Weight loss and physical activity
counseling as needed
Diabetes mellitus Normal
Table 1. Diagnostic criteria for diabetes mellitus, impaired fasting glucose, and impaired glucose tolerance.
Impaired Fasting Impaired Glucose
Test Diabetes Glucose Tolerance
Fasting plasma Fasting plasma glucose is Fasting plasma glucose NA
glucose greater than or equal to 126 is 100125
75-g 2 hr oral glucose Fasting plasma glucose is Fasting plasma glucose 2-hr plasma glucose is
tolerance test greater than or equal to 126 is 100125 140199
or
2-hr plasma glucose is
greater than or equal to 200
have subsequent pregnancies, screening more frequently
has the advantage of detecting abnormal glucose metabo-
lism before pregnancy and provides an opportunity to
ensure preconception glucose control (21). Women
should be encouraged to discuss their GDM history and
need for screening with all of their health care providers.
References
1. Hunt KJ, Schuller KL. The increasing prevalence of diabetes
in pregnancy. Obstet Gynecol Clin North Am 2007;
34:17399, vii.
2. Gestational diabetes. ACOG Practice Bulletin No. 30.
American College of Obstetricians and Gynecologists.
Obstet Gynecol 2001;98:52538.
3. Kaaja RJ, Greer IA. Manifestations of chronic disease during
pregnancy. JAMA 2005;294:27517.
4. Buchanan TA, Xiang AH. Gestational diabetes mellitus.
J Clin Invest 2005;115:48591.
5. Russell MA, Phipps MG, Olson CL, Welch HG, Carpenter
MW. Rates of postpartum glucose testing after gestational
diabetes mellitus. Obstet Gynecol 2006;108:145662.
6. Kim C, Tabaei BP, Burke R, McEwen LN, Lash RW, Johnson
SL, et al. Missed opportunities for type 2 diabetes mellitus
screening among women with a history of gestational dia-
betes mellitus. Am J Public Health 2006;96:16438.
7. Smirnakis KV, Chasan-Taber L, Wolf M, Markenson G,
Ecker JL, Thadhani R. Postpartum diabetes screening in
women with a history of gestational diabetes. Obstet
Gynecol 2005;106:1297303.
8. Schaefer-Graf UM, Buchanan TA, Xiang AH, Peters RK,
Kjos SL. Clinical predictors for a high risk for the devel-
opment of diabetes mellitus in the early puerperium in
COMPENDIUM OF SELECTED PUBLICATIONS 582 582
women with recent gestational diabetes mellitus. Am J
Obstet Gynecol 2002;186:7516.
9. Conway DL, Langer O. Effects of new criteria for type 2 dia-
betes on the rate of postpartum glucose intolerance in
women with gestational diabetes. Am J Obstet Gynecol
1999;181:6104.
10. Albareda M, Caballero A, Badell G, Piquer S, Ortiz A, de
Leiva A, et al. Diabetes and abnormal glucose tolerance in
women with previous gestational diabetes. Diabetes Care
2003;26:1199205.
11. Lee AJ, Hiscock RJ, Wein P, Walker SP, Permezel M.
Gestational diabetes mellitus: clinical predictors and long-
term risk of developing type 2 diabetes: a retrospective
cohort study using survival analysis. Diabetes Care 2007;30:
87883.
12. Kim C, Newton KM, Knopp RH. Gestational diabetes and
the incidence of type 2 diabetes: a systematic review.
Diabetes Care 2002;25:18628.
13. OSullivan JB, Mahan CM. Criteria for the oral glucose tol-
erance test in pregnancy. Diabetes 1964;13:27885.
14. American Diabetes Association. Standards of medical care
in diabetes2008. Diabetes Care 2008;31(suppl 1):S1254.
15. Gabbe SG, Gregory RP, Power ML, Williams SB, Schulkin J.
Management of diabetes mellitus by obstetrician-gynecolo-
gists. Obstet Gynecol 2004;103:122934.
16. Dacus JV, Meyer NL, Muram D, Stilson R, Phipps P, Sibai
BM. Gestational diabetes: postpartum glucose tolerance
testing. Am J Obstet Gynecol 1994;171:92731.
17. Almario CV, Ecker T, Moroz LA, Bucovetsky L, Berghella V,
Baxter JK. Obstetricians seldom provide postpartum dia-
betes screening for women with gestational diabetes. Am J
Obstet Gynecol 2008;198:528.e1528.e5.
18. Hunt KJ, Conway DL. Who returns for postpartum glucose
screening following gestational diabetes mellitus? Am J
Obstet Gynecol 2008;198:404.e1404.e6.
19. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF,
Lachin JM, Walker EA, et al. Reduction in the incidence of
type 2 diabetes with lifestyle intervention or metformin.
Diabetes Prevention Program Research Group. N Engl J
Med 2002;346:393403.
20. Dietz PM, Vesco KK, Callaghan WM, Bachman DJ, Bruce
FC, Berg CJ, et al. Postpartum screening for diabetes after a
gestational diabetes mellitus-affected pregnancy. Obstet
Gynecol 2008;112:86874.
21. Metzger BE, Buchanan TA, Coustan DR, de Leiva A, Dunger
DB, Hadden DR, et al. Summary and recommendations of
the Fifth International Workshop-Conference on Gesta-
tional Diabetes Mellitus [published erratum appears in
Diabetes Care 2007;30:3154]. Diabetes Care 2007;30 (suppl
2):S25160.
Copyright June 2009 by the American College of Obstetricians and
Gynecologists, 409 12th Street, SW, PO Box 96920, Washington, DC
20090-6920. All rights reserved. No part of this publication may be
reproduced, stored in a retrieval system, posted on the Internet, or
transmitted, in any form or by any means, electronic, mechanical,
photocopying, recording, or otherwise, without prior written permis-
sion from the publisher. Requests for authorization to make photo-
copies should be directed to: Copyright Clearance Center, 222
Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
ISSN 1074-861X
Postpartum screening for abnormal glucose tolerance in women who
had gestational diabetes mellitus. ACOG Committee Opinion No.
435. American College of Obstetricians and Gynecologists. Obstet
Gynecol 2009;113:141921.
583 COMMITTEE OPINIONS 583
Number 438 August 2009 (Replaces No. 282, January 2003)
ACOG COMMITTEE OPINION
Update on Immunization and Pregnancy:
Tetanus, Diphtheria, and Pertussis
Vaccination
ABSTRACT: To provide optimal protection for the pregnant woman and her neonate,
preconception immunization is preferred to vaccination during pregnancy. However,
when indicated, the benefits of immunization to the pregnant woman and her neonate
usually outweigh the theoretic risks of adverse effects. To add protection against pertus-
sis or for pregnant women who need tetanus or diphtheria protection during pregnancy,
immunization with the diphtheria and reduced tetanus toxoids and acellular pertussis
vaccine (Tdap) instead of the tetanus and diphtheria toxoids (Td) vaccine may be consid-
ered in the second or third trimester. Pregnant women (including women who are breast-
feeding) who have not received a dose of Tdap previously, should receive it after deliv-
ery and before discharge from the hospital if 2 years or more have elapsed since the
most recent Td vaccination. Current information on the safety of vaccines given during
pregnancy is frequently updated and may be verified from the Centers for Disease
Control and Prevention web site at www.cdc.gov/vaccines.
Committee on
Obstetric Practice
This document reflects
emerging clinical and sci-
entific advances as of the
date issued and is subject
to change. The informa-
tion should not be con-
strued as dictating an
exclusive course of treat-
ment or procedure to be
followed.
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Ideally, vaccinations should be administered
before conception in order to avoid unneces-
sary exposure to the fetus. Prenatal care offers
the opportunity to review immunization sta-
tus. The American College of Obstetricians
and Gynecologists recommends routine
assessment of each pregnant womans immu-
nization status and appropriate immuniza-
tion if indicated. There is no evidence of risk
from vaccinating pregnant women with an
inactivated virus or bacterial vaccines or tox-
oids, and these should be administered if
indicated. However, live vaccines do pose a
theoretic risk to the fetus and generally
should be avoided during pregnancy. The
benefits of vaccines outweigh any unproven
potential concerns about traces of thimerosal
preservative (16). When deciding whether to
immunize a pregnant woman with a vaccine
not routinely recommended in pregnancy,
the risk of exposure to disease as well as the
benefits of vaccination for reducing the dele-
terious effects on the woman and the fetus
must be balanced against unknown risks of
the vaccine. All vaccines administered should
be fully documented in the patients perma-
nent medical record (7).
Immunization guidelines are subject to
change. The most current recommendations
specifically for the immunization of pregnant
women are available at www.cdc.gov/vaccines/
pubs/preg-guide.htm (8). Tables in PDF for-
mat are available at www.cdc.gov/vaccines/
pubsflyers-brochures.htm#preg. Extensive
information for health care providers and
consumers about all vaccines can be obtained
at www.cdc.gov/vaccines. The Advisory Com-
mittee on Immunization Practices (ACIP) of
the Centers for Disease Control and Preven-
tion issues recommendations on immuniza-
tion of pregnant women that are updated
regularly and are available at www.cdc.gov/
vaccines/pubs/ACIP-list.htm
The ACIP recommendations for per-
tussis, tetanus and diphtheria vaccination
have been revised to include routine post-
partum Tdap administration if the woman
has not had Tdap in the past (see Box) (9).
The Committee on Obstetric Practice sup-
ports these recommendations, which are
COMPENDIUM OF SELECTED PUBLICATIONS 584 584
available at: http://www.cdc.gov/mmwr/pdf/rr/ rr57e0514.
pdf.
Health care providers who administer Tdap to preg-
nant women should inform the women of the potential
benefits and risks of immunization. The benefits of Tdap
are the reduced risk of contracting or transmitting tetanus,
diphtheria, and pertussis. There are few data on safety,
immunogenicity, and pregnancy outcomes. Whether
Tdap affects active immunization of the infant after birth
is unknown. Health care providers are encouraged to
report Tdap administration regardless of trimester to the
appropriate manufacturers pregnancy registry (Sanofi
Pasteur 1-800-822-2463, GlaxoSmithKline Biologicals
1-888-825-5249).
Advisory Committee on Immunization Practices
Recommendations for Prevention of Pertussis,
Tetanus, and Diphtheria Among Pregnant and
Postpartum Women and Their Infants
Listed as follows are recommendations and conclusions reported by the Advisory
Committee on Immunization Practices:
Pertussis is still endemic in the United States.
Infants less than 12 months of age suffer the majority of the morbidity and mortality
of pertussis.
Tdap was licensed in 2005 for use in persons 1164 years of age.
Tdap is a combination vaccine with tetanus toxoid, reduced diphtheria toxoid and
acellular pertussis and is given only once during a lifetime.
Immunization with Tdap should be recommended before conception if the woman
has not received Tdap, and if at least 2 years have passed since her last Td booster.
Pregnant women (including women who are breastfeeding) who have not received a
dose of Tdap previously should receive Tdap after delivery and before discharge
from the hospital if 2 years or more have elapsed since the most recent Td adminis-
tration. However, Td booster vaccination should be given during pregnancy if 10
years or more have elapsed since a previous Td booster or if booster protection
against diphtheria is needed.
To add protection against pertussis, Td vaccination during pregnancy can be
deferred and Tdap vaccination given before postpartum discharge from the hospital
in women who are likely to have sufficient tetanus and diphtheria protection until
delivery, who have not previously received Tdap and in whom it has been 2 years or
more since the most recent Td. Having standing orders at the hospital can help facil-
itate this. If Tdap cannot be administered at or before discharge, the woman should
receive the dose as soon as possible thereafter.
To add protection against pertussis or for pregnant women who need tetanus or
diphtheria protection during pregnancy, vaccination with Tdap instead of Td may be
considered in the second or third trimester unless earlier protection is needed
urgently, such as during a community pertussis outbreak
Health care providers and all household and child care provider contacts of infants
aged 12 months or younger should be vaccinated with Tdap.
Advisory Committee on Immunization Practices describes contraindications and pre-
cautions for individuals with a history of adverse reaction after previous doses of
vaccines containing tetanus and diphtheria toxoids.
Tdap is not the same as pediatric vaccines DTP or DTaP (diphtheria and tetanus
toxoids and acellular pertussis antigens).
Murphy TV, Slade BA, Broder KR, Kretsinger K, Tiwari T, Joyce PM, et al. Prevention of pertussis,
tetanus, and diphtheria among pregnant and postpartum women and their infants. Recommen-
dations of the Advisory Committee on Immunization Practices (ACIP). Advisory Committee on
Immunization Practices (ACIP), Centers for Disease Control and Prevention (CDC) [published erratum
appears in MMWR Morb Mortal Wkly Rep 2008;57:723]. MMWR Recomm Rep 2008;57:151.
585 COMMITTEE OPINIONS 585
Resources
Centers for Disease Control and Prevention. Vaccines
and immunizations. Available at: http://www.cdc.gov/
vaccines. Retrieved April 28, 2009.
Centers for Disease Control and Prevention. Flyers and
brochures: immunization and pregnancy. Available at:
http://www.cdc.gov/vaccines/pubs/flyers-brochures.
htm#preg. Retrieved April 28, 2009.
References
1. Thompson WW, Price C, Goodson B, Shay DK, Benson P,
Hinrichsen VL, et al. Early thimerosal exposure and neu-
ropsychological outcomes at 7 to 10 years. Vaccine Safety
Datalink Team. N Engl J Med 2007;357:128192.
2. Centers for Disease Control and Prevention. Mercury and
vaccines (thimerosal). Available at: http://www.cdc.gov/
vaccinesafety/concerns/thimerosal.htm. Retrieved April 28,
2009.
3. Food and Drug Administration (US). Thimerosal in vaccines.
Available at: http://www.fda.gov/cber/vaccine/ thimerosal.
htm. Retrieved April 28, 2009.
4. Joint statement of the American Academy of Pediatrics
(AAP) and the United States Public Health Service (USPHS).
Pediatrics 1999;104:5689.
5. Thimerosal in vaccinesAn interim report to clinicians.
American Academy of Pediatrics. Committee on Infectious
Diseases and Committee on Environmental Health.
Pediatrics 1999;104:5704.
6. Zaman K, Roy E, Arifeen SE, Rahman M, Raqib R, Wilson
E, et al. Effectiveness of maternal influenza immunization
in mothers and infants [published erratum appears in N
Engl J Med 2009;360:648]. N Engl J Med 2008;359:155564.
7. Centers for Disease Control and Prevention. Epidemiology
and prevention of vaccine-preventable diseases. 10th ed.
Atlanta (GA): CDC; 2008. Available at: http://www. cdc.
gov/vaccines/pubs/pinkbook/default.htm. Retrieved April 28,
2009.
8. Centers for Disease Control and Prevention. Guidelines for
vaccinating pregnant women. Atlanta (GA): CDC; 2007.
Available at: http://www.cdc.gov/vaccines/pubs/downloads/
b_preg_guide.pdf. Retrieved April 28, 2009.
9. Murphy TV, Slade BA, Broder KR, Kretsinger K, Tiwari T,
Joyce PM, et al. Prevention of pertussis, tetanus, and diph-
theria among pregnant and postpartum women and their
infants. Recommendations of the Advisory Committee on
Immunization Practices (ACIP). Advisory Committee on
Immunization Practices (ACIP), Centers for Disease
Control and Prevention (CDC) [published erratum appears
in MMWR Morb Mortal Wkly Rep 2008;57:723]. MMWR
Recomm Rep 2008;57:151.
Copyright August 2009 by the American College of Obstetricians
and Gynecologists, 409 12th Street, SW, PO Box 96920, Washington,
DC 20090-6920. All rights reserved. No part of this publication may be
reproduced, stored in a retrieval system, posted on the Internet, or
transmitted, in any form or by any means, electronic, mechanical,
photocopying, recording, or otherwise, without prior written permis-
sion from the publisher. Requests for authorization to make photo-
copies should be directed to: Copyright Clearance Center, 222
Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
ISSN 1074-861X
Update on immunization and pregnancy: tetanus, diphtheria, and per-
tussis vaccination. ACOG Committee Opinion No. 438. American
College of Obstetricians and Gynecologists. Obstet Gynecol 2009;
114:398400.
COMPENDIUM OF SELECTED PUBLICATIONS 586 586
Number 441 September 2009
ACOG COMMITTEE OPINION
Committee on
Obstetric Practice
This document reflects
emerging clinical and sci-
entific advances as of the
date issued and is subject
to change. The information
should not be construed
as dictating an exclusive
course of treatment or pro-
cedure to be followed.
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Oral Intake During Labor
ABSTRACT: There is insufficient evidence to address the safety of any particular
fasting period for solids in obstetric patients. Expert opinion supports that patients under-
going either elective cesarean delivery or elective postpartum tubal ligation should under-
go a fasting period of 68 hours. Adherence to a predetermined fasting period before
nonelective surgical procedures (ie, cesarean delivery) is not possible. Therefore, solid
foods should be avoided in laboring patients.
Over the past 60 years, the incidence of
maternal death because of aspiration has
decreased dramatically. Contributing to this
decrease have been hospital policies and
strategies to reduce maternal gastric volume
and increase gastric pH and improvements in
obstetric anesthesia practice. This has led to
questions about the utility of very restrictive
oral intake policies in laboring patients and
calls to liberalize these policies in low-risk
patients.
There is insufficient evidence to draw
conclusions about the relationship between
fasting times for clear liquids and the risk of
emesis or reflux or both or pulmonary aspi-
ration during labor. Although there is some
disagreement, most experts agree that oral
intake of clear liquids during labor does not
increase maternal complications.
The oral intake of modest amounts of
clear liquids may be allowed for patients with
uncomplicated labor. The patient without
complications undergoing elective cesarean
delivery may have modest amounts of clear
liquids up to 2 hours before induction of
anesthesia. Examples of clear liquids include,
but are not limited to, water, fruit juices with-
out pulp, carbonated beverages, clear tea,
black coffee, and sports drinks. Particulate
containing fluids should be avoided. Patients
with risk factors for aspiration (eg, morbid
obesity, diabetes, and difficult airway), or
patients at increased risk for operative deliv-
ery may require further restrictions of oral
intake, determined on a case-by-case basis.
There is insufficient evidence to address
the safety of any particular fasting period for
solids in obstetric patients. Expert opinion
supports that patients undergoing either
elective cesarean delivery or elective postpar-
tum tubal ligation should undergo a fasting
period of 68 hours. Adherence to a prede-
termined fasting period before nonelective
surgical procedures (ie, cesarean delivery) is
not possible. Therefore, solid foods should be
avoided in laboring patients.
Resource
Practice guidelines for obstetric anesthesia: an
updated report by the American Society of
Anesthesiologists Task Force on Obstetric
Anesthesia. American Society of Anesthesiol-
ogists Task Force on Obstetric Anesthesia.
Anesthesiology2007;106:84363. Available at:
http://www.asahq.org/publicationsAndSer
vices/OBguide.pdf. Retrieved June 11, 2009.
Copyright September 2009 by the American College
of Obstetricians and Gynecologists, 409 12th Street,
SW, PO Box 96920, Washington, DC 20090-6920. All
rights reserved. No part of this publication may be
reproduced, stored in a retrieval system, posted on the
Internet, or transmitted, in any form or by any means,
electronic, mechanical, photocopying, recording, or oth-
erwise, without prior written permission from the pub-
lisher. Requests for authorization to make photocopies
should be directed to: Copyright Clearance Center, 222
Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
ISSN 1074-861X
Oral intake during labor. ACOG Committee Opinion No.
441. American College of Obstetricians and Gynecolo-
gists. Obstet Gynecol 2009;114:714.
587 COMMITTEE OPINIONS 587
Number 443 October 2009 (Replaces No. 264, December 2001)
ACOG COMMITTEE OPINION
Committee on
Obstetric Practice
This document reflects
emerging clinical and sci-
entific advances as of the
date issued and is subject
to change. The information
should not be construed
as dictating an exclusive
course of treatment or
procedure to be followed.
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Air Travel During Pregnancy
ABSTRACT: In the absence of obstetric or medical complications, pregnant women
can observe the same precautions for air travel as the general population and can fly safely.
Pregnant women should be instructed to continuously use their seat belts while seated,
as should all air travelers. Pregnant air travelers may take precautions to ease in-flight
discomfort and, although no hard evidence exists, preventive measures can be used to
minimize risks of venous thrombosis. For most air travelers, the risks to the fetus from
exposure to cosmic radiation are negligible. For pregnant aircrew members and other fre-
quent flyers, this exposure may be higher. Information is available from the FAA to esti-
mate this exposure.
Occasional air travel during pregnancy is
generally safe. Recent cohort studies suggest
no increase in adverse pregnancy outcomes
for occasional air travelers (1, 2). Most com-
mercial airlines allow pregnant women to fly
up to 36 weeks of gestation. Some restrict
pregnant women from international flights
earlier in gestation and some require docu-
mentation of gestational age. For specific air-
line requirements, women should check with
the individual carrier. Civilian and military
aircrew members who become pregnant
should check with their specific agencies for
regulations or restrictions to their flying
duties.
Air travel is not recommended at any
time during pregnancy for women who have
medical or obstetric conditions that may be
exacerbated by flight or that could require
emergency care. The duration of the flight
also should be considered when planning
travel. Pregnant women should be informed
that the most common obstetric emergencies
occur in the first and third trimesters.
In-craft environmental conditions, such
as changes in cabin pressure and low humid-
ity, coupled with the physiologic changes of
pregnancy, do result in adaptations, includ-
ing increased heart rate and blood pressure,
and a significant decrease in aerobic capacity
(3, 4). The risks associated with long hours of
air travel immobilization and low cabin
humidity, such as lower extremity edema and
venous thrombotic events, recently have been
the focus of attention for all air travelers.
Despite the lack of evidence of such events
during pregnancy, certain preventive mea-
sures can be used to minimize these risks, eg,
use of support stockings and periodic move-
ment of the lower extremities, avoidance of
restrictive clothing, occasional ambulation,
and maintenance of adequate hydration.
Because severe air turbulence cannot be
predicted and the subsequent risk for trauma
is significant should this occur, pregnant
women should be instructed to use their
seatbelts continuously while seated. The seat-
belt should be belted low on the hipbones,
between the protuberant abdomen and pelvis.
Several precautions may ease discomfort for
pregnant air travelers. For example, gas-pro-
ducing foods or drinks should be avoided
before scheduled flights because entrapped
gases expand at altitude (5). Preventive anti-
emetic medication should be considered for
women with increased nausea.
Available information suggests that noise,
vibration, and cosmic radiation present a neg-
ligible risk for the occasional pregnant air
traveler (6, 7). Both the National Council on
Radiation Protection and Measurements and
the International Commission on Radiological
Protection recommend a maximum annual
radiation exposure limit of 1 millisievert
(mSv) (100 rem) for members of the general
public and 1 mSv over the course of a
40-week pregnancy (7). Even the longest
available intercontinental flights will expose
COMPENDIUM OF SELECTED PUBLICATIONS 588 588
passengers to no more than 15% of this limit (7); there-
fore, it is unlikely that the occasional traveler will exceed
current exposure limits during pregnancy. However,
aircrew or frequent flyers may exceed these limits. The
Federal Aviation Administration and the International
Commission on Radiological Protection consider aircrew
to be occupationally exposed to ionizing radiation and
recommend that they be informed about radiation expo-
sure and health risks (8, 9). A tool to estimate an individ-
ual exposure to cosmic radiation from a specific flight is
available from the Federal Aviation Administration on its
web site (http://jag.cami.jccbi.gov/cariprofile.asp).
In the absence of a reasonable expectation for obstet-
ric or medical complications, occasional air travel is safe
for pregnant women. Women should check with specific
carriers for airline requirements.
References
1. Chibber R, Al-Sibai MH, Qahtani N. Adverse outcome of
pregnancy following air travel: a myth or a concern? Aust N
Z J Obstet Gynaecol 2006;46:248.
2. Freeman M, Ghidini A, Spong CY, Tchabo N, Bannon PZ,
Pezzullo JC. Does air travel affect pregnancy outcome? Arch
Gynecol Obstet 2004;269:2747.
3. Huch R, Baumann H, Fallenstein F, Schneider KT, Holdener F,
Huch A. Physiologic changes in pregnant women and their
fetuses during jet air travel. Am J Obstet Gynecol 1986;
154:9961000.
4. Artal R, Fortunato V, Welton A, Constantino N, Khodiguian N,
Villalobos L, et al. A comparison of cardiopulmonary adap-
tations to exercise in pregnancy at sea level and altitude.
Am J Obstet Gynecol 1995;172:11708; discussion 1178 80.
5. Bia FJ. Medical considerations for the pregnant traveler.
Infect Dis Clin North Am 1992;6:37188.
6. Morrell S, Taylor R, Lyle D. A review of health effects of air-
craft noise. Aust N Z J Public Health 1997;21:22136.
7. Barish RJ. In-flight radiation exposure during pregnancy.
Obstet Gynecol 2004;103:132630.
8. Federal Aviation Administration. In-flight radiation expo-
sure. Advisory Circular No. 120-61A Washington, DC: FAA;
2006.
9. The 2007 recommendations of the International Commis-
sion on Radiological Protection. International Commission
on Radiological Protection. IRCP Publication 103. Ann
IRCP 2007;37:(24);1332.
Copyright October 2009 by the American College of Obstetricians
and Gynecologists, 409 12th Street, SW, PO Box 96920, Washington,
DC 20090-6920. All rights reserved. No part of this publication may
be reproduced, stored in a retrieval system, posted on the Internet,
or transmitted, in any form or by any means, electronic, mechanical,
photocopying, recording, or otherwise, without prior written permis-
sion from the publisher. Requests for authorization to make photo-
copies should be directed to: Copyright Clearance Center, 222
Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
ISSN 1074-861X
Air travel during pregnancy. ACOG Committee Opinion No. 443.
American College of Obstetricians and Gynecologists. Obstet Gynecol
2009;114:9545.
589 COMMITTEE OPINIONS 589
Number 445 November 2009
ACOG COMMITTEE OPINION
Antibiotics for Preterm Labor
ABSTRACT: The utility of antibiotics to prolong pregnancy and reduce neonatal mor-
bidities in women with preterm labor and intact membranes has been evaluated in
numerous randomized clinical trials. Antibiotic use intended only for pregnancy prolonga-
tion in women with preterm labor with intact membranes does not have short-term
neonatal benefits and may be associated with long-term harm. Thus, antibiotics should
not be used for this indication in women with preterm labor and intact membranes.
Committee on
Obstetric Practice
This document reflects
emerging clinical and sci-
entific advances as of the
date issued and is subject
to change. The informa-
tion should not be con-
strued as dictating an
exclusive course of treat-
ment or procedure to be
followed.
The utility of antibiotics to prolong preg-
nancy and reduce neonatal morbidities in
women with preterm labor and intact mem-
branes has been evaluated in numerous ran-
domized clinical trials. Improved neonatal
outcomes have not been demonstrated with
such treatment, although some trials have
suggested pregnancy prolongation (1). Long-
term follow-up childhood data from these
studies have not been available until recently.
A recent multicenter, randomized, dou-
ble-masked clinical trial provided a 7-year
follow-up of a large group of patients receiv-
ing antibiotics (placebo versus oral ery-
thromycin, amoxicillinclavulanate or both)
for preterm labor with intact membranes.
From this trial, 3,196 children (71% of those
enrolled) had outcome information available
(2). Despite being comparable in acute mor-
bidities and mortality, the study groups were
significantly different on long-term follow-
up. Infants exposed prenatally to erythro-
mycin, had more functional impairment
(42.3% versus 38.3%) and mild functional
impairment(23.9% versus 21.3%) compared
with those who did not receive erythromycin.
Additionally, death or any functional
impairment (31.3% versus 28.3%) and
death or cerebral palsy (5.9% versus 4.3%)
were more common with exposure to ery-
thromycin. Cerebral palsy was more common
with exposure to erythromycin (3.3% versus
1.7%) and amoxicillinclavulanic acid (3.2%
versus 1.9%) relative to those not exposed to
these agents. All of these findings were statis-
tically significant.
Of importance, infant outcomes were
ascertained based on parental reports rather
than on individual infant assessments by
medical personnel. Of note, 64% of infants
in whom preterm labor was initially diag-
nosed were delivered at term. Further, the
previously mentioned adverse findings were
not evident in a similar follow-up evaluation
of women treated with the same antibiotics
after preterm premature rupture of the
membranes (3).
Antibiotic use intended only for preg-
nancy prolongation in women with preterm
labor with intact membranes does not have
short-term neonatal benefits and may be
associated with long-term harm. Thus,
antibiotics should not be used for this indi-
cation in women with preterm labor and
intact membranes. This recommendation is
distinct from recommendations for antibi-
otic use for preterm premature rupture of
membranes (4) and group B streptococcus
carrier status (5) (see Box 1). Given incon-
sistent childhood data regarding potential
long-term risks of erythromycin and amox-
icillinclavulanate, these agents continue to
be considered appropriate for treatment of
acute infections during pregnancy and they
should not be withheld when otherwise
indicated.
The Society for
Maternal Fetal Medicine
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
COMPENDIUM OF SELECTED PUBLICATIONS 590 590
References
1. King JF, Flenady V, Murray L. Prophylactic antibiotics for
inhibiting preterm labour with intact membranes.
Cochrane Database of Systematic Reviews 2002, Issue 4.
Art. No.: CD000246. DOI: 10.1002/14651858.CD000246.
2. Kenyon S, Pike K, Jones DR, Brocklehurst P, Marlow N, Salt
A, et al. Childhood outcomes after prescription of antibi-
otics to pregnant women with spontaneous preterm labour:
7-year follow-up of the ORACLE II trial. Lancet
2008;372:131927.
3. Kenyon S, Pike K, Jones DR, Brocklehurst P, Marlow N, Salt
A, et al. Childhood outcomes after prescription of antibi-
otics to pregnant women with preterm rupture of the mem-
branes: 7-year follow-up of the ORACLE I trial. Lancet
2008;372:13108.
4. Premature rupture of membranes. ACOG Practice Bulletin
No. 80. American College of Obstetricians and Gynecolo-
gists. Obstet Gynecol 2007;109:100719.
5. Prevention of early-onset group B streptococcal disease in
newborns. ACOG Committee Opinion No. 279. American
College of Obstetricians and Gynecologists. Obstet Gynecol
2002;100:140512.
Box 1. Recommendations for Use of
Antibiotics in Women With Preterm
Premature Rupture of Membranes and
Preterm Labor
For patients with preterm labor with intact membranes:
Use intrapartum antibiotics to prevent group B strepto-
coccal perinatal infection.
Do not use antibiotics to prolong pregnancy.
For patients with acute infections requiring antibiotic
treatment during pregnancy:
Erythromycin or amoxicillinclavulanate or both may
be given if appropriate based on known or anticipated
bacterial sensitivities to these agents.
For patients with preterm premature rupture of
membranes:
Use antibiotics to prevent group B streptococcal
perinatal infection.
Use broad-spectrum antibiotics during conservative
management to prolong pregnancy and decrease
short-term neonatal complications for preterm prema-
ture rupture of membranes remote from term.
Copyright November 2009 by the American College of Obstetricians
and Gynecologists, 409 12th Street, SW, PO Box 96920, Washington,
DC 20090-6920. All rights reserved. No part of this publication may be
reproduced, stored in a retrieval system, posted on the Internet, or
transmitted, in any form or by any means, electronic, mechanical,
photocopying, recording, or otherwise, without prior written permis-
sion from the publisher. Requests for authorization to make photo-
copies should be directed to: Copyright Clearance Center, 222
Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
ISSN 1074-861X
Antibiotics for preterm labor. Committee Opinion No. 445. American
College of Obstetricians and Gynecologists. Obstet Gynecol
2009;114:115960.
COMMITTEE OPINIONS
COMMITTEE ON PROFESSIONAL LIABILITY
COMMITTEE OPINIONS
COMMITTEE ON PROFESSIONAL LIABILITY
Disclosure and Discussion of
Adverse Events
ABSTRACT: Disclosure and discussion of adverse events in health care is desired
by patients and championed by safety experts and policy makers. Improving the disclo-
sure process through policies, programmatic training, and accessible resources will
enhance patient satisfaction, strengthen the physicianpatient relationship, and most
importantly, promote a higher quality of health care.
Committee on
Patient Safety and
Quality Improvement
Committee on
Professional Liability
This document reflects
emerging concepts on
patient safety and is sub-
ject to change. The infor-
mation should not be con-
strued as dictating an exclu-
sive course of treatment or
procedure to be followed.
Copyright October 2007
by the American College of
Obstetricians and Gynecol-
ogists, 409 12th Street, SW,
PO Box 96920, Washing-
ton, DC 20090-6920. All
rights reserved. No part of
this publication may be
reproduced, stored in a
retrieval system, posted on
the Internet, or transmitted,
in any form or by any
means, electronic, mechan-
ical, photocopying, record-
ing, or otherwise, without
prior written permission
from the publisher. Re-
quests for authorization to
make photocopies should
be directed to: Copyright
Clearance Center, 222
Rosewood Drive, Danvers,
MA 01923, (978) 750-8400.
Disclosure and discussion
of adverse events. ACOG
Committee Opinion No.
380. American College of
Obstetricians and Gynecol-
ogists. Obstet Gynecol
2007;110:9578
ISSN 1074-861X
Number 380 October 2007
ACOG COMMITTEE OPINION
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Adverse outcomes, preventable or otherwise,
are an uncomfortable reality of medical
care. The Institute of Medicine proposes a
multifaceted approach toward reducing and
managing adverse events, including the
establishment of a national focus on patient
safety, the creation of a mandatory reporting
system, raising standards and expectations
for safety improvements at the national level,
and creating safety systems in health care
organizations (1). Despite continuing efforts
to prevent their occurrence, adverse events
may happen even in the absence of medical
error. Thus, there is a need for health care
providers and institutions to understand how
to best disclose and discuss these adverse
events with patients and their families. The
American College of Obstetricians and
Gynecologists (ACOG) supports these efforts
and seeks to assist members in understand-
ing the value of disclosure and discussion in
the face of preventable and nonpreventable
adverse events and to provide guidance for
such conversations.
The call for health care organizations to
develop processes for disclosure is broad-
based. Patient advocacy groups, patient safety
experts, ethicists, policy makers, accrediting
organizations, and physician groups all advo-
cate the adoption of policies related to the
disclosure and discussion of unanticipated
adverse events. When adverse events occur,
providers should engage the patient and fam-
ily in discussions about the event(s), includ-
ing expressions of sympathy.
The Joint Commission requires that
accredited hospitals tell patients of unantic-
ipated adverse events. According to the Joint
Commission Standard RI.2.90, patients
and, when appropriate, their families are
informed about the events of care, treat-
ment, and services that have been provided.
Further, the responsible licensed indepen-
dent practitioner or his or her designee
informs the patient (and when appropriate,
the family) about those unanticipated out-
comes of care, treatment, and services (2).
Similar statements are in the ethics code of
the American Medical Association, which
states that in cases in which a patient suf-
fers significant medical complications that
may have resulted from a physicians mis-
take . . . the physician is ethically required
to inform the patient of the facts neces-
sary to ensure understanding of what has
occurred(3).
It is important to remember the differ-
ence between expressions of sympathy
(acknowledgement of suffering) and apology
(accountability for suffering). Expressions of
sympathy are always appropriate. The appro-
priateness of an apology, however, will vary
from case to case. When considering whether
an apology is appropriate, the physician may
wish to seek advice from the hospitals risk
manager and the physicians liability carrier.
It is also important to be knowledgeable
about the states laws on apology and disclo-
sure because these laws vary and may have an
effect on the way in which the disclosure is
conducted.
Physicians have an ethical obligation to
communicate honestly with patients. Dis-
closing information about unanticipated
593
COMPENDIUM OF SELECTED PUBLICATIONS 594 594
adverse events likely has benefits for both parties through
a strengthened physicianpatient relationship and a pro-
motion of trust. Studies show that in the event of an
adverse outcome, patients expect and want full disclosure
of the event(s), an acknowledgement of responsibility, an
understanding of what happened, expressions of sympa-
thy, and discussion of what is being done to prevent recur-
rence(s) (4, 5). Additionally, disclosure of adverse events
can be important for the physicians personal healing.
Barriers to full disclosure are many, including shame,
lack of training in how to disclose, and fear of lawsuits (6,
7, 8). Based on surveys, it appears that patients want and
expect timely and honest disclosure of adverse events and
that patients are more likely to sue if they perceive that
such disclosure was absent (9, 10). In studies of patients
who sued their health care providers for adverse perinatal
events, 43% were driven by a suspicion of a cover-up or
by the desire for revenge (11).
Several organizations have reported on the success of
their disclosure programs. One of the oldest programs
advocating full disclosure of medical errors, the Veterans
Affairs Medical Center in Lexington, Kentucky, reported
that their facilitys liability payments were moderate and
comparable to similar institutions despite a proactive dis-
closure policy that might be anticipated to increase litiga-
tion (12). The University of Michigan Health System
reported a 50% reduction in legal fees and actions since
implementing a policy encouraging disclosure and apol-
ogy in 2001 (13, 14).
A number of health care organizations, insurance
carriers, and states have developed programs to educate
physicians about disclosure. Examples include the
University of Michigan Hospitals and Health Centers
Guidelines on How to Disclose Errors and When
Things Go Wrong: Responding to Adverse Events, a con-
sensus statement of the Harvard Hospitals (15). These
can provide valuable guidance and education about the
specifics of disclosure and apology. COPIC, a profession-
al liability carrier for academic and community physi-
cians in Colorado, provides its physicians with a training
program and ongoing support in error disclosure entitled
The 3Rs Program for Recognize, Respond, and Resolve
unanticipated medical events (16).
Health care institutions should have written policies
that address the timing, content, communication, and
documentation of disclosure. Once policies are devel-
oped, health care organizations should educate their
providers on the policies and consider the need for addi-
tional resources and training such as disclosure coaching,
mediation, and emotional support for health care work-
ers involved in harmful medical errors (7, 17). Individual
physicians and physician practice groups may contact
their local hospitals, liability carriers, specialty organiza-
tions, or medical societies for disclosure assistance train-
ing and resources available to them.
REFERENCES
1. Institute of Medicine. To err is human: building a safer
health system. Washington, DC: National Academy Press;
2000.
2. Joint Commission on Accreditation of Healthcare
Organizations. Comprehensive accreditation manual for
hospitals: CAMH. Oakbrook Terrace (IL): JCAHO; 2006.
3. American Medical Association. Code of medical ethics of
the American Medical Association: current opinions with
annotations. 20062007 ed. Chicago (IL): AMA; 2006.
4. Gallagher TH, Waterman AD, Ebers AG, Fraser VJ,
Levinson W. Patients and physicians attitudes regarding
the disclosure of medical errors. JAMA 2003;289:10017.
5. Mazor KM, Simon SR, Yood RA, Martinson BC, Gunter MJ,
Reed GW, et al. Health plan members views about disclo-
sure of medical errors. Ann Intern Med 2004;140:40918.
6. Finkelstein D, Wu AW, Holtzman NA, Smith MK. When a
physician harms a patient by a medical error: ethical, legal,
and risk-management considerations. J Clin Ethics
1997;8:330.
7. Goldberg RM, Kuhn G, Andrew LB, Thomas HA Jr. Coping
with medical mistakes and errors in judgment. Ann Emerg
Med 2002;39:28792.
8. Mello MM, Studdert DM, DesRoches CM, Peugh J, Zapert
K, Brennan TA, et al. Caring for patients in a malpractice
crisis: physician satisfaction and quality of care. Health Aff
(Millwood) 2004;23(4):4253.
9. Vincent C, Young M, Phillips A. Why do people sue doctors?
A study of patients and relatives taking legal action. Lancet
1994;343:160913.
10. Beckman HB, Markakis KM, Suchman AL, Frankel RM.
The doctorpatient relationship and malpractice. Lessons
from plaintiff depositions. Arch Intern Med 1994;154:
136570.
11. Hickson GB, Clayton EW, Githens PB, Sloan FA. Factors
that prompted families to file medical malpractice claims
following perinatal injuries. JAMA 1992;267:135963.
12. Kraman SS, Hamm G. Risk management: extreme honesty
may be the best policy. Ann Intern Med 1999;131:9637.
13. Gallagher TH, Levinson W. Disclosing harmful medical
errors to patients: a time for professional action. Arch
Intern Med 2005;165:181924.
14. Orlovsky C. Proposed legislation encourages hospital dis-
closure initiatives. Glen Carbon (IL): The Sorry Works!
Coalition; 2005. Available at: http://www.sorryworks.
net/media40.phtml. Retrieved March 5, 2007.
15. Massachusetts Coalition for the Prevention of Medical
Errors. When things go wrong: responding to adverse
events: a consensus statement of the Harvard Hospitals.
Burlington (MA): MAC; 2006. Available at: http://www.
macoalition.org/documents/respondingToAdverseEvents.
pdf. Retrieved March 5, 2007.
16. 3Rs program. Denver (CO): Copic Companies. Available at:
http://www.callcopic.com/home/what-we-offer/coveages/
medical-professional-liability-insurance-co/physicians-
medical-practices/special-programs/3rs-program.
Retrieved March 5, 2007.
17. Liebman CB, Hyman CS. A mediation skills model to man-
age disclosure of errors and adverse events to patients.
Health Aff (Millwood) 2004;23(4):2232.
595 COMMITTEE OPINIONS 595
Coping With the Stress of Medical
Professional Liability Litigation
ABSTRACT: Obstetriciangynecologists should recognize that being a defendant in
a medical professional liability lawsuit can be one of lifes most stressful experiences.
Coping with the stress of medical professional liability litigation is an ongoing, complex
process in which physicians often must struggle to regain a sense of personal identity
and professional mastery, as well as control of their clinical practices. Open communication
with family members will assist in reducing emotional isolation and self-blame; however,
legal and clinical aspects of a case must be kept confidential. Peer support and individual
professional counseling can be of great benefit. Rapid intervention facilitates healthier
coping strategies and can restore a sense of equilibrium and self-esteem during an unpre-
dictable time.
Committee on
Professional Liability
This document provides
risk management informa-
tion that is current as of
the date issued and is sub-
ject to change. This docu-
ment does not define a
standard of care nor should
it be interpreted as legal
advice.
Number 406 May 2008 (Replaces No. 309, February 2005)
ACOG COMMITTEE OPINION
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
The American College of Obstetricians and
Gynecologists (ACOG) has long been con-
cerned about the psychologic and emotional
impact of medical professional liability litiga-
tion on physicians, especially because 89.2%
of ACOG Fellows have been sued at least
once in their careers (1). Defendant physi-
cians may experience a wide range of dis-
tressing emotions and increased stress, which
can disrupt their personal lives and the lives
of their families, their relationships with
patients, and their medical practices. Because
a medical professional liability case in obstet-
rics and gynecology usually takes several
years to resolve, this stressful period can seem
interminable for all involved.
Common responses to medical liability
litigation include feelings of shock, outrage,
denial, anxiety, guilt, shame, and despair.
Coping with medical professional liability lit-
igation is an ongoing, complex process in
which physicians often must struggle to
regain a sense of personal identity and pro-
fessional mastery as well as control of their
clinical practices.
Claims managers and defense attorneys
often advise physicians not to speak to any-
one regarding any aspect of the medical lia-
bility case. Nevertheless, physicians often
need to express their emotional responses to
being sued. Literal adherence to the advice
to speak to no one can result in isolation,
increased stress, and dysfunctional behavior.
Guidance on interventions for impaired
or dysfunctional physician behavior is
addressed elsewhere (2). Such behavior may
jeopardize family relationships and also may
affect the physicians ability to function pro-
fessionally and to represent himself or herself
appropriately and effectively during a trial.
Therefore, the physician is encouraged to
inform family members of the lawsuit, the
allegations, the potential for publicity, and
any expected testimony, while maintaining
confidentiality. Children should be told
about the lawsuit and their questions honest-
ly answered, commensurate with their age
and ability to understand the information.
Open communication with family members
will assist in reducing emotional isolation
and self-blame (3).
Certainly, legal and clinical aspects of a
case must be kept confidential. An excep-
tion to this rule, however, might be made in
the context of professional counseling. Any
clinical aspects of a medical professional lia-
bility case that are discussed in counseling
should be disclosed within the confines of a
formal counselorpatient relationship to
ensure the confidentiality privilege. State laws
determine whether confidentiality can be
maintained if the counselor is other than a
COMPENDIUM OF SELECTED PUBLICATIONS 596 596
physician or member of the clergy. Moreover, confiden-
tiality may be lost if third parties are present.
Obstetriciangynecologists should recognize that
being a defendant in a medical professional liability law-
suit can be one of lifes most stressful experiences.
Although negative emotions in response to a lawsuit are
normal, physicians may need help from professionals or
peers to cope with this stress. Residents, as young physi-
cians in training, may be particularly vulnerable to the
psychologic and emotional upheaval that often occurs
when named in a medical liability claim. State or local
medical societies and medical liability insurance carriers
often sponsor support groups for defendant physicians
and their families. Support mechanisms for residents also
may be available through residency program directors,
department chairs, departments of risk management, or
mentors. In the absence of such services, individual pro-
fessional counseling can be of great benefit. Rapid inter-
vention facilitates healthier coping strategies and can
restore a sense of equilibrium and self-esteem during an
unpredictable time.
References
1. Wilson N, Strunk AL. Overview of the 2006 ACOG Survey
on Professional Liability. ACOG Clin Rev 2007;12(2):1,
1316.
2. American College of Obstetricians and Gynecologists.
Guidelines for womens health care: a resource manual. 3rd
ed. Washington, DC: ACOG; 2007.
3. Charles SC, Frish PR. Adverse events, stress, and litigation:
a physicians guide. New York (NY): Oxford University
Press; 2005.
Bibliography
Brazeau CM. Coping with the stress of being sued. Fam Pract
Manag 2001;8(5):414.
Charles SC. How to handle the stress of litigation. Clin Plast
Surg 1999;26:6977, vii.
Charles SC. Medical liability litigation as a disruptive life event.
Bull Am Coll Surg 2005;90(12):1723.
Hutchison JR, Hutchison S. The toughest part of being sued.
Med Econ 1995;72(23):367, 414, 48, passim.
Page L. On the defensive. A physicians confidence can shatter
in the wake of a lawsuit. Mod Healthc 2004;34:51, 54.
Physician Litigation Stress Resource Center. St. Joseph (MI):
PLSRC; 2007. Available at: http://www.physicianlitigationstress.
org. Retrieved November 14, 2007.
Settel KM. The impact of malpractice litigation on physicians.
Forum 1998;19(4):135.
Weiss GG. Youve been sued. Theres help. Med Econ 2003;
80(3):56, 5960.
Copyright May 2008 by the American College of Obstetricians and
Gynecologists, 409 12th Street, SW, PO Box 96920, Washington, DC
20090-6920. All rights reserved. No part of this publication may be
reproduced, stored in a retrieval system, posted on the Internet, or
transmitted, in any form or by any means, electronic, mechanical,
photocopying, recording, or otherwise, without prior written permis-
sion from the publisher. Requests for authorization to make photo-
copies should be directed to: Copyright Clearance Center, 222
Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
Coping with the stress of medical professional liability litigation.
ACOG Committee Opinion No. 406. American College of Obstet-
ricians and Gynecologists. Obstet Gynecol 2008;111:12578.
597 COMMITTEE OPINIONS 597
COMMITTEE OPINIONS
COMMITTEE ON PATIENT SAFETY AND
QUALITY IMPROVEMENT
598
COMMITTEE OPINIONS
COMMITTEE ON PATIENT SAFETY AND
QUALITY IMPROVEMENT
599
Committee on
Quality Improvement
and Patient Safety
Reaffirmed 2007
ACOG
Number 320, November 2005
Committee
Opinion
This document reflects emerging
concepts on patient safety and is
subject to change. The informa-
tion should not be construed as
dictating an exclusive course
of treatment or procedure to be
followed.
Copyright November 2005
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of this
publication may be reproduced,
stored in a retrieval system, or
transmitted, in any form or by any
means, electronic, mechanical,
photocopying, recording, or other-
wise, without prior written per-
mission from the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Partnering with patients to improve
safety. ACOG Committee Opinion
No. 320. American College of
Obstetricians and Gynecologists.
Obstet Gynecol 2005;106:11235.
Partnering With Patients to Improve
Safety
ABSTRACT: Actively involving patients in their care will lead to increased
patient satisfaction, increased diagnostic accuracy, enhanced adherence to
therapeutic recommendations, and ultimately, improved health quality.
Partnering with patients in the office setting by sharing information and
enhancing communication can lead to improved patient health care and
satisfaction.
The foundation for a positive physicianpatient interaction is formed by
establishing a partnership and creating a meaningful dialogue. Accom-
plishing this in a brief office visit may be challenging, but with adequate
planning these encounters can be structured in a positive way. Improving
communication with patients, listening to their concerns, and facilitating
active partnerships should be central to any patient safety strategy (1).
Involving patients in planning and delivering health services also is recom-
mended as a means of improving the quality of services (2). Additionally,
several studies indicate that physicianpatient communication problems may
account for an increase in medical professional liability actions (3, 4).
Information Sharing
Patients are responsible for providing their physicians with the information
that is necessary to reach an accurate diagnosis or treatment plan. To facili-
tate this process, patients should be encouraged to discuss the reasons for
their visits and ask questions such as, What is my primary problem? What
do I need to do? and Why is it important for me to do this?(5). In
response, physicians should actively listen to engage their patients.
Physicians also can solicit the patients concerns and opinions by asking
open-ended questions and asking patients to share key information such as
their medical history (including illnesses, immunizations, and hospitaliza-
tions), medication history (including over-the-counter [OTC] medications,
and dietary supplements), and any allergies, reactions, or sensitivities expe-
rienced after taking medication.
COMPENDIUM OF SELECTED PUBLICATIONS 600 600
Health Literacy
According to an Institute of Medicine report,nearly
half of all American adults90 million people
have difficulty understanding and acting upon health
information (6). The Institute of Medicine defines
health literacy as the degree to which individuals
have the capacity to obtain, process, and understand
basic health information and services needed to
make appropriate health decisions (6). Cultural bar-
riers also can impede physicianpatient communica-
tion. Consequently, it is important for clinicians to
use proven strategies to facilitate communication
with patients. Listed as follows are examples of use-
ful methods:
Speaking slowly and using plain, nonmedical
language
Limiting the amount of information provided
and repeating the information
Using teach-back or show-me techniques (ask-
ing the patient to repeat any instructions given)
to confirm that the patient understands
Making patients feel comfortable to ask ques-
tions (7)
Providing written materials to reinforce oral
explanations
Informed Consent
Informed consent is a process, not a form. At the end
of this process, the patient should understand her
diagnosis, recommended treatment, potential com-
plications, and treatment options. This discussion
should be documented in the medical record. It often
is helpful to invite the patient to bring a relative or a
close friend to this discussion. There are many com-
mercially available videotapes and printed materials,
including those produced by ACOG, that can rein-
forcebut not replacethis process.
Medications
Medication errors are the largest source of preventa-
ble adverse events. It is important for patients to pro-
vide their physicians with a list of the prescription
and nonprescription medications they take. When-
ever new prescriptions are given, patients should be
told why the medication is being prescribed and
given instructions for taking the medication. For
example, if a medication is to be taken three times
per day, the patient should be told what time of day
the medication should be taken, whether it should be
taken with food or without food, how much should
be taken at one time, how long the medication
should be continued, possible interactions with other
medications the patient is taking, and whether any
medications (including OTC medications), foods, or
alcohol are contraindicated while taking this med-
ication. Physicians should encourage their patients
to maintain a list of all the medications, including
herbal supplements and OTC medications, they are
taking and share the list with any other physicians
they may be seeing. Medication forms to facilitate
this process have been developed by some groups
(see Resources).
Follow-up
Physicians should develop a system to track test
results and communicate those results to patients.
Tracking strategies in the office may include log
books or computer prompts. Clinicians should
inform their patients that no news is not necessarily
good news. Patients should be given a reasonable
time frame within which they should expect to hear
about their test results, and they should be encour-
aged to call if they have not heard from the office at
the end of that period.
Conclusion
Partnering with patients to improve communication
results in increased patient satisfaction, increased
diagnostic accuracy, enhanced adherence to thera-
peutic recommendations, and improved health qual-
ity. In addition to the physician, other staff, such as
nurses and physician assistants, may play an impor-
tant role in ensuring appropriate communication.
More time may be required during the patient
encounter, but overall, these measures will save
time, improve patient safety and satisfaction, and
will be worth the additional effort.
References
1. Vincent CA, Coulter A. Patient safety: what about the
patient? Qual Saf Health Care 2002;11:7680.
2. Crawford MJ, Rutter D, Manley C, Weaver T, Bhui K,
Fulop N, et al. Systematic review of involving patients in
the planning and development of health care. BMJ 2002;
325:1263.
601 COMMITTEE OPINIONS 601
3. Hickson GB, Clayton EW, Githens PB, Sloan FA. Factors
that prompted families to file medical malpractice claims
following perinatal injuries. JAMA 1992;267:135963.
4. Hickson GB, Clayton EW, Entman SS, Miller CS,
Githens PB, Whetten-Goldstein K, et al. Obstetricians
prior malpractice experience and patients satisfaction
with care. JAMA 1994;272:15837.
5. Partnership for Clear Health Communication. Ask me 3:
good questions for your good health. Available at:
http://www.askme3.org/pdfs/Patient_Eng.pdf. Retrieved
July 29, 2005.
6. Institute of Medicine (US). Health literacy. A prescription
to end confusion. Washington, DC: National Academies
Press; 2004.
7. Weiss BD. Health literacy: a manual for clinicians.
Chicago (IL): American Medical Association; 2003.
Resources
National Patient Safety Foundation
www.npsf.org
Institute for Safe Medical Practice
www.ismp.org
COMPENDIUM OF SELECTED PUBLICATIONS 602 602
Committee on
Quality Improvement
and Patient Safety
Reaffirmed 2007
ACOG
Number 327, January 2006
Committee
Opinion
This document reflects emerging
concepts on patient safety and is
subject to change. The information
should not be construed as dictat-
ing an exclusive course of treat-
ment or procedure to be followed.
Copyright January 2006
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of this
publication may be reproduced,
stored in a retrieval system,
posted on the Internet, or trans-
mitted, in any form or by any
means, electronic, mechanical,
photocopying, recording, or other-
wise, without prior written per-
mission from the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Do not use abbreviations. ACOG
Committee Opinion No. 327. American
College of Obstetricians and Gynecol-
ogists. Obstet Gynecol 2006;107:
2134
Do Not Use Abbreviations
ABSTRACT: There are numerous abbreviations used in health care that have
several different meanings. Some of these abbreviations may be mistaken for
other abbreviations, numbers, or symbols, and these mistakes can have seri-
ous consequences. Therefore, the Joint Commission on Accreditation of
Healthcare Organizations has established an Official Do Not Use List of
abbreviations as part of its accreditation standards. It is important for obste-
triciangynecologists to consider this list when using these and other abbre-
viations in their practice settings.
In 2004, as part of its National Patient Safety Goals, the Joint Commission
on Accreditation of Healthcare Organizations (Joint Commission) added a
list of do not use abbreviations as part of Goal 2B, standardize a list of
abbreviations, acronyms and symbols that are not to be used throughout the
organization. This list has subsequently been reaffirmed by the Joint
Commission (Table 1).
The list is used for accreditation purposes in all clinical settings. The
scope of this list should apply to all orders, not just medication orders, and
all medication documentation, either handwritten or preprinted. The use of
abbreviations on this list remains one of the most frequent noncompliance
findings of Joint Commission surveys.
There are several other items that may possibly be added to the list,
although they are currently not considered for accreditation purposes:
The symbols > and <
All abbreviations for drug names
Apothecary units (eg, drams or grains)
The symbol @
The abbreviation cc
The abbreviation g
Because of the potential for ambiguity that might result in a medication error
and subsequent patient harm, using fewer or perhaps no abbreviations is
suggested.
603 COMMITTEE OPINIONS 603
Bibliography
Joint Commission on Accreditation of Healthcare Organiza-
tions. Facts about the official do not use list. Available at:
http://www.jcaho.org/accredited+organizations/patient+
safety/dnu_facts.htm. Retrieved September 8, 2005.
Table 1. Official Do Not Use List*
Do Not Use Potential Problem Use Instead
U (unit) Mistaken for 0 (zero), Write unit
the number 4 (four), or cc
IU (International Unit) Mistaken for IV (intravenous) Write International Unit
or the number 10 (ten)
Q.D., QD, q.d., qd (daily) Mistaken for each other Write daily
Q.O.D., QOD, q.o.d., qod Period after the Q mistaken Write every other day
(every other day) for I and the O mistaken
for I
Trailing zero (X.0 mg)
A trailing zero may be used only where required to demonstrate the level of precision of the value
being reported, such as for laboratory results, imaging studies that report size of lesions, or catheter/tube
sizes. It may not be used in medication orders or other medication-related documentation.
Joint Commission on Accreditation of Healthcare Organizations. Official do not use list. Available at:
http://www.jcaho.org/accredited+organizations/laboratory+services/npsg/06_dnu_list.pdf. Retrieved
September 8, 2005.
COMPENDIUM OF SELECTED PUBLICATIONS 604 604
Committee on
Quality Improvement
and Patient Safety
Reaffirmed 2007
ACOG
Number 328, February 2006
Committee
Opinion
This document reflects emerging
concepts on patient safety and is
subject to change. The informa-
tion should not be construed as
dictating an exclusive course of
treatment or procedure to be fol-
lowed.
Copyright February 2006
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of this
publication may be reproduced,
stored in a retrieval system, post-
ed on the Internet, or transmitted,
in any form or by any means,
electronic, mechanical, photo-
copying, recording, or otherwise,
without prior written permission
from the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Patient safety in the surgical environ-
ment. ACOG Committee Opinion No.
328. American College of
Obstetricians and Gynecologists.
Obstet Gynecol 2006;107:42933.
Patient Safety in the Surgical
Environment
ABSTRACT: Ensuring patient safety in the operating room begins before the
patient enters the operative suite and includes attention to all applicable
types of preventable medical errors (including, for example, medication
errors), but surgical errors are unique to this environment. Steps to prevent
wrong-site, wrong-person, or wrong-procedure errors have been recom-
mended. Prevention of surgical errors requires the attention of all personnel
involved in the patients care.
Potentially preventable surgical errors have received increasing attention in
recent years, although they appear to occur relatively infrequently compared
with other classes of medical errors. The Joint Commission on Accreditation
of Healthcare Organizations (JCAHO) has published two Sentinel Event
Alerts addressing wrong-site surgery, the latest in 2001. Sentinel Event Alert
24 reported 150 cases of wrong-site, wrong-person, or wrong-procedure
surgery, of which 126 had root cause analysis information (1). Wrong-site
surgery was most common during orthopedic or podiatric procedures (41%).
Although no obstetric or gynecologic cases were reported in the JCAHO
series, no surgical specialty is immune from surgical errors.
Terminology
The term wrong-site surgery often is used to refer to any surgical procedure
performed on the wrong patient, wrong body part, wrong side of the body,
or at the wrong level of the correctly identified anatomic site. The following
terms can be used to describe the various specific errors:
Wrong-side surgery indicates a surgical procedure performed on the
wrong extremity or side of the patients body (eg, the left ovary rather
than the right ovary).
Wrong-patient surgery describes a surgical procedure performed on a
different person than the one intended to receive the operation.
Wrong-level surgery and wrong-part surgery are used to indicate surgi-
cal procedures that are performed at the correct operative site, but at the
wrong level or part of the operative field or patients anatomy.
605 COMMITTEE OPINIONS 605
Systems Approach
Particularly because of the potential for serious harm
from surgical errors, vigorous efforts are required to
eliminate or reduce their frequency. Preventing this
type of error appears to be amenable to a systems
approach involving a team effort by all individuals
participating in the surgical process. Although all
members of the surgical team share in this responsi-
bility, the primary surgeon should oversee these
efforts. The Joint Commission on Accreditation of
Healthcare Organizations has identified the follow-
ing factors that may contribute to an increased risk
of wrong-site surgery:
Multiple surgeons involved in the case
Multiple procedures during a single surgical
visit
Unusual time pressures to start or complete the
procedure
Unusual physical characteristics, including mor-
bid obesity or physical deformity
A common theme in cases of wrong-site surgery
involves failed communication between the surgeon
or surgeons, the other members of the health care
team, and the patient. Communication is crucial
throughout the surgical process, particularly during
the preoperative assessment of the patient and the
procedures used to verify the operative site. Effective
preoperative patient assessment includes a review of
the medical record or imaging studies immediately
before starting surgery. To facilitate this step, all rel-
evant information sources, verified by a predeter-
mined checklist, should be available in the operating
room and rechecked by the entire surgical team
before the operation begins. Whenever possible, the
patient (or the patients designee) should be involved
in the process of identifying the correct surgical site,
both during the informed consent process and in the
physical act of marking the intended surgical site in
the preoperative area. A formal procedure for final
confirmation of the correct patient and surgical site
(a time out) that requires the participation of all
members of the surgical team may be helpful. It is
inappropriate to place total reliance on the surgeon to
identify the correct surgical site or to assume that the
surgeon should never be questioned. The risk of error
may be reduced by involving the entire surgical team
in the site verification process and encouraging any
member of that team to point out a possible error
without fear of ridicule or reprimand.
The Universal Protocol
In 2003, JCAHO published Universal Protocol for
Preventing Wrong Site, Wrong Procedure, and
Wrong Person Surgery (2). The universal protocol
is based on three levels of activity before initiation
of any surgical procedure:
1. Preoperative verification process
The health care team ensures that all relevant
documents and studies are available before the
procedure starts and that the documents have
been reviewed and are consistent with each
other, with the patients expectations, and with
the teams understanding of the intended
patient, procedure, site, and, as applicable, any
implants. The team must address missing infor-
mation or discrepancies before starting the
procedure.
2. Marking of the operative site
The health care team, including the patient (if
possible), identifies unambiguously the intend-
ed site of incision or insertion by marking all
operative sites involving laterality, multiple
structures, or multiple levels.
3. Time out before starting the procedure
The operative team conducts a final verification
of the correct patient, procedure, site, and, as
applicable, implants.
A relatively new but essential element of this
overall process is the formal enlistment of active
involvement by the patient to avert errors in the
operative arena. Involving the patient in this manner
requires personal effort by the surgeon to educate
the patient during the preoperative evaluation
process. The patient, who has the greatest stake in
avoiding errors, thus becomes integrally involved in
helping ensure that errors are avoided.
Granting Privileges for New Procedures
New techniques and new equipment are important
components for developing and delivering the best
quality care in the operating room, but they also rep-
resent sources of potential surgical error. Prudence
demands that, whenever possible, a surgeon who is
incorporating a new surgical technique should be
assisted or supervised by a colleague more experi-
enced in the technique until competency has been
satisfactorily demonstrated. In some circumstances,
COMPENDIUM OF SELECTED PUBLICATIONS 606 606
however, a technique may be so innovative that no
other surgeon at that locale has more experience. In
such situations, it may be wise to arrange for extra
support staff or surgical backup to be available
should difficulties arise. The surgeon involved
should have already documented skills and experi-
ence in the related surgical arena and should have
solicited and received the advice and support of
other experienced surgeons.
When new equipment is introduced, all mem-
bers of the surgical team must be trained on and
practice with the new equipment as appropriate for
the extent of their involvement, and all personnel
involved must be aware of all safety features, warn-
ings, and alarms of the device. Whenever possible,
the institutions medical engineering department
should inspect the equipment and verify that it is
functioning properly before the equipment is put
into clinical use. Any informational material (eg,
users manuals, operating instructions) provided by
the manufacturer of the equipment should be care-
fully reviewed by the principal users and should be
familiar to anyone using the equipment. Stickers
attached to the device or plastic cards summarizing
instructions for proper use may be helpful until
everyone involved is comfortable with the new
equipment. All necessary adaptors, attachments, and
supplies should be in the room or readily available
before beginning surgery using the new equipment.
Any recommended protective devices, such as eye
shields or special draping material, should be used
for the safety of all concerned. The lead surgeon
using the new equipment should have demonstrated
competency using the device, resulting in the
granting of privileges. Leaders of each surgically
oriented department will determine the specific
requirements for granting privileges to their mem-
bers for the use of new techniques or equipment. It
is never appropriate for nonmedical, noncreden-
tialed individuals, such as industry representatives,
to perform the actual surgery. Such individuals
should be excluded from the operating room if their
presence would present a distraction or discomfort
for any member of the essential operating room team.
Stress and Fatigue
A well-recognized source of human error is unusual
stress and fatigue. According to the Health and
Safety Laboratory, Britains leading industrial health
and safety facility and an agency of the British
Health and Safety Executive, Disrupted sleep pat-
terns and inadequate sleep can result in fatigue and
reduced levels of cognitive performance thus
increasing the risk of an accident. [H]uman error
arising from fatigue may have catastrophic results in
safety critical environments (3). Sleep deprivation
can cause errors in performing even the most famil-
iar tasks; for example, the National Traffic Safety
Administration reports that sleepy drivers cause at
least 100,000 automobile accidents annually in the
United States, resulting in approximately 40,000
injuries and 1,500 deaths (4). For this reason, many
industries have already imposed strict limitations on
working hours for individuals in vulnerable occupa-
tions, such as truck drivers, airline pilots and crew
members, air traffic controllers, and power plant
personnel. The Accreditation Council on Graduate
Medical Education (ACGME) has enacted restric-
tions on resident work hours to prevent sleep depri-
vation, stress, and fatigue that might increase the
risk of error (5, 6). Although no legal restrictions
have yet been imposed on the work hours of practic-
ing physicians, common sense dictates that the sur-
geon and the surgical team should be alert and well
rested when initiating major surgical procedures.
Emergency situations may be particularly hazardous
as an environment for error, especially if the surgi-
cal team is stressed and fatigued already. Adequate
backup personnel should be available to relieve indi-
viduals who detect diminished performance in
themselves or others due to fatigue, so that the risk
of errors is not increased.
Medication Errors
The surgical environment deserves heightened vigi-
lance to prevent medication errors because medica-
tion orders often are given verbally rather than in
writing, making such orders particularly vulnerable
to misinterpretation or misapplication. Increased
stress or confusion during urgent situations in the
operating room may increase the possibility of error
in prescribing, administering, or monitoring med-
ications. For these reasons, medication error in the
surgical arena may not be addressed by the safety
measures (eg, electronic order entry) proved effec-
tive in other environments. It may be wise for the
surgical team to agree on protocols for administer-
ing commonly used medications or treatments and
to practice their implementation. Timely and effec-
tive communication between the surgical and anes-
607 COMMITTEE OPINIONS 607
thesia teams during the entire procedure may help
avoid errors that could result from misunderstanding.
Teaching
Trainees, such as obstetricgynecologic residents,
surgical residents, anesthesiology residents, medical
students, nursing students, and operating room tech-
nician students, may be part of the surgical environ-
ment in the operating room or labor and delivery
suite. The education process in these environments
presents special challenges in protecting patient
safety. It is a fundamental principle that all trainees
must be meticulously supervised and assisted when
participating in surgery. Both the trainee and the
supervisor should be alert, well rested, and well pre-
pared in advance for the surgical procedure being
performed. Because patient safety depends on effec-
tive communication among all members of the
health care team, trainees should be conversant in
the pertinent terminology before starting the proce-
dure. The presence of noninvolved individuals as
observers in the operating room or delivery suite
may be a distraction to the surgical team and, there-
fore, should receive careful consideration before
they are admitted. The current development of virtu-
al surgery training techniques may become useful
for students to learn and practice surgical skills
before attempting procedures in the operating room.
Obstetric Surgery
Operating on pregnant patients creates unique
responsibilities in ensuring patient safety because
two or more patients are involved simultaneously
the woman and the fetus(es)each with different
needs. Adequate personnel who will ensure proper
attention to the condition of each patient must be
present. Particular attention is needed to address
administration of the different medications appropri-
ate for the pregnant patient and her fetus and the
newborn patient or patients, such as dosage and
timing of antibiotics or analgesics for mother or
newborn or both. The obstetric surgeon also is chal-
lenged to communicate with a pediatrics team in a
timely and effective manner to reduce the possibili-
ty of error in care of the neonate. The occasional use
of blood transfusion opens another potential avenue
for introduction of error because calling for the
administration of blood products may take place
under especially stressful and hectic conditions.
Much obstetric surgery is by nature unplanned as the
course of the delivery unfolds, and obstetric emer-
gencies can progress rapidly, increasing the possibil-
ity of error if protocols and standardized procedures
are skipped or abbreviated.
Freestanding Surgical Units
In recent years, many surgical procedures tradi-
tionally performed only in hospitals or similar
institutions have increasingly been performed in
physicians offices, freestanding surgical facilities,
or surgi-centers. This trend has produced cost sav-
ings and convenience for patients as well as
providers and will likely continue. However, because
these facilities may not be subject to the same level
of scrutiny or administrative oversight as hospitals,
surgeons who use these facilities must be particularly
vigilant against inadequate training of personnel,
inappropriate or poorly maintained equipment and
instruments, and ineffective protocols or practices,
all of which may increase the likelihood of medical
error and jeopardy to patient safety.
Distractions
Beepers, radios, telephone calls, and other potential
distractions in the surgical environment should be
kept to a minimum, if allowed at all, especially dur-
ing critical stages of the operation. Nonessential
conversation should be postponed until surgery is
finished. Similarly, it may be preferable to ask
nonessential personnel to remain outside the operat-
ing room while surgery is being performed.
Conclusion
Although medical errors can occur in any aspect of
medicine, the surgical environment presents addi-
tional, special challenges to safeguarding patient
safety. Because these injuries can be serious, partic-
ular care is appropriate in creating systems and rou-
tines that reduce the likelihood of wrong-patient,
wrong-side, and wrong-part surgical errors. The
wide variety of techniques, instruments, and tech-
nology used for surgical procedures makes granting
privileges of surgeons critically important.
Freestanding surgical units may need to be particu-
larly vigilant in ensuring that personnel and equip-
ment are in good condition for surgery. Protocols
and procedures to identify and manage stress and
COMPENDIUM OF SELECTED PUBLICATIONS 608 608
able at http://www.jcaho.org/accredited+organizations/
patient+safety/universal+protocol/wss_universal+
protocol.htm. Retrieved September 15, 2005.
3. Health and Safety Laboratory (UK). Case studies
fatigue and shiftwork in safety critical industries. Avail-
able at: http://www.hsl.gov.uk/case-studies/fatigue.htm.
Retrieved September 15, 2005.
4. National Highway Traffic Safety Administration. The
dangers of drowsy drivingsome startling statistics. Avail-
able at: http://www.nhtsa.dot.gov/people/injury/drowsy_
driving1/human/drows_driving. Retrieved September 15,
2005.
5. Accreditation Council for Graduate Medical Education.
Statement of justification/impact for the final approval of
common standards related to resident duty hours.
Available at: http://www.acgme.org/acwebsite/dutyhours/
dh_impactstatement.pdf. Retrieved September 15, 2005.
6. Buysse D, Barzansky B, Dinges D, Hogan E, Hunt CE,
Owens J, et al. Sleep, fatigue, and medical training: set-
ting an agenda for optimal learning and patient care. Sleep
2003;26:21825.
fatigue in surgical personnel may help to avoid sur-
gical errors and patient injuries. The operating room
is an appropriate educational environment, but the
presence of observers at any level must not be
allowed to compromise patient safety. Patient safety
in surgery demands the full attention of skilled indi-
viduals using well-functioning equipment under
adequate supervision.
References
1. A follow-up review of wrong site surgery. Joint Commis-
sion on Accreditation of Healthcare Organizations.
Sentinel Event Alert 2001;24. Available at: http://www.
jcaho.org/about+us/news+letters/sentinel+event+alert/
sea_24.htm. Retrieved September 15, 2005.
2. Joint Commission on Accreditation of Healthcare
Organizations. Universal protocol for preventing wrong
site, wrong procedure, and wrong person surgery. Avail-
609 COMMITTEE OPINIONS 609
Committee on
Quality Improvement
and Patient Safety
Reaffirmed 2007
ACOG
Number 329, March 2006
Committee
Opinion
This document reflects emerging
concepts on patient safety and is
subject to change. The informa-
tion should not be construed as
dictating an exclusive course of
treatment or procedure to be fol-
lowed.
Copyright March 2006
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of this
publication may be reproduced,
stored in a retrieval system, post-
ed on the Internet, or transmitted,
in any form or by any means,
electronic, mechanical, photo-
copying, recording, or otherwise,
without prior written permission
from the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Tracking and reminder systems.
ACOG Committee Opinion No. 329.
American College of Obstetricians
and Gynecologists. Obstet Gynecol
2006;107:745-7.
Tracking and Reminder Systems
ABSTRACT: An accurate and effective tracking or reminder system is useful
for the modern practice of obstetrics and gynecology. It is not adequate to
rely solely on the patient to complete all ordered studies and to follow up on
physician recommendations. Obstetriciangynecologists have an obligation
to their patients to encourage them to complete studies believed essential for
patient care within an acceptable time frame. Each office should establish a
simple, reliable tracking and reminder system to improve patient safety and
quality of care and to minimize missed diagnoses.
The accurate and timely flow of information between patients and clinicians
is important for safe and effective care. Patient visits often require some form
of follow-up involving further testing, referrals, communication of test
results, or consultations. Physicians offices should have procedures in place
to track these events effectively and to enhance quality of care and patient
safety. An effective and reliable reminder system need not be complex or
expensive but is a necessity for obstetric and gynecologic care in all practice
settings. Failure to follow up may cause delayed or missed diagnoses, which
may result in an adverse patient outcome and potential liability for the physi-
cian. Although it is recognized that patients have responsibility for following
through on their physicians recommendations, courts have held that the
health care professional is responsible for contacting patients about labora-
tory, imaging, or consultation results. An adequate tracking system can help
in reducing risks and providing safe, high-quality patient care. Clinicians
should recognize the potential to improve patient safety by adopting track-
ing and reminder systems.
The process for good patient follow-up begins with the practitioner
explaining to the patient at the initial visit any needed test, referral, or fol-
low-up and documenting this discussion in the chart. Clear information and
instructions will help the patient participate in her care and understand why
a test or appointment is important. The next step is logging these open items
into a tracking or reminder system promptly and reviewing them frequently
and regularly according to the offices established procedures.
An appropriate tracking system can be manual or electronic. A success-
ful system may be in the form of a log book, card files, file folders, comput-
er system, or any system accessible for ongoing updating and monitoring.
COMPENDIUM OF SELECTED PUBLICATIONS 610 610
Computerized systems can be helpful, but they also
may be expensive and time-consuming to establish
and are not necessary. In most clinical situations, a
simple paper-based tickler system can be devel-
oped. No matter what system is used, correct and
prompt data entry is a necessity.
Once information is entered into the system, it
should be retrieved and reviewed regularly with
accompanying documentation of any actions taken
or discussions with the patient. Information on each
patient should be reviewed throughout the entire
process from data input through resolution.
Allowing all personnel who participate in tracking to
provide input into the system design and implemen-
tation should encourage its use. To decrease risk of
system failure, the number of steps should be mini-
mized and the number of responsible people limited.
However, if possible, the responsibility should not
rest with only one person.
Trackable Events
Each office should prioritize items according to their
importance for tracking. As the system is tested and
improved, additional elements can be added. The
following list reflects common tracking needs for
many obstetric and gynecologic practices.
Pap test results and follow-up, need for col-
poscopy
Mammography results and necessary follow-up
All laboratory tests and radiologic studies
Pathology reports
Routine as well as special obstetric testing, such
as multiple marker studies
After-hours and on-call emergencies, including
follow-up on laboratory and radiologic studies
from the hospital and emergency department
Follow-up appointments should be scheduled.
Patients should be reminded about the importance of
keeping their postoperative visits and other follow-
up appointments. Whenever a patient does not
appear for a scheduled appointment, that fact should
be recorded in her medical record. Although patients
cannot be forced to keep their appointments, an
attempt should be made to contact them when an
appointment is missed and to assist them in resched-
uling. Each office should develop a procedure for
dealing with patients who do not appear for an
appointment after several appointments have been
made. Because different state laws apply, the proce-
dure should be appropriate to the state.
Referrals to consultants should be tracked, not-
ing whether the patient has visited with the consul-
tant and whether the consultants report has been
filed in the chart. Referrals of patients from other
clinicians also should be tracked, with notification to
the referring physician once the patient has been
seen.
Suggested Characteristics of the
Reminder System
The following characteristics are important for any
reminder system, whether electronic or paper-based.
Policies and procedures. An office policy and
procedure on tracking should be developed with
input from the staff. All office members should
agree to follow the same protocols. The office
policy should address how to contact the patient
and how to document the follow-up in the
patients chart. Usual time frames for when to
expect various types of results should be
defined, and a protocol should be established for
dealing with delayed or missing reports.
HIPAA compliance. When contacting patients,
physicians and their staff must follow Health
Insurance Portability and Accountability Act
(HIPAA) regulations. For example, postcard
reminders are not compliant. In addition, e-mail
is not HIPAA compliant unless both the office
and the patients systems are secure. Most per-
sonal e-mail services are not secure.
Specificity. The reminder system should contain
specific data and dates, including the dates for
receipt of information and timelines for notify-
ing the patient.
Central location. The reminder system should be
centrally located in the office and should not be
kept in individual patient charts. Reminders
should be accessible to the entire staff.
Reliability. The tracking system should not be
the responsibility of a single individual. It
should be updated and monitored regularly.
Office staff should be cross-trained so that the
system is reliable and efficient.
611 COMMITTEE OPINIONS 611
Sample Tracking Form
A tracking form can pinpoint key follow-up areas.
Listed as follows are the important elements to be
tracked:
Date ordered
Patient name
Identifying number
Test, procedure, consult, or referral
Date of results
Follow-up required
Evaluation completed and patient notified
All printed results, including Pap tests, mammo-
grams, consults, and pathology reports, should be
reviewed, initialed, and dated by a clinician who has
been designated to perform this function. Results
should then be filed permanently in the patient chart,
including a notation of what follow-up testing or
procedures are recommended.
The no news is good news approach is not
recommended as a standard practice for follow-up.
Patients should be made aware of the office practice
for notification of results and should be encouraged
to call back for results if they are not received in a
timely fashion. However, the office should not rely
solely on the patient to call back for results but
should have a more effective system. Computerized
tracking and reminder systems are available with
custom alerts, telephone reminders, and telephone
numbers to call for automated test results using indi-
vidual identifying numbers. Such systems are not
required for appropriate follow-up and patient noti-
fication and can be difficult, time-consuming, and
expensive to implement. Any tracking and reminder
system may seem initially to require extra time
and cost; however, use of tracking systems rapidly
becomes routine for the practice and will enhance
the quality of care, patient outcomes, and patient sat-
isfaction while helping to enhance patient safety.
Designing and implementing a tracking and
reminder system also provide an opportunity to
develop further a culture of safety in the office. A
system that is standardized, simple, and accessible
to all potential users will reduce the likelihood of
error. When problems or mistakes occur, staff should
be encouraged to report them. Errors are a valuable
way to learn why and how systems fail, and explor-
ing the causes of errors provides an opportunity to
improve those systems. Ultimately, an informed and
involved patient, a well-designed tracking system,
and clinicians and staff who feel safe to discuss sys-
tem failures will render safer patient care and
improve outcomes.
Resources
National Patient Safety Foundation
1120 MASS MoCA Way
North Adams, MA 01247
(413) 663-8900
http://www.npsf.org
Joint Commission on Accreditation of Healthcare
Organizations
One Renaissance Boulevard
Oakbrook Terrace, IL 60181
(630) 792-5000
http://www.jcaho.org/accredited+organization/patient+safety
Institute for Healthcare Improvement
20 University Road, 7th Floor
Cambridge, MA 02138
(617) 301-4800
http://www.ihi.org/ihi
Copic Companies
7351 Lowry Boulevard
Denver, CO 80230
(800) 421-1834
http://www.callcopic.com
Norcal Mutual Insurance Company
560 Davis Street
San Francisco, CA 94111
(800) 652-1051
www.norcalmutual.com
COMPENDIUM OF SELECTED PUBLICATIONS 612 612
Committee on
Quality Improvement
and Patient Safety
Reaffirmed 2007
ACOG
Number 331, April 2006
Committee
Opinion
This document reflects emerging
concepts on patient safety and is
subject to change. The information
should not be construed as dictat-
ing an exclusive course of treat-
ment or procedure to be followed.
Copyright April 2006
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of this
publication may be reproduced,
stored in a retrieval system,
posted on the Internet, or trans-
mitted, in any form or by any
means, electronic, mechanical,
photocopying, recording, or oth-
erwise, without prior written per-
mission from the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Safe use of medication. ACOG
Committee Opinion No. 331.
American College of Obstetricians
and Gynecologists. Obstet Gynecol
2006;107:96972.
Safe Use of Medication
ABSTRACT: Medication use errors are the largest single source of pre-
ventable adverse events. To minimize the risk of medication use errors, obste-
triciangynecologists should focus on several elements of medication order
writing, such as the appropriate use of decimals and zeros, standard abbre-
viations, and assuring legibility. Additionally, it is important to assist the
patient in understanding the medical condition for which a medication is
prescribed. Focusing on elements that may prevent prescription errors and
helping patients understand how to use prescribed medication properly may
help lower the occurrence of medication use errors.
Safe use of medication is a systems issue, encompassing more than written
prescriptions. Physicians have an obligation to seek improvement in medica-
tion use safety, which entails the entire process of integrating medications
into the patients clinical setting. The following definition of a medication
error demonstrates the broad areas that the clinician should consider:
A medication error is any preventable event that may cause or lead to inappropri-
ate medication use or patient harm while the medication is in the control of the
health care professional, patient, or consumer. Such events may be related to pro-
fessional practice, health care products, procedures, and systems, including pre-
scribing; order communication; product labeling, packaging, and nomenclature;
compounding; dispensing; distribution; administration; education; monitoring;
and use. (1)
Some events listed in this definition are outside the purview of the physi-
cian, such as product labeling, color of medication, and nomenclature
assigned when a drug is introduced to the public. However, errors in the pre-
scription, formulation, and administration of pharmaceutical agents are com-
mon and, in many cases, preventable causes of patient harm.
Medication Use
As part of their daily practice of medicine, clinicians should become famil-
iar with the medications that are available to treat their patients, and there are
several steps they can take to accomplish this:
Maintaining up-to-date references of current medications
Understanding the indications of the medication considered, including
all alternative therapies
613 COMMITTEE OPINIONS 613
Considering conditions that may affect the effi-
cacy of the medication, such as dosing sched-
ules, route of administration, patient weight, and
renal and hepatic functioning
Understanding the interactions of considered
agents with other medications used by the
patient as well as therapies being considered
(including surgical treatments)
Ensuring that a patients current medication is
continued, if appropriate, when admitting that
patient to the hospital and that additional medica-
tion used during the hospital stay is compatible
with the patients current therapeutic regimen.
Medication ordering errors are the leading cause
of medical errors (2). Much of the published litera-
ture regarding medical errors has focused on the
types and causes of these errors, centering on clin-
ical problems such as allergy-related contraindi-
cations that go undetected, inappropriate dosage
forms, and excessive dosing (34). Medication order-
ing errors also arise from more technical causes,
such as poorly written or misinterpreted handwritten
medication orders.
The complexity of prescribing drugs is attrib-
uted, in part, to the number of agents, which has
increased at a staggering rate. Prescription problems
such as illegible words, missing components, and
the inappropriate use of abbreviations have been
anecdotally reported for many years. The problem
has been compounded in recent years because of the
influx of new drugs with look-alike and sound-
alike names, making prescription interpretation
more difficult (5).
Medication Order Writing
Medication order writing is one aspect of medical
care that is within the control of every prescriber.
The essentials of safely writing medication orders
include focusing on certain elements of the order as
follows:
Medication order legibility
Missing medication order components
Decimals and zeros
Abbreviations
As needed (pro re nata) medication orders
Similarity of trade names
Sound-alike drugs
Verbal medication orders
Order Legibility
Computerized physician order entry systems virtually
eliminate prescription legibility concerns. However,
they are expensive and lack widespread implemen-
tation. Until computerized physician order entry sys-
tems become more widely available, prescribers
should be particularly diligent about the legibility of
their prescription orders (6).
Missing Medication Order Components
To prepare a complete, legible medication order, the
following components must be clearly written on the
medication order form:
Name of the drug
Dose to be given
Route of administration
Frequency of administration (or rate)
Reason or conditions under which the drug
should be administered (if prescribing pro re
nata)
Patients weight and age (if relevant to dosing)
If any of these components are missing, the medica-
tion order is incomplete. Filling an incomplete med-
ication order substantially increases the risk of a
medication error. The prescribers signature and
identification number also should be written or
printed on the prescription.
Decimals and Use of Leading and Trailing Zeroes
One area that contributes to medication errors is the
misuse of leading and trailing zeroes with decimal
points. The decimal point often is not seen when
the medication order is read (especially when a
copy of the order is used to fill the prescription
rather than the original medication order), potent-
ially causing a 10-fold overdose. A leading zero
should always be used when prescribing doses of
less than 1 (Fig. 1). Similarly, a whole number
should never be followed by a decimal point and a
zero (Fig. 2). A mnemonic for these constructions is,
always lead, never follow.
Inappropriate Abbreviations
In medication orders, the use of nonstandardized
abbreviations creates confusion and can contribute
to medication errors if the abbreviations are not
interpreted as they are intended by the prescriber.
Most health care institutions have standardized lists
of acceptable abbreviations. National organizations
COMPENDIUM OF SELECTED PUBLICATIONS 614 614
also have made recommendations about acceptable
abbreviations. Some organizations provide alerts
about dangerous abbreviations and other medication
safety related recommendations on their web sites
(see Resources). The following general guidelines
should be followed when using abbreviations:
Drug names should not be abbreviated.
Q.D. should not be used to abbreviate once
daily. Sometimes the dot that follows the Q
looks like an I and the abbreviation appears to
be QID. There is no safe abbreviation for once
daily; it should always be written out.
O.D. should not be used to abbreviate once
daily. O.D. is properly interpreted as right eye.
Use of this abbreviation to represent once daily
has resulted in prescription administration errors
with liquid medications such as saturated solution
of potassium. There is no safe abbreviation for
once daily; it should always be spelled out.
The metric system should be used.
The word unit should not be abbreviated. The
handwritten U or u may often look like a
0 (zero) and may cause a 10-fold overdose.
Pro Re Nata Medication Orders
When prescribing a medication, it is helpful to pro-
vide the reasons for giving the medication or para-
meters for giving a pro re nata dose. This is particu-
larly helpful in preventing errors with sound-alike
and look-alike medications or for medications that
are to be given on an as-needed basis.
Verbal Medication Orders
Verbal medication orders should be limited to urgent
situations in which written (or electronic) medica-
tion orders are not feasible. To assure accuracy,
verbal medication orders (whether in person or by
telephone) should be followed by a request that the
person receiving the order repeats the order to the
prescriber. Because many drugs have sound-alike
names, it may be helpful to include the indication
for the drug in verbal medication orders.
Patient Education
Clinicians should assist the patient in understanding
the medical condition for which a medication has
been prescribed. Engaging the patient in her own
care improves compliance, outcome, and patient sat-
isfaction and reduces error. This requires the con-
certed effort of all members of the medical team,
both in and out of the hospital. Such education may
take the form of oral communication or handouts
that explain the use, dosage, expected benefits, and
possible side effects of the medication that is pre-
Fig. 1
1 mg
Correct
Fig. 2
0.1 mg
Correct
1.0 mg
Incorrect
.1 mg
Incorrect
615 COMMITTEE OPINIONS 615
scribed. Patients should be given ample opportunity
to ask questions and reiterate, to the clinicians satis-
faction, their understanding of proper use of their
medications. Allergies should be well documented
and reviewed with the patient. A list of other medica-
tions currently in use by the patient should be docu-
mented, and the patient should retain a copy of this
list for personal benefit and to show to other
providers in the future. Including family members
who will assist the patient in medication use in such
education will help assure accurate use of the pre-
scribed medication.
Conclusion
All physicians feel a strong sense of urgency to
reduce the medical errors that occur as a result of
their care. Because obstetricians often deal with both
the pregnant woman and her fetus, they have a mea-
surably increased need to vigilantly protect their
patients. Following these suggestions will not only
reduce errors but, more importantly, will create the
awareness necessary to provide care more safely.
The Committee on Quality Improvement and Patient
Safety encourages physicians to begin examining all
aspects of patient safety, both in the hospital setting
as well as within their offices.
References
1. National Coordinating Council for Medication Error
Reporting and Prevention. About medication errors.
Available at: http://www.nccmerp.org/aboutMedErrors.
html. Retrieved January 28, 2005.
2. Thomas EJ, Studdert DM, Newhouse JP, Zbar BI, Howard
KM, Williams EJ, et al. Cost of medical injuries in Utah
and Colorado. Injury 1999;36:25564.
3. Lesar TS, Briceland L, Stein DS. Factors related to errors
in medication prescribing. JAMA 1997;277:3127.
4. Davis NM, Cohen MR, Teplitsky B. Look-alike and
sound-alike drug names: the problem and the solution.
Hosp Pharm 1992;27:95110.
5. Cabral JDY. Poor physician penmanship. JAMA 1997;278:
11167.
Resources
Institute for Safe Medication Practices
1800 Byberry Road, Suite 810
Huntingdon Valley, PA 19006
Tel: (215) 947-7707
E-mail: ismpinfo@ismp.org
Web: www.ismp.org
National Coordinating Council for Medication Error
Reporting and Prevention
Web: www.nccmerp.org
COMPENDIUM OF SELECTED PUBLICATIONS 616 616
Committee on Quality
Improvement and
Patient Safety
ACOG
Number 353, December 2006
Committee
Opinion
This document reflects emerging
concepts on patient safety and is
subject to change. The informa-
tion should not be construed as
dictating an exclusive course of
treatment or procedure to be fol-
lowed.
Copyright December 2006
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of this
publication may be reproduced,
stored in a retrieval system,
posted on the Internet, or trans-
mitted, in any form or by any
means, electronic, mechanical,
photocopying, recording, or oth-
erwise, without prior written per-
mission from the publisher.
Requests for authorization to
make photocopies should be
directed to:
Copyright Clearance Center
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Medical emergency preparedness.
ACOG Committee Opinion No. 353.
American College of Obstetricians
and Gynecologists. Obstet Gynecol
2006;108:15979.
Medical Emergency Preparedness
ABSTRACT: Patient care emergencies may occur at any time in a hospital or
an outpatient setting. To respond to these emergencies, it is important that
obstetriciangynecologists prepare themselves by assessing potential emer-
gencies that might occur, creating plans that include establishing early
warning systems, designating specialized first responders, conducting emer-
gency drills, and debriefing staff after actual events to identify what went
well and what are opportunities for improvement. Having such systems in
place may reduce or prevent the severity of medical emergencies.
A practicing obstetriciangynecologist may be faced with a sudden patient
emergency at any time. Whether it is severe shoulder dystocia, catastrophic
surgical hemorrhage, or an anaphylactic reaction to an injection in the office,
it will require prompt corrective action. Preparing for potential emergency
events requires planning for potential events, advance provisioning of
resources, establishing an early warning system, designating specialized first
responders, and holding drills to ensure that everyone knows what to do in
an emergency. Beyond these basics, certain principles of communication and
teamwork will enhance the effectiveness of the emergency response.
Planning
Planning for potential emergency events may be simple or complex. At a
minimum, it should involve an assessment of the potential or actual risks
related to the practice setting or the patient population. For instance, in the
outpatient setting, are medications given or procedures performed that may
result in anaphylaxis, airway embarrassment, or hemorrhage? In the inpa-
tient setting, unit data or risk management data may reflect common and
uncommon emergency situations that have occurred.
Advance Provision of Resources
A common practice for health-care-related emergencies is the availability of
the crash cart. All physicians should be familiar with the crash cart. By
placing all necessary items in one place, one ensures that time is not lost
gathering supplies in an emergency. Appropriate changes should be made to
617 COMMITTEE OPINIONS 617
the cart as evidence-based changes are made to the
Advanced Cardiac Life Support protocol. Advance
provision of resources also may be extended to the
management of eclampsia and malignant hyperther-
mia. Physicians in outpatient settings may wish to
create a small kit for handling allergic reactions if
they are not able to maintain a full crash cart. As with
a crash cart, the kit must be maintained regularly to
ensure supplies are not expired. All providers need to
know how to access the kit.
Early Warning Systems
Some emergencies are truly sudden and catastro-
phic, such as a ruptured aneurysm, massive pul-
monary embolus, or complete abruptio placentae in
the setting of trauma. However, many physiologic
emergencies are preceded by a period of instability
during which timely intervention may head off
ensuing disaster. The medical emergency team (dis-
cussed later) is set up to handle such emergencies.
Even without the use of a medical emergency team,
however, nurses and other bedside caregivers need
to realize that certain changes in a patients condi-
tion can indicate an emergency that requires imme-
diate intervention and correction. These changes
include some events not usually understood as
emergencies, such as agitation or new onset diffi-
culty with movement. Ideally, each service will
examine its own historical call data to determine
which events require activation of the early warning
system. It is imperative that bedside personnel be
able to request immediate help, without recrimina-
tion, when such changes occur. For example, the
nurse who calls the medical emergency team
regarding the anxious postoperative patient with
newly onset shortness of breath must not be dis-
missed as failing to recognize a panic attack but
instead thanked for following protocol. The proto-
col should provide for a full evaluation of the
problem. Some organizations have formalized the
emergency communication process with the
development of a communication tool, such as
SBAR (Situation, Background, Assessment, and
Recommendation); all providers are encouraged
to follow it to clearly communicate the patient
care issue. Standardized responses will increase
the efficiency of care and allow a continuous qual-
ity improvement process to assess the effective-
ness of the interventions.
Specialized First Responders
Medical emergency teams are designated emer-
gency response teams. Activation of the team to the
bedside occurs when predefined criteria are met,
although the team also may be activated for other
reasons. Activation should be a no-fault process.
The team is available at all times with authority to
summon further help as needed. By designating cri-
teria that define an emergency, it becomes clear
when to call for help. For example, if a maternal or
postoperative heart rate of more than 140 beats per
minute is the criterion, the nurse who notes such
heart rate must immediately call the medical emer-
gency team. This contrasts with the common prac-
tice of calling an attending physician and awaiting a
call back for orders before intervention. Activation
of the emergency response system before a full
arrest may lead to improved survival of hospitalized
patients and decreased admissions to an intensive
care unit. It is important to emphasize that if there is
a teaching service, calling the house officer does not
substitute triggering the medical emergency team.
Similarly, calling the in-house physician in a non-
teaching setting does not substitute activating the
medical emergency team. Medical emergency teams
usually have advanced practice nurses and respirato-
ry therapists as first responders and are expected to
respond to the problem in a standardized fashion.
The goal of standardized response and rapid effec-
tive recognition and correction of problems is better
met with a small stable group. Creation of medical
emergency teams is one of the patient safety initia-
tives currently being promoted by the Institute for
Healthcare Improvement and the American Medical
Association. Blueprints for setting up such a team,
as well as other resources, may be found at the web
sites of these organizations (see Resources for con-
tact information).
Emergency Drills
The principle that standardized care can result in
safer care applies to emergencies as well as to rou-
tine care. Thus, each service should consider a pro-
tocol for management of common emergencies,
such as emergency cesarean deliveries. The fields of
aviation and anesthesia both have invested heavily in
the concept of simulation training or the emergency
drill. This training may use a sophisticated simulat-
ed environment but it also may use the everyday
work space in a mock event. Protocols also can be
COMPENDIUM OF SELECTED PUBLICATIONS 618 618
reinforced by prominently displayed posters, pocket
cards, or other aids.
Using drills to train physicians to respond to
emergencies has several theoretical advantages.
Adult learning theory supports the importance of
experiential learning. Emergencies do not occur on
paper; they occur in a specific physical setting and
may involve a group of nurses, physicians, and other
health care providers attempting to respond. By con-
ducting a drill in a realistic simulator or in the actu-
al patient care setting, issues related to the physical
environment become obvious. Are the necessary
drugs readily available? Can the personnel in the
patient room easily obtain blood products or does
someone need to be designated to coordinate obtain-
ing products with the nursing station? How much
time does it actually take to get from the farthest cor-
ner of the labor suite to the delivery room?
Emergency drills also allow physicians and oth-
ers to practice principles of effective communication
in a crisis. Many aspects of the medical environment
work against effective communication, including the
often hierarchical nature of the training and work
setting and the different educational backgrounds
and levels of understanding of the care giving team.
Many physicians are accustomed to talking to
nurses. Effective teamwork requires talking with
each other. It requires that there be a team leader
coordinating the response, but it should also empow-
er all members of the team to share information. By
practicing together, barriers hindering communica-
tion and teamwork can be overcome. Effective drills
may lead to improved standardization of response,
provider satisfaction, and patient outcomes.
Conclusion
The obstetriciangynecologist practices in an envi-
ronment where true emergencies will eventually
occur. Preparation for these situations requires that
supplies and an educated team be in place before the
event. The exact nature of the preparation will
depend on the work environment and the resources
available.
Bibliography
Hamman WR. The complexity of team training: what we have
learned from aviation and its application to medicine. Qual Saf
Health Care 2004; 13(suppl):i729.
Resources
Institute for Healthcare Improvement
Establish a Rapid Response Team
20 University Road, 7th Floor
Cambridge, MA 02138
Tel: 866-787-0831
Web: http://www.ihi.org/IHI/Topics/CriticalCare/
IntensiveCare/Changes/EstablishaRapidResponse
Team.htm
American Medical Association
Advancing Quality Improvement in Patient Care
515 N. State Street
Chicago, IL 60610
Tel: 800-621-8335
Web: http://www.ama-assn.org/go/quality
MORE
OB
Managing Obstetrical Risk Efficiently
The Society of Obstetricians and Gynecologists
of Canada
780 Echo Drive
Ottawa, ON K1S 5R7
Tel: 800-561-2416
Web: www.moreob.com
619 COMMITTEE OPINIONS 619
Committee on
Patient Safety and
Quality Improvement
Reaffirmed 2009
This document reflects
emerging concepts on
patient safety and is sub-
ject to change. The infor-
mation should not be con-
strued as dictating an
exclusive course of treat-
ment or procedure to be
followed.
Number 366 May 2007
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
A growing number of organizations recognize
that disruptive behavior may compromise
patient care. Numerous reports of disruptive
physician behavior in the media and litera-
ture demonstrate its effect on patient care
and other staff. The AMA Report of the
Council on Ethical and Judicial Affairs
defines disruptive behavior as a style of
interaction...that interferes with patient
care...[and] that tends to cause distress
among other staff and affect overall morale
within the work environment, undermining
productivity and possibly leading to high
staff turnover or even resulting in ineffective
or substandard care. (1) Several types of
behavior can create distress or negatively
affect morale in the work environment.
Example behaviors include:
Profane or disrespectful language
Yelling at or insulting others
Throwing instruments, charts, or other
objects
Bullying or demeaning behavior
Criticizing other caregivers in front of
patients or other staff
Sexual comments or innuendo (2)
Yelling, insulting others, or a refusal to carry
out duties are among the most common
types of behaviors reported. The targets of
such behavior are often co-workers with less
power than the offending individual as exem-
plified by the relationships between staff
physicians and nurses, residents, or medical
students (3). A consequence of this type of
behavior is corruption of teamwork.
Best estimates suggest that a small num-
ber of physicians (35%) are responsible for
most of the reported disruptive behavior (3).
Although relatively few physicians exhibit
these behaviors, 95% of physician executives
reported knowing of disturbing, disruptive
and potentially dangerous behaviors on a
regular basis (4). A recent study concluded
that many disruptive physicians began to
show evidence of such behavior as medical
students (5), highlighting the potential
importance of recognizing behavioral pat-
terns early in career development.
Ultimately, disruptive behavior may
have a negative effect on patient safety and
quality of care by causing others to avoid the
disruptive physician. Staff may refrain from
asking for help or clarification and hesitate
to make suggestions about care to the dis-
ruptive physician. Additionally, patients who
witness the behavior may lose confidence
in the health care provider as well as the
institution.
Several factors contribute to a reluc-
tance to systematically confront disruptive
behavior, including financial concerns such
as physician referrals and fear of retribution
(eg, lawsuit for antitrust or defamation of
character) (6). Therefore, institutions should
develop a multifaceted approach for dealing
with disruptive behavior. It is essential that
administration fully support and show com-
mitment to addressing disruptive behavior.
Disruptive Behavior
ABSTRACT: Disruptive behavior may have a negative effect on patient care.
Consequently, it is important that a systematic process be in place to discourage, identi-
fy, and remedy episodes of disruptive behavior.
ACOG COMMITTEE OPINION
COMPENDIUM OF SELECTED PUBLICATIONS 620 620
An effective approach would include the following
components (2).
Establishing a Code of Conduct
Institutions should consider establishing a code of
conduct that stipulates behavioral standards and the
consequences for failure to comply. Specific examples
of unacceptable behavior should be included to provide
guidance for leadership, employees, and staff in determin-
ing what constitutes disruptive behavior. If a formal
mechanism is adopted, at appointment and reappoint-
ment, each medical staff member should acknowledge
acceptance of both the behavioral standards and the con-
sequences of failure to comply, as detailed in the code of
conduct, consistent with provisions contained in the
medical staff bylaws. A training program about the code
and attendant behavioral expectations may be included as
part of this approach.
Instituting a Monitoring and Reporting
System
A monitoring system may be considered. Systematic
review could include regular surveys of staff, focus
groups, peer and team member evaluations, and direct
observation to detect incidents of disruptive behavior (2).
Implementing a confidential system for reporting also
could include routine confidential evaluations and formal
analysis of complaints by patients, co-workers, or others.
These evaluations should be provided in a confidential
manner to the appropriate administrative individual,
such as the chair of the department of obstetrics and
gynecology or the chief of staff for resolution. The indi-
vidual in question should be notified and given an oppor-
tunity to respond to the complaint.
Resolution
Any complaints should be handled in a confidential man-
ner with interventions designed to assist in behavioral
change whenever possible. Complaint resolution should
be consistent with medical staff, departmental, or other
institutional policies and procedures. Appropriate steps
should be taken to resolve the problem. Disciplinary
actions should be appropriate to the type of infraction and
frequency of behavior, including any mitigating factors.
Each institution should establish thresholds for taking
action that depend on the severity of the behavior. Some
actions may merit zero tolerance. All attempts to address
disruptive behavior should be clearly and thoroughly doc-
umented. The department chair should be informed of
individuals with persistent problem behaviors and respon-
sible for establishing an appropriate response. The
response may include some or all of the following steps:
Face-to-face meeting with the physician exhibiting
disruptive behavior
A follow-up meeting (if the problem is still unre-
solved), resulting in a behavioral contract setting
forth any disciplinary actions that may be taken if
disruptive behavior persists
Formal counseling
Administrative hearing
Summary suspension for egregious behavior
Assessment and treatment programs that are tailored to
the individual should be made available as necessary.
Special attention should be given to the possibility of sub-
stance abuse or psychiatric diagnosis, which can con-
tribute to disruptive behavior. At least initially, these
programs should attempt to enable the individual to con-
tinue or resume practice.
Conclusion
Disruptive physician behavior creates a difficult working
environment for all staff and threatens the quality of
patient care and, ultimately, patient safety. Colleagues often
find confronting these individuals difficult. Therefore, it is
important that clear standards of behavior are established
and all staff are informed of such standards, as well as
the consequences of persistent disruptive behavior. Con-
fidential reporting systems, as well as assistance programs
for the offending physician, should be established.
References
1. American Medical Association. Physicians with disruptive
behavior. In: Code of medical ethics: current opinions and
annotations. Chicago (IL): AMA: 2006. p. 27980.
2. Porto G, Lauve R. Disruptive clinician: a persistent threat
to patient safety. Patient Saf Qual Healthc 2006;144:
10715.
3. Leape LL, Fromson JA. Problem doctors: is there a system-
level solution? Ann Intern Med 2006;144:107115.
4. Weber DO. For safetys sake disruptive behavior must be
tamed. Physician Exec 2004;30:167.
5. Papadakis MA, Teherani A, Banach MA, Knettler TR,
Rattner SL, Stern DT, et al. Disciplinary action by medical
boards and prior behavior in medical school. N Engl J Med
2005;353:267382.
6. ECRI. Disruptive practitioner behavior. HRC Risk Analysis
Supplement A. Plymouth Meeting (PA): ECRI; 2006.
Copyright May 2007 by the American College of Obstetricians and
Gynecologists, 409 12th Street, SW, PO Box 96920, Washington, DC
20090-6920. All rights reserved. No part of this publication may be
reproduced, stored in a retrieval system, posted on the Internet, or
transmitted, in any form or by any means, electronic, mechanical,
photocopying, recording, or otherwise, without prior written permis-
sion from the publisher. Requests for authorization to make photo-
copies should be directed to: Copyright Clearance Center, 222
Rosewood Drive, Danvers, MA 01923, (978) 750-8400
Disruptive behavior. ACOG Committee Opinion No. 366. American
College of Obstetricians and Gynecologists. Obstet Gynecol 2007;
109:12612.
ISSN 1074-861X
621 COMMITTEE OPINIONS 621
Communication Strategies for Patient
Handoffs
ABSTRACT: Handoff communication, which includes up-to-date information regard-
ing patient care, treatment and service, condition, and any recent or anticipated changes,
should be interactive to allow for discussion between the giver and receiver of patient
information. It requires a process for verification of the received information, including
read-back or other methods as appropriate.
Committee on
Patient Safety and
Quality Improvement
Reaffirmed 2009
This document reflects
emerging concepts on
patient safety and is sub-
ject to change. The infor-
mation should not be con-
strued as dictating an
exclusive course of treat-
ment or procedure to be
followed.
Number 367 June 2007
ACOG COMMITTEE OPINION
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Accurate communication of information
about a patient from one physician to anoth-
er is a critical element of patient care and
safety; it is also one of the least studied and
taught elements of patient care that physi-
cians use on a daily basis. In its 1999 publica-
tion, To Err is Human: Building a Safer
Health System, the Institute of Medicine
estimated that between 44,000 and 98,000
patients die each year in U.S. hospitals
because of injuries that result from errors (1).
One of the leading causes of these errors is a
breakdown in communication. Ineffective
communication was cited as the root cause of
66% of all reported sentinel events from 1995
to 2004 and accounted for 85% of sentinel
events related to maternal death and injury in
2005 (2). This breakdown in communication
may occur between health care providers at
every level of the health care system.
Physician-to-physician handoff of patient
information is one of the most important
factors to focus on to prevent discontinuity of
care, eliminate preventable errors, and pro-
vide a safer patient environment.
Communication is the process by which
information is exchanged between individu-
als, groups, and organizations. In order to be
effective, communication should be com-
plete, clear, concise, and timely. Barriers to
effective communication include factors such
as lack of time, hierarchies, defensiveness,
varying communication styles, distraction,
fatigue, conflict, and workload.
A handoff may be described as the trans-
fer of patient information and knowledge
along with authority and responsibility from
one physician or team of physicians to
another physician or provider. The Joint
Commission requires implementation of a
standardized approach to handoff communi-
cations (National Patient Safety Goal [NPSG]
2E) (3). Properly executed handoffs are inter-
active and include the opportunity for ques-
tions and answers. A handoff may occur
during the transfer of care in any of several
circumstances, including from one on-call
physician to another, from the office physi-
cian to the hospital laborist or vice versa, or
from the generalist obstetrician gynecologist
to the intensivist. It also may occur between
the attending physician and a resident or
between the attending physician and nursing
staff. Every important aspect of the patients
condition and circumstance must be accu-
rately communicated and acknowledged
from one party to the other for a safe and
effective handoff to occur. Communication at
the time of the handoff should result in a
clear understanding by each provider about
who is responsible for which aspects of the
patients care. Unacknowledged messages,
such as voice mail, do not constitute an
acceptable form of handoff.
Patient handoffs can be improved.
Addressing aspects such as physical environ-
ment, confidentiality, language, organiza-
tional culture, communication method, and
documentation are key to improving the
process.
Physical Environment
The physical environment in which the
transfer takes place may hinder effective
COMPENDIUM OF SELECTED PUBLICATIONS 622 622
communication. For example, a noisy nursing station is a
less desirable setting for communicating handoff infor-
mation than a quiet conference room located away from
other distractions. Having discussions in an environment
without distractions will enhance communication during
handoffs. Clinical acuity of the patients condition must
be considered in deciding the circumstances, the setting,
and the content of the handoff.
Confidentiality
Care must be taken to maintain patient confidentiality by
allowing only those involved with her care to hear or view
protected health care information. Physicians must be
aware of and comply with Health Insurance Portability
and Accountability Act (HIPAA) regulations.
Language
Language differences may interfere with the accurate
transfer of information. Using standardized medical ter-
minology avoids errors in communication that may
occur when colloquialisms are used. Awareness of cultur-
al and gender differences in communication style is an
important factor in how handoffs may be presented and
received.
Organizational Culture
The hierarchy of personnel, particularly in teaching set-
tings, also may inhibit the transfer of important informa-
tion about the patient. When information about the
patients care is being conveyed, a first-year resident
should be made to feel as comfortable talking with the
senior attending physician as with another resident. Every
member of the health care team that is present should be
encouraged to participate in and contribute to the trans-
fer of information without reluctance.
Communication Method
The method of communication may be a significant
barrier to the effective transfer of vital information.
Structured forms of communication, such as the Situa-
tion-Background-Assessment-Recommendation (SBAR)
technique, should be considered. Communication may be
verbal, written, or both (4). The Joint Commission NPSG
2A requires that the person receiving a verbal or phone
order or test result read back the complete order or test
result for verification (3). Verbal communication includes
a face-to-face conversation or a telephone call. Face-to-
face exchange of information is generally the preferred
form of verbal communication because it allows direct
interaction among those present. Not only may questions
be asked and answered, but further nonverbal informa-
tion may be expressed by body language and facial
expression. Written communication may assist the person
handing off the patient in organizing his or her thoughts
and presenting important details. It also allows the receiv-
ing party to have a paper- or computer-generated hard
copy of information for reference. Written communica-
tion, however, lacks the subjective interpersonal aspect of
verbal communication. The most effective handoff of
patient information includes both verbal and written
components.
Documentation
The written component of the handoff may be produced
by hand or by computer using an electronic medical
record (EMR). One of the main advantages of an EMR is
that it eliminates illegibility. Illegible handwriting has
been shown to be a major contributor to errors in patient
care. This issue is being addressed by many different
groups, including the Joint Commission. Although there
is no universally accepted protocol for all of the informa-
tion that a written handoff should contain, there are sev-
eral key elements that should be present in any transfer of
patient care. These include pertinent demographic infor-
mation, a brief history and the results of a physical exam-
ination, an active problem list, medications and allergies,
pending test results, ongoing or anticipated therapy, and
any other critical information. Such information as code
status, psychosocial status, family issues, and long-term
care issues also may be included as circumstances warrant.
Conclusion
Providing a safer health care environment for patients
must become the hallmark of future health care. By
improving the process for transferring information that
occurs during physician handoffs, the care that patients
receive will be optimized and ideally should be seamless.
Studies are currently underway to determine the most
effective methods to perform and teach the transfer of
patient information. Physicians must strive to improve
their communication skills, not only with each other, but
also when interacting with other members of the health
care team. Awareness of the importance and challenges of
effective communication and implementation of effective
communication processes, especially as it relates to hand-
offs, will decrease errors that result in adverse events and
provide a safer patient environment.
References
1. Institute of Medicine (US). To err is human: building a safer
health system. Washington, DC: The Institute; 1999.
2. Joint Commission on Accreditation of Healthcare Organ-
izations. Sentinal event statistics. Oakbrook Terrace (IL):
JCAHO; 2006. Available at: http://www.jointcommission.
org/sentinel events/statistics. Retrieved February 15, 2007.
3. Joint Commission on Accreditation of Healthcare Organ-
izations. Comprehensive accreditation manual for hospi-
tals: CAMH. Oakbrook Terrace (IL): JCAHO; 2006.
4. Institute for Healthcare Improvement. SBAR technique for
communication: a situational briefing model. Cambridge
(MA): IHI; 2006. Available at: http://www.ihi.org/IHI/
Topics/PatientSafety/SafetyGeneral/Tools/SBARTechniquef
orCommunicationASituationalBriefingModel.htm.
Retrieved February 15, 2007.
623 COMMITTEE OPINIONS 623
Additional Resources
JCAHOs 2006 National Patient Safety Goals: handoffs are
biggest challenge. Hosp Peer Rev 2005;30:8993.
Solet DJ, Norvell JM, Rutan GH, Frankel RM. Lost in translation:
challenges and opportunities in physician-to-physician commu-
nication during patient handoffs. Acad Med 2005;80:1094
Focus on five: strategies to improve hand-off communication:
implementing a process to resolve questions. Jt Comm Perspect
Pat Saf 2005;5(7):11.
Copyright June 2007 by the American College of Obstetricians and
Gynecologists, 409 12th Street, SW, PO Box 96920, Washington, DC
20090-6920. All rights reserved. No part of this publication may be
reproduced, stored in a retrieval system, posted on the Internet, or
transmitted, in any form or by any means, electronic, mechanical,
photocopying, recording, or otherwise, without prior written permis-
sion from the publisher. Requests for authorization to make photo-
copies should be directed to: Copyright Clearance Center, 222
Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
Communication strategies for patient handoffs. ACOG Committee
Opinion No. 367. American College of Obstetricians and Gynecolo-
gists. Obstet Gynecol 2007;109:15035.
ISSN 1074-861X
COMPENDIUM OF SELECTED PUBLICATIONS 624 624
Fatigue and Patient Safety
ABSTRACT: It has long been recognized that fatigue can affect human cognitive and
physical function. Although there are limited published data on the effects of fatigue on
health care providers, including full-time practicing physicians, there is increasing aware-
ness within the patient safety movement that fatigue, even partial sleep deprivation,
impairs performance. Most of the current literature reviews resident function after recent
work reform changes. However, the information available from many studies in health
care and other occupations can be applied to the work habits of practicing
obstetriciangynecologists.
Committee on
Patient Safety and
Quality Improvement
This document reflects
emerging concepts on
patient safety and is sub-
ject to change. The infor-
mation should not be con-
strued as dictating an
exclusive course of treat-
ment or procedure to be
followed.
A safe and effective health care system must
be structured to minimize error and confu-
sion. Individuals who are tired are more like-
ly to make mistakes. Reducing fatigue may
improve patient care and safety as well as
reduce the risk of adverse outcomes, improve
health care providers satisfaction, and
increase communication. One of the most
significant limitations in evaluating fatigue is
the absence of an available metric for mea-
suring accurately fatigue and its subsequent
effect on patient care.
Physicians are expected to offer safe and
effective care to their patients. Maturity as a
clinician requires recognition that medicine
is a human endeavor. As individuals develop
their clinical skills, they become aware of
their own unique strengths and weaknesses.
Professionals regularly seek consultations
when a problem exceeds their experience or
expertise. Seeking assistance when one is
fatigued is beginning to be seen in a similar
light. Fatigue may greatly affect health care
providers skills and abilities, communica-
tion, and possibly outcomes. Because of a
lack of research on the subject, there are no
current guidelines placing any limits on the
volume of deliveries and procedures per-
formed by a single individual or the length of
time one may be on call and still perform
procedures. Each physician must recognize
his or her limitations caused by fatigue that
can occur from an excessively busy practice
and impose limits. External factors not relat-
ed to the practice of medicine also must be
considered. Physicians at all stages in their
careers need to be cognizant of the demands
placed on them professionally and personal-
ly and should strive to achieve a balance that
will not lead to excessive fatigue or overcom-
mitment.
The National Sleep Foundation (www.
sleepfoundation.org) recommends 8 hours
of sleep per night for an adult (1). The aver-
age American adult sleeps only approximate-
ly 7 hours per night. Sleep deprivation can be
caused by insufficient sleep, fragmented
sleep, or both. Although there is wide varia-
tion in sleep needs, individuals do not get
accustomed to less sleep than their biologic
requirement. One cannot store up sleep.
Recovery from a period of insufficient sleep
requires at least two or three full nights of
adequate uninterrupted sleep (1).
A number of uncontrolled studies have
looked at the effect of sleep restriction on
cognitive function (24). One small study
compared reaction times and performance
on a driving simulator between residents
who had ingested alcohol but were rested and
residents who were on a call rotation every
fourth night and found a correlation.
Emergency department physicians who were
rested have been compared with others on
sequential night call. The disruption of sleep
produced by shift work had a significant
impact on both visual memory and cognitive
performance (5, 6).
Several reviews of the literature show
that even a single night of missed sleep
measurably affects cognitive performance.
When adults do not sleep at least 5 hours
per night, language and numeric skills,
retention of information, short-term mem-
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Number 398 February 2008
ACOG COMMITTEE OPINION
625 COMMITTEE OPINIONS 625
ory, and concentration all decline on standardized test-
ing. Speed of performance may be affected more than
accuracy. For example, surgeons operated more slowly
in simulated procedures when sleep deprived; emer-
gency department physicians took longer to intubate a
mannequin (710).
In other industries, fatigue often is invoked as a cause
of error and accident. The National Transportation Safety
Board rates excessive sleepiness as the second leading
cause of driving accidents in the United States (11). A
recent study by the Federal Railroad Administration
showed that human factor errors are responsible for
almost 40% of all train accidents over the past 5 years and
that fatigue played a role in approximately 25% of the
accidents (12). However, there is no clear evidence in
health care that restricting work hours improves patient
outcome. Several potential explanations for this exist. In
the residency setting, work-hour restriction often has
been achieved through a night-float system, which has
not been shown to decrease fatigue. Repeated episodes of
night work may result in accumulating sleep debt as
physicians find themselves unable to rest during the day.
Even a single night of complete sleep loss can require up
to 3 days for recovery. Thus, any resident schedule of
every fourth night or more frequent call schedules,
regardless of total hours worked, may result in reduced
acuity and function. Reduced hours may not be enough
to show reduced fatigue or improved outcomes. Further,
supervision of residents by other caregivers may intercept
incipient errors (6, 13).
The inability to document improved outcome after
residency work-hour reform does not mean that fatigue
can safely be ignored by practicing physicians. Memory
consolidation and insight formation require sleep. Sleep-
deprived adults tend to exhibit impaired complex prob-
lem solving and to continue with solutions that do not
work (14). The need for sleep, like the need for food, can
affect decision making. Fatigue may drive people to avoid
work responsibilities to address sleep deprivation. Safe
and effective care requires mindful communication
between the patient and the physician and between the
physician and other caregivers. Mood may be even more
affected by sleep deprivation than cognitive or motor per-
formance and may have a significant impact on a physi-
cians ability to communicate effectively (9).
Although the implication of the studies mentioned is
that quality of care may be enhanced by increased physi-
cian rest, there is no current evidence that proves this
premise. We should continue to study and consider the
potential benefit of limiting physician call schedules bal-
anced against loss of continuity of care.
It would be prudent to consider adapting, when fea-
sible, the following guidelines from the National Highway
Traffic Safety Administration to medical work (11):
Structure work to take advantage of circadian in-
fluences.
Recognize that the drive to sleep is very strong
between 2 AM and 9 AM, and especially between 3 AM
and 5 AM. Avoid unnecessary work at that time.
Sleep when sleepy.
Provide for backup during times impairment is likely.
After working a night shift, go immediately to sleep
to maximize sleep length.
Apply good sleep habits. The sleep environment
should be quiet and dark. It should have adequate
ventilation and a comfortable temperature to allow
daytime sleep.
Recognize behavioral changes such as irritability that
may indicate dangerous levels of fatigue.
Use naps strategically. A 2-hour nap before a night
shift will help prevent sleepiness. If a 2-hour nap can-
not be scheduled, then sleep no more than 45 min-
utes to avoid deep sleep and subsequent difficulty
with arousal.
Each practicing physician and every group should
review their work habits with these principles in mind.
Even though there may be some economic impact of
changing schedules to accommodate avoidance of fatigue,
patient care and safety must take priority over economic
concerns. A balance needs to be found between reducing
work hours and providing appropriate continuity of care
for individual patients.
Each provider should consider the following questions:
Should I work a half day or a full clinic day after a
night on call (or work at all)?
Should I perform surgery if I have been awake most
of the previous night or should the procedure be
rescheduled?
What back-up system is available if I recognize a
worrisome level of fatigue?
What adjustments should be made to my call sched-
ule to avoid a worrisome level of fatigue?
Because physicians may not easily be able to assess
the degree of their own fatigue, it also may be prudent for
groups or departments to develop processes that provide
backup care when physician fatigue may diminish the
quality of care. Physicians should consider postponing
tasks that can be performed more safely at a later time.
Departments and groups also should recognize that
fatigue may arise from obligations outside the workplace.
Some departments have systems that encourage collabo-
ration between practices when a provider has not had a
sufficient period of uninterrupted sleep.
There is no question that the human factor of fatigue
can affect performance. Because of the issues of patient
safety, fatigue should be addressed by all practitioners,
and efforts should be made to adjust workloads, work
hours, and time commitments to avoid fatigue when car-
ing for patients. Physicians should not fear economic or
other penalties for requesting assistance.
COMPENDIUM OF SELECTED PUBLICATIONS 626 626
Additional research on the effects of fatigue on expe-
rienced practicing obstetriciangynecologists is necessary
before specific national guidelines that are evidence based
can be promulgated to improve overall patient safety and
care. In the meantime, practicing physicians should eval-
uate the effects that fatigue has on their professional and
personal lives.
References
1. Malik SW, Kaplan J. Sleep deprivation. Prim Care 2005;
32:47590.
2. Arnedt JT, Owens J, Crouch M, Stahl J, Carskadon MA.
Neurobehavioral performance of residents after heavy night
call vs after alcohol ingestion. JAMA 2005;294:102533.
3. Dawson D, Reid K. Fatigue, alcohol and performance
impairment. Nature 1997;388:235.
4. Australian Transport Safety Bureau. Development of mea-
sures of fatigue: using an alcohol comparison to validate the
effects of fatigue on performance. Road Safety Research
Report CR 189. Canberra: ATSB; 2000. Available at: http://
www.atsb.gov.au/publications/2000/pdf/Fatig_Alc.pdf.
Retrieved September 4, 2007.
5. Rollinson DC, Rathlev NK, Moss M, Killiany R, Sassower
KC, Auerbach S, et al. The effects of consecutive night shifts
on neuropsychological performance of interns in the emer-
gency department: a pilot study. Ann Emerg Med 2003;
41:4006.
6. Dula DJ, Dula NL, Hamrick C, Wood GC. The effect of
working serial night shifts on the cognitive functioning of
emergency physicians. Ann Emerg Med 2001;38:1525.
7. Pilcher JJ, Huffcutt AI. Effects of sleep deprivation on per-
formance: a meta-analysis. Sleep 1996;19:31826.
8. Jha AK, Duncan BW, Bates DW. Fatigue, sleepiness, and
medical errors. In: Agency for Healthcare Research and
Quality. Making health care safer: a critical analysis of
patient safety practices. Evidence Report/Technology
Assessment No. 43. Rockville (MD): AHRQ; 2001. p.
52337. Available at: http://www.ahrq.gov/clinic/ptsafety/
chap46a.htm. Retrieved August 27, 2007.
9. Friedman WA. Resident duty hours in American neuro-
surgery. Neurosurgery 2004;54:92531; discussion 9313.
10. Smith-Coggins R, Rosekind MR, Hurd S, Buccino KR.
Relationship of day versus night sleep to physician perfor-
mance and mood. Ann Emerg Med 1994;24:92834.
11. National Transportation Safety Board. Factors that affect
fatigue in heavy truck accidents. NTSB Report No.
NTSB/SS-95/01. Washington, DC: NTSB; 1995.
12. Federal Railroad Administration. The railroad fatigue risk
management program at the federal railroad administra-
tion: past, present and future. Washington, DC: FRA; 2006.
Available at: http://www.fra.dot.gov/downloads/safety/
fatiguewhitepaper112706.pdf. Retrieved September 4, 2007.
13. Kuhn G. Circadian rhythm, shift work, and emergency
medicine. Ann Emerg Med 2001;37:8898.
14. Ellenbogen JM. Cognitive benefits of sleep and their loss
due to sleep deprivation. Neurology 2005;64:E257.
Copyright February 2008 by the American College of Obstetricians
and Gynecologists, 409 12th Street, SW, PO Box 96920,
Washington, DC 20090-6920. All rights reserved. No part of this pub-
lication may be reproduced, stored in a retrieval system, posted on
the Internet, or transmitted, in any form or by any means, electronic,
mechanical, photocopying, recording, or otherwise, without prior
written permission from the publisher. Requests for authorization to
make photocopies should be directed to: Copyright Clearance Center,
222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
Fatigue and patient safety. ACOG Committee Opinion No. 398.
American College of Obstetricians and Gynecologists. Obstet Gynecol
2008;111:4713.
ISSN 1074-861X
627 COMMITTEE OPINIONS 627
Technologic Advances to Reduce
Medication-Related Errors
ABSTRACT: The Institute of Medicine estimates that up to 7,000 individuals die
each year as a result of medication errors. Despite the significant national attention med-
ical errors are receiving, they continue to pervade the U.S. health care system.
Medication-related errors consistently rank at the top of all medical errors, accounting for
thousands of deaths annually in the United States. Many new technologies are available
that, when integrated into the various medication-related processes, can significantly
reduce the incidence of preventable medication errors. Practicing obstetriciangynecolo-
gists should be familiar with these technologies and the evidence supporting their use.
Committee on
Patient Safety and
Quality Improvement
This document reflects
emerging concepts on
patient safety and is sub-
ject to change. The infor-
mation should not be con-
strued as dictating an
exclusive course of treat-
ment or procedure to be
followed.
Number 400 March 2008
ACOG COMMITTEE OPINION
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
A report by the Institute of Medicine (IOM)
on medication-related errors suggests that
despite the attention and progress in patient
safety since the book To Err is Human:
Building a Safer Health System was published
in 2000 (1), medication-related errors consis-
tently rank at the top of all medical errors
(2). Errors are common at every step of the
medication administration process. In hospi-
tals, errors occur most frequently when med-
ication is prescribed and administered. There
is at least one medication error per hospital
patient per day (2), but not all errors result in
injury. Studies indicate, however, that
400,000 preventable drug-related injuries
occur each year in hospitals (2). It is estimat-
ed that preventable drug-related injuries in
hospitals resulted in at least $3.5 billion in
additional medical costs in 2007 (2).
Human factors inherently limit the safe-
ty of health care processes. These factors
include fatigue, inattention, memory lapse,
ignorance, failure to communicate, use of
poorly designed equipment, noisy working
conditions, and numerous other personal
and environmental factors. Leading patient
safety organizations universally have focused
on improving practices involving medication
administration and have endorsed automat-
ed systems technology to reduce harmful
medication-related errors. The Committee
on Patient Safety and Quality Improvement
considers three of these automated systems
to have potential relevance to practicing
obstetriciangynecologists: 1) computerized
physician order entry, 2) bar coding, and 3)
intravenous infusion technology; ie, smart
pumps (Table 1).
Table 1. Summary of Automated System Technologies for Medication Error Reduction
Computerized Order
Entry Bar Coding Smart Pumps
Medication Process OrderingTranscription Dispensing Administration
Affected Administration
Estimated time to 1836 months 6+ months 3+ months
implementation
Strength of supporting Good Fair Fair
evidence*
*Harris RP, Helfand M, Woolf SH, Lohr KN, Mulrow CD, Teutsch SM, et al. Current methods of the US Preventive Services Task Force:
a review of the process. Methods Work Group, Third US Preventive Services Task Force. Am J Prev Med 2001;20(suppl):2135.
COMPENDIUM OF SELECTED PUBLICATIONS 628 628
Computerized Physician Order Entry
Computerized physician order entry refers to a comput-
er-based system of ordering medications, laboratory tests,
diagnostic tests, and consultations. Practitioners directly
enter orders into a computer system that ensures stan-
dardized, legible, and complete orders. To maximize its
benefits, computerized physician order entry should be
linked to some form of a clinical decision support system.
A clinical decision support system is an active knowledge
system that uses two or more items of patient data to gen-
erate case-specific advice (3). The system typically is
designed to integrate a medical knowledge base, patient
data, and an inference engine to generate case-specific
advice. Computerized physician order entry has been
evaluated and endorsed by the IOM, Agency for
Healthcare Research and Quality, The Leapfrog Group,
National Quality Forum, Institute for Safe Medication
Practices, and the American Hospital Association (2, 4, 5).
Benefits
Computerized physician order entry is a useful tool for
preventing medication-related errors as follows:
Eliminates adverse drug events related to illegible
handwriting and decimal point errors
Improves processes when linked to a clinical decision
support system by including defaults for drug dosages,
routes, and frequencies; alerting health care profes-
sionals to drugdrug and drugallergy interactions;
screening for drug dosage according to patient age,
weight, or renal function; and reducing problems
with look-alike or sound-alike drugs, duplicate ther-
apies, and dosage calculations
Eliminates transcription errors, if implemented with
an electronic medication administration record
Standardizes care by incorporating approved order
sets that improve compliance with evidence-based
best practices
Improves efficiency of care delivery by reducing calls,
turnaround time, and data re-entry
Reduces costs by alerting physicians to charges asso-
ciated with diagnostic tests and medications
It also should be noted that although e-prescribing is
a function usually found within computerized physician
order entry systems and embedded in many, if not all,
electronic medical records, there also are freestanding e-
prescribing solutions that are very inexpensive to imple-
ment. These programs are Web accessible and can be used
with existing office computers or wireless personal digital
assistants. These systems can contribute to patient safety
by reducing the chances that illegible prescriptions or
improper unsafe dosages are accidentally written. In
addition, the direct transmission of a prescription to the
pharmacy, and the formulary checks many systems can
perform, have the potential to reduce phone calls from
pharmacists requesting clarification.
Brigham and Womens Hospital recently reported
significant return on investment with its internally devel-
oped and implemented computerized physician order
entry system. Brigham and Womens Hospital spent $11.8
million to develop, implement, and operate the system
between 1993 and 2002. Over 10 years, Brigham and
Womens Hospital saved $28.5 million, including cumu-
lative net savings of $16.7 million and net operating bud-
get savings of $9.5 million, given the institutional 80%
prospective reimbursement rate (6). Other organizations
have documented similar improvements:
In 1995, Latter Day Saints Hospital in Salt Lake City
experienced a 70% reduction in antibiotic-related
adverse drug events and drug costs with further
reductions in length of stay and overall hospital costs
after implementation of a computerized physician
order entry system with a clinical decision support
system (7).
In 2000, Ohio State University Medical Center
reported reductions in medication turnaround time
(64%), radiologic procedure completion time (43%),
and laboratory result reporting time (25%) (8).
Limitations
The computerized physician order entry system primari-
ly is beneficial during the ordering and transcription
processes. Errors still can occur if physicians override sys-
tem alerts and they can occur during the administration
steps.
Bar Coding for Medication
Administration
Bar coding refers to methods of encoding data for fast
and accurate electronic readability. Barcodes are a series
of alternating bars and spaces representing encoded
information that can be read by electronic readers. The
U.S. Food and Drug Administration (FDA) requires bar
coding on most prescription drugs, certain over-the-
counter drugs, and blood and blood components intend-
ed for transfusion.
Benefits
In order to achieve reductions in dispensing errors, all
administered medications should have bar codes. The use
of bar coding also can help prevent medication-related
medical errors in the following ways:
Adds automation to help ensure the traditional five
rights (right patient, right medication, right dosage,
right route, and right time) of medication adminis-
tration
Streamlines nurse workflow if bar coding is imple-
mented with an electronic medication administration
record. The medication record immediately is updat-
ed in the hospital information system, ensuring accu-
racy and saving nurses time in the charting process.
629 COMMITTEE OPINIONS 629
Positive outcomes have been reported from the use
of bar coding. In 1994, the medication-related error rate
was reduced by 71% at the North Colorado Medical
Center (9). In 2001, at Veterans Administrations
Colmery-ONeill Medical Center, the overall medication-
related error rate was reduced from 22 incidents per
100,000 units dispensed to 3 incidents per 100,000 units
dispensed, an 86% reduction (10).
Limitations
When the bar-code rule was fully implemented in 2006,
FDA estimated that it would help prevent nearly 500,000
adverse drug events and transfusion errors in 20 years.
The economic benefit of reducing health care costs,
patient pain and suffering, and lost work time is estimat-
ed at $93 billion over the same period (1114). However,
no national standard has been established for the medica-
tion bar-code format. It is estimated that less than 50% of
all available medications are currently bar coded at the
unit-dose level.
Intravenous Infusion Technology:
Smart Pumps
Approximately 38% of adverse drug events occur during
the administration steps with only 2% intercepted before
the event occurs (15). Advances with smart pumps now
offer programmable limits and other safety mechanisms
beyond the standard free-flow protection, which can
reduce risks of dosage errors. A smart pump is a parenter-
al infusion pump equipped with intravenous medication
error-prevention software that alerts operators or inter-
rupts the infusion process when a pump setting is pro-
grammed outside of preconfigured limits. Smart pumps
are designed to recognize prescription errors, dosage mis-
interpretations, and keypad programming errors (16, 17).
Benefits
Smart pumps have the following features that work to
reduce the rates of medication-related errors:
Smart pumps incorporate dose error reduction sys-
tems, a safety feature that warns users when a pro-
grammed dose falls outside predefined limits.
Dose limits can be set for minimal and maximal lim-
its and may be categorized as soft or hard alerts.
An event tracking log captures programming details,
and data can be exported to a spreadsheet for analy-
sis and performance improvement.
Positive outcomes have been reported with the use of
smart pumps. Pooled analysis of aggregated tracking data
from seven hospitals (average size, 350 beds) demonstrat-
ed that one potentially life-threatening intravenous med-
ication-related error was averted every 2.6 days using
smart pumps (18). At the Nebraska Medical Center, over
8 months, 157 infusions were reprogrammed; 17 infu-
sions (11%) involved potentially fatal errors (19).
Limitations
As with computerized physician order entry and bar cod-
ing, smart pumps alone will not prevent all medication-
related errors. For example, dose error reduction systems
will not detect that a wrong patient, medication, or time
has been selected unless bar-coding technology also is
incorporated.
Global Challenges
Major challenges are involved in implementing automat-
ed system technology. Listed as follows are challenges that
can significantly affect their adoption, or effectiveness, or
both:
Lack of definitive standards and clear state-of-the-art
products with responsive, intuitive user interfaces
Cost to implement
Involvement of clinicians early in system design and
integration into health care processes
Clinician resistance to change and fears regarding
loss of control over clinical care and how data will be
used
Clinician workarounds that intentionally bypass
safety features
Studies have shown that physician acceptance of a
clinical decision support system is significantly improved
if they trust the system to help them take better care of
their patients, remind them of something they may have
forgotten, or provide them with information that was
previously unavailable (20).
Conclusion
In 2001, the IOM Committee on Quality Health Care in
America indicated that Healthcare has safety and quality
problems because it relies on outmoded systems of work.
Poor designs set the workforce up to fail, regardless of
how hard they try. If we want safer, higher-quality care, we
will need to have redesigned systems of care, including the
use of information technology to support clinical and
administrative processes (21).
It is clear from review of available evidence that auto-
mated health care technologies hold perhaps the greatest
potential for dramatically reducing the incidence of harm
related to medical errors and, in particular, medication-
related errors. The evidence supporting the efficacy of
these technologies ranges from good (computerized
physician order entry systems) to fair (bar coding and
smart pumps). Equally clear is the fact that the impact of
these technologies depends on the speed with which
national standards emerge and the success with which
they are integrated into well-designed care processes.
References
1. Institute of Medicine (US). To err is human: building a safer
health system. Washington, DC: National Academies Press;
2000.
COMPENDIUM OF SELECTED PUBLICATIONS 630 630
2. Institute of Medicine (US). Preventing medication errors.
Washington, DC: National Academies Press; 2007.
3. Wyatt J, Spiegelhalter D. Field trials of medical decision-
aids: potential problems and solutions. Proc Annu Symp
Comput Appl Med Care 1991;1991:37.
4. Kaushal R, Bates DW. Computerized physician order entry
(CPOE) with clinical decision support systems (CDSSs). In:
Agency for Healthcare Research and Quality. Making health
care safer: a critical analysis of patient safety practices.
Evidence Report/Technology Assessment No. 43. Rockville
(MD): AHRQ; 2001. p. 5969.
5. National Quality Forum. Safe practices for better healthcare
2006 update: a consensus report. Washington, DC: NQF;
2006.
6. Kaushal R, Jha AK, Franz C, Glaser J, Shetty KD, Jaggi T, et
al. Return on investment for a computerized physician
order entry system. Brigham and Womens Hospital CPOE
Working Group. J Am Med Inform Assoc 2006;13:2616.
7. Evans RS, Pestotnik SL, Classen DC, Clemmer TP, Weaver
LK, Orme JF Jr, et al. A computer-assisted management
program for antibiotics and other antiinfective agents. N
Engl J Med 1998;338:2328.
8. Mekhjian HS, Kumar RR, Kuehn L, Bentley TD, Teater P,
Thomas A, et al. Immediate benefits realized following
implementation of physician order entry at an academic
medical center. J Am Med Inform Assoc 2002;9:52939.
9. Puckett F. Medication-management component of a point-
of-care information system. Am J Health Syst Pharm
1995;52:13059.
10. Johnson CL, Carlson RA, Tucker CL, Willette C. Using
BCMA software to improve patient safety in Veterans
Administration Medical Centers. J Healthc Inf Manag
2002;16:4651.
11. Bar code label requirement for human drug products and
biological products. Final rule. Food and Drug
Administration, HHS. Fed Regist 2004;69:911971.
12. Bar code label requirements. 21 CFR 201.25 (2007).
13. Bar code label requirements. 21 CFR 610.67 (2007).
14. Container label. 21 CFR 606.121 (2007).
15. Bates DW, Cullen DJ, Laird N, Petersen LA, Small SD, Servi
D, et al. Incidence of adverse drug events and potential
adverse drug events. Implications for prevention. ADE
Prevention Study Group. JAMA 1995;274:2934.
16. FAQs for the Joint Commissions 2007 national patient safe-
ty goals. (Updated 1/07). Oakbrook Terrace (IL): JC; 2007.
Available at http://www.jointcommission.org/NR/rdon-
lyres/B423198E-8EB1-468C-B01E-DBB0324B5C60/
0/07_NPSG_FAQs_3.pdf. Retrieved November 27, 2007.
17. The Joint Commission. Sentinel event statistics - June 30,
2007. Oakbrook Terrace (IL): JC; 2007. Available at:
http://www.jointcommission.org/SentinelEvents/Statistics.
Retrieved October 24, 2007.
18. Fields M, Peterman J. Intravenous medication safety system
averts high-risk medication errors and provides actionable
data. Nurs Adm Q 2005;29:7887.
19. Malashock CM, Shull SS, Gould DA. Effect of smart infu-
sion pumps on medication errors related to infusion device
programming. Hosp Pharm 2004;39:4609.
20. Sittig DF, Krall MA, Dykstra RH, Russell A, Chin HL. A sur-
vey of factors affecting clinician acceptance of clinical deci-
sion support. BMC Med Inform Decis Mak 2006;6:6.
21. Institute of Medicine (US). Crossing the quality chasm: a
new health system for the 21st century. Washington, DC:
National Academies Press; 2001.
Copyright March 2008 by the American College of Obstetricians
and Gynecologists, 409 12th Street, SW, PO Box 96920,
Washington, DC 20090-6920. All rights reserved. No part of this pub-
lication may be reproduced, stored in a retrieval system, posted on
the Internet, or transmitted, in any form or by any means, electronic,
mechanical, photocopying, recording, or otherwise, without prior
written permission from the publisher. Requests for authorization to
make photocopies should be directed to: Copyright Clearance Center,
222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
Technologic advances to reduce medication-related errors. ACOG
Committee Opinion No. 400. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2008;111:7958.
ISSN 1074-861X
631 COMMITTEE OPINIONS 631
Number 447 December 2009 (Replaces No. 286, October 2003)
ACOG COMMITTEE OPINION
Patient Safety in Obstetrics and
Gynecology
ABSTRACT: Since publication of the Institute of Medicines landmark report To Err is
Human: Building a Safer Health System, emphasis on patient safety has steadily increased.
Obstetriciangynecologists should continuously incorporate elements of patient safety into
their practices and also encourage others to use these practices.
The American College of Obstetricians and
Gynecologists (ACOG) is committed to
improving quality and safety in womens
health care. The Institute of Medicine report,
To Err Is Human: Building a Safer Health
System, notes that errors in health care are a
significant cause of death and injury (1).
Despite disagreements over the actual num-
bers cited, all health care professionals agree
that patient safety is extremely important
and should be addressed by the overall health
care system. The American College of
Obstetricians and Gynecologists continues to
emphasize its long-standing commitment
to quality and patient safety by codifying a set
of objectives that should be adopted by
obstetriciangynecologists in their practices.
Obstetriciangynecologists are encouraged
to promulgate these principles in the hospi-
tals and other settings where they practice.
Patient Safety Objectives
I. Develop a commitment to encourage a
culture of patient safety
Safety should be viewed as an essential
component of a broader commitment to
the provision of optimal health care for
women. Promoting safety requires that all
those in the health care environment rec-
ognize that the potential for errors exists
systemically. Womens health care should
be delivered in a learning environment
that encourages disclosure and exchange
of information in the event of errors, near
misses, and adverse outcomes.
A culture of safety should be the
framework for any effort to reduce
medical errors. According to the Agency
for Healthcare Research and Quality
(AHRQ), a safety culture refers to a
commitment to safety that permeates all
levels of an organization, from frontline
personnel to executive management
(2). Associated with a safety culture is the
concept of a just culture, which recog-
nizes that competent professionals make
mistakes and acknowledges that even
competent professionals may develop
unhealthy norms, such as shortcuts or
routine rule violations, but has zero
tolerance for reckless behavior (2).
Frontline personnel feel comfortable
disclosing errorsincluding their own
while maintaining professional account-
ability (2). A just culture recognizes that
some rate of human error is inevitable,
especially in complex endeavors such as
the delivery of health care. Therefore, the
first step in the delivery of safe health
care should be to identify and study the
patterns and causes of error occurrence
within delivery systems. Obstetrician
gynecologists should adopt and develop
those safe practices that reduce the likeli-
hood of system failures that can cause
adverse outcomes. Just culture also rec-
ognizes the responsibility of all health
care providers to follow these safe prac-
tices once established, and to avoid
behaviors that would be characterized as
at-risk behavior or reckless behavior.
At-risk behavior is the type of rule bend-
ing that tends to naturally occur over
time in systems where the rate of
Committee on Patient
Safety and Quality
Improvement
This document reflects
emerging concepts on
patient safety and is sub-
ject to change. The infor-
mation should not be con-
strued as dictating an
exclusive course of treat-
ment or procedure to be
followed.
The American College
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
COMPENDIUM OF SELECTED PUBLICATIONS 632 632
adverse outcomes is very low. Reckless behavior is
the type of behavior that clearly puts patients at sig-
nificant risk of harm and shows a conscious disre-
gard of unreasonable risk. In a just culture, instances
of adverse outcomes or failure to follow safety pro-
tocols are investigated fairly and openly. The general
principle when dealing with these situations is sum-
marized as console the human error; coach the at-
risk behavior; and punish the reckless behavior (3).
Institution of these principles establishes an
atmosphere where all caregivers feel safe in report-
ing errors, near misses, and at-risk behaviors by
themselves and others. This will promote and
increase error reporting and identify potentially hid-
den problems, as well as motivate health care
providers to find system problems and collaborate
to resolve system failures.
The role of leadership, whether in the inpatient
or outpatient setting, is essential in facilitating an
effective patient safety program. Strong leadership
within obstetrics and gynecology is necessary to
advocate for the provision of both financial and
human resources to achieve patient safety goals.
Efforts devoted to optimizing communication and
collaboration among the various members of the
health care team are equally important in promot-
ing these principles of patient safety.
II. Implement recommended safe medication practices
Most medical errors are caused by problems associ-
ated with the use of medications; therefore, efforts
to reduce the occurrence of these errors should be
ongoing. Although computerized physician order
entry systems can be effective in reducing prescrib-
ing errors, they are costly and may not collect data
that support quality improvement activities (4, 5).
In the absence of computerized physician order
entry systems, the following steps should be adopted
to reduce errors in prescribing and administering
medications (6):
Improve legibility of handwriting
Avoid use of nonstandard abbreviations
Check for drug allergies and sensitivities
Always use a leading 0 for doses of less than 1
unit (eg, 0.1 mg, not .1 mg), and never use a trail-
ing 0 after a decimal (eg, 1 mg, not 1.0 mg):
always lead, never follow
All verbal orders should be written down by the
individual receiving the order and read back to
the prescriber verbatim to ensure accuracy
III. Reduce the likelihood of surgical errors
Surgical errors may involve the performance of the
incorrect operation or a procedure on the wrong site
or wrong patient. Although these errors occur much
less frequently than medication errors, the conse-
quences of these errors are always significant. The
attending obstetriciangynecologist who is ulti-
mately responsible for the patients care should work
with other operating room personnel, such as nurses
and anesthesiologists, to be certain that systems are
in place to ensure proper patient and procedure
identification. The obstetriciangynecologist also
should use a preoperative verification process to
confirm, with the patient, the intended procedure to
be performed.
There are several resources available to promote
this verification process. The Joint Commission
developed the Universal Protocol and associated
Speak Up program to address this. It is designed to
ensure correct person, correct site, and correct
procedure through the elements of a preprocedure
verification process, marking the procedure site, and
performing a time-out before starting the proce-
dure. The World Health Organizations Safe Surgery
Saves Lives program, endorsed by the International
Federation of Gynecology and Obstetrics (FIGO), has
recently been shown to significantly reduce surgical
morbidity and mortality in multiple settings (7). It is
a 19-item safe surgery checklist that includes a sign-in
procedure before induction of anesthesia, a time-out
procedure before skin incision, and a sign-out proce-
dure before the patient leaves the operating room.
Universal application of these techniques should be
strongly advocated for and practiced by all obstetri-
ciangynecologists as proven methods to improve
the safety of our patients in the operating room.
IV. Improve communication with health care providers
Communication between all members of the health
care team is a crucial element in patient safety. In its
analysis of sentinel events, the Joint Commission
found that almost two thirds of the events involved
communication failure as a root cause (8). Training
in teamwork and communication techniques is
increasingly being recognized as a cornerstone of a
robust patient safety program; AHRQ developed the
TeamSTEPPS program to address this issue (9).
One key communication tool that it advocates is
SBARSituation, Background, Assessment, and
Recommendation or Request. It is a structured sys-
tem to communicate critical information clearly
and efficiently. It allows caregivers to provide infor-
mation on what is happening to the patient, what
the clinical background is, what they think the prob-
lem is, and what they would recommend or what
action is being requested. This information can then
be appropriately understood and acted upon.
A time of great potential for miscommunication
is during patient handoffs. This occurs during shift
changes for nurses, laborists, or practice partners.
The Joint Commission states: The primary objec-
633 COMMITTEE OPINIONS 633
tive of a handoff is to provide accurate information
about a patients care, treatment and services, cur-
rent condition, and any recent or anticipated
changes. The information communicated during a
handoff must be accurate to meet patient safety
goals (10). TeamSTEPPS includes a structured
technique for handoffs, which may facilitate the
transmission of clinical and patient safety informa-
tion in a way that prevents the omission of critical
aspects of the treatment plan.
An increased awareness of the importance of
clear communication between all members of the
health care team will measurably enhance the safety
of the care delivered by obstetriciangynecologists.
Training around these issues for all health care
providers is highly recommended.
V. Improve communication with patients
Communication is a core element of the physi-
cianpatient relationship and is essential for the
delivery of high quality, safe patient care. According
to the Code of Professional Ethics of the American
College of Obstetricians and Gynecologists, the
patientphysician relationship has an ethical basis
and is built on confidentiality, trust, and honesty
(11). It also states the obstetriciangynecologist
should deal honestly with patients and colleagues.
Communication should be complete, clear, concise,
and timely (12). To be prepared for occurrences of
adverse events, ACOG encourages the development
and use of written policies that address the timing,
content, communication, and documentation of
disclosure. The American College of Obstetricians
and Gynecologists believes that it is the moral oblig-
ation of every physician to communicate honestly
with patients, particularly those who experience an
adverse outcome. Open communication and trans-
parency in health care will increase trust, improve
patient satisfaction, and may decrease liability expo-
sure (13).
VI. Establish a partnership with patients to improve
safety
Patients who are involved in making their health
care decisions have better outcomes than those who
are not (14). According to the ACOG Committee
Opinion, Informed Consent, the involvement of
patients in [decisions about their own medical care]
is good for their healthnot only because it is a
protection against treatment that patients might
consider harmful, but because it contributes posi-
tively to their well-being (15). Patients should be
encouraged to ask questions about medical proce-
dures, the medications they are taking, and any
other aspect of their care. Patient education materi-
als developed by ACOG and other organizations are
available.
VII. Make safety a priority in every aspect of practice
The discipline of obstetrics and gynecology has a
long tradition of leadership in quality assessment
activities, which have been associated with an in-
crease in patient safety. The quest for patient safety
is an ongoing, continuously refined process incor-
porating information sharing and collaboration into
daily practice. Emphasizing compassion, communi-
cation, and patient-focused care will aid in creating
a culture of excellence. Opportunities to improve
patient safety should be used whenever identified.
References
1. Institute of Medicine (US). To err is human: building a safer
health system. Washington, DC: National Academy Press;
2000.
2. Agency for Healthcare Research and Quality. Patient safety
network: glossary. Available at: http://www.psnet.ahrq.gov/
glossary.aspx. Retrieved July 31, 2009.
3. Marx D. Patient safety and the just culture: a primer for
health care executives. New York (NY): Trustees of
Columbia University in the City of New York. 2001.
Available at http://www.mers-tm.org/support/Marx_Primer.
pdf. Retrieved June 29, 2009.
4. Kelly WN, Rucker TD. Compelling features of a safe
medication-use system. Am J Health Syst Pharm. 2006;
63:14618.
5. Agency for Healthcare Research and Quality. Womens
health care in the United States: selected findings from the
2004 National Healthcare Quality and Disparities Reports.
AHRQ Pub No. 05-P021. Rockville (MD): AHRQ; 2005.
Available at http://www.ahrq.gov/qual/nhqrwomen/nhqr-
women.htm. Retrieved July 30, 2009.
6. Safe use of medication. ACOG Committee Opinion No. 331.
American College of Obstetricians and Gynecologists. Obstet
Gynecol 2006;107:96972.
7. Haynes AB, Weiser TG, Berry WR, Lipsitz SR, Breizat AH,
Dellinger EP, et al. A surgical safety checklist to reduce
morbidity and mortality in a global population. Safe Surgery
Saves Lives Study Group. N Engl J Med 2009;360:4919.
8. Joint Commission. Preventing infant death and injury dur-
ing delivery. Sentinel Event Alert Issue No. 30. Oakbrook
Terrace (IL): Joint Commission; 2004. Available at:
http://www.jointcommission.org/SentinelEvents/Sentinel
EventAlert/sea_30.htm. Retrieved June 12, 2009.
9. Agency for Healthcare Research and Quality. TeamSTEPPS:
national implementation. Available at: http://teamstepps.
ahrq.gov/index.htm. Retrieved July 30, 2009.
10. Joint Commission on Accreditation of Healthcare
Organizations. Patient safety: essentials for healthcare. 4th ed.
Oakbrook Terrace (IL): Joint Commission Resources; 2006.
11. American College of Obstetricians and Gynecologists. Code
of professional ethics of the American College of Obstet-
ricians and Gynecologists. Washington, DC: ACOG; 2008.
Available at: http://www.acog.org/from_home/acogcode.pdf.
Retrieved July 30, 2009.
12. Communication strategies for patient handoffs. ACOG
Committee Opinion No. 367. American College of
COMPENDIUM OF SELECTED PUBLICATIONS 634 634
Obstetricians and Gynecologists. Obstet Gynecol 2007;109:
15035.
13. Kraman SS, Hamm G. Risk management: extreme honesty
may be the best policy. Ann Intern Med 1999;131:9637.
14. Kaplan SH, Gandek B, Greenfield S, Rogers W, Ware JE.
Patient and visit characteristics related to physicians partic-
ipatory decision-making style. Results from the Medical
Outcomes Study. Med Care 1995;33:117687.
15. Informed consent. ACOG Committee Opinion No. 439.
American College of Obstetricians and Gynecologists. Obstet
Gynecol 2009;114:4018.
Additional Resources
Agency for Healthcare Research and Quality. Medical
errors and patient safety. Available at http://www.ahrq.
gov/qual/errorsix.htm. Retrieved July 30, 2009.
Joint Commission. Universal protocol for preventing
wrong site, wrong person surgery. Oakbrook Terrace (IL):
Joint Commission; 2009. Available at http://www. joint-
commission.org/PatientSafety/UniversalProtocol.
Retrieved June 10, 2009.
National Patient Safety Foundation. 268 Summer Street,
6th Floor, Boston, MA 02210, (617) 391-9900, http://
www. npsf.org.
The Just Culture Community, 2200 W. Spring Creek
Parkway, Suite A, Plano, TX 75023, (214) 778-2010, http://
www.justculture.org.
U.S. Department of Veterans Affairs. National Center for
Patient Safety. Available at http://www.patientsafety.gov.
Retrieved July 30, 2009.
World Health Organization: Safe surgery saves lives: the
second global patient safety challenge. Geneva: WHO;
2009. Available at http://www.who.int/patientsafety/
safesurgery/en. Retrieved July 30, 2009.
Copyright December 2009 by the American College of Obstetricians
and Gynecologists, 409 12th Street, SW, PO Box 96920, Washington,
DC 20090-6920. All rights reserved. No part of this publication may be
reproduced, stored in a retrieval system, posted on the Internet, or
transmitted, in any form or by any means, electronic, mechanical,
photocopying, recording, or otherwise, without prior written permis-
sion from the publisher. Requests for authorization to make photo-
copies should be directed to: Copyright Clearance Center, 222
Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
ISSN 1074-861X
Patient safety in obstetrics and gynecology. ACOG Committee
Opinion No. 447. American College of Obstetricians and Gynecolo-
gists. Obstet Gynecol 2009;114:14247.
635 PRACTICE BULLETINS
READING THE MEDICAL LITERATURE
READING THE MEDICAL LITERATURE
Reading the
Medical
Literature
Applying Evidence to Practice
Reading the Medical Literature is designed as a resource for Fellows of the
American College of Obstetricians and Gynecologists (ACOG) and others to
offer a better understanding of evidence-based medicine, particularly as it
relates to the development of ACOGs clinical practice guidelines. As evidence-
based medicine continues to develop and to be integrated into clinical practice,
an understanding of its basic elements is critical in translating the medical lit-
erature into appropriate clinical practice. The emphasis on evidence-based
medicine has taken on new and greater importance as the environment of clin-
ical practice grows more diverse, with increased access to more information by
both physicians and patients and the changing allocation of resources.
Practice guidelines are a formal synthesis of evidence, developed according to
a rigorous research and review process. This document provides an overview
of ACOGs guideline development process, including elements of study design
that are linked to the strength of the evidence. Reading the Medical Literature
is not intended to serve as a comprehensive overview of the scientific methods
of epidemiology and study design. Rather, it is provided to serve as a readily
available introduction to and overview of the topic.
In 1995, ACOG began developing scientifically based practice guidelines,
formerly known as Practice Patterns and subsequently as Practice Bulletins.
The guidelines are derived from the best available evidence of clinical effi-
cacy and consideration of costs, with recommendations explicitly linked to
the evidence. These evidence-based practice guidelines are intended to be a
means of improving the quality of health care, decreasing its cost, and dimin-
ishing professional liability. They are proscriptive in nature and, therefore,
directive in their approach.
This document describes how ACOG Practice Committees identify, eval-
uate, and synthesize evidence from the medical literature to produce practice
guidelines. In particular, this document briefly describes various study
Developed under the direction
of the ACOG Committee on
Practice Patterns:
James R. Scott, MD, Chair
Daniel W. Cramer, MD, ScD
Herbert B. Peterson, MD
Benjamin P. Sachs, MD
Mary L. Segars Dolan, MD, MPH
Stanley Zinberg, MD
Director of Practice Activities
Nancy E. OReilly, MHS
Manager, Practice Activities
Peter J. Sebeny
Research Associate
637
COMPENDIUM OF SELECTED PUBLICATIONS 638
designs evaluated in the production of evidence-based
guidelines and the decision-making steps used to construct
evidence-based recommendations on clinical issues. Also
highlighted are potential major flaws in study design that
affect the validity and applicability of study results, as well
as the strength of the evidence. This document includes a
glossary of commonly encountered epidemiologic and bio-
statistic terms found in reports of scientific evidence, as
well as suggestions for further reading.
Selection of Topics
Topics developed into evidence-based practice guidelines
are selected based on clinical issues in obstetrics and
gynecology with unexplained variations in practice or
because there are differences between what is known sci-
entifically and what is practiced. Once a topic has been
identified, objectives of the guideline are developed and
research questions are formulated to guide the literature
search. The research questions highlight the most impor-
tant aspects of a particular clinical issue, focusing on areas
relevant to practice and useful in patient management.
Searching the Literature
In the ACOG Resource Center, medical librarians with
extensive subject expertise perform a literature search
based on the clinical questions and objectives. The search
includes a review of the MEDLINE database, the
Cochrane Library, ACOGs internal resources and docu-
ments, and other databases as appropriate. In addition,
ACOG librarians review more than 200 journals. This
process locates relevant articles from journals not indexed
in MEDLINE and those not yet indexed.
The search is limited to documents published in
English, and a specific strategy may be used to refine the
search further. This filter strategy restricts the search by
study design or publication type and is similar to the
process used by the Cochrane Library. No further screen-
ing or elimination of records is done by the librarians.
Updated searches are conducted as the topic is developed
or further revised.
Literature Analysis
After results of the literature search are compiled, the study
abstracts are reviewed to assess the relevance of each study
or report. Those articles appropriate for further critical
appraisal are obtained and subdivided according to the
research question they address. The bibliographies of these
articles are also reviewed to identify additional studies that
may not have been identified in the initial literature search.
The data in the literature are evaluated to provide
answers to the clinical questions. The articles obtained for
review are organized by study design to ascertain the pos-
sible strengths and weaknesses inherent in each study, as
well as the quality of evidence they may provide. Certain
aspects of a clinical issue may not be addressed in re-
search studies, and expert opinion may be used and iden-
tified as such.
The levels of evidence used are based on the method
used by the U.S. Preventive Services Task Force. The U.S.
Preventive Services Task Force was a 20-member panel of
scientific and medical experts charged with developing
recommendations on appropriate use of clinical interven-
tions. Their recommendations were based on a systematic
review of the evidence of clinical effectiveness.
Types of Study Designs
Intervention Studies
Level I Evidence
Commonly referred to as clinical trials, intervention stud-
ies are characterized by the investigators roles in assign-
ing subjects to exposed and nonexposed groups and
following the subjects to assess outcome. Intervention
studies may involve the use of a comparison group, which
may include subjects under another treatment, drug, test,
or placebo.
Randomized controlled trials are characterized by the
prospective assignment of subjects, through a random
method, into an experimental group and a control (place-
bo) group. The experimental group receives the drug
or treatment to be evaluated, while the control group
receives a placebo, no treatment, or the standard of care.
Both groups are followed for the outcome(s) of interest.
Randomization is the most reliable method to ensure that
the participants in both groups are as similar as possible
with respect to all known or unknown factors that might
affect the outcome.
Example
Postmenopausal women are identified from a
population and randomly assigned either to a
study group that will be prescribed hormone
replacement therapy or to a control group that
will be prescribed a placebo. Both groups of
women are observed prospectively to determine
who in each group subsequently develops
endometrial cancer. The rate at which women
prescribed hormone replacement therapy devel-
op endometrial cancer is compared to that of
women in the control group.
Death
Dysfunction
Healthy
Healthy
Dysfunction
Death
Death from Vaginal Cancer
Long-Term Disability
Cured
Cured
Long-Term Disability
Death from Cervical Cancer
Surgical Death
Recovers
Recovers
Surgical Death
Operative
Complication
Uneventful
Uneventful
Operative
Complication
Total
Subtotal
Hysterectomy
Fig. 2. Decision model. Square at far left, choice between two treatment options: total or subtotal hysterectomy. Round nodes,
chance outcomes; end branches, final outcome states.
(Scott JR, Sharp HT, Dodson MK, Norton PA, Warner HR. Subtotal hysterectomy in modern gynecology: a decision analysis. Am J Obstet Gynecol
1997;176:1187. Reprinted with permission.)
COMPENDIUM OF SELECTED PUBLICATIONS 642
in providing health benefits. In a cost-effectiveness analysis,
the net monetary costs of a health care intervention are com-
pared with some measure of clinical outcome or effective-
ness. In a cost-benefit analysis, the net monetary costs of a
health care intervention typically are compared with the net
monetary costs of the clinical outcome or effectiveness.
Therefore, a cost-benefit analysis compares costs associated
with an intervention with monetary benefits from the use of
that intervention. The advantage of a cost-benefit analysis is
the ability to use dollars for comparison across interventions.
The disadvantage is the difficulty in assigning a monetary
value to health status or quality of life.
Developing Evidence-Based
Recommendations
Having stated the clinical question and assembled and grad-
ed the literature using the levels just outlined, recommenda-
tions are formulated according to the quality and quantity of
evidence. Based on the highest available level of evidence,
recommendations are provided and graded according to the
following categories:
A There is good evidence to support the recommendation.
B There is fair evidence to support the recommendation.
C There is insufficient evidence to support the recommen-
dation; however, the recommendation may be made on
other grounds.
D There is fair evidence against the recommendation.
E There is good evidence against the recommendation.
This method explicitly links recommendations to the evi-
dence. Determination of the quality of the evidence and the
strength of recommendations are based on good, fair, or
insufficient evidence. These descriptors address the levels of
evidence and also provide a qualitative review of the evi-
dence in terms of its methodologic strengths and weakness-
es. A prerequisite for inclusion of each study in the analysis
is that it provides overall evidence of good quality.
It is important to note that an exact correlation does not
exist between the strength of the recommendation and the
level of evidence (ie, an A grade does not necessarily
require Level I evidence, nor does Level I evidence neces-
sarily lead to an A grade). For example, for some clinical
issues a randomized trial is not possible for medical or ethi-
cal reasons, and recommendations must be based on evi-
dence from other types of studies (Level II-2, II-3). In other
cases, high-quality studies have produced conflicting results,
or evidence of significant benefit is offset by evidence of
important harm from the intervention. Although these stud-
ies may be randomized controlled trials (Level I), insuffi-
cient or conflicting evidence would result in a C recom-
mendation.
Implications for Practice
Medicine will continue to face the rapid introduction of
new technologies, rationing of health resources, and
increasing attention to the quality and outcomes of med-
ical care. Physicians will have to acquire the skills neces-
sary to review the medical literature critically to identify
the best evidence in managing patients. This process for
developing practice guidelines identifies available evi-
dence and constructs recommendations based on the best
evidence so that obstetriciangynecologists can continue
to provide the highest quality of care.
Glossary
*
Accuracy: The degree to which a measurement or an esti-
mate based on measurements represents the true value of
the attribute that is being measured.
Bias: Deviation of results or inferences from the truth, or
processes leading to such deviation; it is any trend in the
collection, analysis, interpretation, publication, or review
of data that can lead to conclusions that are systematically
different from the truth. Three frequently occurring types
of bias include selection bias, information bias, and con-
founding. Selection bias is error due to systematic differ-
ences in characteristics between those who are selected for
study and those who are not. Information bias, also called
observational bias, is a flaw in measuring exposure or out-
come data that results in different quality (accuracy) of
information between comparative groups. Recall bias is an
example of information bias. The third example of bias,
confounding, describes a situation in which the effects of
two processes are not separated; it is the distortion of the
apparent effect of an exposure on risk brought about by the
association with other factors that can influence the out-
come.
Confidence interval: An indication of the variability of a
point estimate, such as an odds ratio or relative risk. In
general, the wider the confidence interval, the less precise
the point estimate. The 95% confidence interval is often
used. As an example, if the 95% confidence interval does
not overlap 1.0, then one would reject the null hypothesis.
Confounding variable (syn: confounder): A variable that
can cause or prevent the outcome of interest, is not an
intermediate variable, and is associated with the factor
under investigation. Unless it is possible to adjust for con-
founding variables, their effects cannot be distinguished
from those factor(s) being studied. Bias can occur when
adjustment is made for any factor that is caused in part by
the exposure and is also correlated with the outcome.
*Adapted from A Dictionary of Epidemiology, third edition. Last JM, ed. Used
by permission of Oxford University Press.
643 PRACTICE BULLETINS
Incidence: The number of instances of illness commenc-
ing, or persons falling ill, during a given period in a spec-
ified population. More generally, the number of new
events (eg, new cases of a disease in a defined population)
within a specified period.
Null hypothesis (test hypothesis): The statistical hypothe-
sis that one variable has no association with another vari-
able or set of variables, or that two or more population
distributions do not differ from one another. In simplest
terms, the null hypothesis states that the results observed
in a study, experiment, or test are no different from what
might have occurred as a result of the operation of chance
alone.
Odds ratio (syn: cross product ratio, relative odds): The
ratio of two odds. The exposure odds ratio for a set
of case control data is the ratio of the odds in favor
of exposure among the cases (a/b) to the odds in favor of
exposure among noncases (c/d). A 2 2 table (Table 1) can
be used to illustrate this calculation of odds ratios.
Table 1. Odds Ratio Calculations*
Exposed Unexposed
Disease a b
No disease c d
*The odds ratio is ad/bc.
P-value: The probability that a test statistic would be as
extreme or more extreme than observed if the null hypoth-
esis were true. The letter P, followed by the abbreviation
n.s. (not significant) or by the symbol < (less than) and a
decimal notation such as 0.01 or 0.05, is a statement of the
probability that the difference observed could have
occurred by chance if the groups were really alike (ie,
under the null hypothesis). Investigators may arbitrarily
set their own significance levels, but in most biomedical
and epidemiologic work, a study result whose probability
value is less than 5% (P <0.05) or 1% (P <0.01) is con-
sidered sufficiently unlikely to have occurred by chance
and would justify the designation statistically signifi-
cant. By convention, most investigators choose P <0.05
as statistically significant.
Power (statistical power): The ability of a study to demon-
strate an association if one exists. The power of the study
is determined by several factors, including the frequency
of the condition under study, the magnitude of the effect,
the study design, and sample size.
Prevalence: The number of events (eg, instances of a given
disease or other condition) in a given population at a des-
ignated time; sometimes used to mean prevalence rate.
When used without qualification, the term usually refers to
the situation at a specified time (point prevalence).
Relative risk: The ratio of risk of disease or death among
the exposed to that of the risk among the unexposed; this
usage is synonymous with risk ratio. If the relative risk is
above 1.0, then there is a positive association between the
exposure and the disease; if it is less than 1.0, then there is
a negative association.
Sensitivity and specificity: Sensitivity is the proportion of
truly diseased persons in the screened population who are
identified as diseased by the screening test. Specificity is
the proportion of truly nondiseased persons who are so
identified by the screening test. Table 2 illustrates these
quantities.
In screening and diagnostic tests, the probability that a
person with a positive test is a true positive (ie, does have
the condition) is referred to as the predictive value of a pos-
itive test. The predictive value of a negative test is the prob-
ability that a person with a negative test does not have the
condition. The predictive value of a screening test is deter-
mined by the sensitivity and specificity of the test and by
the prevalence of the condition for which the test is being
used.
Positive predictive value = a/a+b
Negative predictive value = d/c+d
Table 2. Sensitivity and Specificity Calculations
True Status
Screening Test
Results Diseased Not Diseased Total
Positive a b a + b
Negative c d c + d
Total a + c b + d a + b + c + d
a = Diseased individuals detected by the test (true positives)
b = Nondiseased individuals positive by the test (false positives)
c = Diseased individuals not detected by the test (false negatives)
d = Nondiseased individuals negative by the test (true negatives)
Sensitivity = a/a+c; specificity = d/b+d.
Type I error: The error of rejecting a true null hypothesis
(ie, declaring that a difference exists when it does not).
Type II error: The error of failing to reject a false null
hypothesis (ie, declaring that a difference does not exist
when in fact it does).
COMPENDIUM OF SELECTED PUBLICATIONS 644
Suggested Reading
Asilomar Working Group on Recommendations for Reporting
of Clinical Trials in the Biomedical Literature. Checklist of
information for inclusion in reports of clinical trials. Ann Intern
Med 1996;124:741743
Chalmers TC, Smith H Jr, Blackburn B, Silverman B, Schroeder
B, Reitman D, et al. A method for assessing the quality of a ran-
domized control trial. Control Clin Trials 1981; 2:3149
DuRant RH. Checklist for the evaluation of research articles.
J Adolesc Health 1994;15:48
Grisso JA. Making comparisons. Lancet 1993;342:157160
Guyatt GH, Sackett DL, Cook DJ. Users guides to the medical
literature. II. How to use an article about therapy or prevention.
A. Are the results of the study valid? Evidence-Based Medicine
Working Group. JAMA 1993;270:25982601
Guyatt GH, Sackett DL, Cook DJ. Users guides to the medical
literature. II. How to use an article about therapy or prevention.
B. What were the results and will they help me in caring for my
patients? Evidence-Based Medicine Working Group. JAMA
1994;271:5963
Guyatt GH, Sackett DL, Sinclair JC, Hayward R, Cook DJ,
Cook RJ. Users guides to the medical literature. IX. A method
for grading health care recommendations. Evidence-Based
Medicine Working Group. JAMA 1995;274:18001804
Hadorn DC, Baker D, Hodges JS, Hicks N. Rating the quality
of evidence for clinical practice guidelines. J Clin Epidemiol
1996;49:749754
Hayward RS, Wilson MC, Tunis SR, Bass EB, Guyatt G. Users
guides to the medical literature. VIII. How to use clinical prac-
tice guidelines. A. Are the recommendations valid? The
Evidence-Based Medicine Working Group. JAMA 1995;
274:570574
Jaeschke R, Guyatt GH, Sackett DL. Users guides to the med-
ical literature. III. How to use an article about a diagnostic test.
B. What are the results and will they help me in caring for my
patients? The Evidence-Based Medicine Working Group.
JAMA 1994;271:703707
Laupacis A, Wells G, Richardson WS, Tugwell P. Users guides
to the medical literature. V. How to use an article about progno-
sis. Evidence-Based Medicine Working Group. JAMA
1994;272:234237
Naylor CD, Guyatt GH. Users guides to the medical literature.
X. How to use an article reporting variations in the outcomes of
health services. The Evidence-Based Medicine Working Group.
JAMA 1996;275:554558
Naylor CD, Guyatt GH. Users guides to the medical literature.
XI. How to use an article about a clinical utilization review.
Evidence-Based Medicine Working Group. JAMA 1996;275:
14351439
Oxman AD. Checklists for review articles. BMJ 1994;309:
648651
Oxman AD, Cook DJ, Guyatt GH. Users guides to the medical
literature. VI. How to use an overview. Evidence-Based
Medicine Working Group. JAMA 1994;272:13671371
Oxman AD, Sackett DL, Guyatt GH. Users guides to the med-
ical literature. I. How to get started. The Evidence-Based
Medicine Working Group. JAMA 1993;270:20932095
Peipert JF, Gifford DS, Boardman LA. Research design and
methods of quantitative synthesis of medical evidence. Obstet
Gynecol 1997;90:473478
Richardson WS, Detsky AS. Users guides to the medical liter-
ature. VII. How to use a clinical decision analysis. A. Are the
results of the study valid? Evidence-Based Medicine Working
Group. JAMA 1995;273:12921295
Wilson MC, Hayward RS, Tunis SR, Bass EB, Guyatt G. Users
guides to the medical literature. VIII. How to use clinical prac-
tice guidelines. B. What are the recommendations and will they
help you in caring for your patients? The Evidence-Based
Medicine Working Group. JAMA 1995;274:16301632
Copyright 1998
The American College of Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
PRACTICE BULLETINS
COMMITTEE ON PRACTICE BULLETINSOBSTETRICS
PRACTICE BULLETINS
COMMITTEE ON PRACTICE BULLETINSOBSTETRICS
647
CLINICAL MANAGEMENT GUIDELINES FOR
OBSTETRICIANGYNECOLOGISTS
NUMBER 4, MAY 1999
(Replaces Educational Bulletin Number 147, October 1990)
Prevention of Rh D
Alloimmunization
Before the introduction of anti-D immune globulin (formerly referred to as
Rho[D] immune globulin), hemolytic disease of the fetus and newborn affected
910% of pregnancies and was a major cause of perinatal morbidity and mor-
tality (1, 2). Among Rh D-alloimmunized pregnancies, mild-to-moderate
hemolytic anemia and hyperbilirubinemia occur in 2530% of fetuses/neonates,
and hydrops fetalis occurs in another 25% of such cases (3). The administration
of anti-D immune globulin is successful in reducing the rate of developing anti-
bodies to the D antigen. Protocols for the antenatal and postpartum administra-
tion of anti-D immune globulin have been responsible for the dramatic decrease
in alloimmunization and subsequent hemolytic disease in the past two decades.
However, Rh D alloimmunization remains a clinical concern, with many cases
due to failure to follow established protocols. Finally, there is concern that
overuse of anti-D immune globulin may lead to a worldwide shortage. The pur-
pose of this document is to provide direction for the appropriate and efficient
management of patients at risk in order to further decrease the frequency of Rh
D alloimmunization.
Background
Nomenclature
Nomenclature of blood group systems, including the Rh system, may appear
confusing to the clinician. According to the American Medical Association
Manual of Style, erythrocyte antigen and phenotype terminology should use sin-
gle letters or dual letters depending on the antigen in question (eg, O, AB, Le,
Rh) (4). A second designation should be used for specific subtypes (eg, Rh D, Rh
C). This publication uses the designation Rh D to signify the erythrocyte antigen.
This Practice Bulletin was
developed by the ACOG Com-
mittee on Practice Bulletins
Obstetrics with the assistance
of Michael L. Socol, MD, and
T. Flint Porter, MD, MPH. The
information is designed to aid
practitioners in making deci-
sions about appropriate obstet-
ric and gynecologic care.
These guidelines should not be
construed as dictating an ex-
clusive course of treatment or
procedure. Variations in prac-
tice may be warranted based on
the needs of the individual pa-
tient, resources, and limitations
unique to the institution or type
of practice.
Reaffirmed 2009
ACOG
PRACTICE
BULLETIN
COMPENDIUM OF SELECTED PUBLICATIONS 648
Women who carry the Rh D antigen are identified as Rh D
positive, and those who do not carry the Rh D antigen are
identified as Rh D negative. The use of immune globulin to
counter the Rh D antigen is referred to as anti-D immune
globulin.
Causes of Rh D Alloimmunization
One study indicates that 17% of Rh D-negative women
who do not receive anti-D immune globulin prophylaxis
during pregnancy will become alloimmunized (5). Nearly
90% of these cases result from fetomaternal hemorrhage at
delivery. Approximately 10% of cases result from sponta-
neous antenatal fetomaternal hemorrhage, and most of
these cases occur in the third trimester. The amount of Rh
D-positive blood required to cause alloimmunization is
small. Most women who become alloimmunized do so as
a result of fetomaternal hemorrhage of less than 0.1 mL
(6).
Several first- and second-trimester clinical events may
cause Rh D alloimmunization. Therapeutic and sponta-
neous abortions are associated respectively with a 45%
and a 1.52% risk of alloimmunization in susceptible
(nonalloimmunized) women (68). Ectopic pregnancy also
is associated with alloimmunization in susceptible women.
Threatened abortion infrequently causes alloimmuniza-
tion, although approximately 10% of women with threat-
ened abortion have evidence of fetomaternal hemorrhage
(9).
Clinical procedures, which may breach the integrity of
the choriodecidual space, also may cause Rh D alloimmu-
nization. Chorionic villus sampling is associated with a
14% risk of fetomaternal hemorrhage (10) of more than
0.6 mL (11), and amniocentesis is associated with a
715% risk of fetomaternal hemorrhage, even if the pla-
centa is not traversed (5, 12). Likewise, cordocentesis and
other percutaneous fetal procedures pose a risk for feto-
maternal hemorrhage, although the actual risk of alloim-
munization has not been quantified (13, 14). External
cephalic version, whether or not it is successful, results in
fetomaternal hemorrhage in 26% of cases (15, 16).
Anti-D Immune Globulin to Prevent
Alloimmunization
The correct administration of anti-D immune globulin dra-
matically reduces the rate of alloimmunization. Initial
studies proved that the postpartum administration of a sin-
gle dose of anti-D immune globulin to susceptible Rh D-
negative women within 72 hours of delivery reduced the
alloimmunization rate by 90% (17). It was subsequently
recognized that third-trimester antenatal alloimmunization
posed a lingering and significant problem; later it was
shown that the routine antenatal administration of anti-D
immune globulin to Rh D-negative women at 2829 weeks
of gestation reduced the rate of third-trimester alloimmu-
nization from nearly 2% to 0.1% (6). With the effective-
ness of anti-D immune globulin clearly demonstrated,
authorities recommended its administration to Rh D-neg-
ative women who were undergoing clinical events or
procedures associated with potential fetomaternal hemor-
rhage.
In the United States, recommendations for the
administration of anti-D immune globulin were intro-
duced in the 1970s. The current antenatal immunopro-
phylaxis regimen of a single dose of 300 g at 28 weeks
of gestation was based on recommendations from the
1977 McMaster Conference, and is associated with a low
failure rate (18). The efficacy of the single antenatal dose
of 300 g at 28 weeks of gestation is comparable to the
same dose given at both 28 weeks and 34 weeks of ges-
tation (6). In one study of antenatal prophylaxis, three
women who delivered more than 12 weeks after their
antenatal dose was administered became alloimmunized.
Based on these limited data, some authorities recommend
that if delivery has not occurred within 12 weeks of the
injection, at 28 weeks of gestation, a second 300 g dose
of anti-D immune globulin should be given (5).
In the United Kingdom, recommendations (19, 20)
differ somewhat from those in the United States in that
antenatal prophylaxis is given at both 28 weeks and 34
weeks of gestation, and the dose for each antenatal ad-
ministration, as well as the dose given after delivery, is
100 g. These recommendations are based on two stud-
ies (21, 22) that demonstrated the superiority of a regi-
men of 100 g of anti-D immune globulin at 28 weeks
and 34 weeks of gestation and postpartum compared with
a regimen of only postpartum administration. The British
regimen uses less anti-D immune globulin (300 g ver-
sus 600 g) to achieve similarly low rates of alloimmu-
nization (7, 20), but requires a third injection at 34 weeks
of gestation.
Anti-D immune globulin is extracted by cold alcohol
fractionation from plasma donated by individuals with
high-titer D immune globulin G antibodies. It has been
shown experimentally that one prophylactic dose of 300
g of anti-D immune globulin can prevent Rh D alloim-
munization after an exposure to up to 30 mL of Rh D-
positive blood or 15 mL of fetal cells (23). For exposure
to larger volumes of Rh D-positive blood, more anti-D
immune globulin is required. Accordingly, the American
Association of Blood Banks and the National Blood
Transfusion Service of the United Kingdom recommend
that Rh D-negative mothers delivering Rh D-positive
infants undergo a test to screen for fetomaternal hemor-
rhage in excess of the amount covered by the standard
dose of anti-D immune globulin. This test will determine
if additional anti-D immune globulin is necessary (24,
25). In the past, the American College of Obstetricians
649 PRACTICE BULLETINS
and Gynecologists recommended that only women with
certain high-risk conditions, such as those experiencing
abruptio placenta or manual removal of the placenta, be
screened for excess fetomaternal hemorrhage. However,
this policy has been shown to miss 50% of cases requiring
more than the standard postpartum dose of anti-D immune
globulin (26).
The risk of transmission of viral infections (human
immunodeficiency virus [HIV] and hepatitis B and hepati-
tis C viruses) through anti-D immune globulin is minimal
to absent (27). All plasma lots used for the production of
anti-D immune globulin have been tested for viral infec-
tion since 1985. Moreover, the fractionation process used
to prepare anti-D immune globulin effectively removes
any viral particles that may be present.
Failure to Prevent Rh D
Alloimmunization
In spite of recommendations for immunoprophylaxis,
0.10.2% of susceptible Rh D-negative women still
become alloimmunized (21). There are two primary rea-
sons for the continuing problem.
One reason women become alloimmunized is failure
to implement recommended immunoprophylaxis pro-
tocols, resulting in preventable Rh D alloimmunizations.
Two recent studies from the United Kingdom emphasize
the scope of the problem. One study of more than 900 Rh
D-negative women reported that only 59% received rec-
ommended treatment with anti-D immune globulin after
potentially alloimmunizing clinical events (8). Another
study showed that 16% of 63 cases of Rh D alloimmu-
nization occurred because of failure to follow recommen-
dations for administration of anti-D immune globulin (28).
Preventable Rh D alloimmunization occurs in susceptible
Rh D-negative women for the following three reasons:
1. Failure to administer an antenatal dose of anti-D
immune globulin at 2829 weeks of gestation
2. Failure to recognize clinical events that place patients
at risk for alloimmunization and failure to administer
anti-D immune globulin appropriately
3. Failure to administer or failure to administer timely
anti-D immune globulin postnatally to women who
have given birth to an Rh D-positive or untyped fetus
The second reason for the continuing problem of Rh
D alloimmunization is the small rate (0.10.2%) of spon-
taneous immunization despite the recommended prophy-
laxis protocol. These cases most often occur in pregnancies
during which there have been no prior overt sensitizing
events. This problem may become the largest single cause
of new Rh D alloimmunization, because alloimmunization
from other causes has decreased proportionally (28).
Potential Shortage of Anti-D Immune
Globulin
Anti-D immune globulin is collected by apheresis from
volunteer donors who have high titers of circulating anti-
Rh D antibodies. The donated plasma is pooled and frac-
tionated by commercial manufacturers, and anti-D
immune globulin is prepared in varying doses. The num-
ber of potential donors may be dwindling worldwide,
raising concern about future supplies of anti-D immune
globulin (29, 30). Experts in the United Kingdom estimate
that supplies of anti-D immune globulin are inadequate
for immunoprophylaxis of all susceptible Rh D-negative
women, both primigravidas and multiparas, if standard
recommendations are followed (19). In Australia, a short-
age prompted importation of anti-D immune globulin.
Subsequently, some physicians proposed strictly limiting
the dose given for first-trimester indications and discon-
tinuing administration of anti-D immune globulin after
external cephalic version (unless fetomaternal hemorrhage
is documented), ectopic pregnancy, or threatened miscar-
riage (31). Others disagreed, considering it unethical to
withhold anti-D immune globulin in any situation.
Estimates regarding future needs compared with poten-
tial supply in the United States have not been published;
however, limiting doses for first-trimester indications and
using lower doses of Rh D immune globulin for antena-
tal prophylaxis may be necessary.
Cost-Effectiveness of Rh D Prophylaxis
Programs
The cost-effectiveness of preventing perinatal mortality
and morbidity secondary to Rh D hemolytic disease of
the newborn is an important consideration. Economic
analysis of anti-D immune globulin prophylaxis is based
on the cost of anti-D immune globulin and the number of
alloimmunizations that would be prevented. In 1977, the
McMaster Conference concluded that routine postnatal
prophylaxis was cost-effective but that routine antenatal
treatment should be undertaken only if supplies of anti-D
immune globulin were adequate and if cases of hemolytic
disease of the newborns occurred that might have been
prevented by antenatal treatment (7). Some experts con-
cluded that antenatal prophylaxis is effective only in
primigravidas (32), and the debate regarding the cost-
effectiveness of antenatal prophylaxis of all pregnant
women remains unsettled (20, 3237). The Scottish
National Blood Transfusion Service has concluded that
the administration of 100 g of anti-D immune globulin
at 28 weeks and 34 weeks of gestation is cost-effective
only in primigravidas (38). Others estimate that the most
cost-effective antenatal regimen is a single dose of 250 g
of anti-D immune globulin at 28 weeks of gestation (39).
COMPENDIUM OF SELECTED PUBLICATIONS 650
The use of anti-D prophylaxis in the case of certain
clinical events is even more controversial. For example, the
risk of Rh D alloimmunization from threatened abortion in
the first trimester is uncertain, though probably very small.
The cost-effectiveness of anti-D immune globulin for
threatened abortion, which has never been studied, is ques-
tionable (19).
In summary, the cost-effectiveness of antenatal Rh D
immune globulin to all Rh D-negative pregnant women
and in all circumstances wherein fetomaternal hemorrhage
might occur has not been proved. Available data support
that third-trimester antenatal prophylaxis is cost-effective
in primigravidas. As long as the supply of anti-D immune
globulin is adequate and data do not exist to support other
recommendations, most experts believe that it is unethical
to withhold anti-D immune globulin from any patient at
risk of Rh D alloimmunization (19). Recommendations for
the use of anti-D immune globulin in this document will be
made accordingly.
Clinical Considerations and
Recommendations
Should anti-D immune globulin ever be with-
held from a woman undergoing sterilization?
The use of anti-D immune globulin following postpartum
and postabortal sterilization should be guided by the
patients desire for protection against any chance of
alloimmunization. Proponents of its use maintain that anti-
D immune globulin administration will preserve the future
option of transfusing Rh D-positive blood in times of emer-
gency (40). Opponents of this view cite the low probability
of sensitization with the previous pregnancy and the
improbability of receiving Rh D-incompatible blood (41).
How should one deal with the issue of paternity?
If the father is known to be Rh D negative, antenatal pro-
phylaxis is unnecessary. If there is doubt about the fathers
identity or his blood type, anti-D immune globulin pro-
phylaxis should be given.
Is it necessary to repeat antibody screening in
patients at 28 weeks of gestation prior to the
administration of anti-D immune globulin?
The American Association of Blood Banks recommends
that the physician should consider a repeat antibody screen
prior to the administration of antenatal anti-D immune
globulin if the patient was screened for antibodies prior to
28 weeks of gestation (24). The primary rationale for
repeating the antibody screen is to identify women who
have become alloimmunized before 28 weeks of gestation
in order to manage their pregnancies properly. However,
the incidence of Rh D alloimmunization occurring prior
to 28 weeks of gestation is reported to be as low as 0.18%
(18), and the cost-effectiveness of routinely repeating the
antibody test has not been studied. The consequences of
antenatal Rh D alloimmunization can be severe, but the
decision to obtain a repeat antibody screen should be dic-
tated by individual circumstances and left to the judg-
ment of the physician.
Is anti-D immune globulin indicated in a sen-
sitized pregnancy?
If Rh D antibodies are present, anti-D immune globulin
is not beneficial, and management should proceed in
accordance with protocols for Rh D-alloimmunized preg-
nancies.
How should a D
u
blood type be interpreted,
and what management should be undertaken?
In the past, a woman whose blood was typed as D
u
was
thought to have blood cells positive for a variant of the
Rh D antigen. Nomenclature and practice have changed
in recent years, and currently the D
u
designation has been
changed to weak D positive (24). Patients with this
designation are considered Rh D positive and should not
receive anti-D immune globulin. In some centers, the D
u
antigen is not assessed, and women may unnecessarily
receive anti-D immune globulin. In the rare circumstance
of delivery by a woman whose antenatal Rh status is neg-
ative or unknown and whose postpartum screen reveals a
D
u
-positive or weak D-positive result, anti-D immune
globulin should be given, and the possibility of fetoma-
ternal hemorrhage should be investigated (24).
Is threatened abortion an indication for anti-D
immune globulin prophylaxis?
Whether to administer anti-D immune globulin to a
patient with threatened abortion and a live embryo or fetus
at or before 12 weeks of gestation is controversial, and no
evidence-based recommendation can be made. The Rh D
antigen has been reported on fetal erythrocytes as early as
38 days of gestation (42), and fetomaternal hemorrhage
has been documented in women with threatened abortion
from 7 to 13 weeks of gestation (9). However, Rh D allo-
immunization apparently attributable to threatened
abortion is exceedingly rare. Experts have compared the
overall benefit with the cost of the widespread use of anti-
D immune globulin for a condition as common as threat-
ened abortion (19, 43), and, thus, many physicians do not
routinely administer anti-D immune globulin to women
with threatened abortion and a live embryo or fetus up to
12 weeks of gestation.
ACOG
PRACTICE
BULLETIN
This Practice Bulletin was
developed by the ACOG Com-
mittee on Practice Bulletins
Obstetrics. The information is
designed to aid practitioners
in making decisions about
appropriate obstetric and gyne-
cologic care. These guidelines
should not be construed as
dictating an exclusive course of
treatment or procedure. Varia-
tions in practice may be war-
ranted based on the needs of the
individual patient, resources,
and limitations unique to the
institution or type of practice.
Reaffirmed 2009
COMPENDIUM OF SELECTED PUBLICATIONS 690
pared with earlier gestations. Preterm version attempts are
associated with high initial success rates but also with high-
er reversion rates, necessitating additional procedures (4, 5).
Third, if complications arise during an attempted version,
emergency delivery of a term infant can be accomplished
(6). Finally, most of the evidence pertaining to ECV comes
from recent studies that selected patients near term.
There is scant information concerning ECV attempts
among women who have a preexisting uterine scar or who
undergo the procedure during the early stages of labor.
For women with a previous cesarean delivery, compared
with those who had not experienced cesarean delivery,
results from one small randomized controlled trial indi-
cate that they experience comparable success rates (7).
Although no serious adverse events occurred in a small
series (8), larger studies would be needed to establish the
risk of uterine rupture. There are scattered reports of suc-
cessful ECV performed during early labor; to date, how-
ever, no large study has been published (4, 5, 9, 10).
Contraindications to ECV are based on a common-
sense approach designed to minimize the risks of an
adverse outcome and to maximize the chances for suc-
cess. Clearly any indication for a cesarean delivery in a
patient, such as placenta previa, would be a contraindica-
tion to ECV (4, 9, 1120), but there is insufficient evi-
dence to construct a comprehensive list.
What are the benefits and risks of external
cephalic version?
The immediate benefit of successful version is an
increased probability that the fetus will be in a vertex pre-
sentation for delivery. The ultimate goal is an uncompli-
cated vaginal delivery. Reports from published studies
indicate there are fewer cesarean deliveries among women
who have undergone successful version compared with
women who have not undergone attempted version (4, 6,
18, 2124). One randomized trial found no significant dif-
ference between the cesarean delivery rates of patients
with an ECV attempt and controls who did not undergo
ECV (25). In this study, however, the majority of patients
undergoing ECV were between 33 and 36 weeks of gesta-
tion rather than closer to term as in the other reports. An
additional randomized trial reported similar rates of
cesarean delivery for women who underwent ECV and for
those who did not, but the rate of breech vaginal deliveries
was very high; approximately 80% of breech presentations
in each group was delivered vaginally, resulting in an
unusually low cesarean delivery rate (4).
Fetal heart rate changes during attempted versions are
not uncommon but usually stabilize when the procedure is
discontinued (4, 21, 23, 26, 27). Serious adverse effects
associated with ECV do not occur often, but there have
been a few reported cases of placental abruption and
preterm labor. A report from Copenhagen described two
cases of intrauterine death 2 and 5 weeks after version
among 316 women and one instance of premature partial
separation of the placenta 2 days following an unsuc-
cessful version attempt, but the two deaths could not be
causally linked to ECV with certainty (16). In the study
including mothers at 36 weeks of gestation or less, two
placental abruptions and one premature labor occurred
shortly after version, resulting in one neonatal and two
fetal deaths (25). Subsequently, there has been a follow-up
study at the same institution, but changes in management
practices and selection criteria had been made (18). Only
term gestations were selected, and tocolytic agents as well
as fetal monitoring were used during version attempts.
There were no fetal deaths causally linked to ECV. The
authors concluded that ECV can substantially decrease
breech presentations and the cesarean delivery rate for
these patients (18). A more recent study reported a placen-
tal abruption during an ECV attempt requiring emergency
cesarean delivery of a viable but depressed infant (28). It
was the only major complication attributed to ECV among
113 women. Although the incidence of serious complica-
tions associated with ECV is low, the potential is present,
making it prudent to perform ECV in a facility that has
ready access to cesarean delivery services.
What are the success rates for external
cephalic version, and what factors are
predictive of either success or failure?
A review of 20 studies indicates that success rates for
ECV range from 35% to 86%, with an average success
rate of 58% (4, 6, 9, 1214, 1618, 2125, 27, 2931).
Most authors report a positive association between parity
and successful version (4, 6, 13, 2125, 30, 31). A trans-
verse or oblique lie is associated with higher immediate
success rates (13, 29, 30). Opinion is divided about the
predictiveness of other factors, including amniotic fluid
volume, location of placenta, and maternal weight. Some
reports indicate an association between normal or
increased amounts of amniotic fluid and successful ECV
(12, 13, 24, 32), whereas other reports do not (20). Two
authors reported an association between successful ECV
and placenta location (20, 24), whereas others failed to
find an association (12, 13, 29). Two authors found obe-
sity to be associated with a higher failure rate (23, 30),
whereas others found maternal weight not to be a signif-
icant predictor of success (12, 13, 19, 20).
Although scoring systems have been developed to
predict which candidates will have a successful version
Consider
retrial of
version
Confirmed breech presentation at
36 completed weeks of gestation
Review contraindications
Obtain informed consent
Consider tocolytics
for nulliparas
Assess nonstress test
or biophysical profile
Cephalic version attempt
Successful
Unsuccessful
Revert to breech Spontaneously
converts to vertex
Consider retrial
of version
Continues vertex
Remains breech
No further
attempts
at version
Figure 1. Algorithm for patient
management for external cephal-
ic version.
693 PRACTICE BULLETINS
What are the cost implications of external
cephalic version?
A recent decision analysis measuring cost implications
associated with four potential methods of managing term
pregnancies with breech presentations predicted that use
of ECV would result in fewer cesarean deliveries and
lower costs than either scheduled cesarean delivery or
trial of labor without an ECV attempt (41). Even if failed
ECV attempts were followed by routine cesarean deliv-
ery, the overall cesarean delivery rate would be lower
than that of a trial of labor without an ECV attempt.
Sensitivity analysis revealed that as long as less than 52%
of all breech presentations are eligible for a trial of labor,
a policy of attempting ECV followed by either a trial of
labor or routine cesarean delivery (for failed attempts)
would be less expensive than a policy of routine cesare-
an delivery or trial of labor without ECV (41). It should
be noted that the decision analysis included X-ray
pelvimetry to assess eligibility for a trial of labor, a prac-
tice that may not be widely accepted.
Summary
The following recommendation is based on good
and consistent scientific evidence (Level A):
Because the risk of an adverse event occurring as a
result of ECV is small and the cesarean delivery rate
is significantly lower among women who have
undergone successful version, all women near term
with breech presentations should be offered a ver-
sion attempt.
The following recommendations are based on lim-
ited or inconsistent scientific evidence (Level B):
Patients should have completed 36 weeks of gesta-
tion before attempting ECV.
Previous cesarean delivery is not associated with a
lower rate of success; however, the magnitude of the
risk of uterine rupture is not known.
There is insufficient evidence to recommend routine
tocolysis for ECV attempts for all patients, but it
may particularly benefit nulliparous patients.
Evidence is inconsistent regarding the benefits of
anesthesia use during ECV attempts.
Cost-effectiveness depends upon utilization of vagi-
nal breech deliveries and costs of the version protocol
at a particular institution, but at least one decision
analysis suggests the policy is cost effective.
The following recommendations are based primar-
ily on consensus and expert opinion (Level C):
Fetal assessment before and after the procedure is
recommended.
External cephalic version should be attempted only
in settings in which cesarean delivery services are
readily available.
References
1. Ventura SJ, Martin JA, Curtin SC, Mathews TJ. Births:
final data for 1997. Natl Vital Stat Rep 1999;47(18):196
(Level II-3)
2. Hickok DE, Gordon DC, Milberg JA, Williams MA,
Daling JR. The frequency of breech presentation by gesta-
tional age at birth: a large population-based study. Am J
Obstet Gynecol 1992;166:851852 (Level II-2)
3. Westgren M, Edvall H, Nordstrom L, Svalenius E,
Ranstam J. Spontaneous cephalic version of breech pre-
sentation in the last trimester. Br J Obstet Gynaecol 1985;
92:1922 (Level II-3)
4. Van Veelen AJ, Van Cappellen AW, Flu PK, Straub MJ,
Wallenburg HC. Effect of external cephalic version in
late pregnancy on presentation at delivery: a randomized
controlled trial. Br J Obstet Gynaecol 1989;96:916921
(Level I)
5. Kornman MT, Kimball KT, Reeves KO. Preterm external
cephalic version in an outpatient environment. Am J
Obstet Gynecol 1995;172:17341738; discussion
17381741 (Level II-2)
6. Goh JT, Johnson CM, Gregora MG. External cephalic ver-
sion at term. Aust N Z J Obstet Gynaecol
1993;33:364366 (Level II-2)
7. Flamm BL, Fried MW, Lonky NM, Giles WS. External
cephalic version after previous cesarean section. Am J
Obstet Gynecol 1991;165;370372 (Level I)
8. de Meeus JB, Ellia F, Magnin G. External cephalic version
after previous cesarean section: a series of 38 cases. Eur J
Obstet Gynecol Reprod Biol 1998;81:6568 (Level III)
9. Cook HA. Experience with external cephalic version and
selective vaginal breech delivery in private practice.
Am J Obstet Gynecol 1993;168:18861889; discussion
18891890 (Level II-3)
10. Ferguson JE 2d, Dyson DC. Intrapartum external cephalic
version. Am J Obstet Gynecol 1985;152:297298 (Level
II-3)
11. Lau TK, Stock A, Rogers M. Fetomaternal haemorrhage
after external cephalic version at term. Aust N Z J Obstet
Gynaecol 1995;35:173174 (Level III)
12. Shalev E, Battino S, Giladi Y, Edelstein S. External cephal-
ic version at termusing tocolysis. Acta Obstet Gynecol
Scand 1993;72:455457 (Level II-3)
13. Hellstrom AC, Nilsson B, Stange L, Nylund L. When does
external cephalic version succeed? Acta Obstet Gynecol
Scand 1990;69:281285 (Level II-3)
*Cunningham FG, Gant NF, Leveno KJ, Gilstrap LC III, Hauth JC,
Wenstrom KD. Hypertensive disorders in pregnancy. In: Williams
obstetrics. 21st ed. New York: McGraw-Hill, 2001:567618
2 15 40
High-Dose 6
6 15 40
6
6, 3, 1 2040 42
*Seitchik J, Amico JA, Castillo M. Oxytocin augmentation of dysfunctional labor.
V. An alternative oxytocin regimen. Am J Obstet Gynecol 1985;151:75761.
Hauth JC, Hankins GD, Gilstrap LC 3rd, Strickland DM, Vance P. Uterine con-
traction pressures with oxytocin induction/augmentation. Obstet Gynecol
1986;68:3059.
Satin AJ, Maberry MC, Leveno KJ, Sherman ML, Kline DM. Chorioamnionitis: a
harbinger of dystocia. Obstet Gynecol 1992;79:9135.
COMPENDIUM OF SELECTED PUBLICATIONS 864
decelerations in the active phase of labor in the amnioto-
my group (55). Importantly, there was no difference in
nonreassuring heart rates or operative deliveries. Amniot-
omy was associated with a decreased need for oxytocin
augmentation (36% versus 76%) and a shorter active phase
of labor (4 hours, 35 minutes, versus 5 hours, 56 minutes).
Another randomized trial addressed the impact of
amniotomy after an arrest disorder was diagnosed in the
active phase (14). Women with an active phase arrest were
randomized to receive either oxytocin with intact mem-
branes or oxytocin with amniotomy and internal monitor-
ing. A trend toward longer labor (44 minutes longer) was
seen in the intact group with no differences in cesarean
deliveries. The amniotomy group had a higher incidence
of fever. Thus, amniotomy may enhance progress in the
active phase and negate the need for oxytocin augmenta-
tion but may increase the risk of chorioamnionitis.
Should electronic fetal monitoring be used
during oxytocin augmentation?
No overwhelming evidence has identified the most effec-
tive method of fetal heart rate surveillance when oxytocin
is used for augmentation. A systematic review of contin-
uous electronic heart rate monitoring for fetal assessment
during labor identified 13 randomized trials addressing
efficacy and safety of electronic fetal monitoring (56).
Routine electronic fetal monitoring was associated with a
statistically significant decrease in neonatal seizures.
(RR, 0.51; 95% CI 0.32, 0.82). No differences were seen
in low Apgar scores, neonatal intensive care unit admis-
sions, perinatal deaths, or cerebral palsy. Electronic fetal
monitoring was associated with an increase in cesarean
deliveries (RR, 1.41; 95% CI 1.23, 1.61) and operative
vaginal deliveries (RR, 1.2; 95% CI 1.11, 1.3). Well-con-
trolled studies of intermittent auscultation of the fetal
heart rate have shown it to be equivalent to continuous
electronic fetal monitoring when performed at specific
intervals with a one-to-one nurse-to-patient ratio (5761).
There are no comparative data indicating the optimal fre-
quency at which intermittent auscultation should be per-
formed in the absence of risk factors.
Summary of
Recommendations
The following recommendations are based on
good and consistent scientific evidence (Level A):
Patients should be counseled that walking during
labor does not enhance or improve progress in labor
nor is it harmful.
Continuous support during labor from caregivers
should be encouraged because it is beneficial for
women and their newborns.
The following recommendations are based on lim-
ited or inconsistent scientific evidence (Level B):
Active management of labor may shorten labor in
nulliparous women, although it has not consistently
been shown to reduce the rate of cesarean delivery.
Amniotomy may be used to enhance progress in
active labor, but may increase the risk of maternal
fever.
X-ray pelvimetry alone as a predictor of dystocia
has not been shown to have benefit, and, therefore,
is not recommended.
The following recommendations are based primar-
ily on consensus and expert opinion (Level C):
Intrauterine pressure catheters may be helpful in the
management of dystocia in selected patients, such as
those who are obese.
Women with twin gestations may undergo augmen-
tation of labor.
References
1. Martin JA, Hamilton BE, Ventura SJ, Menacker F, Park
MM, Sutton PD. Births: final data for 2001. Natl Vital Stat
Rep 2002;51(2):1102. (Level II-3)
2. Gifford DS, Morton SC, Fiske M, Keesey J, Keeler E,
Kahn KL. Lack of progress in labor as a reason for cesare-
an. Obstet Gynecol 2000;95:58995. (Level II-3)
3. Cunningham FG, Gant NF, Leveno KJ, Gilstrap LC 3rd,
Hauth JC, Wenstrom KD. Dystocia: abnormal labor and
fetopelvic disproportion. In: Williams Obstetrics. 21st
ed. New York (NY): McGraw-Hill; 2001. p. 42550.
(Level III)
4. Kilpatrick SJ, Laros RK Jr. Characteristics of normal
labor. Obstet Gynecol 1989;74:857. (Level II-3)
5. Zhang J, Yancey MK, Klebanoff MA, Schwarz J,
Schweitzer D. Does epidural analgesia prolong labor and
increase risk of cesarean delivery? A natural experiment.
Am J Obstet Gynecol 2001;185:12834. (Level II-2)
6. Hauth JC, Hankins GD, Gilstrap LC 3rd, Strickland DM,
Vance P. Uterine contraction pressures with oxytocin
induction/augmentation. Obstet Gynecol 1986;68:3059.
(Level II-2)
7. Rouse DJ, Owen J, Goldenberg RL, Cliver SP. The effec-
tiveness and costs of elective cesarean delivery for fetal
macrosomia diagnosed by ultrasound. JAMA 1996;276:
14806. (Decision analysis)
In the United States, doxylamine is available as the active ingredient in some over-the-counter sleep aids; one half of a scored
25-mg tablet can be used to provide a 12.5-mg dose of doxylamine.
Thiamine, intravenously, 100 mg daily for 23 days (followed by intravenous multivitamins), is recommended for every woman
who requires intravenous hydration and has vomited for more than 3 weeks. No study has compared different fluid replace-
ments for nausea and vomiting of pregnancy.
Corticosteroids appear to increase risk for oral clefts in the first 10 weeks of gestation.
Safety, particularly in the first trimester of pregnancy, not yet determined; less effect on nausea.
Dehydration
Intravenous fluid replacement
discounted
in meta-analysis)
Prochlorperazine
Chlorpromazine
Perphenazine
Benzodiazepines
Diazepam
5-Hydroxytryptamine 3
receptor agonists
Ondansetron One trial found equal effectiveness to No malformations noted
promethazine
Steroids Pooled results do not suggest benefit in
decreasing nausea and vomiting of
pregnancy
Adrenocorticotropic hormone
Corticosteroids Small increased risks of clefts
*The drug has been evaluated in at least 1 randomized, controlled trial.
Rumeau-Rouquette C, Goujard J, Huel G. Possible teratogenic effect of phenothiazines in human beings. Teratology 1977;15:5764.
Data from Jewell D, Young G. Interventions for nausea and vomiting in early pregnancy (Cochrane Review). In: The Cochrane Library, Issue 4, 2003. Chichester, UK:
John Wiley & Sons, Ltd.; and Magee LA, Mazzotta P, Koren G. Evidence-based view of safety and effectiveness of pharmacologic therapy for nausea and vomiting of
pregnancy (NVP). Am J Obstet Gynecol 2002;186:S25661.
875 PRACTICE BULLETINS
recurrent vomiting, the tapered dose may be stopped and
the patient continued on the effective dose for up to 6
weeks. To limit serious maternal side effects, corticos-
teroids should not be continued beyond this period for
the treatment of hyperemesis gravidarum (77).
Is there a role for laboratory or radiologic
assessment in the diagnosis of hyperemesis
gravidarum?
Most patients with nausea and vomiting of pregnancy do
not require laboratory evaluation, but in those with nau-
sea and vomiting of pregnancy that is severe, prolonged,
or extended, laboratory assessment may help in the dif-
ferential diagnosis of hyperemesis gravidarum and to
assess the severity of the condition. Common laboratory
abnormalities in hyperemesis gravidarum include
increased liver enzymes (usually <300 U/L), serum
bilirubin (<4 mg/dL), and serum amylase or lipase con-
centrations (up to 5 times greater than normal levels).
Primary hepatitis as a cause of nausea and vomiting of
pregnancy results in increased liver enzyme levels, often
in the thousands; bilirubin concentrations usually are
greatly increased as well. Acute pancreatitis may cause
vomiting and elevated amylase concentrations, but
serum amylase concentrations usually are 510 times
greater than the elevations associated with nausea and
vomiting of pregnancy. A hypochloremic metabolic
alkalosis can be seen with severe vomiting of any cause.
Serum concentrations of hCG are not helpful in deter-
mining whether vomiting is caused by hyperemesis
gravidarum. Urinalysis may show elevated specific grav-
ity or ketonuria or both. Patients with persistent hyper-
emesis gravidarum that is unresponsive to standard
therapy may have an ulcer; treatment with antibiotics
and H
2
receptor antagonists is safe (78, 79) and has been
reported to be beneficial in case reports (80).
Up to 70% of patients with hyperemesis gravidarum
will have suppressed thyroid-stimulating hormone levels
or elevated free thyroxine concentrations (81). For the
patient who has no history of hyperthyroidism before
pregnancy and no goiter, the hyperthyroidism of hyper-
emesis gravidarum can be expected to resolve by
20 weeks of gestation without specific antithyroid ther-
apy. Hyperthyroidism itself rarely may present with
significant vomiting (82), but in the patient who has no
goiter, thyroid tests are not needed routinely to clarify
the differential diagnosis. To confirm the diagnosis of
hyperthyroidism in the setting of nausea and vomiting of
pregnancy, measurement of free thyroxine and free tri-
iodothyronine concentrations should be obtained.
An ultrasound evaluation may be useful in cases of
severe presumed nausea and vomiting of pregnancy. It
may identify a predisposing factor, such as multiple ges-
tation or molar gestation.
When is enteral or parenteral nutrition
recommended?
The principal criterion for introducing additional nutri-
tional strategies is persistent weight loss. Serious compli-
cations of hyperemesis gravidarum for the woman and
fetus arise in the group of women who cannot maintain
their weight despite antiemetic therapy. Intravenous
hydration should be used for the patient who cannot toler-
ate oral liquids for a prolonged period or if clinical signs
of dehydration are present. Correction of ketosis and vita-
min deficiency should be strongly considered. Dextrose
and vitamins, especially thiamine, should be included in
the therapy when prolonged vomiting is present.
No randomized trials compare enteral with par-
enteral nutrition in women with nausea and vomiting of
pregnancy who continue to lose weight despite antiemet-
ic therapy. Several case reports and a small series (83)
suggest that enteral tube feeding is well tolerated in
pregnancy. Because life-threatening complications of
parenteral nutrition have been described (35, 36, 84), it
is reasonable to attempt enteral tube feeding initially.
Peripheral parenteral nutrition using a high-lipid formu-
la can be used for patients whose calorie requirements
are not great and those whose length of treatment is
anticipated to be no more than several days. For women
who need longer-term support and who cannot tolerate
enteral tube feedings, the use of total parenteral nutrition
has been described for hyperemesis gravidarum in case
reports and 2 small series (35, 85). A peripherally insert-
ed central catheter can be used to avoid some of the com-
plications of central access (86), but it is still associated
with significant morbidity (87).
When is hospitalization indicated?
No controlled trials compare hospitalization with outpa-
tient management of hyperemesis gravidarum. When a
woman cannot tolerate liquids without vomiting and has
not responded to outpatient management, hospitalization
for evaluation and treatment is recommended. After the
patient has been hospitalized on one occasion and a
workup for other causes of severe vomiting has been
undertaken, intravenous hydration, nutritional support,
and modification of antiemetic therapy often can be
accomplished at home. Nevertheless, the option of hos-
pitalization for observation and further assessment
should be preserved for patients who experience a
change in vital signs or a change in affect or who con-
tinue to lose weight.
Stillbirth
Neonatal death
Postneonatal death
COMPENDIUM OF SELECTED PUBLICATIONS 894
term pregnancy in which women with favorable cervices
were managed expectantly, there was no indication that
expectant management had a deleterious effect on the
outcome, but results were not stratified according to the
condition of the cervix (31, 32, 38, 42, 51, 52).
For women who are experiencing postterm pregnan-
cies and have favorable cervices, data are insufficient to
determine whether labor induction or expectant manage-
ment yields a better outcome. However, labor generally is
induced in postterm pregnancies in which the cervix is
favorable because the risk of failed induction and subse-
quent cesarean delivery is low.
For a postterm patient with an unfavorable
cervix, does the evidence support labor induc-
tion or expectant management?
Both expectant management and labor induction are asso-
ciated with low complication rates and good perinatal
outcomes in low-risk postterm women with unfavorable
cervices (2436, 39, 40). However, there appears to be a
small advantage to labor induction using cervical ripening
agents, when indicated, regardless of parity or method of
induction. The introduction of preinduction cervical mat-
uration has resulted in fewer failed and serial inductions,
reduced fetal and maternal morbidity, reduced medical
cost, and possibly a reduced rate of cesarean delivery in
the general obstetric population (2, 35, 36, 5355).
Although postterm pregnancy is defined as a preg-
nancy of 42 weeks or more of gestation, several large
multicenter randomized studies of management of preg-
nancy beyond 40 weeks of gestation reported favorable
outcomes with routine induction as early as the beginning
of 41 weeks of gestation (2, 35, 36). The largest study to
date randomly assigned 3,407 low-risk women with
uncomplicated singleton pregnancies at 41 weeks of ges-
tation to labor induction (with or without cervical ripen-
ing agents) within 4 days of randomization or expectant
management until 44 weeks of gestation (35). Elective
induction resulted in a lower cesarean delivery rate
(21.2% versus 24.5%), primarily related to fewer surg-
eries performed for nonreassuring fetal heart rate trac-
ings. However, the authors could not identify a particular
cause related to postterm pregnancy status. Patient satis-
faction was significantly higher in women randomly
assigned to labor induction.
A meta-analysis of 19 trials of routine versus selec-
tive labor induction in postterm patients found that rou-
tine induction after 41 weeks of gestation was associated
with a lower rate of perinatal mortality (OR, 0.2; 95% CI,
0.060.7) and no increase in the cesarean delivery rate
(OR, 1.02; 95% CI, 0.751.38) (2). Routine labor induc-
tion also had no effect on the instrumental delivery rate,
use of analgesia, or incidence of fetal heart rate abnor-
mality. The risk of meconium-stained amniotic fluid was
reduced, but the risks of meconium aspiration syndrome
and neonatal seizures were unaffected (2). The actual risk
of stillbirth during the 41st week of gestation is estimat-
ed at 1.041.27 per 1,000 undelivered women, compared
with 1.553.1 per 1,000 women at or beyond 42 weeks of
gestation (56). Taken together, these data suggest that
routine induction at 41 weeks of gestation has fetal ben-
efit without incurring the additional maternal risks of a
higher rate of cesarean delivery (2, 20).
This conclusion has not been universally accepted.
Smaller studies report mixed results regarding cesarean
delivery rates; some show an increase (33, 38), and oth-
ers show no difference in the cesarean delivery rate (31,
34, 36, 37, 39, 40). Two studies reported an increase in
cesarean delivery rates only among certain subgroups of
patients (eg, high-risk groups) (32, 42).
What is the role of prostaglandin prepara-
tions in managing a postterm pregnancy?
Prostaglandin (PG) is a valuable tool for improving cer-
vical ripeness and inducing labor. Several placebo-con-
trolled clinical trials have reported significant changes in
Bishop scores, shorter durations of labor, lower maximum
doses of oxytocin, and a reduced incidence of cesarean
delivery among postterm patients who received PGE
2
gel
(5759). In contrast, a National Institute of Child Health
and Human Development study reported no reduction in
the cesarean delivery rate or the induction-to-delivery
interval among postterm patients who were randomized to
receive PGE
2
gel as compared with those receiving place-
bo, although the gel was more effective in initiating per-
sistent contractions in nulliparous women (36). Both
PGE
2
(dinoprostone) (31, 33, 35, 36, 42, 5962) and PGE
1
(misoprostol) preparations (6365) have been used for
labor induction in postterm pregnancies.
Although multiple studies have used PG to induce
labor in postterm pregnancies, no standardized dose or
dosing interval has been established. Overall, the med-
ications were well tolerated with few reported side
effects. Higher doses of PG (especially PGE
1
) have been
associated with an increased risk of uterine tachysystole
and hyperstimulation leading to nonreassuring fetal test-
ing results (55, 66). As such, lower doses are preferable.
When PG is used, fetal heart rate monitoring should be
done routinely to assess fetal well-being because of the
risk of uterine hyperstimulation.
Is there a role for vaginal birth after cesarean
delivery in the management of postterm
pregnancy?
Vaginal birth after cesarean delivery (VBAC) has been
promoted as a reasonable alternative to elective repeat
Fetal assessment
k Mild Routine obstetric care
Ko Mild Routine obstetric care
Kp
a
Mild Routine obstetric care
Kp
b
Mild Routine obstetric care
Js
a
Mild Routine obstetric care
Js
b
Mild Routine obstetric care
Rh (non-D) E Mild to severe
Fetal assessment
C Mild to severe
Fetal assessment
C Mild to severe
Fetal assessment
Duffy Fy
a
Mild to severe
Fetal assessment
Fy
b
Routine obstetric care
By
3
Mild Routine obstetric care
Kidd Jk
a
Mild to severe Fetal assessment
Jk
b
Mild Routine obstetric care
Jk
3
Mild Routine obstetric care
MNSs M Mild to severe Fetal assessment
N Mild Routine obstetric care
S Mild to severe Fetal assessment
s Mild to severe Fetal assessment
U Mild to severe Fetal assessment
Mi
a
Moderate Fetal assessment
MSSs Mt
a
Moderate Fetal assessment
Vw Mild Routine obstetric care
Mur Mild Routine obstetric care
Hil Mild Routine obstetric care
Hut Mild Routine obstetric care
Lutheran Lu
a
Mild Routine obstetric care
Lu
b
Mild Routine obstetric care
Diego D1
a
Mild to severe Fetal assessment
Di
b
Mild to severe Fetal assessment
Xg Xg
a
Mild Routine obstetric care
P PP
1pk
(Tj
a
) Mild to severe Fetal assessment
Public antigens Yt
a
Moderate to severe Fetal assessment
Yt
b
Mild Routine obstetric care
Lan Mild Routine obstetric care
En
a
Moderate Fetal assessment
Ge Mild Routine obstetric care
Jr
a
Mild Routine obstetric care
Co
a
Severe Fetal assessment
Co
1-b-
Mild Routine obstetric care
Private antigens Batty Mild Routine obstetric care
Becker Mild Routine obstetric care
Berrens Mild Routine obstetric care
(continued)
943 PRACTICE BULLETINS
with a history of a previously affected fetus or neonate,
serial titer assessment is inadequate for surveillance of
fetal anemia. Titer values are reported as the integer of
the greatest tube dilution with a positive agglutination
reaction. Variation in titer results from different laborato-
ries is not uncommon, so titers should be obtained in the
same laboratory when monitoring a patient, and a change
of more than one dilution is significant. A critical titer is
that titer associated with a significant risk for severe
erythroblastosis fetalis and hydrops, and in most centers
this is between 1:8 and 1:32. If the initial antibody titer is
1:8 or less, the patient may be monitored with titer
assessment every 4 weeks. For patients with alloimmu-
nization involving antigens other than D, similar titer lev-
els should be used to guide care except in Kell-sensitized
patients because Kell antibodies do not correlate with
fetal status (19).
What ancillary tests should follow identifica-
tion of maternal antibodies to diagnose
hemolytic disease in the fetus?
Determination of Paternal Genotype
The initial management of a pregnancy involving an
alloimmunized patient is determination of the paternal
erythrocyte antigen status. If the father is negative for the
erythrocyte antigen in question (and it is certain that he is
the father of the fetus), further assessment and interven-
tion are unnecessary. In cases of Rh-D alloimmunization
in which the father is Rh positive, the probability that he
Anti-D Immune Globulin to Prevent
Alloimmunization
Anti-D immune globulin is not indicated for patients pre-
viously sensitized to D. However, it is indicated for
patients who might be sensitized to other blood group
antigens.
Clinical Considerations and
Recommendations
What are the best screening methods for
detecting alloimmunization in women?
All pregnant women should be tested at the time of the
first prenatal visit for ABO blood group and Rh-D type
and screened for the presence of erythrocyte antibodies.
These laboratory assessments should be repeated in each
subsequent pregnancy. The American Association of
Blood Banks also recommends repeated antibody screen-
ing before administration of anti-D immune globulin at
28 weeks of gestation, postpartum, and at the time of any
event in pregnancy. Patients who are weak D (D
u
) posi-
tive are not at risk for alloimmunization and should not
receive anti-D immunoprophylaxis.
At what antibody titer should an additional
evaluation be initiated?
The usefulness of maternal serum antibody titers is deter-
mined by the patients reproductive history. For a woman
Table 1. Atypical Antibodies and Their Relationship to Fetal Hemolytic Disease (continued)
Blood Group Antigens Related to
System Hemolytic Disease Hemolytic Disease Severity Proposed Management
Private antigens Biles Moderate Fetal assessment
Evans Mild Routine obstetric care
Gonzales Mild Routine obstetric care
Good Severe Fetal assessment
Heibel Moderate Fetal assessment
Hunt Mild Routine obstetric care
Jobbins Mild Routine obstetric care
Radin Moderate Fetal assessment
Rm Mild Routine obstetric care
Ven Mild Routine obstetric care
Wright
a
Severe Fetal assessment
Wright
b
Mild Routine obstetric care
Zd Moderate Fetal assessment
*Not a proven cause of hemolytic disease of the newborn
Figure 1. Hemoglobin concentrations in 265 healthy fetuses and 111 fetuses that underwent cor-
docentesis. The reference range in the healthy fetuses was between 0.84 and 1.16 times the median
(corresponding to the 5th and 95th percentiles). Values for the 111 fetuses that underwent cordo-
centesis are plotted individually. Solid circles indicate fetuses with hydrops. (Mari G, Deter RL,
Carpenter RL, Rahman F, Zimmerman R, Moise KJ Jr, et al. Noninvasive diagnosis by Doppler ultra-
sonography of fetal anemia due to maternal red-cell alloimmunization. Collaborative Group for
Doppler Assessment of the Blood Velocity of Anemic Fetuses. N Engl J Med 2000:342:914. Copyright
2000 Massachusetts Medical Society. All rights reserved.)
M
u
l
t
i
p
l
e
s
o
f
t
h
e
m
e
d
i
a
n
H
e
m
o
g
l
o
b
i
n
(
g
/
d
L
)
18
17
16
15
14
13
12
11
10
9
8
7
6
5
4
3
2
1
0
16 18 20 22 24 26 28 30 32 34 36
Gestational age (weeks)
1.16
Median
0.84
0.65
0.55
Mild anemia
Moderate anemia
Severe anemia
COMPENDIUM OF SELECTED PUBLICATIONS 946
Recommendations and
Conclusions
The following recommendations are based on
good and consistent scientific evidence (Level A):
In a center with trained personnel and when the
fetus is at an appropriate gestational age, Doppler
measurement of peak systolic velocity in the fetal
middle cerebral artery is an appropriate noninvasive
means to monitor pregnancies complicated by red
cell alloimmunization.
The initial management of a pregnancy involving an
alloimmunized patient is determination of the pater-
nal erythrocyte antigen status.
Serial titers are not useful for monitoring fetal status
when the mother has had a previously affected fetus
or neonate.
Antibody titers are not appropriate for monitoring
Kell-sensitized patients because Kell antibodies do
not correlate with fetal status.
Anti-D immune globulin is indicated only in Rh-neg-
ative women who are not previously sensitized to D.
Proposed Performance
Measure
Further evaluation of patients found to have significant
antibodies associated with fetal anemia
References
1. American College of Obstetricians and Gynecologists.
Prevention of Rh D alloimmunization. ACOG Practice
Bulletin No. 4. Washington, DC: ACOG; 1999.
2. Race RR, Sanger R. Blood groups in man. 6th ed. Oxford
(UK): Blackwell Scientific Publications; 1975. (Level III)
3. Rote NS. Pathophysiology of Rh isoimmunization. Clin
Obstet Gynecol 1982;25:24353. (Level III)
4. McKenna DS, Nagaraja HN, OShaughnessy R.
Management of pregnancies complicated by anti-Kell
isoimmunization. Obstet Gynecol 1999;93:66773.
(Level II-3)
5. Cohen F, Zuelzer WW, Gustafson DC, Evans MM.
Mechanisms of isoimmunization. I. The transplacental
passage of fetal erythrocytes in homospecific pregnancies.
Blood 1964;23:62146. (Level III)
6. Lloyd LK, Miya F, Hebertson RM, Kochenour NK, Scott
JR. Intrapartum fetomaternal bleeding in Rh-negative
women. Obstet Gynecol 1980;5:2858. (Level III)
7. Woodrow JC. Rh immunisation and its prevention. Ser
Haematol 1970;3:1151. (Level III)
8. Zipursky A, Israels LG. The pathogenesis and prevention
of Rh immunization. Can Med Assoc J 1967;97:124557.
(Level III)
9. Stedman CM, Baudin JC, White CA, Cooper ES. Use of
the erythrocyte rosette test to screen for excessive fetoma-
ternal hemorrhage in Rh-negative women. Am J Obstet
Gynecol 1986;154:13639. (Level III)
10. Ness PM, Baldwin ML, Niebyl JR. Clinical high-risk des-
ignation does not predict excess fetal-maternal hemor-
rhage. Am J Obstet Gynecol 1987;156:1548. (Level II-3)
11. Bowman JM. The management of Rh-isoimmunization.
Obstet Gynecol 1978;52:116. (Level III)
12. Davey M. The prevention of rhesus-isoimmunization.
Clin Obstet Gynaecol 1979;6:50930. (Level III)
13. Litwalk O, Taswell HF, Banner EA, Keith L. Fetal eryth-
rocytes in maternal circulation after spontaneous abor-
tion. JAMA 1970;214:5314. (Level II-3)
14. Von Stein GA, Munsick RA, Stiver K, Ryder K.
Fetomaternal hemorrhage in threatened abortion. Obstet
Gynecol 1992;79:3836. (Level II-3)
15. Dayton VD, Anderson DS, Crosson JT, Cruikshank SH. A
case of Rh isoimmunization: should threatened first-
trimester abortion be an indication for Rh immune globu-
lin prophylaxis? Am J Obstet Gynecol 1990;163:634.
(Level III)
16. Leong M, Duby S, Kinch RA. Fetal-maternal transfusion
following early abortion. Obstet Gynecol 1979;54:4246.
(Level II)
17. Katz J, Marcus RG. The risk of Rh isoimmunization in
ruptured tubal pregnancy. Br Med J 1972;3(828):6679.
(Level III)
18. Mennuti MT, Brummond W, Crombleholme WR,
Schwarz RH, Arvan DA. Fetal-maternal bleeding associ-
ated with genetic amniocentesis. Obstet Gynecol 1980;
55:4854. (Level II-3)
19. Hackney DN, Knudtson EJ, Rossi KQ, Krugh D,
OShaughnessy RW. Management of pregnancies compli-
cated by anti-c isoimmunization. Obstet Gynecol 2004;
103:2430. (Level III)
20. Van den Veyver IB, Moise KJ Jr. Fetal RhD typing by
polymerase chain reaction in pregnancies complicated by
rhesus alloimmunization. Obstet Gynecol 1996;88:
10617. (Level III)
21. Moise KJ Jr. Management of rhesus alloimmunization in
pregnancy [published erratum appears in Obstet Gynecol
2002;100:833]. Obstet Gynecol 2002;100:60011. (Level
III)
22. Lo YM, Hjelm NM, Fidler C, Sargent IL, Murphy MF,
Chamberlain PF, et al. Prenatal diagnosis of fetal RhD sta-
tus by molecular analysis of maternal plasma. N Engl J
Med 1998;339:17348. (Level II-3)
23. Gautier E, Benachi A, Giovangrandi Y, Ernault P, Olivi M,
Gaillon T, et al. Fetal RhD genotyping by maternal serum
analysis: a two-year experience. Am J Obstet Gynecol
2005;192:6669. (Level III)
8287*
Second trimester
Triple screen (MSAFP, hCG,
unconjugated estriol) 69*
Quadruple screen (MSAFP, hCG,
unconjugated estriol, inhibin A) 81*
First Plus Second Trimester
Integrated (NT, PAPP-A, quad screen) 9496*
Serum integrated (PAPP-A, quad screen) 8588*
Stepwise sequential 95*
First-trimester test result:
Positive: diagnostic test offered
Negative: second-trimester test
offered
Final: risk assessment incorporates first
and second results
Contingent sequential 8894%
(%)
BUN
8,216 61 79
FASTER
33,557 84 83
SURUSS
47,053 101 83
OSCAR
#
15,030 82 90
Total 103,856 328 84
*First-trimester detection rate (DR) at 5% of false-positive rate (FPR)
Wapner RJ, Thom EA, Simpson JL, Pergament E, Silver R, Filkins K, et al. First-trimester screening for trisomies
21 and 18. First Trimester Maternal Serum Biochemistry and Fetal Nuchal Translucency Screening (BUN) Study
Group. N Engl J Med 2003;349:140513.
Malone FD, Wald NJ, Canick JA, Ball RH, Nyberg DA, Comstock CH, et al. First- and second-trimester evalua-
tion of risk (FASTER) trial: principal results of the NICHD multicenter Down syndrome screening study
[abstract]. Am J Obstet Gynecol 2003;189:(suppl 1):s56.
Wald NJ, Rodeck C, Hackshaw AK, Walters J, Chitty L, Mackinson AM. First and second trimester antenatal
screening for Downs syndrome: the results of the Serum, Urine and Ultrasound Screening Study (SURUSS)
[published erratum appears in J Med Screen 2006;13:512]. J Med Screen 2003;10:56104.
#Spencer K, Spencer CE, Power M, Dawson C, Nicolaides KH. Screening for chromosomal abnormalities in the
first trimester using ultrasound and maternal serum biochemistry in a one-stop clinic: a review of three years
prospective experience. BJOG 2003;110:2816.
Reprinted from: Wapner RJ. First trimester screening: the BUN study. Semin Perinatol 2005;29:2369. With per-
mission from Elsevier.
961 PRACTICE BULLETINS
mately 90%, but at a higher screen-positive rate (approxi-
mately 1622%) (12, 13). For women of all ages, 90% of
trisomy 18 cases are detected at a 2% screen-positive rate
(13).
What is the advantage of first-trimester
screening?
The advantage of first-trimester screening is that women
who present for prenatal care before 14 weeks of gesta-
tion can have information sooner. If the woman is found
to be at an increased risk of fetal aneuploidy, she can be
offered genetic counseling and CVS, if the procedure is
available. Alternatively, she may choose to have a sec-
ond-trimester amniocentesis.
Should first- and second-trimester screening
tests be performed independently?
When first-trimester and second-trimester screening tests
are performed during the pregnancy and interpreted inde-
pendently, there is a high Down syndrome detection rate
(9498%); however, the false-positive rates are additive,
leading to many more unnecessary invasive procedures
(1117%) (12, 14). For this reason, women who have had
first-trimester screening for aneuploidy should not
undergo independent second-trimester serum screening
in the same pregnancy. Instead, women who want a high-
er detection rate can have an integrated or a sequential
screening test, which combines both first- and second-
trimester screening results.
What is integrated screening?
The integrated approach to screening uses both the first-
trimester and second-trimester markers to adjust a
womans age-related risk of having a child with Down syn-
drome (15). The results are reported only after both first-
and second-trimester screening tests are completed. In the
FASTER (First- and Second-Trimester Evaluation of Risk)
trial, the detection rate was 9496% at a 5% screen-positive
rate (12). Similar results were achieved in the SURUSS
(Serum, Urine, and Ultrasound Screening Study) trial (16).
Further refinements in interpretation may result in addi-
tional sensitivity and reduction of screen-positive rates.
Integrated screening also can be performed using
only first- and second-trimester serum markers, without
incorporating a nuchal translucency measurement. In the
FASTER trial, the serum integrated screen resulted in an
8588% detection rate (12). This approach is ideal for
patients without access to nuchal translucency measure-
ment or for whom reliable measurement cannot be
obtained. A recent prospective trial of serum-only inte-
grated screening in a population with limited access to
CVS reported acceptance of this screening algorithm by
most patients surveyed (17).
What are the advantages and disadvantages
of having an integrated first- and second-
trimester Down syndrome screening test
(first- and second-trimester markers analyzed
together [integrated], with only one result
given in the second trimester)?
Integrated screening best meets the goal of screening by
providing the highest sensitivity with the lowest false-
positive rate. The lower false-positive rate results in
fewer invasive tests and thus fewer procedure-related
losses of normal pregnancies (12, 18). Although some
patients value early screening, others are willing to wait
several weeks if doing so results in an improved detection
rate and less chance that they will need an invasive diag-
nostic test (19). Concerns about integrated screening
include possible patient anxiety generated by having to
wait 34 weeks between initiation and completion of the
screening and the loss of the opportunity to consider CVS
if the first-trimester screening indicates a high risk of
aneuploidy (20). The possibility that patients might fail
to complete the second-trimester portion of the screening
test after performing the first-trimester component is
another potential disadvantage because the patient would
be left with no screening results.
Is there an advantage to using a sequential
screening test for Down syndrome?
Sequential screening approaches that obviate some of the
disadvantages of integrated screening have been devel-
oped. With this strategy, the patient is informed of the
first-trimester screening result. Those at highest risk
might opt for an early diagnostic procedure and those at
lower risk can still take advantage of the higher detection
rate achieved with additional second-trimester screening.
Two strategies have been proposed: stepwise sequen-
tial screening and contingent sequential screening. In
the stepwise model, women determined to be at high risk
(Down syndrome risk above a predetermined cutoff) after
the first-trimester screen are offered genetic counseling
and the option of invasive diagnostic testing, and women
below the cutoff are offered second-trimester screening.
Contingent sequential screening has been proposed as a
model, but large clinical trials using this approach have not
yet been published. The contingent model classifies preg-
nancy risk as high, intermediate, or low on the basis of the
first-trimester screen results; women at high risk would be
offered CVS, and those at low risk would have no further
screening or testing. Only women at intermediate risk
COMPENDIUM OF SELECTED PUBLICATIONS 962
would be offered second-trimester screening. Hence,
fewer women would go on to second-trimester screening.
In both the stepwise and contingent models, the patients at
highest risk identified by first-trimester screening are
offered an early diagnostic procedure. Both first- and sec-
ond-trimester results are used to calculate a final risk for
aneuploidy in patients at lower risk. The sequential
approach takes advantage of the higher detection rate
achieved by incorporating the first- and second-trimester
results with only a marginal increase in the false-positive
rate. Theoretically, the contingent approach should main-
tain high detection rates with low false-positive rates while
reducing the number of second-trimester tests performed.
What subsequent evaluation should be
offered after first-trimester screening?
Women found to have an increased risk of aneuploidy with
first-trimester screening should be offered genetic counsel-
ing and diagnostic testing by CVS or a second-trimester
genetic amniocentesis. Neural tube defect screening
should be offered in the second trimester to patients who
elected to have only first-trimester screening for aneu-
ploidy or who have had a normal result from CVS. Neural
tube defect screening may include second-trimester serum
AFP screening or ultrasonography. Patients who have a
fetal nuchal translucency measurement of 3.5 mm or
greater in the first trimester, despite a negative result on an
aneuploidy screen, normal fetal chromosomes, or both,
should be offered a targeted ultrasound examination, fetal
echocardiogram, or both, because such fetuses are at a sig-
nificant risk for nonchromosomal anomalies, including
congenital heart defects, abdominal wall defects, diaphrag-
matic hernias, and genetic syndromes (2125).
Patients with abnormal first-trimester serum markers
or an increased nuchal translucency measurement also
may be at increased risk for an adverse pregnancy out-
come such as spontaneous fetal loss before 24 weeks of
gestation, fetal demise, low birth weight, or preterm birth
(26, 27). At the present time, there are no data indicating
whether or not fetal surveillance in the third trimester
will be helpful in the care of these patients.
The significance of ultrasonographic markers identi-
fied by a second-trimester ultrasound examination in a
patient who has had a negative first-trimester screening test
result is unknown. A variety of ultrasound findings have
been associated with Down syndrome. A major anomaly,
such as a cardiac defect, deserves further evaluation. More
subtle findings (soft markers), such as pyelectasis, short-
ened femur or humerus, or echogenic bowel individually,
do not significantly increase the risk of Down syndrome.
However, these findings should be considered in the con-
text of the screening results, patients age, and history.
Are there other first-trimester ultrasono-
graphic markers that are useful for Down
syndrome screening?
Several other first-trimester ultrasonographic markers,
including nonvisualized nasal bone, tricuspid regurgita-
tion, crownrump length, femur and humeral length,
head and trunk volumes, and umbilical cord diameters,
have been evaluated as potential markers for aneuploidy
in the first trimester. Studies in high-risk first-trimester
populations indicate a high rate of nonvisualization of
the nasal bone in fetuses with Down syndrome. Three
European studies reported a 66.780% Down syndrome
detection rate at a 0.21.4% false-positive rate (2830).
The value of nasal bone assessment as a Down syndrome
screening test in the general population is controversial.
A first-trimester study performed in the United States
did not find the test to be useful (12). In addition, there
are considerable ethnic differences in the prevalence of
absent nasal bone; absence of the nasal bone in a euploid
fetus is found in only 2.8% of Caucasians, compared
with 6.8% of Asians and 10.4% of Afro-Caribbeans (31).
It has been suggested that standardization of nasal bone
assessment (32), along with extensive teaching and qual-
ity control programs, should be developed before this
technique is used in the general population (33).
Strategies restricting assessment of nasal bone to a sub-
set of pregnant women at the highest risk after first-
trimester combined screening, rather than the entire
population, appear to be more practical and are being
investigated.
What are the benefits and limitations of
second-trimester ultrasound examination
as a screening test for Down syndrome?
Individual second-trimester ultrasonographic markers,
such as echogenic bowel, intracardiac echogenic focus,
and dilated renal pelvis, have a low sensitivity and speci-
ficity for Down syndrome particularly when used to
screen a low-risk population (34). Studies indicate that
the highest detection rate is achieved with systematic
combination of ultrasonographic markers and gross
anomalies, such as thick nuchal fold or cardiac defects
(35, 36). Studies done in high-risk populations have
reported detection rates of approximately 5075% in the
second trimester. However, the false-positive rates are
high (eg, a 21.9% false-positive rate for a 100% Down
syndrome detection rate) (37). One group has reported
that if no abnormal ultrasonographic markers are identi-
fied after a carefully performed scan at a specialized cen-
ter with skilled ultrasonographers, the a priori risk of
Down syndrome in a high-risk patient (advanced mater-
963 PRACTICE BULLETINS
nal age, abnormal serum screen) may be reduced by
8288% (38). Because the RADIUS (Routine Antenatal
Diagnostic Imaging With Ultrasound) trial (39) and
others showed that even major fetal anomalies are fre-
quently missed by ultrasound examination, the disadvan-
tages of relying solely on ultrasonography for Down
syndrome screening should be considered carefully.
Combining second-trimester ultrasonographic and bio-
chemical markers is a relatively new development that
has been shown to be a feasible method to improve
Down syndrome screening performance over either
ultrasonography or second-trimester serum markers by
themselves (40), provided that the ultrasound examination
is performed as part of a specific screening protocol (37).
A major limitation of the use of second-trimester
ultrasonographic markers has been the lack of standardiza-
tion in measurements and definitions of what constitutes
abnormal findings. This has contributed to variability in
the diagnostic performance reported by different groups.
Recent prospective studies that used specific criteria to
define abnormal markers in large groups of unselected
patients in the United States confirm a statistically sig-
nificant increase in the frequency of individual ultra-
sonographic markers in Down syndrome compared with
normal second-trimester cases (41, 42). At this time, risk
adjustment based on second-trimester ultrasonographic
markers should be limited to centers with ultrasonograph-
ic expertise and centers engaged in clinical research to
develop a standardized approach to evaluating these mark-
ers. However, an abnormal second-trimester ultrasound
finding identifying a major congenital anomaly signifi-
cantly increases the risk of aneuploidy and warrants fur-
ther counseling and the offer of a diagnostic procedure.
How does screening for aneuploidy differ in
multifetal gestations?
Serum screening tests are not as sensitive in twin or
triplet gestations, in part because data from multiple ges-
tations that include an aneuploid fetus is so scarce that
expected analyte levels must be estimated by mathemat-
ical modeling. In addition, analytes from both the normal
and the affected fetuses enter the maternal serum and are
in effect averaged together, thus masking the abnormal
levels of the affected fetus. In monochorionic twin
pregnancies, the median nuchal translucency values are
larger in 38% of twin pairs destined to develop severe
twintwin transfusion syndrome (43). Furthermore,
counseling is more complex because women must con-
sider a different set of options in the event that only one
of the fetuses is affected. Nuchal translucency screening
in the first trimester with the option of a CVS and earlier
selective reduction may be desirable for some women.
Experience is limited with triplet gestations, but studies
suggest that nuchal translucency measurement is feasible.
Until further studies are done, however, risk assessment
in multiple gestations should be performed judiciously,
and patients who are at increased risk of aneuploidy
should be counseled regarding diagnostic testing.
Should invasive diagnostic testing for aneu-
ploidy be available to all women?
All women, regardless of age, should have the option of
invasive testing. A womans decision to have an amnio-
centesis or CVS is based on many factors, including the
risk that the fetus will have a chromosomal abnormality,
the risk of pregnancy loss from an invasive procedure,
and the consequences of having an affected child if diag-
nostic testing is not done. Studies that have evaluated
womens preferences have shown that women weigh
these potential outcomes differently. The decision to
offer invasive testing should take into account these pref-
erences and should not be solely age based. The differ-
ences between screening and diagnostic testing should
be discussed with all women. Thus, maternal age of 35
years alone should no longer be used as a cutoff to deter-
mine who is offered screening versus who is offered
invasive testing.
With so many Down syndrome screening tests
available, how do I decide which tests to offer?
The goal is to offer screening tests with high detection
rates and low false-positive rates that also provide
patients with the diagnostic options they might want to
consider. Ideally, patients seen early in pregnancy should
be offered aneuploidy screening that combines first- and
second-trimester testing (integrated or sequential). The
screening strategy chosen will depend on availability of
CVS and of personnel trained in nuchal translucency
measurement in the area. When CVS is not available, it
makes sense to offer integrated screening to patients who
present in the first trimester in order to take advantage of
the improved detection rate and low false-positive rate
and to offer second-trimester screening to patients who
present after 13
6
7 weeks. If nuchal translucency mea-
surement is not available or cannot be obtained in an
individual patient, a reasonable approach is to offer
serum integrated screening to patients who present early
and second-trimester screening to those who present
later. In areas where every screening strategy is possible,
it is reasonable to choose two screening strategies for the
practice, such as sequential screening for patients who
present for prenatal care before 14 weeks of gestation
(because it provides them with a first-trimester risk
assessment and the option of waiting until the second
COMPENDIUM OF SELECTED PUBLICATIONS 964
Integrated first- and second-trimester screening is
more sensitive with lower false-positive rates than
first-trimester screening alone.
Serum integrated screening is a useful option in
pregnancies where nuchal translucency measure-
ment is not available or cannot be obtained.
An abnormal finding on second-trimester ultra-
sound examination identifying a major congenital
anomaly significantly increases the risk of aneu-
ploidy and warrants further counseling and the offer
of a diagnostic procedure.
Patients who have a fetal nuchal translucency mea-
surement of 3.5 mm or higher in the first trimester,
despite a negative aneuploidy screen, or normal fetal
chromosomes, should be offered a targeted ultra-
sound examination, fetal echocardiogram, or both.
Down syndrome risk assessment in multiple gesta-
tion using first- or second-trimester serum analytes
is less accurate than in singleton pregnancies.
First-trimester nuchal translucency screening for
Down syndrome is feasible in twin or triplet gesta-
tion but has lower sensitivity than first-trimester
screening in singleton pregnancies.
The following recommendations are based pri-
marily on consensus and expert opinion (Level C):
After first-trimester screening, subsequent second-
trimester Down syndrome screening is not indicated
unless it is being performed as a component of the
integrated test, stepwise sequential, or contingent
sequential test.
Subtle second-trimester ultrasonographic markers
should be interpreted in the context of a patients
age, history, and serum screening results.
Proposed Performance
Measure
Percentage of patients with documentation of discussion
regarding Down syndrome screening
trimester for an adjusted risk assessment that includes
their second-trimester serum results), and second-
trimester serum screening for patients who present after
13
6
7 weeks of gestation. In some instances, patients who
would consider first-trimester termination of pregnancy
but not second-trimester termination of pregnancy may
want only first-trimester screening.
Summary of
Recommendations and
Conclusions
The following recommendations are based on
good and consistent scientific evidence (Level A):
First-trimester screening using both nuchal translu-
cency measurement and biochemical markers is an
effective screening test for Down syndrome in the
general population. At the same false-positive rates,
this screening strategy results in a higher Down syn-
drome detection rate than does the second-trimester
maternal serum triple screen and is comparable to
the quadruple screen.
Measurement of nuchal translucency alone is less
effective for first-trimester screening than is the
combined test (nuchal translucency measurement
and biochemical markers).
Women found to have increased risk of aneuploidy
with first-trimester screening should be offered
genetic counseling and the option of CVS or sec-
ond-trimester amniocentesis.
Specific training, standardization, use of appropriate
ultrasound equipment, and ongoing quality assess-
ment are important to achieve optimal nuchal
translucency measurement for Down syndrome risk
assessment, and this procedure should be limited to
centers and individuals meeting these criteria.
Neural tube defect screening should be offered in
the second trimester to women who elect only first-
trimester screening for aneuploidy.
The following recommendations are based on lim-
ited or inconsistent scientific evidence (Level B):
Screening and invasive diagnostic testing for aneu-
ploidy should be available to all women who present
for prenatal care before 20 weeks of gestation
regardless of maternal age. Women should be coun-
seled regarding the differences between screening
and invasive diagnostic testing.
Glossary
Aneuploidy: In this condition there is an extra or
missing chromosome.
Screen-positive rate: percentage of the population
with a positive screening test result. This includes true
positives and false positives.
Nuchal translucency measurement: Accumulated
fluid behind the fetal neck is measured in a standard-
ized way.
965 PRACTICE BULLETINS
References
1. Merkatz IR, Nitowsky HM, Macri JN, Johnson WE. An
association between low maternal serum alpha-fetopro-
tein and fetal chromosomal abnormalities. Am J Obstet
Gynecol 1984;148:88694. (Level II-2)
2. Wald NJ, Kennard A, Hackshaw A, McGuire A. Antenatal
screening for Downs syndrome. Health Technol Assess
1998;2:iiv,1112. (Level III)
3. Spencer K, Wallace EM, Ritoe S. Second-trimester dimer-
ic inhibin-A in Downs syndrome screening. Prenat Diagn
1996;16:110110. (Level II-3)
4. Nicolaides KH, Snijders RJ, Gosden CM, Berry C,
Campbell S. Ultrasonographically detectable markers of
fetal chromosomal abnormalities. Lancet 1992;340:
7047. (Level III)
5. Malone FD, Berkowitz RL, Canick JA, DAlton ME.
First-trimester screening for aneuploidy: research or stan-
dard of care? Am J Obstet Gynecol 2000;182:4906.
(Level III)
6. Nicolaides KH, Heath V, Liao AW. The 11-14 week scan.
Baillieres Best Pract Res Clin Obstet Gynaecol
2000;14:58194. (Level III)
7. Snijders RJ, Thom EA, Zachary JM, Platt LD, Greene N,
Jacson LG, et al. First-trimester trisomy screening: nuchal
translucency measurement training and quality assurance
to correct and unify technique. Ultrasound Obstet
Gynecol 2002;19:3539. (Level III)
8. Cuckle H. Biochemical screening for Down syndrome. Eur
J Obstet Gynecol Reprod Biol 2000;92:97101. (Level III)
9. Spencer K, Souter V, Tul N, Snijders R, Nicolaides KH. A
screening program for trisomy 21 at 10-14 weeks using
fetal nuchal translucency, maternal serum free beta-
human chorionic gonadotropin and pregnancy-associated
plasma protein-A. Ultrasound Obstet Gynecol 1999;13:
2317. (Level II-3)
10. Snijders RJ, Noble P, Sebire N, Souka A, Nicolaides KH.
UK multicentre project on assessment of risk of trisomy
21 by maternal age and fetal nuchal-translucency thick-
ness at 10-14 weeks of gestation. Fetal Medicine
Foundation First Trimester Screening Group. Lancet
1998;352:3436. (Level III)
11. Nicolaides KH. Nuchal translucency and other first-
trimester sonographic markers of chromosomal abnormal-
ities. Am J Obstet Gynecol 2004;191:4567. (Level III)
12. Malone F, Canick JA, Ball RH, Nyberg DA, Comstock
CH, Buckowski R, et al. First-trimester or second-
trimester screening, or both, for Downs syndrome. First-
and Second-Trimester Evaluation of Risk (FASTER)
Research Consortium. N Engl J Med 2005;353:200111.
(Level II-2)
13. Wapner R, Thom E, Simpson JL, Pergament E, Silver R,
Filkins K, et al. First-trimester screening for trisomies 21
and 18. First Trimester Maternal Serum Biochemistry and
Fetal Nuchal Translucency Screening (BUN) Study
Group. N Engl J Med 2003;349:140513. (Level II-3)
14. Platt LD, Greene N, Johnson A, Zachary J, Thom E,
Krantz D, et al. Sequential pathways of testing after first
trimester screening for trisomy 21. First Trimester
Maternal Serum Biochemistry and Fetal Nuchal
Translucency Screening (BUN) Study Group. Obstet
Gynecol 2004;104:6616. (Level II-3)
15. Wald NJ, Watt HC, Hackshaw AK. Integrated screening
for Downs syndrome on the basis of tests performed dur-
ing the first and second trimesters. N Engl J Med 1999;
341:4617. (Level III)
16. Wald NJ, Rodeck C, Hackshaw AK, Walters J, Chitty L,
Mackinson AM. First and second trimester antenatal
screening for Downs syndrome: the results of the Serum,
Urine and Ultrasound Screening Study (SURUSS) [pub-
lished erratum appears in J Med Screen 2006;13:512]. J
Med Screen 2003;10:56104 (Level II-2)
17. Palomaki GE, Knight GJ, Neveux LM, Pandian R,
Haddow JE. Maternal serum invasive trophoblast antigen
and first-trimester Down syndrome screening. Clin Chem
2005;51:1499504. (Level II-3)
18. Wald NJ, Rodeck C, Hackshaw AK, Rudnicka A.
SURUSS in perspective. BJOG 2004;111:52131. (Level
II-2)
19. Bishop AJ, Marteau TM, Armstrong D, Chitty LS,
Longworth L, Buxton MJ, et al. Women and health care
professionals preferences for Downs syndrome screen-
ing tests: a conjoint analysis study. BJOG 2004;111:
7759. (Level III)
20. Copel JA, Bahado-Singh RO. Prenatal screening for
Downs syndromea search for the familys values. N
Engl J Med 1999;341:5212. (Level III)
21. Makrydimas G, Sotiriadis A, Huggon IC, Simpson J,
Sharland G, Carvalho JS, et al. Nuchal translucency and
fetal cardiac defects: a pooled analysis of major fetal
echocardiography centers. Am J Obstet Gynecol
2005;192:8995. (Level II-3)
22. Bahado-Singh RO, Wapner R, Thom E, Zachary J, Platt L,
Mahoney MJ, et al. Elevated first-trimester nuchal
translucency increases the risk of congenital heart defects.
First Trimester Maternal Serum Biochemistry and Fetal
Nuchal Translucency Screening Study Group. Am J
Obstet Gynecol 2005;192:135761. (Level II-3)
23. Hyett J, Perdu M, Sharland G, Snijders R, Nicolaides KH.
Using fetal nuchal translucency to screen for major con-
genital cardiac defects at 10-14 weeks of gestation: popula-
tion based cohort study. BMJ 1999;318:815. (Level II-3)
24. Souka AP, Von Kaisenberg CS, Hyett JA, Sonek JD,
Nicolaides KH. Increased nuchal translucency with nor-
mal karyotype [published erratum appears in Am J Obstet
Gynecol 2005;192:2096]. Am J Obstet Gynecol 2005;
192:100521. (Level III)
25. Comstock CH, Malone FD, Ball RH, Nyberg DA, Saade
GR, Berkowitz RL, et al. Is there a nuchal translucency
millimeter measurement above which there is no added
benefit from first trimester serum screening? FASTER
Research Consortium. Am J Obstet Gynecol 2006;195:
8437. (Level III)
26. Dugoff L, Hobbins JC, Malone FD, Porter TF, Luthy D,
Comstock CH, et al. First-trimester maternal serum
PAPP-A and free-beta subunit human chorionic gonado-
tropin concentrations and nuchal translucency are associ-
COMPENDIUM OF SELECTED PUBLICATIONS 966
35. Vintzileos AM, Campbell WA, Rodis JF, Guzman ER,
Smulian JC, Knuppel RA. The use of second-trimester
genetic sonogram in guiding clinical management of
patients at increased risk for fetal trisomy 21. Obstet
Gynecol 1996;87:94852. (Level II-3)
36. Bromley B, Benacerraf BR. The genetic sonogram scor-
ing index. Semin Perinatol 2003;27:1249. (Level III)
37. Bahado-Singh RO, Oz U, Mendilicioglu I, Mahoney M.
The mid-trimester genetic sonogram. Semin Perinatol
2005;29:20914. (Level III)
38. Yeo L, Vintzileos AM. The use of genetic sonography
to reduce the need for amniocentesis in women at high
risk of Down syndrome. Semin Perinatol 2003;27;1529.
(Level III)
39. Ewigman BG, Crane JP, Frigoletto FD, LeFevre ML, Bain
RP, McNellis D. Effect of prenatal ultrasound screening
on perinatal outcome. RADIUS Study Group. N Engl J
Med 1993;329:8217. (Level I)
40. Benn PA, Kaminsky LM, Ying J, Borgida AF, Egan JF.
Combined second-trimester biochemical and ultrasound
screening for Down syndrome. Obstet Gynecol 2002;
100:116876. (Level II-3)
41. Schluter PJ, Pritchard B. Mid trimester sonographic find-
ings for the prediction of Down syndrome in a sono-
graphically screened population. Am J Obstet Gynecol
2005;192:106. (Level II-2)
42. Benacerraf BR. The role of the second trimester genetic
sonogram in screening for fetal Down syndrome. Semin
Perinatol 2005;29:38694. (Level III)
43. Sebire NJ, DErcole C, Hughes K, Carvalho M,
Nicolaides KH. Increased nuchal translucency thickness
at 1014 weeks of gestation as a predictor of severe twin-
to-twin transfusion syndrome. Ultrasound Obstet Gynecol
1997;10:869. (Level II-3)
ated with obstetric complications: a population-based
screening study (the FASTER Trial). Am J Obstet
Gynecol 2004;191:144651. (Level II-3)
27. Smith GC, Shah I, Crossley JA, Aitken DA, Pell JP,
Nelson SM, et al. Pregnancy-associated plasma protein A
and alpha-fetoprotein and prediction of adverse perinatal
outcome. Obstet Gynecol 2006;107:1616. (Level II-2)
28. Zoppi MA, Ibba RM, Axiana C, Floris M, Manca F,
Monni G. Absence of fetal nasal bone and aneuploides at
first-trimester nuchal translucency screening in unselected
pregnancies. Prenat Diagn 2003;23:496500. (Level III)
29. Orlandi F, Bilardo CM, Campogrande M, Krantz D,
Hallahan T, Rossi C, et al. Measurement of nasal bone
length at 11-14 weeks of pregnancy and its potential role
in Down syndrome risk assessment. Ultrasound Obstet
Gynecol 2003;22:369. (Level II-3)
30. Viora E, Masturzo B, Errante G, Sciarrone A, Bastonero
S, Campogrande M. Ultrasound evaluation of fetal nasal
bone at 11 to 14 weeks in a consecutive series of 1906
fetuses. Prenat Diagn 2003;23:7847. (Level II-3)
31. Cicero S, Longo D, Rembouskos G, Sacchini C,
Nicolaides KH. Absent nasal bone at 11-14 weeks of ges-
tation and chromosomal defects. Ultrasound Obstet
Gynecol 2003:22:315. (Level III)
32. Sonek JD. Nasal bone evaluation with ultrasonography: a
marker for fetal aneuploidy. Ultrasound Obstet Gynecol
2003;22:115. (Level III)
33. Senat MV, Bernard JP, Boulvain M, Ville Y. Intra- and
interoperator variability in fetal nasal bone assessment at
11-14 weeks of gestation. Ultrasound Obstet Gynecol
2003;22:13841. (Level III)
34. Smith-Bindman R, Hosmer W, Feldstein V, Deeks J,
Goldberg J. Second-trimester ultrasound to detect fetuses
with Down syndrome. JAMA 2001;285:104455. (Meta-
analysis)
967 PRACTICE BULLETINS
The MEDLINE database, the Cochrane Library, and the
American College of Obstetricians and Gynecologists own
internal resources and documents were used to conduct a
literature search to locate relevant articles published be-
tween January 1985 and September 2006. The search was
restricted to articles published in the English language. Pri-
ority was given to articles reporting results of original re-
search, although review articles and commentaries also
were consulted. Abstracts of research presented at sympo-
sia and scientific conferences were not considered adequate
for inclusion in this document. Guidelines published by or-
ganizations or institutions such as the National Institutes of
Health and ACOG were reviewed, and additional studies
were located by reviewing bibliographies of identified arti-
cles. When reliable research was not available, expert opin-
ions from obstetriciangynecologists were used.
Studies were reviewed and evaluated for quality according
to the method outlined by the U.S. Preventive Services Task
Force:
I Evidence obtained from at least one properly de-
signed randomized controlled trial.
II-1 Evidence obtained from well-designed controlled
trials without randomization.
II-2 Evidence obtained from well-designed cohort or
casecontrol analytic studies, preferably from more
than one center or research group.
II-3 Evidence obtained from multiple time series with or
without the intervention. Dramatic results in uncon-
trolled experiments also could be regarded as this
type of evidence.
III Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees.
Based on the highest level of evidence found in the data,
recommendations are provided and graded according to the
following categories:
Level ARecommendations are based on good and consis-
tent scientific evidence.
Level BRecommendations are based on limited or incon-
sistent scientific evidence.
Level CRecommendations are based primarily on con-
sensus and expert opinion.
Copyright January 2007 by the American College of Obstetricians
and Gynecologists. All rights reserved. No part of this publication may
be reproduced, stored in a retrieval system, posted on the Internet, or
transmitted, in any form or by any means, electronic, mechanical, pho-
tocopying, recording, or otherwise, without prior written permission
from the publisher.
Requests for authorization to make photocopies should be directed to
Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA
01923, (978) 750-8400.
ISSN 1099-3630
The American College of Obstetricians and Gynecologists
409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920
Screening for fetal chromosomal abnormalities. ACOG Practice
Bulletin No. 77. American College of Obstetricians and Gynecologists.
Obstet Gynecol 2007;109:21727.
COMPENDIUM OF SELECTED PUBLICATIONS 968
CLINICAL MANAGEMENT GUIDELINES FOR
OBSTETRICIANGYNECOLOGISTS
NUMBER 78, JANUARY 2007
(Replaces Practice Bulletin Number 64, July 2005)
This Practice Bulletin was
developed by the ACOG Com-
mittee on Practice Bulletins
Obstetrics with the assistance
of John Williams III, MD. The
information is designed to aid
practitioners in making deci-
sions about appropriate obstet-
ric and gynecologic care. These
guidelines should not be con-
strued as dictating an exclusive
course of treatment or proce-
dure. Variations in practice may
be warranted based on the
needs of the individual patient,
resources, and limitations
unique to the institution or type
of practice.
Reaffirmed 2008
Hemoglobinopathies in
Pregnancy
The hemoglobinopathies are a heterogeneous group of single-gene disorders
that includes the structural hemoglobin variants and the thalassemias. More
than 270 million people worldwide are heterozygous carriers of hereditary dis-
orders of hemoglobin, and at least 300,000 affected homozygotes or compound
heterozygotes are born each year (1). The purpose of this document is to review
the most common hemoglobinopathies and to provide recommendations for
screening and clinical management of hemoglobinopathies during pregnancy.
Background
Hemoglobin Structure
Hemoglobin consists of four interlocking polypeptide chains, each of which has
an attached heme molecule. The polypeptide chains are called alpha (), beta
(), gamma (), delta (), epsilon (), and zeta (). Adult hemoglobins consist
of two -chains and either two -chains (hemoglobin A), two -chains (hemo-
globin F), or two -chains (hemoglobin A
2
). Hemoglobin F (fetal hemoglobin,
Hb F) is the primary hemoglobin of the fetus from 12 to 24 weeks of gestation.
In the third trimester, production of Hb F decreases as production of -chains
and Hb A begins. The genes that code for -globin chains are located on the
short arm of chromosome 16, and the -globin gene is located on the short arm
of chromosome 11.
Sickle Cell Disease
Sickle cell disease refers to a group of autosomal recessive disorders involving
abnormal hemoglobin (hemoglobin S). Hemoglobin S differs from the normal
Hb A because of a single nucleotide substitution of thymine for adenine in the
-globin gene; this alteration causes a substitution of valine for glutamic acid in
the number six position of the -globin polypeptide. Asymptomatic individuals
ACOG
PRACTICE
BULLETIN
969 PRACTICE BULLETINS
with heterozygous Hb S genotypes (carriers) are said to
have sickle cell trait. The most severe form of the disease,
Hb SS (homozygous Hb S), is called sickle cell anemia.
Sickle cell disorders are found not only in patients
who have the hemoglobin genotype SS, but also in those
who have Hb S and one other abnormality of -globin
structure or -globin production. The most common of
these are Hb SC disease and Hb S/-thalassemia. In Hb C,
the same nucleotide involved in the Hb S mutation is
altered with the substitution of adenine for guanine,
which results in the amino acid substitution of lysine for
glutamic acid. This and other abnormal hemoglobins,
when inherited with Hb S, may cause clinically signifi-
cant vasoocclusive phenomena and hemolytic anemia
similar to Hb SS.
Sickle cell disease occurs most commonly in people
of African origin. Approximately 1 in 12 African Ameri-
cans has sickle cell trait (2). One in every 300 African-
American newborns has some form of sickle cell disease,
and approximately 1 in 600 has sickle cell anemia. Hemo-
globin S also is found in high frequency in other popula-
tions such as Greeks, Italians (particularly Sicilians),
Turks, Arabs, Southern Iranians, and Asian Indians (3).
The classical clinical feature of patients with sickle
cell disease is seen under conditions of decreased oxygen
tension, in which the red blood cells become distorted
into various shapes, some of which resemble sickles. The
distorted red cells lead to increased viscosity, hemolysis,
and anemia and a further decrease in oxygenation. When
sickling occurs within small blood vessels, it can cause
logjams that can interrupt blood supply to vital organs
(vasoocclusive crisis). Repeated vasoocclusive crises
result in widespread microvascular obstruction with
interruption of normal perfusion and function of several
organs, including the spleen, lungs, kidneys, heart, and
brain. Adults with Hb SS are functionally asplenic, hav-
ing undergone autosplenectomy by adolescence. Absence
of the spleen contributes to the increased incidence and
severity of infection in patients with sickle cell disease.
The most significant threat to patients with sickle
cell disease is acute chest syndrome. Chest syndrome is
characterized by a pulmonary infiltrate with fever that
leads to hypoxemia and acidosis. The infiltrates are not
infectious in origin but rather are due to vasoocclusion
from sickling or embolization of marrow from long
bones affected by sickling (4).
The diagnosis of hemoglobinopathies, including
sickle cell disorders, is made by hemoglobin electro-
phoresis. In the homozygous form, nearly all the hemo-
globin is Hb S with small amounts of Hb A
2
and Hb F.
Heterozygous sickle cell trait (Hb AS) is identified by a
larger percentage of Hb A and an asymptomatic course.
Solubility tests (Sickledex) alone are inadequate for diag-
nosis of sickle cell disorders because they cannot distin-
guish between the heterozygous AS and homozygous SS
genotypes. In addition, they fail to detect other patho-
logic variants such as Hb C trait, -thalassemia trait,
Hb E trait, Hb B trait, and Hb D trait.
The Thalassemias
The thalassemias represent a wide spectrum of hemato-
logic disorders that are characterized by a reduced syn-
thesis of globin chains, resulting in microcytic anemia.
Thalassemias are classified according to the globin chain
affected, with the most common types being -thal-
assemia and -thalassemia. Many different molecular
mechanisms lead to thalassemia in populations from dif-
ferent areas of the world (5).
Alpha-Thalassemia
Alpha-thalassemia usually results from a gene deletion of
two or more copies of the four -globin genes. Deletion
of one -globin gene (-/) is clinically unrecogniz-
able, and laboratory testing yields normal results.
Deletion of two -globin genes causes -thalassemia
trait, a mild asymptomatic microcytic anemia. The dele-
tions can be on the same chromosome or in cis (/--),
or on each chromosome or in trans (-/-). Individuals
with these chromosomal abnormalities are referred to as
carriers and are at an increased risk for having a child
with a more severe form of thalassemia caused by dele-
tions of three or four copies of the -globin gene (-thal-
assemia major). The possible genetic combinations are
summarized in Table 1.
Alpha-thalassemia trait (-thalassemia minor) is
common among individuals of Southeast Asian, African,
and West Indian descent. It also is common in individuals
with Mediterranean ancestry. Individuals with Southeast
Asian ancestry are more likely to carry two gene dele-
tions in cis or on the same chromosome (--/) and are
at an increased risk for offspring with Hb Barts or Hb H
disease. Hemoglobin H disease, which is caused by the
deletion of three -globin genes, usually is associated
with mild to moderate hemolytic anemia. Alpha-thal-
assemia major (Hb Barts) results in the absence of -
globin (--/--); this is associated with hydrops fetalis,
intrauterine death, and preeclampsia (3).
In individuals of African descent, -thalassemia usu-
ally is due to a deletion of a single -globin gene on each
chromosome 16 (-/-). This is in contrast to the com-
mon Asian genotype, which is a deletion of both -glo-
bin genes on one chromosome 16 (cis) (/--).
Hemoglobin Barts disease does not typically develop in
fetuses of -thalassemia carriers of African origin.
Because Hb S results from an abnormality of the
-chain, both heterozygous (AS) and homozygous (SS)
COMPENDIUM OF SELECTED PUBLICATIONS 970
forms can be inherited with heterozygous or homozy-
gous
+
-thalassemia. In individuals with sickle cell trait
(Hb AS), -thalassemia lowers the proportion of
Hb S, and in those with Hb SS, it lessens the severity of
sickle cell disease.
Alpha-thalassemia also may occur as a result of a
gene mutation. In this case, the genes are present but not
functioning normally. This may result from mutation in
the stop codon leading to synthesis of a longer and unsta-
ble -chain (Hb Constant Spring), from substitutions
impairing dimer formation (Hb Qong Sze), and from
point substitutions in the poly A region at the 3' end of
the gene (
TSaudi
).
Beta-Thalassemia
Beta-thalassemia is caused by a mutation in the -globin
gene that causes deficient or absent -chain production,
which results in absence of Hb A. Classification of
-thalassemias is based on a description of the molecu-
lar mutation or by clinical manifestations. Individuals
who are heterozygous for this mutation have -thalas-
semia minor. Those who are homozygous have -thal-
assemia major (Cooleys anemia) or a milder form
called thalassemia intermedia. Beta-thalassemia major
is characterized by severe anemia with resultant
extramedullary erythropoesis, delayed sexual develop-
ment, and poor growth. Elevated levels of Hb F in indi-
viduals with -thalassemia major partially compensate
for the absence of Hb A; however, death usually occurs
by age 10 years unless treatment is begun early with
periodic blood transfusions. With transfusion, the severe
anemia is reversed and extramedullary erythropoesis is
suppressed. In homozygotes with the less severe
+
-thal-
assemia mutations, often referred to as -thalassemia
intermedia, variable but decreased amounts of -chains
are produced and, as a result, variable amounts of Hb A
are produced. The genes for Hb S and -thalassemia usu-
ally behave as alleles, with only one gene inherited from
each parent. The expression of the resulting Hb S/-thal-
assemia is determined by the type of -thalassemia
mutation (6).
Beta-thalassemia minor, common in individuals of
Mediterranean, Asian, Middle Eastern, Hispanic, and West
Indian descent, varies in severity of disease. Depending
on the amount of -chain production, it usually is asso-
ciated with asymptomatic mild anemia. Beta-thal-
assemia minor often occurs in association with Hb S. In
the most severe form, no normal -globin chains are
produced. This results in a clinically severe syndrome
called sickle cell
0
-thalassemia, in which no Hb A is
produced.
Clinical Considerations and
Recommendations
Who should be screened for hemoglobinopa-
thies and how should this be accomplished?
Genetic screening can identify couples at risk for off-
spring with hemoglobinopathies and allow them to make
informed decisions regarding reproduction and prenatal
diagnosis (3). Individuals of African, Southeast Asian,
and Mediterranean ancestry are at a higher risk for being
carriers of hemoglobinopathies and should be offered
carrier screening. Ethnic groups considered to be at low
risk for hemoglobinopathies include northern Euro-
peans, Japanese, Native Americans, Inuit (Eskimo), and
Koreans. If both parents are determined to be carriers,
genetic counseling is recommended. It should be noted
Table 1. Classification of Alpha-Thalassemias
Number of Clinical
Globin Genes Genotype Description Features
4 / Normal Normal
3 -/ Heterozygous Asymptomatic
+
-thalassemia
2 -/- Homozygous Mild
+
-thalassemia anemia
/-- Heterozygous
o
-thalassemia
1 -/--
+
-Thalassemia/ Hb H disease
o
-thalassemia hemolytic anemia
0 --/-- Homozygous Hb Barts disease
o
-thalassemia hydrops fetalis
971 PRACTICE BULLETINS
ous hemoglobinopathies, such as Hb S/-thalassemia and
Hb SC disease. Solubility testing may be valuable, how-
ever, for rapid screening for sickling when this informa-
tion is critical for immediate patient care.
Determination of mean corpuscular volume (MCV)
is recommended for patients who are at risk for - or
-thalassemia. Patients who have a low MCV (less than
80 fL) may have one of the thalassemia traits and are
candidates for hemoglobin electrophoresis. These indi-
viduals also may have iron deficiency anemia, and
measurement of serum ferretin levels is recommended.
Beta-thalassemia is associated with elevated Hb F and
elevated Hb A
2
levels (more than 3.5%). Neither hemo-
globin electrophoresis nor solubility testing can identify
individuals with -thalassemia trait; only molecular
genetic testing can identify this condition. If the MCV is
below normal, iron deficiency anemia has been excluded,
and the hemoglobin electrophoresis is not consistent with
-thalassemia trait (ie, there is no elevation of Hb A
2
or
Hb F), then DNA-based testing should be used to detect
-globin gene deletions characteristic of -thalassemia.
The hematologic features of some of the common
hemoglobinopathies are shown in Table 2. If both part-
that ethnicity is not always a good predictor of risk
because individuals from at-risk groups may marry out-
side their ethnic group (3).
A combination of laboratory tests may be required to
provide the information necessary to counsel couples
who are carriers of one of the thalassemias or sickle cell
disease (Fig. 1). To ensure accurate hemoglobin identifi-
cation, which is essential for genetic counseling, a
complete blood count (CBC) is the appropriate initial
laboratory test for individuals of non-African descent. In
individuals of African descent, a hemoglobin elec-
trophoresis should be performed in addition to a CBC.
Several tests, including solubility testing such as a test for
the presence of Hb S (Sickledex), isoelectric focusing,
and high-performance liquid chromatography (HPLC),
have been used for primary screening. However, solubil-
ity tests alone are inadequate for screening and fail to
identify important transmissible hemoglobin gene abnor-
malities affecting fetal outcome (eg, Hb C trait, -thal-
assemia trait, Hb E trait, Hb B trait, Hb D trait). Many
individuals with these genotypes are asymptomatic, but if
their partners have the sickle cell trait or other hemoglo-
binopathies, they may produce offspring with more seri-
CBC and RBC indices
Patients of Southeast Asian or Mediterranean descent Patients of African descent
No abnormality
Anemia (with reduced MCV
and normal iron status)
Hemoglobin electrophoresis
Normal
Hb AS, AC, SS, SC, elevated A
2
, and
other abnormal hemoglobin
If Southeast Asian, evaluate for -thalassemia
Not a carrier of
-thalassemia
Carrier of
-thalassemia
Offer testing of partner to assess reproductive risk
Figure 1. Specialized antepartum evaluation for hematologic assessment of patients of African,
Southeast Asian, or Mediterranean descent. Patients of Southeast Asian or Mediterranean descent
should undergo electrophoresis if their blood test results reveal anemia. Abbreviations: CBC, complete
blood count; Hb, hemoglobin; MCV, mean corpuscular volume; RBC, red blood cell.
COMPENDIUM OF SELECTED PUBLICATIONS 972
ners are identified as carriers of a gene for abnormal
hemoglobins, genetic counseling is recommended.
For couples with an increased risk for having
an affected offspring, what methods are
available for genetic diagnosis of the fetus or
embryo?
Couples at risk for having a child with a hemoglobinopa-
thy may benefit from genetic counseling to review the
natural history of these disorders, prospects for treatment
and cure, their risk, availability of prenatal genetic testing,
and reproductive options. Prenatal diagnostic testing for
the single mutation responsible for sickle cell disease is
widely available. Testing for - and -thalassemia is pos-
sible if the mutations and deletions have been previously
identified in both parents. These DNA-based tests can be
performed using chorionic villi obtained by chorionic
villus sampling (CVS) at 1012 weeks of gestation or
using cultured amniotic fluid cells obtained by amnio-
centesis after 15 weeks of gestation. For some couples,
preimplantation genetic diagnosis in combination with in
vitro fertilization may be a desirable alternative to avoid
termination of an affected pregnancy. Preimplantation
genetic diagnosis has been successfully performed for
sickle cell disease and most cases of -thalassemia.
Although the advances in prenatal diagnosis of
hemoglobinopathies have been impressive, use of the
technology has been somewhat limited because of ethi-
cal, social, and cultural concerns. Prenatal diagnosis is
most commonly requested by families who have had a
child with sickle cell disease and who wish to be certain
that their next child is not affected. In many respects,
these families are self-counseled. The difficulty in
counseling families who have not had an affected child
lies in the variable severity of the disease and the inabil-
ity to predict its course (6). One investigator found that
nearly 70% of families in whom prenatal diagnosis con-
firmed that the fetus was affected with Hb SS elected to
continue the pregnancy (7).
How is sickle cell disease in pregnancy
managed?
Pregnancy in women with sickle cell disease is associat-
ed with an increased risk of morbidity and mortality
because of the combination of underlying hemolytic
anemia and multiorgan dysfunction associated with this
disorder. Morbidity and mortality have decreased
markedly over the past 3 decades because of improve-
ments in general medical care for patients with sickle cell
disease, improvements in transfusion medicine, and
advancements in neonatal care (8, 9). In spite of the
decline in maternal and perinatal mortality rates, how-
ever, pregnancy is still a significant clinical risk for many
patients with sickle cell disease. The magnitude of the
Table 2. Hematologic Features of Main Hemoglobinopathies
Disorder Heterozygous State Homozygous State DNA Analysis
+
Thalassemia (-) 02% Hb Barts at birth 510% Hb Barts in the neonatal S. blot: -gene probe,
period, low MCV abnormal band with Bam H1
o
Thalassemia (--) 510% Hb Barts in the neonatal Hb Barts hydrops fetalis S. blot or PCR: absence of:
period, low MCV, normal Hb A
2
-gene band in homozygote
o
Thalassemia Low MCH & MCV, Hb A
2
3.57.0% Thalassemia major: Hb F 98% PCR, ASO dot blot, S. blot
Hb A
2
2% -gene probe
+
Thalassemia (severe) Low MCH & MCV, Hb A
2
3.57.0% Thalassemia major: Hb F 7095% PCR, ASO dot blot, S. blot
-gene probe
+
Thalassemia (mild) Low MCH & MCV, Hb A
2
3.57.0% Thalassemia intermedia: PCR, ASO dot blot, S. blot
Hb F 2040% -gene probe
Hb S Hb A, Hb S, Hb A
2
Hb S, Hb F (115%), Hb A
2
PCR: Dde 1 digestion
PCR, ASO dot blot
Hb S/-Thalassemia If
o
thalassemia, severe sickle PCR: Dde 1 digestion
cell anemia; if
+
thalassemia, PCR, ASO dot blot
less severe
Hb E/-Thalassemia Thalassemia major or intermedia: PCR: Hb E by Mnl 1 digestion
Hb E 6070%, Hb F 3040%
Abbreviations: ASO, allele specific oligonucleotide; Hb, hemoglobin; MCH, mean corpuscular hemoglobin; MCV, mean corpuscular volume; PCR, polymerase chain
reaction; S. blot, Southern blot.
Modified from Milunsky, Aubrey, MB.B.Ch., D.Sc., F.R.C.P., F.A.C.M.G., D.C.H., ed. Genetic Disorders and the Fetus, fifth edition: Diagnosis, Prevention, and Treatment.
pp. 665, Table 19.1. 2004 Aubrey Milunsky. Reprinted with permission of The Johns Hopkins University Press.
973 PRACTICE BULLETINS
risk varies with genotype and severity of anemia. When
compared with Hb AA patients, women with Hb SS have
increased risk for maternal complications, such as pre-
term labor, premature rupture of membranes, antepartum
hospitalization, and postpartum infection. In addition,
patients with Hb SS are at higher risk for fetal complica-
tions, such as intrauterine growth restriction (IUGR), low
birth weight, and preterm delivery (9, 10). Patients with
Hb SC disease also are at risk for the aforementioned
complications but to a lesser extent than patients with
Hb SS disease (10).
Pregnant patients with sickle cell disease need
increased prenatal folic acid supplementation. The stan-
dard 1 mg of folate in prenatal vitamins is not adequate
for patients with hemoglobinopathies; 4 mg per day of
folic acid should be prescribed because of the continual
turnover of red blood cells.
Routine cesarean delivery for women with sickle cell
disease is not indicated and should be performed only for
obstetric indications. Epidural analgesia usually is well
tolerated as long as care is taken to avoid hypotension
and hypoxemia. Pregnant patients should, if possible, be
cared for at institutions that are able to manage both the
complications of sickle cell disease and high-risk preg-
nancies. They also should have regular prenatal care by
or in consultation with obstetricians who are experienced
in the management of sickle cell disease.
The most common cause of recurrent morbidity in
Hb SS disease is painful crisis. If possible, precipitating
factors, such as cold environment, heavy physical exer-
tion, dehydration, and stress, should be avoided. Hydroxy-
urea has been shown to reduce the frequency of painful
crises in nonpregnant patients with severe sickle cell dis-
ease (11). However, the use of hydroxyurea is not recom-
mended during pregnancy because it is teratogenic.
Painful crises in pregnancy as well as in the non-
pregnant patient are managed with rapid assessment of
the level of pain and prompt administration of analgesia.
Pain, respiratory rate, and level of sedation should be
assessed until pain is controlled. Opiates can be given
orally or parenterally by the intravenous, intramuscular,
or subcutaneous route. Oxygen should be given if the O
2
saturation is less than 95% by pulse oximetry. The initial
clinical assessment also should focus on detection of
serious medical complications requiring specific therapy,
such as acute chest syndrome (fever tachypnea, chest
pain, and hypoxia), infection, dehydration, severe ane-
mia, cholecystitis, and hypersplenism. A multidiscipli-
nary approach should be used involving obstetricians,
hematologists, and anesthesiologists (12). Painful crises
in the third trimester may have a prolonged course and
may not resolve until after delivery.
What is the role of transfusion or prophylac-
tic exchange transfusion for pregnancies
complicated by sickle cell anemia?
Controversy exists regarding the role of prophylactic
blood transfusion in the management of sickle cell dis-
ease in pregnancy (1315). By limiting transfusion to
situations in which it is clinically indicated, patients are
not subjected to the increased risk for alloimmunization
(16), viral infections, and iron overload. Major compli-
cations (eg, worsening anemia; intrapartum complica-
tions such as hemorrhage, septicemia, and cesarean
delivery; painful crisis; and chest syndrome) may
require intervention with an exchange transfusion. There
is no consensus regarding the exact hematocrit value
below which transfusion should be considered.
However, when a transfusion is clinically indicated in
the patient with sickle cell disease, the objective is to
lower the percentage of Hb S to approximately 40%
while simultaneously raising the total hemoglobin con-
centration to about 10 g/dL. Hemoglobin levels and the
percentage of Hb S should be monitored serially during
the remainder of the pregnancy to determine the need for
subsequent transfusions.
Prophylactic exchange transfusion was first pro-
posed by Ricks in 1965, who recommended exchange
transfusion 46 weeks before the delivery date (17).
Preliminary results appeared to show a benefit in that all
women and infants survived (18). Subsequently, several
studies have shown improvement in maternal and fetal
outcome with prophylactic transfusion (15, 19). How-
ever, the evidence is not conclusive that transfusion is
responsible for the improvement; similar improvement
has been observed in programs that do not use prophy-
lactic transfusion. In the only randomized controlled trial
published to date, prophylactic transfusion was associ-
ated with a decreased risk for painful crisis and severe
anemia, but no difference was observed for pregnancy
outcome (14). It appears from the available evidence that
the reduction in morbidity and mortality of sickle cell
disease in pregnancy is attributable to improvements in
general management of pregnancy rather than prophy-
lactic transfusion per se.
Is fetal surveillance useful in pregnancies
complicated by sickle cell anemia?
Pregnancies in women with sickle cell disease are at
increased risk for spontaneous abortion, preterm labor,
IUGR, and stillbirth (20). For this reason, a plan for ser-
ial ultrasound examinations and antepartum fetal testing
is reasonable. Published data on antenatal fetal surveil-
lance in women with sickle cell disease are limited. In a
COMPENDIUM OF SELECTED PUBLICATIONS 974
retrospective review of 58 pregnancies in women with
sickle cell disease undergoing prophylactic transfusion,
no patients had a nonreactive nonstress test result or pos-
itive contraction stress test result (21). All pregnancy
outcomes were normal. The investigators concluded that
placental reserve and fetal reactivity were uncompro-
mised and that these tests were as sensitive for assess-
ment of fetal well-being in women with sickle cell
disease as for women with other indications for antenatal
testing.
Because patients with sickle cell crisis usually
require narcotics for pain control, the results of abnormal
antepartum testing should be interpreted with caution.
One small study has shown that nonstress test results and
biophysical profiles may be abnormal during an episode
of crisis but revert back to normal with resolution of the
episode (22). The clinical significance of this is unclear.
How is thalassemia in pregnancy managed?
The course of pregnancy in women with the -thalas-
semia trait is not significantly different from that of
women with normal hemoglobin. Pregnancy in women
with Hb H disease has been reported, and with the
exception of mild to moderate chronic anemia, outcomes
have been favorable. However, the number of reports is
too few to draw definite conclusions regarding pregnan-
cy outcome in all women with Hb H disease (23).
Until recently, pregnancy in women with -thalas-
semia major was extremely rare. Initially, this was
because delay of growth and sexual development and
early death in untreated patients prevented reproduction.
After the introduction of transfusion therapy in the 1960s,
pregnancy was still uncommon because of infertility
(secondary to hypothalamic dysfunction and anovulation
caused by hemosiderin deposition). Since the introduc-
tion of hypertransfusion and iron chelation therapy with
deferoxamine in the late 1970s, several reports and case
series have documented favorable pregnancy outcomes in
women with -thalassemia major (24, 25). Pregnancy in
women with -thalassemia major is recommended only
for those with normal cardiac function who have had pro-
longed hypertransfusion therapy to maintain hemoglobin
levels at 10 g/dL and iron chelation therapy with defer-
oxamine (25). During pregnancy, hemoglobin levels
should be maintained at or near 10 g/dL with transfu-
sions. Deferoxamine usually is discontinued because the
safety of iron chelation therapy during pregnancy has not
been established. Fetal growth should be monitored with
serial ultrasonography. In cases in which fetal growth is
suboptimal, patients should have fetal surveillance. The
mode of delivery should be individualized, with cesarean
delivery reserved for obstetric indications.
Beta-thalassemia minor usually causes mild asympto-
matic anemia. In the absence of documented iron defi-
ciency, replacement beyond prophylactic doses of iron is
not indicated. Studies involving fairly small numbers of
patients suggest that pregnancy outcome is favorable in
women with -thalassemia minor. A study of 261 pregnant
women with -thalassemia minor found a significantly
higher rate of IUGR and oligohydramnios than is found in
nonthalassemic patients (26). No differences were noted in
perinatal outcomes such as low Apgar scores, congenital
malformations, or perinatal mortality (26).
Summary of
Recommendations and
Conclusions
The following recommendations are based on
good and consistent scientific evidence (Level A):
Individuals of African, Southeast Asian, and
Mediterranean descent are at increased risk for
being carriers of hemoglobinopathies and should be
offered carrier screening and, if both parents are
determined to be carriers, genetic counseling.
A complete blood count and hemoglobin electro-
phoresis are appropriate laboratory tests for screen-
ing for hemoglobinopathies. Solubility tests alone
are inadequate for screening because they fail to
identify important transmissible hemoglobin gene
abnormalities affecting fetal outcome.
Couples at risk for having a child with sickle cell
disease or thalassemia should be offered genetic
counseling to review prenatal testing and reproduc-
tion options. Prenatal diagnosis of hemoglobin-
opathies is best accomplished by DNA analysis of
cultured amniocytes or chorionic villi.
References
1. Angastiniotis M, Modell B. Global epidemiology of hemo-
globin disorders. Ann N Y Acad Sci 1998;850:25169.
(Level II-3)
2. Motulsky AG. Frequency of sickling disorders in U.S.
blacks. N Engl J Med 1973;288:313. (Level III)
3. Davies SC, Cronin E, Gill M, Greengross P, Hickman M,
Normand C. Screening for sickle cell disease and thalas-
semia: a systematic review with supplementary research.
Health Technol Assess 2000;4:iv, 199. (Level III)
4. Duffy TP. Hematologic aspects of pregnancy. In: Burrow
GN, Duffy TP, Copel JA, editors. Medical complications
975 PRACTICE BULLETINS
patients with sickle cell hemoglobinopathies: benefit ver-
sus risk. Obstet Gynecol 1980;56:27480. (Level III)
16. Brumfield CG, Huddleston JF, DuBois LB, Harris BA Jr.
A delayed hemolytic transfusion reaction after partial
exchange transfusion for sickle cell disease in pregnancy:
a case report and review of literature. Obstet Gynecol
1984;63(suppl):13s15s. (Level III)
17. Ricks P Jr. Exchange transfusion in sickle cell anemia in
pregnancy. Obstet Gynecol 1965;25:1179. (Level III)
18. Ricks P Jr. Further experience with exchange transfusion
in sickle cell anemia in pregnancy. Am J Obstet Gynecol
1968;100:108790. (Level III)
19. Morrison JC, Wiser WL. The use of prophylactic partial
exchange transfusion in pregnancies associated with sickle
cell hemoglobinopathies. Obstet Gynecol 1976;48:51620.
(Level III)
20. Serjeant GR, Loy LL, Crowther M, Hambleton IR, Thame
M. Outcome of pregnancy in homozygous sickle cell dis-
ease. Obstet Gynecol 2004;103:127885. (Level II2)
21. Morrison JC, Blake PG, McCoy C, Martin JN Jr, Wiser
WL. Fetal health assessment in pregnancies complicated
by sickle hemoglobinopathies. Obstet Gynecol 1983;61:
224. (Level III)
22. Anyaegbunam A, Morel MI, Merkatz IR. Antepartum
fetal surveillance tests during sickle cell crisis. Am J
Obstet Gynecol 1991;165:10813. (Level II-2)
23. Ong HC, White JC, Sinnathuray TA. Haemoglobin H dis-
ease and pregnancy in a Malaysian woman. Acta
Haematol 1977;58:22933. (Level III)
24. Jensen CE, Tuck SM, Wonke B. Fertility in beta thalas-
semia major: a report of 16 pregnancies, preconceptual
evaluation and a review of the literature. Br J Obstet
Gynaecol 1995;102:6259. (Level III)
25. Aessopos A, Karabatsos F, Farmakis D, Katsantoni A,
Hatziliami A, Youssef J, et al. Pregnancy in patients with
well-treated beta-thalassemia: outcome for mothers and
newborn infants. Am J Obstet Gynecol 1999;180:3605.
(Level III)
26. Sheiner E, Levy A, Yerushalmi R, Katz M. Beta-thalas-
semia minor during pregnancy. Obstet Gynecol 2004;103:
12737. (Level II-2)
during pregnancy. 6th ed. Philadelphia (PA): Elsevier
Saunders; 2004. p. 6986. (Level III)
5. Kazazian HH Jr. The thalassemia syndromes: molecular
basis and prenatal diagnosis in 1990. Semin Hematol
1990;27:20928. (Level III)
6. Serjeant GR, Serjeant BE. Sickle cell disease. 3rd ed. New
York (NY): Oxford University Press; 2001. (Level III)
7. Alter BP. Prenatal diagnosis of hematologic diseases,
1986 update. Acta Haematol 1987;78:13741. (Level II-3)
8. Smith JA, Espeland M, Bellevue R, Bonds D, Brown AK,
Koshy M. Pregnancy in sickle cell disease: experience of
the Cooperative Study of Sickle Cell Disease. Obstet
Gynecol 1996;87:199204. (Level II-2)
9. Sun PM, Wilburn W, Raynor BD, Jamieson D. Sickle cell
disease in pregnancy: twenty years of experience at Grady
Memorial Hospital, Atlanta, Georgia. Am J Obstet
Gynecol 2001;184:112730. (Level II-2)
10. Powars DR, Sandhu M, Niland-Weiss J, Johnson C, Bruce
S, Manning PR. Pregnancy in sickle cell disease. Obstet
Gynecol 1986;67:21728. (Level II-3)
11. Charache S. Mechanism of action on hydroxyurea in the
management of sickle cell anemia in adults. Semin
Hematol 1997;34(suppl 3):1521. (Level I)
12. Rees DC, Olujohungbe AD, Parker NE, Stephens AD,
Telfer P, Wright J. Guidelines for the management of the
acute painful crisis in sickle cell disease. British
Committee for Standards in Haematology General
Haematology Task Force by the Sickle Cell Working
Party. Br J Haematol 2003;120:74452. (Level III)
13. Tuck SM, James CE, Brewster EM, Pearson TC, Studd
JW. Prophylactic blood transfusion in maternal sickle cell
syndromes. Br J Obstet Gynaecol 1987;94:1215. (Level
III)
14. Koshy M, Burd L, Wallace D, Moawad A, Baron J.
Prophylactic red-cell transfusions in pregnant patients
with sickle cell disease. A randomized cooperative study.
N Engl J Med 1988;319:144752. (Level I)
15. Morrison JC, Schneider JM, Whybrew WD, Bucovaz ET,
Menzel DM. Prophylactic transfusions in pregnant
COMPENDIUM OF SELECTED PUBLICATIONS 976
The MEDLINE database, the Cochrane Library, and
ACOGs own internal resources and documents were used
to conduct a literature search to locate relevant articles pub-
lished between January 1985 and March 2005. The search
was restricted to articles published in the English language.
Priority was given to articles reporting results of original
research, although review articles and commentaries also
were consulted. Abstracts of research presented at sympo-
sia and scientific conferences were not considered adequate
for inclusion in this document. Guidelines published by or-
ganizations or institutions such as the National Institutes of
Health and the American College of Obstetricians and Gy-
necologists were reviewed, and additional studies were
located by reviewing bibliographies of identified articles.
When reliable research was not available, expert opinions
from obstetriciangynecologists were used.
Studies were reviewed and evaluated for quality according
to the method outlined by the U.S. Preventive Services Task
Force:
I Evidence obtained from at least one properly de-
signed randomized controlled trial.
II-1 Evidence obtained from well-designed controlled
trials without randomization.
II-2 Evidence obtained from well-designed cohort or
casecontrol analytic studies, preferably from more
than one center or research group.
II-3 Evidence obtained from multiple time series with or
without the intervention. Dramatic results in uncon-
trolled experiments also could be regarded as this
type of evidence.
III Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees.
Based on the highest level of evidence found in the data,
recommendations are provided and graded according to the
following categories:
Level ARecommendations are based on good and consis-
tent scientific evidence.
Level BRecommendations are based on limited or incon-
sistent scientific evidence.
Level CRecommendations are based primarily on con-
sensus and expert opinion.
Copyright January 2007 by the American College of Obste-
tricians and Gynecologists. All rights reserved. No part of this
publication may be reproduced, stored in a retrieval system,
posted on the Internet, or transmitted, in any form or by any
means, electronic, mechanical, photocopying, recording, or
otherwise, without prior written permission from the publisher.
Requests for authorization to make photocopies should be
directed to Copyright Clearance Center, 222 Rosewood Drive,
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
Hemoglobinopathies in pregnancy. ACOG Practice Bulletin No. 78.
American College of Obstetricians and Gynecologists. Obstet Gynecol
2007;109:22937.
977 PRACTICE BULLETINS
CLINICAL MANAGEMENT GUIDELINES FOR
OBSTETRICIANGYNECOLOGISTS
NUMBER 80, APRIL 2007
(Replaces Practice Bulletin Number 1, June 1998)
This Practice Bulletin was
developed by the ACOG Com-
mittee on Practice Bulletins
Obstetrics with the assistance
of Brian Mercer, MD. The in-
formation is designed to aid
practitioners in making deci-
sions about appropriate obste-
tric and gynecologic care. These
guidelines should not be con-
strued as dictating an exclusive
course of treatment or proce-
dure. Variations in practice
may be warranted based on the
needs of the individual patient,
resources, and limitations
unique to the institution or type
of practice.
Premature Rupture of
Membranes
Preterm delivery occurs in approximately 12% of all births in the United States
and is a major factor contributing to perinatal morbidity and mortality (1, 2).
Despite extensive research in this area, the rate of preterm birth has increased
by 38% since 1981 (3). Premature rupture of membranes (PROM) is a compli-
cation in approximately one third of preterm births. It typically is associated
with brief latency between membrane rupture and delivery, increased potential
for perinatal infection, and in utero umbilical cord compression. Because of
this, both PROM at and before term can lead to significant perinatal morbidity
and mortality. There is some controversy over the optimal approaches to clini-
cal assessment and treatment of women with term and preterm PROM.
Management hinges on knowledge of gestational age and evaluation of the rel-
ative risks of preterm birth versus intrauterine infection, abruptio placentae,
and cord accident that could occur with expectant management. The purpose of
this document is to review the current understanding of this condition and to
provide management guidelines that have been validated by appropriately con-
ducted outcome-based research. Additional guidelines on the basis of consen-
sus and expert opinion also are presented.
Background
The definition of PROM is rupture of membranes before the onset of labor.
Membrane rupture that occurs before 37 weeks of gestation is referred to as
preterm PROM. Although term PROM results from the normal physiologic
process of progressive membrane weakening, preterm PROM can result from a
wide array of pathologic mechanisms acting individually or in concert (4). The
gestational age and fetal status at membrane rupture have significant implica-
tions in the etiology and consequences of PROM. Management may be dictat-
ACOG
PRACTICE
BULLETIN
COMPENDIUM OF SELECTED PUBLICATIONS 978
ed by the presence of overt intrauterine infection,
advanced labor, or fetal compromise. When such factors
are not present, especially with preterm PROM, obstetric
management may have a significant impact on maternal
and infant outcomes. An accurate assessment of gesta-
tional age and knowledge of the maternal, fetal, and
neonatal risks are essential to appropriate evaluation,
counseling, and care of patients with PROM.
Etiology
Membrane rupture may occur for a variety of reasons. At
term, weakening of the membranes may result from
physiologic changes combined with shearing forces cre-
ated by uterine contractions (58). Intraamniotic infec-
tion has been shown to be commonly associated with
preterm PROM, especially if preterm PROM occurs at
earlier gestational ages (9). In addition, factors such as
low socioeconomic status, second- and third-trimester
bleeding, low body mass index (calculated as weight in
kilograms divided by the square of height in meters) less
than 19.8, nutritional deficiencies of copper and ascorbic
acid, connective tissue disorders (eg, EhlersDanlos syn-
drome), maternal cigarette smoking, cervical conization
or cerclage, pulmonary disease in pregnancy, uterine
overdistention, and amniocentesis have been linked to the
occurrence of preterm PROM (1019). The risk of recur-
rence for preterm PROM is between 16% and 32% (20,
21). In addition, women with a previous preterm birth
(especially if it is due to PROM), those with a short cer-
vical length (less than 25 mm) in the second trimester,
and women with preterm labor or symptomatic contrac-
tions in the current pregnancy are at increased risk for
PROM (12, 22). Although each of these risk factors can
act individually or in concert to cause PROM, in many
cases PROM will occur in the absence of recognized risk
factors. As a result, it has been difficult to identify effec-
tive treatment strategies for the prevention of PROM.
Recent studies have suggested progesterone therapy to
reduce the risk of recurrent spontaneous preterm birth
resulting from preterm labor or PROM (23, 24).
However, because most cases of PROM occur in women
without identifiable risk factors, the mainstay of care has
been treatment after membrane rupture occurs.
Term Premature Rupture
of Membranes
At term, PROM complicates approximately 8% of preg-
nancies and generally is followed by the prompt onset of
spontaneous labor and delivery. In a large randomized trial,
half of women with PROM who were managed expectant-
ly gave birth within 5 hours, and 95% gave birth within 28
hours of membrane rupture (25). The most significant
maternal risk of term PROM is intrauterine infection, a risk
that increases with the duration of membrane rupture
(2529). Fetal risks associated with term PROM include
umbilical cord compression and ascending infection.
Leakage of Fluid After
Amniocentesis
When leakage of amniotic fluid occurs after amniocente-
sis, the outcome is better than after spontaneous preterm
PROM. In studies involving women who had second-
trimester amniocentesis for prenatal diagnosis of genetic
disorders, the risk of PROM was 11.2%, and the attrib-
utable risk of pregnancy loss was 0.06% (30). In most
patients, the membranes reseal with restoration of normal
amniotic fluid volume (31, 32).
Preterm Premature
Rupture of Membranes
Regardless of obstetric management or clinical presenta-
tion, birth within 1 week is the most likely outcome for
any patient with preterm PROM in the absence of adjunc-
tive treatments. The earlier in gestation that PROM
occurs, the greater is the latency period. With expectant
management, 2.813% of women can anticipate cessa-
tion of fluid leakage and possible restoration of normal
amniotic fluid volume (28, 32).
Of women with preterm PROM, clinically evident
intraamniotic infection occurs in 1360%, and postpar-
tum infection occurs in 213% (3337). The incidence of
infection increases with decreasing gestational age at
membrane rupture (38, 39) and increases with digital
vaginal examination (40). Fetal malpresentation is
increased with preterm PROM. Abruptio placentae affects
412% of pregnancies with preterm PROM (41, 42). How-
ever, serious maternal sequelae are uncommon (35, 43).
The most significant risks to the fetus after preterm
PROM are complications of prematurity. At all gestation-
al ages before term, respiratory distress has been report-
ed to be the most common complication of preterm birth
(4, 44). Other serious forms of morbidity, including
neonatal infections, intraventricular hemorrhage, and
necrotizing enterocolitis, also are associated with prema-
turity, but these are less common nearer to term. Preterm
PROM and exposure to intrauterine inflammation have
been associated with an increased risk of neurodevelop-
mental impairment (9, 45). Early gestational age at mem-
979 PRACTICE BULLETINS
brane rupture also has been associated with an increased
risk of neonatal white matter damage (P <.001), after
controlling for corticosteroid administration, latency
interval, gestational age at delivery, and birth weight
(46). However, no data exist that suggest immediate
delivery after presentation with PROM will avert these
risks. The presence of maternal infection poses the addi-
tional risk of neonatal infection. Infection, cord accident,
and other factors contribute to the 12% risk of antena-
tal fetal demise after preterm PROM (43).
Previable Premature
Rupture of Membranes
The fetal survival rate subsequent to PROM at 2426
weeks of gestation has been reported to be approximate-
ly 57% (47). A recent systematic review of 201 cases
from 11 studies revealed a 21% perinatal survival rate
after expectant management of PROM before viability
(48). Survival data may vary by institution. Most studies
of second-trimester and previable PROM have been ret-
rospective and have included only those patients appro-
priate for and accepting of expectant management,
potentially exaggerating latency and improving apparent
outcomes.
A small number of patients with previable PROM
will have an extended latency period. In a review of 12
studies evaluating patients with second-trimester PROM,
the mean latency period ranged from 10.6 to 21.5 days
(47), with 57% of patients giving birth within 1 week
and 22% remaining pregnant for 1 month or more. The
incidence of stillbirth subsequent to PROM at 1628
weeks of gestation ranges from 3.8% to 22% (11, 33, 49)
compared with 02% at 3036 weeks of gestation (50,
51). This increased rate of death may be explained by
increased susceptibility of the umbilical cord to com-
pression or of the fetus to hypoxia and intrauterine infec-
tion. Alternatively, this finding may reflect the lack of
intervention for fetal compromise before viability.
Significant maternal complications occurring after
second trimester and previable PROM have been report-
ed to include intraamniotic infection, endometritis,
abruptio placentae, retained placenta, and postpartum
hemorrhage. Maternal sepsis is a rare but serious com-
plication reported in approximately 1% of cases, and
isolated maternal deaths due to infection have been
reported in this setting (52). Outcomes of survivors of
preterm PROM depend on the gestational age, presence
of infection, length of latency, and other maternal and
fetal complications.
A variety of conditions associated with fetal lung
compression or oligohydramnios or both can result in
pulmonary hypoplasia. Reported risks of pulmonary
hypoplasia after PROM at 1626 weeks of gestation vary
from less than 1% to 27% (37, 52). Lethal pulmonary
hypoplasia rarely occurs with membrane rupture subse-
quent to 24 weeks of gestation, presumably because
alveolar growth adequate to support postnatal develop-
ment already has occurred (53, 54). Early second-
trimester membrane rupture, severe oligohydramnios,
and duration of membrane rupture longer than 14 days
are primary determinants of the risk of pulmonary
hypoplasia (55, 56). Prolonged oligohydramnios also is
associated with in utero deformation, including abnor-
mal facies (ie, low-set ears and epicanthal folds) and
limb contractures and other positioning abnormalities.
Clinical Considerations and
Recommendations
How is premature rupture of membranes
diagnosed?
Most cases of PROM can be diagnosed on the basis of
the patients history and physical examination.
Examination should be performed in a manner that min-
imizes the risk of introducing infection, particularly
before term. Because digital cervical examinations
increase the risk of infection and add little information to
that available with speculum examination, digital exam-
inations should be avoided unless the patient is in active
labor or imminent delivery is planned (40, 5759).
Sterile speculum examination provides an opportunity to
inspect for cervicitis and umbilical cord or fetal pro-
lapse, assess cervical dilatation and effacement, and
obtain cultures as appropriate.
The diagnosis of membrane rupture is confirmed by
the visualization of fluid passing from the cervical canal.
If the diagnosis remains in question, the pH of the vagi-
nal sidewalls or from fluid in the posterior vaginal fornix
can be assessed. The pH of the vaginal secretions is gen-
erally 4.56.0, whereas amniotic fluid usually has a pH
of 7.17.3. False-positive results may occur in the pres-
ence of blood or semen contamination, alkaline antisep-
tics, or bacterial vaginosis. Alternatively, false-negative
results may occur with prolonged leakage and minimal
residual fluid. Additional information can be obtained by
swabbing the posterior fornix (avoiding cervical mucus)
and allowing the vaginal fluid to dry on a microscope
slide. The presence of arborization (ferning) under micro-
scopic visualization further suggests membrane rupture.
Ultrasound examination of amniotic fluid volume
may be a useful adjunct in documenting oligohydram-
nios, but is not diagnostic. When the clinical history or
COMPENDIUM OF SELECTED PUBLICATIONS 980
The largest randomized study to date found that oxy-
tocin induction reduced the time interval between PROM
and delivery as well as the frequencies of chorioamnioni-
tis, postpartum febrile morbidity, and neonatal antibiotic
treatments, without increasing cesarean deliveries or
neonatal infections (25). These data suggest that for
women with PROM at term, labor should be induced at
the time of presentation, generally with oxytocin infu-
sion, to reduce the risk of chorioamnionitis. An adequate
time for the latent phase of labor to progress should be
allowed.
When is delivery recommended for the
preterm fetus in the presence of premature
rupture of membranes?
The decision to deliver is based on gestational age and
fetal status (Table 1), and the time considered optimal
may vary among institutions. At 3233 completed weeks
of gestation, the risk of severe complications of prema-
turity is low if fetal pulmonary maturity is evident by
amniotic fluid samples collected vaginally or by amnio-
centesis (51). Therefore, labor induction may be consid-
ered if pulmonary maturity has been documented. If
pulmonary maturity cannot be established, expectant
management may be beneficial. The efficacy of cortico-
steroid use at 3233 completed weeks of gestation has
not been specifically addressed for women with PROM
but has been recommended by some experts.
Because of the increased risk of chorioamnionitis
(63, 64), and because antenatal corticosteroids are not
recommended after 34 weeks of gestation to accelerate
fetal pulmonary maturity, delivery is recommended when
PROM occurs at or beyond 34 weeks of gestation. The
patient who experiences PROM between 24 weeks and
31 completed weeks of gestation should be cared for
expectantly if no maternal or fetal contraindications exist
until 33 completed weeks of gestation. Prophylaxis using
antibiotics to prolong latency and a single course of ante-
natal corticosteroids can help reduce the risks of infec-
tion and gestational age-dependent neonatal morbidity.
What general approaches are used in cases of
preterm PROM managed expectantly?
Expectant management of preterm PROM generally con-
sists of modified bed rest to enhance reaccumulation of
amniotic fluid and complete pelvic rest. Patients should
be assessed periodically for evidence of infection, abrup-
tio placentae, umbilical cord compression, fetal well-
being, and labor. There is no consensus on the frequency
of assessment that is optimal, but an acceptable strategy
would include periodic ultrasound monitoring of amni-
otic fluid volume and fetal heart rate monitoring. In a
physical examination is unclear, membrane rupture can
be diagnosed unequivocally with ultrasonographically
guided transabdominal instillation of indigo carmine dye
(1 mL in 9 mL of sterile normal saline), followed by
observation for passage of blue fluid from the vagina.
What does the initial management involve
once PROM has been confirmed?
In all patients with PROM, gestational age, fetal presen-
tation, and well-being should be determined. At any ges-
tational age, a patient with evident intrauterine infection,
abruptio placentae, or evidence of fetal compromise is
best cared for by expeditious delivery. In the absence of
an indication for immediate delivery, swabs for diagno-
sis of Chlamydia trachomatis and Neisseria gonor-
rhoeae may be obtained from the cervix, if appropriate.
The need for group B streptococcal intrapartum prophy-
laxis should be determined if preterm PROM occurs
(60).
In patients with preterm PROM, electronic fetal
heart rate monitoring and uterine activity monitoring
offer the opportunity to identify occult umbilical cord
compression and to evaluate for asymptomatic contrac-
tions. In one study, variable decelerations occurred in
32% of women with preterm PROM (61). Biophysical
profile test scores of 6 or less within 24 hours of delivery
also have been demonstrated to correlate with positive
amniotic fluid cultures and perinatal infection. At least
eight studies have confirmed this association (62). Most
of these studies have included daily fetal assessment
after preterm PROM. An abnormal test result should lead
to reassessment of the clinical circumstances and may
lead to a decision to proceed to delivery. It is important
to remember that heart rate testing at less than 32 weeks
of gestation may not yield a reactive result in an imma-
ture but otherwise healthy fetus. However, once a reac-
tive result has been achieved, a subsequently nonreactive
test should be considered suspicious. Consensus has not
been reached among experts on the optimal frequency of
and modality of fetal testing in the face of PROM.
What is the optimal method of initial man-
agement for a patient with PROM at term?
Fetal heart rate monitoring should be used to assess fetal
status. Dating criteria should be reviewed to assign ges-
tational age because virtually all aspects of subsequent
care will hinge on that information. Because optimal
results are seen with 4 hours between group B strepto-
coccal prophylaxis and birth, when the decision to deliv-
er is made, group B streptococcal prophylaxis should be
given based on prior culture results or risk factors if cul-
tures have not been previously performed (60).
981 PRACTICE BULLETINS
patient with preterm PROM, a temperature exceeding
38.0C (100.4F) may indicate infection, although some
investigators have suggested that fever, with additional
factors such as uterine tenderness and maternal or fetal
tachycardia, is a more accurate indicator of maternal
infection (34, 65). Leukocyte counts are nonspecific
when there is no clinical evidence of infection, especial-
ly if antenatal corticosteroids have been administered.
Low initial amniotic fluid volume (amniotic fluid
index less than 5 cm or maximum vertical fluid pocket
less than 2 cm) has been associated with shorter latency
to delivery and an increased risk of neonatal morbidity,
including respiratory distress syndrome (RDS), but not
with increased maternal or neonatal infection after
PROM (66). However, the predictive value of a low
amniotic fluid volume for adverse outcomes is poor.
Several investigators have evaluated the utility of
endovaginal ultrasound assessment of cervical length for
prediction of latency during expectant management of
PROM remote from term. Some experts have suggested
a short cervical length after PROM to be associated with
shorter latency (6769). In the most recent study, the
likelihood of delivery within 7 days was 83% if the ini-
tial cervical length was 110 mm (versus 18% for cervi-
cal length more than 30 mm); however, the number of
women in these categories was small (N = 24 and 17,
respectively) (67). Although the combination of clinical
and ultrasound markers may yield improved predictive
models in the future, initial amniotic fluid volume deter-
mination and cervical length generally should not be
used in isolation to direct management of PROM.
Should tocolytics be considered for patients
with preterm PROM?
Use of prophylactic tocolysis after preterm PROM has
been shown to prolong latency in the short term (7072),
whereas the use of therapeutic tocolysis (ie, instituting
tocolysis only after contractions have ensued) has not
been shown to prolong latency (73). A retrospective
study compared the use of aggressive tocolysis (84% of
antepartum days) with limited tocolysis as needed for
contractions only during the first 48 hours (7% of
antepartum days). Aggressive therapy was found not to
be associated with significantly longer latency to deliv-
ery (3.8 versus 4.5 days, P = .16) (74). However, a recent
retrospective study compared the prolonged use of tocol-
ysis for longer than 48 hours plus antibiotics and steroids
with gestational age-matched infants not treated for
PROM. The investigators concluded that chorioamnioni-
Table 1. Management of Premature Rupture of Membranes Chronologically
Gestational Age Management
Term (37 weeks or more) Proceed to delivery, usually by induction of labor
Group B streptococcal prophylaxis recommended
Near term (34 weeks to 36 completed Same as for term
weeks)
Preterm (32 weeks to 33 completed Expectant management, unless fetal pulmonary
weeks) maturity is documented
Group B streptococcal prophylaxis recommended
Corticosteroidno consensus, but some experts
recommend
Antibiotics recommended to prolong latency if there
are no contraindications
Preterm (24 weeks to 31 completed Expectant management
weeks) Group B streptococcal prophylaxis recommended
Single-course corticosteroid use recommended
Tocolyticsno consensus
Antibiotics recommended to prolong latency if there
are no contraindications
Less than 24 weeks* Patient counseling
Expectant management or induction of labor
Group B streptococcal prophylaxis is not recommended
Corticosteroids are not recommended
Antibioticsthere are incomplete data on use in pro-
longing latency
*The combination of birthweight, gestational age, and sex provide the best estimate of chances of survival and should
be considered in individual cases.
COMPENDIUM OF SELECTED PUBLICATIONS 982
tis and a latency of greater than 1 week achieved by pro-
longed use of tocolysis lessens the advantages of extend-
ed gestational age and decreased predischarge neonatal
morbidity (75).
The effect of tocolysis to permit antibiotic and ante-
natal corticosteroid administration in the patient with
preterm PROM who is having contractions has yet to be
conclusively evaluated; therefore, specific recommenda-
tions for or against tocolysis administration cannot be
made. As detailed as follows, use of both antibiotics and
antenatal corticosteroids improves outcome in patients
with preterm PROM who are being treated expectantly.
Should antenatal corticosteroids be adminis-
tered to patients with preterm PROM?
The impact of antenatal corticosteroid administration
after preterm PROM on neonatal outcomes has been
evaluated in a number of clinical trials. Multivariate
analysis of prospective observational trials also has sug-
gested a benefit of antenatal corticosteroid use regardless
of membrane rupture (76), and the National Institutes of
Health Consensus Development Panel has recommended
a single course of antenatal corticosteroids for women
with PROM before 32 weeks of gestation in the absence
of intraamniotic infection (77, 78). Several meta-analyses
have addressed this issue (7982). Early reviews resulted
in conflicting conclusions regarding the impact of ante-
natal steroids on the occurrence of RDS. Two more
recent meta-analyses suggest that steroid therapy signifi-
cantly reduces the risks of RDS, intraventricular hemor-
rhage, and necrotizing enterocolitis without increasing
the risks of maternal or neonatal infection regardless of
gestational age (82, 83). The risk of infection from corti-
costeroid use at 3233 completed weeks of gestation is
unclear, but based on available evidence, their use has
been recommended by some experts, particularly if pul-
monary immaturity is documented. Studies of the com-
bined use of corticosteroids and prophylactic antibiotics
after preterm PROM suggest significant reductions in
RDS, perinatal mortality, and other morbidities with no
evident increase in perinatal infections after steroid
administration (84, 85).
Should antibiotics be administered to patients
with preterm PROM?
The issue of adjunctive antibiotic therapy to treat or pre-
vent ascending decidual infection in order to prolong
pregnancy and reduce neonatal infections and gestational
age-dependent morbidity has been widely studied (43,
86, 87). In the most recent meta-analysis, investigators
suggested prophylactic antibiotic administration to delay
delivery and reduce major markers of neonatal morbid-
ity, but suggested that amoxicillinclavulanic acid be
avoided because of the increased risk of neonatal necro-
tizing enterocolitis (87).
Two large, multicenter clinical trials have adequate
power to evaluate the utility of adjunctive antibiotics in
this setting (65, 88). The National Institutes of Child
Health and Human Development Maternal Fetal
Medicine Research Units (NICHD-MFMU) Research
Network found that the combination of initial intravenous
therapy (48 hours) with ampicillin and erythromycin, fol-
lowed by oral therapy of limited duration (5 days) with
amoxicillin and enteric-coated erythromycin-base at
2432 weeks of gestation, decreased the likelihood of
chorioamnionitis and delivery for up to 3 weeks, as well
as the number of infants with one or more major morbidi-
ties (defined as death, RDS, early sepsis, severe intraven-
tricular hemorrhage, or severe necrotizing enterocolitis)
(65). In addition, therapy reduced the likelihood of indi-
vidual gestational agedependent morbidities, including
RDS, stage 34 necrotizing enterocolitis, patent ductus
arteriosus, and chronic lung disease. Neonatal sepsis and
pneumonia were less frequent in the antibiotic group for
those who were not carriers of group B streptococci.
(Group B streptococci carriers in both study arms received
ampicillin for 1 week and then again during labor.)
A second large multicenter trial that examined the
use of oral antibiotic therapy with erythromycin, amoxi-
cillinclavulanic acid, or both for up to 10 days after
preterm PROM before 37 weeks of gestation found that
oral erythromycin therapy 1) prolonged pregnancy only
briefly (not significant at 7 days), 2) reduced the need for
supplemental oxygen, and 3) reduced the frequency of
positive blood cultures with no improvement in the pri-
mary outcome (one or more outcomes of death, chronic
lung disease, or major cerebral abnormality on ultra-
sonography) (88). Oral amoxicillinclavulanic acid
reduced delivery within 7 days and reduced the need for
supplemental oxygen but was associated with an
increased risk of necrotizing enterocolitis (1.9% versus
0.5%, P = .001) without preventing other neonatal mor-
bidities. The finding of increased necrotizing enterocoli-
tis with oral amoxicillinclavulanic acid differs from the
NICHD-MFMU trial finding of reduced stage 2 or 3
necrotizing enterocolitis with amoxicillinerythromycin
therapy in a higher risk population, and review of the
current literature does not reveal a consistent pattern
regarding an increased risk with broad-spectrum antibi-
otic therapy. Several recent studies have attempted to
determine whether a shorter duration of antibiotic ther-
apy is adequate after preterm PROM, but these studies
are of inadequate size and power to demonstrate equiva-
lent effectiveness against infant morbidity (89, 90).
983 PRACTICE BULLETINS
Based on available information, a 7-day course of
parenteral and oral therapy with ampicillin or amoxi-
cillin and erythromycin is recommended during expec-
tant management of preterm PROM remote from term to
prolong pregnancy and to reduce infectious and gesta-
tional age-dependent neonatal morbidity. Use of the
combination of oral erythromycin and extended-spec-
trum ampicillinclavulanic acid in women near term
does not appear to be beneficial, may be harmful, and is
not recommended. Antibiotic administration to prolong
latency must be distinguished from well-established pro-
tocols directed at prevention of group B streptococcal
infection in term and preterm patients (60). The prophy-
lactic antibiotic regimen would appropriately treat group
B streptococcal infections during expectant management
of preterm PROM remote from term. However, women
with PROM and a viable fetus, who are known carriers
of group B streptococci and those who give birth before
carrier status can be delineated, should receive intra-
partum prophylaxis to prevent vertical transmission
regardless of earlier treatments.
Can preterm PROM be managed with home
care?
Generally, hospitalization for bed rest and pelvic rest is
indicated after preterm PROM once viability is reached.
Recognizing that latency is frequently brief, that
intrauterine and fetal infection may occur suddenly, and
that the fetus is at risk for umbilical cord compression,
ongoing surveillance of both the woman and her fetus is
recommended once the limit of potential viability has
been reached.
For a woman with preterm PROM and a viable
fetus, the safety of expectant management at home has
not been established. One clinical trial of discharge after
preterm PROM suggested that relatively few patients
will be eligible for discharge to home care (91). Only 67
of 349 women (18%) were eligible for antepartum home
care after 72 hours (negative cervical cultures and no evi-
dent labor, intrauterine infection, or fetal compromise).
There were no identifiable differences in latency or in
the incidences of intraamniotic infection, variable decel-
erations, or cesarean delivery. Infant outcomes were sim-
ilar, but the power of this study to identify differences in
these outcomes was low. Although the potential for a
reduction in health care costs with antepartum discharge
is enticing, it is important to ensure that such manage-
ment will not be associated with increased risks and
costs related to perinatal morbidity and mortality. Any
cost savings from antenatal discharge may be rapidly lost
with a small increase in the stay in the neonatal intensive
care unit.
How should a patient with preterm PROM
and a cervical cerclage be treated?
There are no prospective studies available with which to
guide the care of women with preterm PROM and a cer-
vical cerclage in situ. Retrospective studies have found
that removal of cerclage after PROM is associated with
similar pregnancy outcomes to those with PROM but no
cerclage (92, 93). Cerclage retention after preterm
PROM has been associated with trends toward increased
maternal infectious morbidity (9496), reaching statisti-
cal significance in one evaluation (97), and with only
brief pregnancy prolongation. One study found increased
infant mortality and sepsis-related death when the cer-
clage was left in place after PROM (94). One study
found significant pregnancy prolongation with cerclage
retention by comparing differing practices at two institu-
tions; however, this could reflect population or practice
differences at these institutions (95). Because the avail-
able studies are small and nonrandomized, the optimal
timing of cerclage removal is unclear. However, no con-
trolled study has found cerclage retention after PROM to
improve neonatal outcomes. The risks and benefits of
short-term cerclage retention pending completion of
antenatal corticosteroid therapy to enhance fetal matura-
tion have not been evaluated.
What is the optimal treatment for a patient
with preterm PROM and herpes simplex
virus infection?
Neonatal herpes simplex virus infection usually results
from maternalfetal transmission during the delivery
process. Neonatal infection occurs in 3480% of infants
delivered in the setting of primary maternal infection, and
in 15% with secondary infections (98, 99). Based on a
small case series of women with active genital herpes
infection in 1971, totaling just 36 patients, it has been
believed that latency of more than 46 hours after mem-
brane rupture is associated with an increased risk of
neonatal infection (100, 101). However, a more recent
case series of 29 women treated expectantly with active
recurrent herpes simplex virus lesions and PROM before
32 weeks of gestation found none of the infants developed
neonatal herpes infection (102). Latency from membrane
rupture to delivery ranged from 1 to 35 days, and cesare-
an delivery was performed if active lesions were present
at the time of delivery. These data suggest that the risk of
prematurity should be weighed against the potential risk
of neonatal herpes simplex virus in considering expectant
management of PROM complicated by recurrent mater-
nal herpes simplex virus infection. Prophylactic treatment
with antiviral agents (eg, acyclovir) may be considered.
COMPENDIUM OF SELECTED PUBLICATIONS 984
A 48-hour course of intravenous ampicillin and ery-
thromycin followed by 5 days of amoxicillin and
erythromycin is recommended during expectant
management of preterm PROM remote from term to
prolong pregnancy and to reduce infectious and ges-
tational agedependent neonatal morbidity.
All women with PROM and a viable fetus, includ-
ing those known to be carriers of group B strepto-
cocci and those who give birth before carrier status
can be delineated, should receive intrapartum chemo-
prophylaxis to prevent vertical transmission of group
B streptococci regardless of earlier treatments.
A single course of antenatal corticosteroids should
be administered to women with PROM before 32
weeks of gestation to reduce the risks of RDS, peri-
natal mortality, and other morbidities.
The following recommendations and conclusions
are based on limited and inconsistent scientific
evidence (Level B):
Delivery is recommended when PROM occurs at or
beyond 34 weeks of gestation.
With PROM at 3233 completed weeks of gesta-
tion, labor induction may be considered if fetal pul-
monary maturity has been documented.
Digital cervical examinations should be avoided in
patients with PROM unless they are in active labor
or imminent delivery is anticipated.
The following recommendations and conclusions
are based primarily on consensus and expert opin-
ion (Level C):
A specific recommendation for or against tocolysis
administration cannot be made.
The efficacy of corticosteroid use at 3233 complet-
ed weeks is unclear based on available evidence, but
treatment may be beneficial particularly if pul-
monary immaturity is documented.
For a woman with preterm PROM and a viable
fetus, the safety of expectant management at home
has not been established.
Proposed Performance
Measure
The percentage of patients with PROM and a viable fetus
who are known group B streptococci carriers or whose
status as a carrier is unknown who receive intrapartum
group B streptococcal prophylaxis
How does care differ for patients with PROM
that occurs before the threshold of potential
neonatal viability?
Women presenting with PROM before potential viability
should be counseled regarding the impact of immediate
delivery and the potential risks and benefits of expectant
management. Counseling should include a realistic
appraisal of neonatal outcomes, including the availability
of obstetric monitoring and neonatal intensive care facil-
ities. Because of advances in perinatal care, morbidity
and mortality rates continue to improve rapidly (43, 44,
103). An attempt should be made to provide parents with
the most up-to-date information possible.
Although no evidence or consensus of opinion
exists regarding the benefit of an initial period of inpa-
tient observation in these patients, this approach may
include strict bed and pelvic rest to enhance the oppor-
tunity for resealing, as well as early identification of
infection and abruptio placentae if expectant manage-
ment is pursued. In addition to clinical follow-up, it
may be useful to instruct patients to abstain from inter-
course, limit their activities, and monitor their tempera-
tures.
Typically, women with previable PROM who have
been cared for as outpatients are readmitted to the hospi-
tal for bed rest and observation for infection, abruptio
placentae, labor, and nonreassuring fetal heart rate pat-
terns once the pregnancy has reached the limit of viabil-
ity. Administration of antenatal corticosteroids for fetal
maturation is appropriate at this time given that early
delivery remains likely.
Summary of
Recommendations and
Conclusions
The following recommendations and conclusions
are based on good and consistent scientific evi-
dence (Level A):
For women with PROM at term, labor should be
induced at the time of presentation, generally with
oxytocin infusion, to reduce the risk chorioamni-
onitis.
Patients with PROM before 32 weeks of gestation
should be cared for expectantly until 33 completed
weeks of gestation if no maternal or fetal con-
traindications exist.
985 PRACTICE BULLETINS
References
1. Goldenberg RL, Rouse DJ. Prevention of premature birth.
N Engl J Med 1998;339:31320. (Level III)
2. Mathews TJ, Mac Dorman MF. Infant mortality statistics
from the 2003 period linked birth/infant death data set.
Natl Vital Stat Rep 2006;54(16):129. (Level II-3)
3. Martin JA, Hamilton BE, Sutton PD, Ventura SJ,
Menacker F, Kirmeyer S. Births: final data for 2004. Natl
Vital Stat Rep 2006;5(1):1101. (Level II-3)
4. Mercer BM. Preterm premature rupture of the mem-
branes. Obstet Gynecol 2003;101:17893. (Level III)
5. Lavery JP, Miller CE, Knight RD. The effect of labor on
the rheologic response of chorioamniotic membranes.
Obstet Gynecol 1982;60:8792. (Level II-3)
6. McLaren J, Taylor DJ, Bell SC. Increased incidence of
apoptosis in non-labour-affected cytotrophoblast cells in
term fetal membranes overlying the cervix. Hum Reprod
1999;14:2895900. (Level II-3)
7. El Khwad M, Stetzer B, Moore RM, Kumar D, Mercer B,
Arikat S, et al. Term human fetal membranes have a weak
zone overlying the lower uterine pole and cervix before
onset of labor. Biol Reprod 2005;72:7206. (Level II-3)
8. Moore RM, Mansour JM, Redline RW, Mercer BM,
Moore JJ. The physiology of fetal membrane rupture:
insight gained from the determination of physical proper-
ties. Placenta 2006;27:103751. (Level II-3).
9. Yoon BH, Romero R, Park JS, Kim CJ, Kim SH, Choi JH,
et al. Fetal exposure to an intra-amniotic inflammation
and the development of cerebral palsy at the age of three
years. Am J Obstet Gynecol 2000;182:67581. (Level
II-3)
10. Harger JH, Hsing AW, Tuomala RE, Gibbs RS, Mead PB,
Eschenbach DA, et al. Risk factors for preterm premature
rupture of fetal membranes: a multicenter case-control
study. Am J Obstet Gynecol 1990;163:1307. (Level II-2)
11. Taylor J, Garite TJ. Premature rupture of membranes
before fetal viability. Obstet Gynecol 1984;64:61520.
(Level II-3)
12. Mercer BM, Goldenberg RL, Meis PJ, Moawad AH,
Shellhaas C, Das A, et al. The Preterm Prediction Study:
prediction of preterm premature rupture of membranes
using clinical findings and ancillary testing. The National
Institute of Child Health and Human Development
MaternalFetal Medicine Units Network. Am J Obstet
Gynecol 2000;183:73845. (Level II-2)
13. Minkoff H, Grunebaum AN, Schwarz RH, Feldman J,
Cummings M, Crombleholme W, et al. Risk factors for
prematurity and premature rupture of membranes: a
prospective study of the vaginal flora in pregnancy. Am J
Obstet Gynecol 1984;150:96572. (Level II-2)
14. Naeye RL. Factors that predispose to premature rupture of
the fetal membranes. Obstet Gynecol 1982;60:938.
(Level II-3)
15. Naeye RL, Peters EC. Causes and consequences of pre-
mature rupture of fetal membranes. Lancet 1980;1:1924.
(Level II-3)
16. Charles D, Edwards WR. Infectious complications of cer-
vical cerclage. Am J Obstet Gynecol 1981;141:106571.
(Level II-3)
17. Hadley CB, Main DM, Gabbe SG. Risk factors for
preterm premature rupture of the fetal membranes. Am J
Perinatol 1990;7:3749. (Level II-2)
18. Siega-Riz AM, Promislow JH, Savitz DA, Thorp JM Jr,
McDonald T. Vitamin C intake and the risk of preterm
delivery. Am J Obstet Gynecol 2003;189:51925. (Level
II-2)
19. Gold RB, Goyert GL, Schwartz DB, Evans MI, Seabolt
LA. Conservative management of second-trimester post-
amniocentesis fluid leakage. Obstet Gynecol 1989;74:
7457. (Level II-3)
20. Lee T, Carpenter M, Heber WW, Silver HM. Preterm pre-
mature rupture of membranes: risks of recurrent compli-
cations in the next pregnancy among a population-based
sample of gravid women. Am J Obstet Gynecol
2003;188:20913. (Level II-2)
21. Asrat T, Lewis DF, Garite TJ, Major CA, Nageotte MP,
Towers CV, et al. Rate of recurrence of preterm prema-
ture rupture of membranes in consecutive pregnancies.
Am J Obstet Gynecol 1991;165:11115. (Level III)
22. Guinn DA, Goldenberg RL, Hauth JC, Andrews WW,
Thom E, Romero R. Risk factors for the development of
preterm premature rupture of the membranes after arrest
of preterm labor. Am J Obstet Gynecol 1995;173:13105.
(Level II-2)
23. Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai
B, Moawad AH, et al. Prevention of recurrent preterm
delivery by 17 alpha-hydroxyprogesterone caproate.
National Institute of Child Health and Human Devel-
opment Maternal-Fetal Medicine Units Network [pub-
lished erratum appears in N Engl J Med 2003;349:1299].
N Engl J Med 2003;348:237985. (Level I)
24. da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M.
Prophylactic administration of progesterone by vaginal
suppository to reduce the incidence of spontaneous
preterm birth in women at increased risk: a randomized
placebo-controlled double-blind study. Am J Obstet
Gynecol 2003;188:41924. (Level I)
25. Hannah ME, Ohlsson A, Farine D, Hewson SA, Hodnett
ED, Myhr TL, et al. Induction of labor compared with
expectant management for prelabor rupture of the mem-
branes at term. TERMPROM Study Group. N Engl J
Med 1996;334:100510. (Level I)
26. Wagner MV, Chin VP, Peters CJ, Drexler B, Newman
LA. A comparison of early and delayed induction of
labor with spontaneous rupture of membranes at term.
Obstet Gynecol 1989;74:937. (Level II-1)
27. Guise JM, Duff P, Christian JS. Management of term
patients with premature rupture of membranes and an
unfavorable cervix. Am J Perinatol 1992;9:5660. (Level
II-2)
28. Johnson JW, Egerman RS, Moorhead J. Cases with rup-
tured membranes that reseal. Am J Obstet Gynecol
1990;163:102430; discussion 10302. (Level II-2)
COMPENDIUM OF SELECTED PUBLICATIONS 986
29. Novak-Antolic Z, Pajntar M, Verdenik I. Rupture of the
membranes and postpartum infection. Eur J Obstet
Gynecol Reprod Biol 1997;71:1416. (Level II-3)
30. Eddleman K, Malone F, Sullivan L, Dukes K, Berkowitz
R, Kharbutli Y, et al. Pregnancy loss rates after mid-
trimester amniocentesis. Obstet Gynecol 2006;108:
106772. (Level II-2)
31. Borgida AF, Mills AA, Feldman DM, Rodis JF, Egan JF.
Outcome of pregnancies complicated by ruptured mem-
branes after genetic amniocentesis. Am J Obstet Gynecol
2000;183:9379. (Level II-3)
32. Gold RB, Goyert GL, Schwartz DB, Evans MI, Seabolt
LA. Conservative management of second trimester post-
amniocentesis fluid leakage. Obstet Gynecol 1989;74:
7457. (Level II-3).
33. Mercer BM. Management of premature rupture of mem-
branes before 26 weeks gestation. Obstet Gynecol Clin
North Am 1992;19:33951. (Level III)
34. Beydoun SN, Yasin SY. Premature rupture of the mem-
branes before 28 weeks: conservative management. Am J
Obstet Gynecol 1986;155:4719. (Level II-3)
35. Garite TJ, Freeman RK. Chorioamnionitis in the preterm
gestation. Obstet Gynecol 1982;59:53945. (Level II-3)
36. Simpson GF, Harbert GM Jr. Use of beta-methasone in
management of preterm gestation with premature rupture
of membranes. Obstet Gynecol 1985;66:16875. (Level
II-2)
37. Vergani P, Ghidini A, Locatelli A, Cavallone M, Ciarla I,
Cappellini A. Risk factors for pulmonary hypoplasia in
second-trimester premature rupture of membranes. Am J
Obstet Gynecol 1994;170:135964. (Level II-3)
38. Hillier SL, Martius J, Krohn M, Kiviat N, Holmes KK,
Eschenbach DA. A case-control study of chorioamnionic
infection and histologic chorioamnionitis in prematurity.
N Engl J Med 1988;319:9728. (Level II-2)
39. Morales WJ. The effect of chorioamnionitis on the devel-
opmental outcome of preterm infants at one year. Obstet
Gynecol 1987;70:1836. (Level II-3)
40. Alexander JM, Mercer BM, Miodovnik M, Thurnau GR,
Goldenberg RL, Das AF, et al. The impact of digital cer-
vical examination on expectantly managed preterm rup-
ture of membranes. Am J Obstet Gynecol 2000;183(4):
10037. (Level II-3)
41. Ananth CV, Savitz DA, Williams MA. Placental abrup-
tion and its association with hypertension and prolonged
rupture of membranes: a methodologic review and meta-
analysis. Obstet Gynecol 1996;88:30918. (Meta-analy-
sis)
42. Gonen R, Hannah ME, Milligan JE. Does prolonged
preterm premature rupture of the membranes predispose
to abruptio placentae? Obstet Gynecol 1989;74:34750.
(Level II-2)
43. Mercer BM, Arheart KL. Antimicrobial therapy in expec-
tant management of preterm premature rupture of the
membranes [published erratum appears in Lancet
1996;347:410]. Lancet 1995;346:12719. (Meta-analysis)
44. Lemons JA, Bauer CR, Oh W, Korones SB, Papile LA,
Stoll BJ, et al. Very low birth weight outcomes of the
National Institute of Child Health and Human Devel-
opment Neonatal Research Network, January 1995
through December 1996. NICHD Neonatal Research
Network. Pediatrics 2001;107:E1. (Level II-2)
45. Spinillo A, Capuzzo E, Stronati M, Ometto A, Orcesi S,
Fazzi E. Effect of preterm premature rupture of mem-
branes on neurodevelopmental outcome: follow up at two
years of age. Br J Obstet Gynaecol 1995;102:8827.
(Level II-3)
46. Locatelli A, Ghidini A, Paterlini G, Patane L, Doria V,
Zorloni C, et al. Gestational age at preterm premature rup-
ture of membranes: a risk factor for neonatal white matter
damage. Am J Obstet Gynecol 2005;193:94751. (Level II-3)
47. Schucker JL, Mercer BM. Midtrimester premature rupture
of the membranes. Semin Perinatol 1996;20:389400.
(Level III)
48. Dewan H, Morris JM. A systematic review of pregnancy
outcome following preterm premature rupture of mem-
branes at a previable gestational age. Aust N Z J Obstet
Gynaecol 2001;41:38994. (Meta-analysis)
49. Bengtson JM, VanMarter LJ, Barss VA, Greene MF,
Tuomala RE, Epstein MF. Pregnancy outcome after pre-
mature rupture of the membranes at or before 26 weeks
gestation. Obstet Gynecol 1989;73:9217. (Level II-3)
50. Cox SM, Leveno KJ. Intentional delivery versus expectant
management with preterm ruptured membranes at 3034
weeks gestation. Obstet Gynecol 1995;86:8759. (Level I)
51. Mercer BM, Crocker LG, Boe NM, Sibai BM. Induction
versus expectant management in premature rupture of the
membranes with mature amniotic fluid at 32 to 36 weeks:
a randomized trial. Am J Obstet Gynecol 1993;169:77582.
(Level I)
52. Moretti M, Sibai BM. Maternal and perinatal outcome of
expectant management of premature rupture of the mem-
branes in the midtrimester. Am J Obstet Gynecol 1988;
159:3906. (Level II-3)
53. Rotschild A, Ling EW, Puterman ML, Farquharson D.
Neonatal outcome after prolonged preterm rupture of
the membranes. Am J Obstet Gynecol 1990;162:4652.
(Level II-3)
54. van Eyck J, van der Mooren K, Wladimiroff JW. Ductus
arteriosus flow velocity modulation by fetal breathing
movements as a measure of fetal lung development. Am J
Obstet Gynecol 1990;163:55866. (Level II-3)
55. Winn HN, Chen M, Amon E, Leet TL, Shumway JB,
Mostello D. Neonatal pulmonary hypoplasia and perinatal
mortality in patients with midtrimester rupture of amni-
otic membranesa critical analysis. Am J Obstet
Gynecol 2000;182:163844. (Level II-2)
56. Shumway J, Al-Malt A, Amon E, Cohlan B, Amini S,
Abboud M, et al. Impact of oligohydramnios on maternal
and perinatal outcomes of spontaneous premature rupture
of the membranes at 1828 weeks. J Matern Fetal Med
1999;8:203. (Level II-2)
57. Munson LA, Graham A, Koos BJ, Valenzuela GJ. Is there
a need for digital examination in patients with sponta-
neous rupture of the membranes? Am J Obstet Gynecol
1985;153:5623. (Level II-3)
987 PRACTICE BULLETINS
58. Brown CL, Ludwiczak MH, Blanco JD, Hirsch CE.
Cervical dilation: accuracy of visual and digital examina-
tions. Obstet Gynecol 1993;81:2156. (Level II-2)
59. Lewis DF, Major CA, Towers CV, Asrat T, Harding JA,
Garite TJ. Effects of digital vaginal examinations on
latency period in preterm premature rupture of mem-
branes. Obstet Gynecol 1992;80:6304. (Level II-3)
60. American College of Obstetricians and Gynecologists.
Prevention of early-onset group B streptococcal disease in
newborns. ACOG Committee Opinion No. 289. Obstet
Gynecol 2002;100:140512. (Level III)
61. Smith CV, Greenspoon J, Phelan JP, Platt LD. Clinical
utility of the nonstress test in the conservative manage-
ment of women with preterm spontaneous premature rup-
ture of the membranes. J Reprod Med 1987;32:14.
(Level II-3)
62. Hanley ML, Vintzileos AM. Biophysical testing in prema-
ture rupture of the membranes. Semin Perinatol 1996;
20:41825. (Level III)
63. Naef RW 3rd, Allbert JR, Ross EL, Weber BM, Martin
RW, Morrison JC. Premature rupture of membranes at 34
to 37 weeks gestation: aggressive versus conservative
management. Am J Obstet Gynecol 1998;178:12630.
(Level I)
64. Neerhof MG, Cravello C, Haney EI, Silver RK. Timing of
labor induction after premature rupture of membranes
between 32 and 36 weeks gestation. Am J Obstet
Gynecol 1999;180:34952. (Level II-3)
65. Mercer BM, Miodovnik M, Thurnau GR, Goldenberg RL,
Das AF, Ramsey RD, et al. Antibiotic therapy for reduc-
tion of infant morbidity after preterm premature rupture of
the membranes. A randomized controlled trial. National
Institute of Child Health and Human Development
MaternalFetal Medicine Units Network. JAMA 1997;
278:98995. (Level I)
66. Mercer BM, Rabello YA, Thurnau GR, Miodovnik M,
Goldenberg RL, Das AF, et al. The NICHD-MFMU
antibiotic treatment of preterm PROM study: impact of
initial amniotic fluid volume on pregnancy outcome.
NICHD-MFMU Network. Am J Obstet Gynecol 2006;
194:43845. (Level II-2)
67. Tsoi E, Fuchs I, Henrich W, Dudenhausen JW, Nicolaides
KH. Sonographic measurement of cervical length in
preterm prelabor amniorrhexis. Ultrasound Obstet
Gynecol 2004;24:5503. (Level II-3)
68. Rizzo G, Capponi A, Angelini E, Vlachopoulou A, Grassi
C, Romanini C. The value of transvaginal ultrasonograph-
ic examination of the uterine cervix in predicting preterm
delivery in patients with preterm premature rupture of
membranes. Ultrasound Obstet Gynecol 1998;11:239.
(Level II-2)
69. Carlan SJ, Richmond LB, OBrien WF. Randomized trial
of endovaginal ultrasound in preterm premature rupture of
membranes. Obstet Gynecol 1997;89:45861. (Level I)
70. Christensen KK, Ingemarsson I, Leideman T, Solum H,
Svenningsen N. Effect of ritodrine on labor after prema-
ture rupture of the membranes. Obstet Gynecol 1980;55:
18790. (Level I)
71. Levy DL, Warsof SL. Oral ritodrine and preterm prema-
ture rupture of membranes. Obstet Gynecol 1985;66:
6213. (Level II-1)
72. Weiner CP, Renk K, Klugman M. The therapeutic effica-
cy and cost-effectiveness of aggressive tocolysis for pre-
mature labor associated with premature rupture of the
membranes [published erratum appears in Am J Obstet
Gynecol 1991;165:785]. Am J Obstet Gynecol 1988;159:
21622. (Level I)
73. Garite TJ, Keegan KA, Freeman RK, Nageotte MP. A ran-
domized trial of ritodrine tocolysis versus expectant man-
agement in patients with premature rupture of membranes
at 25 to 30 weeks of gestation. Am J Obstet Gynecol
1987;157:38893. (Level II-1)
74. Combs CA, McCune M, Clark R, Fishman A. Aggressive
tocolysis does not prolong pregnancy or reduce neonatal
morbidity after preterm premature rupture of the mem-
branes. Am J Obstet Gynecol 2004;190:17238; discus-
sion 172831. (Level I)
75. Wolfensberger A, Zimmermann R, von Mandach U.
Neonatal mortality and morbidity after aggressive long-
term tocolysis for preterm premature rupture of the mem-
branes. Fetal Diagn Ther 2006;21:36673. (Level II-2)
76. Wright LL, Verter J, Younes N, Stevenson D, Fanaroff
AA, Shankaran S, et al. Antenatal corticosteroid adminis-
tration and neonatal outcome in very low birth weight
infants: the NICHD Neonatal Research Network. Am J
Obstet Gynecol 1995;173:26974. (Level II-3)
77. Antenatal corticosteroids revisited: repeat courses
National Institutes of Health Consensus Development
Conference Statement, August 1718, 2000. National
Institutes of Health Consensus Development Panel.
Obstet Gynecol 2001;98:14450. (Level III)
78. Antenatal corticosteroid therapy for fetal maturation.
ACOG Committee Opinion No. 273. American College of
Obstetricians and Gynecologists. Obstet Gynecol 2002;
99:8713. (Level III)
79. Ohlsson A. Treatments of preterm premature rupture of
the membranes: a meta-analysis. Am J Obstet Gynecol
1989;160:890906. (Meta-analysis)
80. Crowley PA. Antenatal corticosteroid therapy: a meta-
analysis of the randomized trials, 1972 to 1994. Am J
Obstet Gynecol 1995;173:32235. (Meta-analysis)
81. Lovett SM, Weiss JD, Diogo MJ, Williams PT, Garite TJ.
A prospective, double-blind, randomized, controlled clin-
ical trial of ampicillin-sulbactam for preterm premature
rupture of membranes in women receiving antenatal cor-
ticosteroid therapy. Am J Obstet Gynecol 1997;176:
10308. (Level I)
82. Roberts D, Dalziel S. Antenatal corticosteroids for accel-
erating fetal lung maturation for women at risk of preterm
birth. Cochrane Database of Systematic Reviews 2006,
Issue 3. Art. No.: CD004454. DOI: 10.1002/14651858.
CD004454.pub2. (Meta-analysis)
83. Harding JE, Pang J, Knight DB, Liggins GC. Do antena-
tal corticosteroids help in the setting of preterm rupture of
membranes? Am J Obstet Gynecol 2001;184:1319.
(Meta-analysis)
COMPENDIUM OF SELECTED PUBLICATIONS 988
84. Lewis DF, Brody K, Edwards MS, Brouillette RM,
Burlison S, London SN. Preterm premature ruptured
membranes: a randomized trial of steroids after treatment
with antibiotics. Obstet Gynecol 1996;88:8015. (Level I)
85. Pattinson RC, Makin JD, Funk M, Delport SD,
Macdonald AP, Norman K, et al. The use of dexametha-
sone in women with preterm premature rupture of mem-
branesa multicentre, double-blind, placebo-controlled,
randomised trial. Dexiprom Study Group. S Afr Med J
1999;89:86570. (Level I)
86. Egarter C, Leitich H, Karas H, Wieser F, Husslein P,
Kaider A, et al. Antibiotic treatment in premature rupture
of membranes and neonatal morbidity: a metaanalysis.
Am J Obstet Gynecol 1996;174:58997. (Meta-analysis)
87. Kenyon S, Boulvain M, Neilson J. Antibiotics for preterm
rupture of membranes. Cochrane Database of Systematic
Reviews 2003, Issue 2. Art No.: CD001058. DOI: 10.
1002/14651858.CD001058. (Meta-analysis)
88. Kenyon SL, Taylor DJ, Tarnow-Mordi W. Broad spectrum
antibiotics for preterm, prelabor rupture of fetal mem-
branes: the ORACLE I randomized trial. ORACLE
Collaborative Group [published erratum appears in Lancet
2001;358:156]. Lancet 2001;357:97988. (Level I)
89. Lewis DF, Adair CD, Robichaux AG, Jaekle RK, Moore
JA, Evans AT, et al. Antibiotic therapy in preterm prema-
ture rupture of membranes: are seven days necessary? A
preliminary, randomized clinical trial. Am J Obstet Gyne-
col 2003;188:14136; discussion 14167. (Level I)
90. Segel SY, Miles AM, Clothier B, Parry S, Macones GA.
Duration of antibiotic therapy after preterm premature
rupture of fetal membranes. Am J Obstet Gynecol
2003;189:799802. (Level I)
91. Carlan SJ, OBrien WF, Parsons MT, Lense JJ. Preterm
premature rupture of membranes: a randomized study of
home versus hospital management. Obstet Gynecol
1993;81:614. (Level I)
92. Blickstein I, Katz Z, Lancet M, Molgilner BM. The out-
come of pregnancies complicated by preterm rupture of
the membranes with and without cerclage. Int J Gynaecol
Obstet 1989;28:23742. (Level II-3)
93. Yeast JD, Garite TR. The role of cervical cerclage in the
management of preterm premature rupture of the mem-
branes. Am J Obstet Gynecol 1988;158:10610. (Level II-3)
94. Ludmir J, Bader T, Chen L, Lindenbaum C, Wong G. Poor
perinatal outcome associated with retained cerclage in
patients with premature rupture of membranes. Obstet
Gynecol 1994;84:8236. (Level II-3)
95. Jenkins TM, Berghella V, Shlossman PA, McIntyre CJ,
Maas BD, Pollock MA, et al. Timing of cerclage removal
after preterm premature rupture of membranes: maternal
and neonatal outcomes. Am J Obstet Gynecol 2000;183:
84752. (Level II-3)
96. McElrath TF, Norwitz ER, Lieberman ES, Heffner LJ.
Perinatal outcome after preterm premature rupture of
membranes with in situ cervical cerclage. Am J Obstet
Gynecol 2002;187:114752. (Level II-3)
97. Kuhn RJ, Pepperell RJ. Cervical ligation: a review of 242
pregnancies. Aust N Z J Obstet Gynecol 1977;17:7983.
(Level II-3)
98. Chuang T. Neonatal herpes: incidence, prevention, and
consequences. Am J Prev Med 1988;4:4753. (Level III)
99. Amstey MS. Management of pregnancy complicated by
genital herpes virus infection. Obstet Gynecol 1971;37:
51520. (Level II-3)
100. Nahmias AJ, Josey WE, Naib ZM, Freeman MG,
Fernandez RJ, Wheeler JH. Perinatal risk associated with
maternal genital herpes simplex virus infection. Am J
Obstet Gynecol 1971;110:82537. (Level II-3)
101. Gibbs RS, Amstey MS, Lezotte DC. Role of cesarean
delivery in preventing neonatal herpes virus infection.
JAMA 1993;270:945. (Level III)
102. Major CA, Towers CV, Lewis DF, Garite TJ. Expectant
management of preterm premature rupture of membranes
complicated by active recurrent genital herpes. Am J
Obstet Gynecol 2003;188:15514; discussion 15545.
(Level II-3)
103. Perinatal care at the threshold of viability. ACOG Practice
Bulletin No. 38. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2002;100:61724. (Level
III)
989 PRACTICE BULLETINS
The MEDLINE database, the Cochrane Library, and
ACOGs own internal resources and documents were used
to conduct a literature search to locate relevant articles pub-
lished between January 1985 and November 2006. The
search was restricted to articles published in the English
language. Priority was given to articles reporting results of
original research, although review articles and commentar-
ies also were consulted. Abstracts of research presented at
symposia and scientific conferences were not considered
adequate for inclusion in this document. Guidelines pub-
lished by organizations or institutions such as the National
Institutes of Health and the American College of Obstetri-
cians and Gynecologists were reviewed, and additional
studies were located by reviewing bibliographies of identi-
fied articles. When reliable research was not available,
expert opinions from obstetriciangynecologists were used.
Studies were reviewed and evaluated for quality according
to the method outlined by the U.S. Preventive Services Task
Force:
I Evidence obtained from at least one properly de-
signed randomized controlled trial.
II-1 Evidence obtained from well-designed controlled
trials without randomization.
II-2 Evidence obtained from well-designed cohort or
casecontrol analytic studies, preferably from more
than one center or research group.
II-3 Evidence obtained from multiple time series with or
without the intervention. Dramatic results in uncon-
trolled experiments also could be regarded as this
type of evidence.
III Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees.
Based on the highest level of evidence found in the data,
recommendations are provided and graded according to the
following categories:
Level ARecommendations are based on good and consis-
tent scientific evidence.
Level BRecommendations are based on limited or incon-
sistent scientific evidence.
Level CRecommendations are based primarily on con-
sensus and expert opinion.
Copyright April 2007 by the American College of Obstetri-
cians and Gynecologists. All rights reserved. No part of this
publication may be reproduced, stored in a retrieval system,
posted on the Internet, or transmitted, in any form or by any
means, electronic, mechanical, photocopying, recording, or
otherwise, without prior written permission from the publisher.
Requests for authorization to make photocopies should be
directed to Copyright Clearance Center, 222 Rosewood Drive,
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
The American College of Obstetricians and Gynecologists
409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920
Premature rupture of membranes. ACOG Practice Bulletin No. 80.
American College of Obstetricians and Gynecologists. Obstet Gynecol
2007;109:100719.
COMPENDIUM OF SELECTED PUBLICATIONS 990
CLINICAL MANAGEMENT GUIDELINES FOR
OBSTETRICIANGYNECOLOGISTS
NUMBER 82, JUNE 2007
(Replaces Practice Bulletin Number 8, October 1999)
This Practice Bulletin was
developed by the ACOG Com-
mittee on Practice Bulletins
Obstetrics with the assistance
of Lisa Hollier, MD. The infor-
mation is designed to aid prac-
titioners in making decisions
about appropriate obstetric and
gynecologic care. These guide-
lines should not be construed as
dictating an exclusive course of
treatment or procedure. Varia-
tions in practice may be war-
ranted based on the needs of the
individual patient, resources,
and limitations unique to the
institution or type of practice.
Reaffirmed 2009
Management of Herpes
in Pregnancy
Genital herpes simplex virus (HSV) infection during pregnancy poses a risk to
the developing fetus and newborn. Genital herpes infection occurs in one in five
women in the United States. Because many women of childbearing age are
infected or are becoming infected with HSV, the risk of maternal transmission
of this virus to the fetus or newborn is a major health concern. The purpose of
this document is to outline the spectrum of maternal and neonatal infection,
including risks of transmission, and provide management guidelines supported
by appropriately conducted outcome-based research. Additional guidelines
based on consensus and expert opinion also are presented to permit a review of
most clinical aspects of HSV.
Background
Etiology
Herpes simplex virus is a double-stranded DNA virus that can be differentiated
into HSV type 1 (HSV-1) and HSV type 2 (HSV-2) based on the glycoproteins
in the lipid bilayer envelope. Glycoprotein G2 is associated with HSV-2, and
glycoprotein G1 is associated with HSV-1. Herpes simplex virus type 1 is the
primary etiologic agent of herpes labialis, gingivostomatitis, and keratocon-
junctivitis. Most genital infections with HSV are caused by HSV-2, but genital
HSV-1 infections are becoming increasingly common, particularly among ado-
lescent and young women (1).
Herpes simplex virus is transmitted from person to person through direct
contact. Infection is initiated when the virus contacts mucosa or abraded skin.
The incubation period after acquisition of HSV-1 or HSV-2 ranges from 2 days
to 12 days. Herpes simplex virus then replicates in the epidermis and dermis, with
resulting cellular destruction and inflammation. During the initial infection, the
virus gains access to the sensory neurons, and then the infection becomes latent
ACOG
PRACTICE
BULLETIN
991 PRACTICE BULLETINS
in the sensory ganglia. Reactivation of viral replication
occurs and may manifest clinically as recurrent ulcerative
lesions or subclinically as asymptomatic viral shedding.
Both the cellular and humoral immune systems play an
important role in controlling this viral infection (2).
Herpes virus has a characteristic protein coat, and
each of the viral types has identifiable proteins. Type-
specific antibodies to the viral proteins develop within
the first several weeks of infection and persist. Antibod-
ies to HSV can be detected by most assays within 23
weeks after infection with the virus (3).
Genital infection with HSV is a primary infection
when HSV-1 or HSV-2 is detected in individuals with no
evidence of antibodies to either viral type in the serum. An
outbreak is considered a nonprimary first episode when one
viral type is detected in an individual with serologic evi-
dence of past infection with the other viral type. Recurrent
episodes are characterized by isolation of HSV-1 or HSV-2
in the presence of antibodies of the same serotype.
Incidence
Herpes simplex virus infection of the genital tract is one
of the most common sexually transmitted infections. The
true incidence of genital HSV infection is not known
because it is not a reportable disease. It is estimated
that approximately 45 million adolescent and adult
Americans have been infected with HSV-2 (4). In a large,
national serologic study, it was found that approximately
26% of women had serologic evidence of HSV-2 infec-
tion (4). It should be emphasized that serologic studies of
HSV-2 underestimate the prevalence of genital herpes
because HSV-1 also causes genital disease.
Most individuals who are infected with HSV are
unaware that they have contracted the virus. Only
approximately 515% of infected individuals report
recognition of their infection (4, 5). The increasing bur-
den of infection has important implications for health
care providers. The number of initial visits to physicians
offices as a result of genital HSV infection increased
from approximately 75,000 per year in 1978 to nearly
270,000 per year in 2004 (6). Risk factors for HSV infec-
tion include female gender, duration of sexual activity,
minority ethnicity, previous genital infection, family
income, and number of sex partners (4, 7).
Whereas HSV-2 is virtually always a genital
pathogen, HSV-1 is increasingly recognized as the etio-
logic agent of genital herpes infection. Up to 80% of new
genital infections among all women may be caused by
HSV-1 (8, 9). This increase in initial infections with
HSV-1 is particularly pronounced in the adolescent and
young adult populations. In these populations, genital
infection with HSV-1 may have surpassed new genital
infection with HSV-2 (1).
Among women with serologic test results that indi-
cate susceptibility to HSV infection, the incidence of new
HSV-1 or HSV-2 infection during pregnancy is approxi-
mately 2% (10). Approximately 10% of women who are
HSV-2 seronegative have partners who are seropositive
and are at risk for transmission of HSV-2 during the preg-
nancy (11). Consistent with nonpregnant patients, most
new infections in pregnant patients are asymptomatic
(10). The timing of infection is relatively evenly distrib-
uted, with approximately one third of women becoming
infected in each trimester (10). Among women with
recurrent genital HSV, approximately 75% can expect
at least one recurrence during pregnancy, and approxi-
mately 14% of patients will have prodromal symptoms or
clinical recurrence at delivery (12, 13).
Neonatal herpes usually is acquired during the intra-
partum period through exposure to the virus in the geni-
tal tract, although in utero and postnatal infections are
rare but can occur. Approximately 80% of infected
infants are born to mothers with no reported history of
HSV infection (14). Although the actual incidence is
unknown because neonatal herpes infection is not a
reportable disease, estimates suggest that approximately
1,2001,500 cases occur each year in the United States
(15). Approximately one third to one half of cases of
neonatal herpes are caused by HSV-1 (15, 16). Neonatal
HSV infections can be classified as disseminated disease
(25%); central nervous system disease (30%); and dis-
ease limited to the skin, eyes, or mouth (45%) (14).
Mortality has decreased substantially over the past two
decades, decreasing to 30% for disseminated disease and
4% for central nervous system disease. Approximately
20% of survivors of neonatal herpes have long-term neu-
rologic sequelae (17).
Clinical Considerations and
Recommendations
How can the diagnosis of herpes simplex
virus be established?
All suspected herpes virus infections should be con-
firmed through viral or serological testing. A diagnosis of
genital herpes based on the clinical presentation alone
has a sensitivity of 40% and specificity of 99% and a
false-positive rate of 20% (18). The tests used to confirm
the presence of HSV infection can be divided into two
basic groups: 1) viral detection techniques and 2) anti-
body detection techniques. Primary viral DNA testing
techniques are viral culture and HSV antigen detection
by polymerase chain reaction (PCR). The antibody detec-
tion techniques include the use of both laboratory-based
COMPENDIUM OF SELECTED PUBLICATIONS 992
and point-of-care serologic tests to detect the presence of
antibodies to either HSV-1 or HSV-2. With viral detec-
tion techniques, negative results do not rule out the
presence of infection. The diagnosis of HSV should be
confirmed either serologically or with viral culture.
Isolation of HSV in cell culture is the preferred viro-
logic test for patients who seek medical treatment for
genital ulcers or other mucocutaneous lesions and allows
differentiation of the type of virus (HSV-1 versus HSV-
2) (18). The sensitivity of this test is limited because of
several issues related to sampling and transportation of
the specimen (19). Primary lesions are more likely than
recurrent lesions to yield positive cultures (80% versus
40% of patients, respectively) (20, 21). Additionally, as
the lesions heal, they are less likely to be culture positive
(21). Thus, a positive genital culture provides conclusive
evidence of genital HSV infection; however, a negative
result does not exclude the presence of infection. When
a genital specimen is collected for HSV culture, the vesi-
cles should be unroofed, if present, and vesicular fluid
should be collected.
Polymerase chain reaction techniques involve the
amplification of particular sequences of DNA or RNA
before detection and can thus detect evidence of viral
DNA at low concentrations. Because of the increased
sensitivity of PCR, unroofing vesicles is unnecessary. In
one very large study, PCR results were three to five times
more likely to be positive than were cultures (19).
Cultures were more likely to be positive at increasing
concentrations of virus, as demonstrated by a linear rela-
tionship between the proportion of positive cultures and
copy numbers of HSV DNA in samples. Polymerase
chain reaction techniques are commercially available
and can differentiate between HSV-1 and HSV-2.
Polymerase chain reaction provides increased sensitiv-
ity over culture (19, 20, 22) and may ultimately replace
culture as the standard of care for diagnosis. Presently,
however, there are no interlaboratory standards that
ensure that identical specimens processed in different
laboratories will yield identical results. Additionally,
the PCR tests are not U.S. Food and Drug Administra-
tion (FDA) approved for clinical testing of genital spec-
imens (18).
For patients who do not present with active lesions
or whose lesions have negative culture or PCR test
results, accurate type-specific serologic assays that accu-
rately distinguish between HSV-1 and HSV-2 antibodies
are now commercially available. Currently, there are sev-
eral FDA-approved type-specific tests, and others are
under development (see box). The sensitivity of these
assays varies from 93100% and specificity from
9398% (23). The predictive value of a positive test
result is influenced by the prevalence of the disease in
the population tested. In a high-risk population, the pos-
itive predictive value for the ELISA test results was
8094% (24, 25). Repeat testing, using a different type-
specific assay, has been shown to increase the positive
predictive value of a single test result, and this may be
especially important in populations with low HSV preva-
lence (24).
Because HSV-2 is an uncommon cause of oral
infection, detection of HSV-2 antibodies is virtually
diagnostic of genital HSV infection (26). Conversely,
detection of HSV-1 antibodies alone may represent oro-
labial infection or may be indicative of genital infection.
Correlation with direct viral identification techniques
and the patients symptoms is important.
How can primary herpes simplex virus infec-
tion be distinguished from a nonprimary first
episode during pregnancy?
It is not possible to distinguish primary from nonprimary
herpes simplex virus infection on the basis of clinical
findings alone (27). Diagnosis is based on the combina-
tion of positive viral detection and negative serologic test
results or evidence of seroconversion.
A primary outbreak in the first trimester of preg-
nancy has been associated with neonatal chorioretinitis,
microcephaly, and skin lesions in rare cases (28).
Although HSV has been associated with an increased
risk for spontaneous abortion, recent studies do not sup-
port such a risk (29).
How should a primary outbreak be managed
in pregnancy?
At the time of the initial outbreak, antiviral treatment
may be administered orally to pregnant women to reduce
the duration and the severity of the symptoms as well as
reduce the duration of viral shedding (Table 1) (30). In
patients who have severe disease, oral treatment can be
U.S. Food and Drug Administration-
Approved Type-Specific Tests
Laboratory-based assays
HerpeSelect-1 and 2 ELISA IgG
HerpeSelect 1 and 2 Immunoblot IgG
Captia HSV-1 and 2 ELISA
Rapid tests (formerly known as the POCkit test)
BiokitHSV-2 Rapid Test
Sure-Vue HSV-2
993 PRACTICE BULLETINS
deliveries for clinical herpes recurrences was reduced;
however, the total number of cesarean deliveries in the
treatment and placebo groups was similar. The number of
deliveries was insufficient to evaluate efficacy of antivi-
ral treatment to prevent neonatal herpes. Evidence of the
effectiveness of cesarean delivery before labor for the
prevention of vertical transmission is lacking.
How should recurrent herpes simplex virus
infection in pregnant women be managed?
All women should be asked early in pregnancy about
symptoms of genital herpes, including prodromal symp-
toms. Women with a history of herpes should be exam-
ined for external herpetic lesions when they present for
evaluation in labor and delivery (6).
Among women with recurrent lesions at the time of
delivery, the rate of transmission with a vaginal delivery
is only 3% (36). For women with a history of recurrent
disease and no visible lesions at delivery, the transmis-
sion risk has been estimated to be 2/10,000 (15, 36). The
low risk is in part attributed to the presence and transpla-
cental passage of antiherpes antibodies (15, 34, 36).
Cesarean delivery is not indicated in women with a his-
tory of HSV in the absence of active genital lesions or
prodromes.
The efficacy of suppressive therapy during preg-
nancy to prevent recurrences near term has been evalu-
ated in numerous studies (13, 35, 3741). Because many
of the individual trials were small, a recent systematic
review of randomized controlled trials was performed to
assess the effectiveness of acyclovir suppression therapy
given to prevent a clinical recurrence at delivery, ces-
arean delivery for recurrent genital herpes, and the detec-
tion of HSV at delivery (42). The risk of recurrence at
extended for more than 10 days if lesions are incom-
pletely healed at that time (18).
Acyclovir may be administered intravenously to
pregnant women with severe genital HSV infection or
with disseminated herpetic infections. Case reports have
associated significant improvement in expected survival
with acyclovir treatment in cases of pregnant women
with disseminated HSV, herpes pneumonitis, herpes
hepatitis, and herpes encephalitis (3133).
Primary genital herpes infection during pregnancy
constitutes a higher risk for perinatal transmission than
does recurrent infection. The risk of vertical transmission
to the neonate when a primary outbreak occurs at the
time of delivery is approximately 3060% (10, 15).
Several factors likely contribute to the increased risk.
First, when women have acquired infection near the time
of delivery, there is likely reduced transplacental passage
of protective HSV-2 specific antibodies. Higher titers of
neutralizing antibodies in the neonate have been associ-
ated with a reduced risk of neonatal infection (34).
Second, neonatal exposure to the virus in the genital tract
may be increased. The genital viral shedding in women
with primary infection is of higher concentration and
longer duration than shedding that occurs with recurrent
episodes. Women with primary herpes that is untreated
have a mean duration of viral shedding of 15 days (30).
In addition, cervical shedding was detected by viral cul-
ture in 90% of women with primary infection (30).
Data regarding interventions to reduce vertical
transmission in the specific setting of primary herpes are
limited. One randomized trial of acyclovir versus pla-
cebo given from 36 weeks of gestation until delivery to
women with their first episode of genital herpes infection
during pregnancy found a significant reduction in clini-
cal recurrences at delivery (35). The number of cesarean
Table 1. Recommended Doses of Antiviral Medications for Herpes in Pregnancy
Indication Acyclovir Valacyclovir
Primary or first-episode infection 400 mg orally, three times daily, 1 g orally, twice daily, for 710* days
for 710* days
Symptomatic recurrent episode 400 mg orally, three times daily, 500 mg orally, twice daily, for 3 days
for 5 days or 800 mg orally, or 1 g orally, daily, for 5 days
twice daily, for 5 days
Daily suppression 400 mg orally, three times daily, 500 mg orally, twice daily, from 36
from 36 weeks estimated weeks estimated gestational age until
gestational age until delivery delivery
Severe or disseminated disease 510 mg/kg, intravenously, every
8 hours for 27 days, then oral
therapy for primary infection to
complete 10 days
*Treatment may be extended if healing is incomplete after 10 days.
Adapted from Sexually transmitted diseases treatment guidelines, 2006 [published erratum appears in MMWR Recomm Rep
2006;55:997]. Centers for Disease Control and Prevention. MMWR Recomm Rep 2006;55(RR11):194.
COMPENDIUM OF SELECTED PUBLICATIONS 994
delivery was reduced by 75%, and the rate of cesarean
delivery for recurrent genital herpes was reduced by 40%
for women who received suppression therapy after 36
weeks of gestation. Viral detection at delivery using cul-
ture or PCR was reduced by 90% among treated women,
but shedding was not completely eliminated (in one trial,
virus was detected in one woman receiving acyclovir)
(13). There were no cases of neonatal herpes in any of the
studies. Several trials demonstrating similar efficacy of
valacyclovir have been published since the meta-analysis
(12, 43). Women with active recurrent genital herpes
should be offered suppressive viral therapy at or beyond
36 weeks of gestation. The doses of antiviral medication
used in the randomized trials in pregnancy are higher
than the corresponding doses in nonpregnant women.
(Table 1.) Although neutropenia is a recognized, tran-
sient complication of acyclovir treatment of neonatal
HSV infection, it has not been reported following mater-
nal suppressive therapy (17). The acyclovir concentra-
tions at which neutropenia occurred were approximately
530 times higher than were observed in umbilical vein
plasma in a pharmacokinetic study of valacyclovir in
pregnancy (44).
What medications are available for treatment
of herpes simplex virus infection during
pregnancy?
There are three antiviral agents that are commonly used
to treat HSV infections. Acyclovir, famciclovir, and vala-
cyclovir are all FDA pregnancy category B medications.
These drugs are all approved for the treatment of prima-
ry genital herpes, the treatment of episodes of recurrent
disease, and the daily treatment for suppression of out-
breaks of recurrent genital herpes.
Acyclovir is a nucleoside analogue that enters virally
infected cells and acts specifically to inhibit the viral
thymidine kinase and, thus, DNA replication. The
bioavailability of oral acyclovir is approximately 20%,
which necessitates more frequent dosage intervals (45).
Valacyclovir is a prodrug of acyclovir and is rapidly con-
verted to acyclovir after metabolism in the liver. The
bioavailability of acyclovir after doses with valacyclovir
is approximately 54% (46). This is three to five times
higher than achieved with oral acyclovir and, at a dose of
1 gm, approximates levels achieved with intravenous
doses of acyclovir. The pharmacokinetics of both drugs
have been evaluated in pregnancy. After doses of acy-
clovir and valacyclovir, there was evidence of acyclovir
concentration in the amniotic fluid but no evidence of
preferential fetal drug accumulation (44, 47).
Famciclovir also is a prodrug that is rapidly transformed
into penciclovir in the body. The bioavailability of the
active drug from an oral dose is approximately 77%, so
the dosage interval is less frequent than with acyclovir
(48). There are no published data on the use of famci-
clovir in pregnancy.
Development of viral resistance to acyclovir has not
been a problem in immunocompetent patients. In two
large, laboratory-based studies, a very low prevalence of
acyclovir resistance in viruses isolated from immuno-
competent patients has been estimated (0.30.6%),
whereas acyclovir-resistant HSV infections occur more
commonly among patients who are immunocompro-
mised (67%) (49, 50).
There are no documented increases in adverse fetal
effects because of medication exposure (39, 50, 51). The
manufacturer of acyclovir and valacyclovir, in coopera-
tion with the Centers for Disease Control and Prevention,
maintained a registry for exposure to these drugs during
pregnancy through 1999. More than 700 infants reported
were exposed to acyclovir during the first trimester, and
there was no increase in adverse fetal or neonatal effects,
although the safety has not been definitely established
(18). There are insufficient data on valacyclovir and fam-
ciclovir exposure in the pregnancy registry for analyses
(52). Topical therapy offers limited benefit and should be
discouraged.
Is there a role for routine screening for
genital herpes during pregnancy or at
delivery?
In the past, screening referred to the use of a viral detec-
tion method, most commonly culture, to assess whether
viral shedding was present. Asymptomatic shedding dur-
ing the antepartum period does not predict asymptomatic
shedding at delivery (53, 54). Thus, routine antepartum
genital HSV cultures in asymptomatic patients with
recurrent disease are not recommended.
With the advent of serologic tests that can reliably
detect disease in asymptomatic patients, screening now
refers to the detection of HSV infection. Maternal HSV
screening has been proposed to reduce neonatal herpes
by identifying women infected (seropositive) with geni-
tal herpes and offering suppressive antiviral therapy near
term. It also may identify susceptible women (seronega-
tive) whose partners could be offered screening, allowing
for counseling of at-risk couples about strategies to
reduce the possibility of new maternal infection during
pregnancy. Several analyses have evaluated the cost-
effectiveness of various screening protocols for pregnant
patients to reduce the incidence of neonatal HSV infec-
tion (5559). The results from these analyses are highly
variableestimates of the cost to prevent one case of
neonatal herpes range from $200,000 to $4,000,000.
995 PRACTICE BULLETINS
A number of factors influence these cost estimates, includ-
ing the costs of testing and counseling, effectiveness of
antiviral therapy, the probability of lesions or shedding at
delivery in asymptomatic women in whom HSV has been
diagnosed only by the screening test, and the likelihood of
neonatal herpes with vaginal delivery (54, 55). Currently,
there is no evidence of cost-effectiveness of screening
strategies from clinical trials or well-designed cohort stud-
ies in pregnancy. Whereas screening may be beneficial in
particular populations or couples, routine HSV screening
of pregnant women is not recommended.
When should cesarean delivery be performed
to prevent perinatal herpes simplex virus
transmissions?
Cesarean delivery is indicated in women with active gen-
ital lesions or prodromal symptoms, such as vulvar pain
or burning at delivery, because these symptoms may indi-
cate an impending outbreak. The incidence of neonatal
disease is low when there is recurrent maternal disease,
but cesarean delivery is recommended because of the
potentially serious nature of the disease. In a large cohort
study, women who had given birth by cesarean delivery
were much less likely to transmit HSV infection to their
infants (15). Among women with HSV detected at deliv-
ery, neonatal herpes occurred in 1.2% of infants delivered
by cesarean delivery compared with 7.7% of infants
delivered vaginally (15).
Cesarean delivery does not completely prevent verti-
cal transmission to the neonate. Transmission has been
documented in the setting of cesarean delivery performed
before membrane rupture (14, 60). Cesarean delivery is
not recommended for women with a history of HSV
infection but no active genital disease during labor (61).
Is cesarean delivery recommended for women
with recurrent herpes simplex virus lesions
on the back, thigh, or buttock?
Cesarean delivery is not recommended for women with
nongenital lesions. These lesions may be covered with an
occlusive dressing, and the patient then can give birth
vaginally. However, women with lesions elsewhere also
may have cervical lesions and should be examined.
The risk of transmission among women with recur-
rent HSV at the time of labor is low, estimated to be less
than 1% (18, 62). As with other women with recurrent
herpes, the low risk is probably related to preexisting
maternal type-specific antibodies. Thus, the risk of
neonatal HSV associated with vaginal delivery in a
woman with recurrent HSV and nongenital lesions would
appear to be very low.
In a patient with active herpes simplex virus
genital infection and ruptured membranes,
should cesarean delivery be performed to
prevent perinatal transmission?
In patients with active HSV infection and ruptured mem-
branes at or near term, a cesarean delivery should be
performed as soon as the necessary personnel and equip-
ment can be readied. There is no evidence that there is a
duration of rupture of membranes beyond which the
fetus does not benefit from cesarean delivery (63). At
any time after rupture of membranes, cesarean delivery
is recommended.
How should a woman with active herpes sim-
plex virus and preterm premature rupture of
membranes be managed?
In a patient with preterm premature rupture of membranes
and active HSV, the risks of prematurity should be
weighed against the risk of neonatal HSV disease in con-
sidering expectant management. In pregnancies remote
from term, especially in women with recurrent disease,
there is increasing support for continuing the pregnancy to
gain benefit from time and use of corticosteroids (64, 65).
There is no consensus on the gestational age at which the
risks of prematurity outweigh the risks of HSV. When
expectant management is elected, treatment with an antivi-
ral agent may be considered. The decision to use cortico-
steroids should be based on the balance between the risk
of pulmonary immaturity and the risk of neonatal herpes.
Are invasive procedures contraindicated in
pregnant women with herpes simplex virus?
In women with a history of recurrent HSV, transabdominal
invasive procedures, such as chorionic villus sampling,
amniocentesis, and percutaneous umbilical cord blood
sampling, may be performed even when genital lesions are
present. Because cervical shedding is associated with gen-
ital recurrences, it seems reasonable to delay transcervical
procedures until lesions appear to have resolved.
Invasive monitoring, such as fetal scalp electrodes, is
a risk factor for transmission of HSV, increasing the risk
of neonatal infection approximately six times compared
with externally monitored patients (15). However, if there
are indications for fetal scalp monitoring, it is reasonable
in a woman who has a history of recurrent HSV and no
active lesions.
Should women with active herpes simplex
virus breastfeed or handle their infants?
Unless there is a lesion on the breast, breastfeeding is not
contraindicated. To prevent postnatal transmission,
COMPENDIUM OF SELECTED PUBLICATIONS 996
mothers with herpetic lesions on any part of the body
should be advised to take special consideration of hand-
washing. Postnatally acquired disease can be as lethal as
that acquired during delivery. Oropharyngeal or cuta-
neous lesions can be an effective source of virus for
transmission to the newborn. Because the herpes virus is
transmitted through direct contact (eg, hand-to-mouth),
neonatal infection may be acquired from family mem-
bers other than the mother and from sites other than the
genital tract (66, 67). Most strains of HSV responsible
for nosocomial neonatal disease are HSV-1 rather than
HSV-2. Mothers with active lesions should use caution
when handling their babies.
Valacyclovir appears to be safe for breastfeeding
mothers. Although acyclovir was found in the breast milk
in concentrations that were higher than the maternal
serum, the amount of acyclovir in the breast milk was only
2% of that used for therapeutic doses in neonates (68).
Summary of
Recommendations and
Conclusions
The following recommendations and conclusions
are based on limited or inconsistent scientific evi-
dence (Level B):
Women with active recurrent genital herpes should
be offered suppressive viral therapy at or beyond 36
weeks of gestation.
Cesarean delivery is indicated in women with active
genital lesions or prodromal symptoms, such as
vulvar pain or burning at delivery, because these
symptoms may indicate an impending outbreak.
The following recommendations and conclusions
are based primarily on consensus and expert
opinion (Level C):
In women with premature rupture of membranes,
there is no consensus on the gestational age at which
the risks of prematurity outweigh the risks of HSV.
Cesarean delivery is not recommended for women
with a history of HSV infection but no active geni-
tal disease during labor.
Routine antepartum genital HSV cultures in asymp-
tomatic patients with recurrent disease are not rec-
ommended.
Routine HSV screening of pregnant women is not
recommended
Proposed Performance
Measure
The percentage of pregnant women who have been asked
about their history of herpes
References
1. Roberts CM, Pfister JR, Spear SJ. Increasing proportion
of herpes simplex virus type 1 as a cause of genital herpes
infection in college students. Sex Transm Dis 2003;
30:797800. (Level II-3)
2. Pertel PE, Spear PG. Biology of herpesviruses. In Holmes
KK, Mardh PA, Sparling PF, Lemon SM, Stamm WE,
Piot P, et al editors. Sexually transmitted diseases. 3rd ed.
New York (NY): McGraw-Hill 1999. p.26983. (Level III)
3. Brown ZA, Gardella C, Wald A, Morrow RA, Corey L.
Genital herpes complicating pregnancy [published erra-
tum appears in Obstet Gynecol 2006;107:428]. Obstet
Gynecol 2005;106:84556. (Level III)
4. Fleming DT, McQuillan GM, Johnson RE, Nahmias AJ,
Aral SO, Lee FK. Herpes simplex virus type 2 in the
United States, 1976 to 1994. N Engl J Med 1997;337:
110511. (Level II-3)
5. Leone P, Fleming DT, Gilsenan AW, Li L, Justus S.
Seroprevalence of herpes simplex virus-2 in suburban pri-
mary care offices in the United States. Sex Transm Dis
2004;31:3116. (Level II-2)
6. Centers for Disease Control and Prevention. Sexually
transmitted disease surveillance 2004. Atlanta (GA):
CDC; 2005. Available at: http://www.cdc.gov/std/stats/
04pdf/2004SurveillanceAll.pdf. Retrieved November 29,
2006. (Level II-2)
7. Mertz GJ, Benedetti J, Ashley R, Selke SA, Corey L. Risk
factors for the sexual transmission of genital herpes. Ann
Intern Med 1992;116:197202. (Level II-3)
8. Lafferty WE, Downey L, Celum C, Wald A. Herpes sim-
plex virus type 1 as a cause of genital herpes: impact on
surveillance and prevention. J Infect Dis 2000;181:
14547. (Level II-3)
9. Nilsen A, Myrmel H. Changing trends in genital herpes
simplex virus infection in Bergen, Norway. Acta Obstet
Gynecol Scand 2000;79:6936. (Level II-3)
10. Brown ZA, Selke S, Zeh J, Kopelman J, Maslow A,
Ashley RL, et al. The acquisition of herpes simplex virus
during pregnancy. N Engl J Med 1997;337:50915.
(Level II-2)
11. Gardella C, Brown Z, Wald A, Selke S, Zeh J, Morrow
RA, et al. Risk factors for herpes simplex virus transmis-
sion to pregnant women: a couples study. Am J Obstet
Gynecol 2005;193:18919. (Level II-2)
12. Sheffield JS, Hill JB, Hollier LM, Laibl VR, Roberts SW,
Sanchez PJ, et al. Valacyclovir prophylaxis to prevent
recurrent herpes at delivery: a randomized clinical trial
[published erratum appears in Obstet Gynecol 2006;
108:695]. Obstet Gynecol 2006;108:1417. (Level I)
997 PRACTICE BULLETINS
26. Wald A, Ericsson M, Krantz E, Selke S, Corey L. Oral
shedding of herpes simplex virus type 2 [published erra-
tum appears in Sex Transm Infect 2004;80:546]. Sex
Transm Infect 2004;80:2726. (Level II-2)
27. Hensleigh PA, Andrews WW, Brown Z, Greenspoon J,
Yasukawa L, Prober CG. Genital herpes during preg-
nancy: inability to distinguish primary and recurrent
infections clinically. Obstet Gynecol 1997;89:8915.
(Level II-2)
28. Hutto C, Arvin A, Jacobs R, Steele R, Stagno S, Lyrene R,
et al. Intrauterine herpes simplex virus infections. J
Pediatr 1987;110:97101. (Level II-3)
29. Ratanajamit C, Vinther Skriver M, Jepsen P,
Chongsuvivatwong V, Olsen J, Sorensen HT. Adverse
pregnancy outcome in women exposed to acyclovir dur-
ing pregnancy: a population-based observational study.
Scand J Infect Dis 2003;35:2559. (Level II-2)
30. Bryson YJ, Dillon M, Lovett M, Acuna G, Taylor S,
Cherry JD, et al. Treatment of first episodes of genital her-
pes simplex virus infection with oral acyclovir. A ran-
domized double-blind controlled trial in normal subjects.
N Engl J Med 1983;308:91621. (Level I)
31. Young EJ, Chafizadeh E, Oliveira VL, Genta RM.
Disseminated herpesvirus infection during pregnancy.
Clin Infect Dis 1996;22:518. (Level III)
32. Grover L, Kane J, Kravitz J, Cruz A. Systemic acyclovir
in pregnancy: a case report. Obstet Gynecol 1985;65:
2847. (Level III)
33. Lagrew DC Jr, Furlow TG, Hager WD, Yarrish RL.
Disseminated herpes simplex virus infection in pregnancy.
Successful treatment with acyclovir. JAMA 1984;252:
20589. (Level III)
34. Prober CG, Sullender WM, Yasukawa LL, Au DS, Yeager
AS, Arvin AM. Low risk of herpes simplex virus infec-
tions in neonates exposed to the virus at the time of vagi-
nal delivery to mothers with recurrent genital herpes
simplex virus infections. N Engl J Med 1987;316:2404.
(Level II-3)
35. Scott LL, Sanchez PJ, Jackson GL, Zeray F, Wendel GD
Jr. Acyclovir suppression to prevent cesarean delivery
after first-episode genital herpes. Obstet Gynecol 1996;
87:6973. (Level I)
36. Brown ZA, Benedetti J, Ashley R, Burchett S, Selke S,
Berry S, et al. Neonatal herpes simplex virus infection in
relation to asymptomatic maternal infection at the time of
labor. N Engl J Med 1991;324:124752. (Level II-2)
37. Braig S, Luton D, Sibony O, Edlinger C, Boissinot C,
Blot P, et al. Acyclovir prophylaxis in late pregnancy pre-
vents recurrent genital herpes and viral shedding. Eur J
Obstet Gynecol Reprod Biol 2001;96:558. (Level I)
38. Brocklehurst P, Kinghorn G, Carney O, Helsen K, Ross E,
Ellis E, et al. A randomised placebo controlled trial of
suppressive acyclovir in late pregnancy in women with
recurrent genital herpes infection. Br J Obstet Gynaecol
1998;105:27580. (Level I)
39. Scott LL, Hollier LM, McIntire D, Sanchez PJ, Jackson
GL, Wendel GD Jr. Acyclovir suppression to prevent
clinical recurrences at delivery after first episode genital
13. Watts DH, Brown ZA, Money D, Selke S, Huang ML,
Sacks SL, et al. A double-blind, randomized, placebo-con-
trolled trial of acyclovir in late pregnancy for the reduction
of herpes simplex virus shedding and cesarean delivery.
Am J Obstet Gynecol 2003;188:83643. (Level I)
14. Whitley RJ, Corey L, Arvin A, Lakeman FD, Sumaya CV,
Wright PF, et al. Changing presentation of herpes simplex
virus infection in neonates. J Infect Dis 1988;158:
109116. (Level II-3)
15. Brown ZA, Wald A, Morrow RA, Selke S, Zeh J, Corey L.
Effect of serologic status and cesarean delivery on trans-
mission rates of herpes simplex virus from mother to
infant. JAMA 2003;289:2039. (Level II-2)
16. Whitley R, Arvin A, Prober C, Burchett S, Corey L,
Powell D, et al. A controlled trial comparing vidarabine
with acyclovir in neonatal herpes simplex virus infection.
Infectious Diseases Collaborative Antiviral Study Group.
N Engl J Med 1991;324:4449. (Level I)
17. Kimberlin DW, Lin CY, Jacobs RF, Powell DA, Corey L,
Gruber WC, et al. Safety and efficacy of high-dose intra-
venous acyclovir in the management of neonatal herpes
simplex virus infections. National Institute of Allergy and
Infectious Diseases Collaborative Antiviral Study Group.
Pediatrics 2001;108:2308. (Level II-3)
18. Sexually transmitted diseases treatment guidelines, 2006
[published erratum appears in MMWR Recomm Rep
2006;55:997]. Centers for Disease Control and Preven-
tion. MMWR Recomm Rep 2006;55(RR-11):194.
(Level III)
19. Wald A, Huang ML, Carrell D, Selke S, Corey L.
Polymerase chain reaction for detection of herpes simplex
virus (HSV) DNA on mucosal surfaces: comparison with
HSV isolation in cell culture. J Infect Dis 2003;188:
134551. (Level II-3)
20. Moseley RC, Corey L, Benjamin D, Winter C, Remington
ML. Comparison of viral isolation, direct immunofluores-
cence, and indirect immunoperoxidase techniques for
detection of genital herpes simplex virus infection. J Clin
Microbiol 1981;13:9138. (Level II-2)
21. Cone RW, Hobson AC, Palmer J, Remington M, Corey L.
Extended duration of herpes simplex virus DNA in geni-
tal lesions detected by the polymerase chain reaction. J
Infect Dis 1991;164:75760. (Level II-3)
22. Slomka MJ, Emery L, Munday PE, Moulsdale M, Brown
DW. A comparison of PCR with virus isolation and direct
antigen detection for diagnosis and typing of genital her-
pes. J Med Virol 1998;55:17783. (Level II-3)
23. Ashley RL. Performance and use of HSV type-specific
serology test kits. Herpes 2002;9:3845. (Level III)
24. Morrow RA, Friedrich D, Meier A, Corey L. Use of
biokit HSV-2 Rapid Assay to improve the positive pre-
dictive value of Focus HerpeSelect HSV-2 ELISA. BMC
Infect Dis 2005;5:8490. (Level II-3)
25. Turner KR, Wong EH, Kent CK, Klausner JD. Serologic
herpes testing in the real world: validation of new type-
specific serologic herpes simplex virus tests in a public
health laboratory. Sex Transm Dis 2002;29:4225.
(Level II-3)
COMPENDIUM OF SELECTED PUBLICATIONS 998
herpes in pregnancy: an open-label trial. Infect Dis Obstet
Gynecol 2001;9:7580. (Level II-2)
40. Scott LL, Hollier LM, McIntire D, Sanchez PJ, Jackson
GL, Wendel GD Jr. Acyclovir suppression to prevent
recurrent genital herpes at delivery. Infect Dis Obstet
Gynecol 2002;10:717. (Level I)
41. Stray-Pedersen B. Acyclovir in late pregnancy to prevent
neonatal herpes simples [letter]. Lancet 1990;336:756.
(Level I)
42. Sheffield JS, Hollier LM, Hill JB, Stuart GS, Wendel GD.
Acyclovir prophylaxis to prevent herpes simplex virus
recurrence at delivery: a systematic review. Obstet
Gynecol 2003;102:1396403. (Level I)
43. Andrews WW, Kimberlin DF, Whitley R, Cliver S,
Ramsey PS, Deeter R. Valacyclovir therapy to reduce
recurrent genital herpes in pregnant women. Am J Obstet
Gynecol 2006;194:77481. (Level I)
44. Kimberlin DF, Weller S, Whitley RJ, Andrews WW,
Hauth JC, Lakeman F, et al. Pharmacokinetics of oral
valacyclovir and acyclovir in late pregnancy. Am J Obstet
Gynecol 1998:179:84651. (Level II-3)
45. de Miranda P, Blum MR. Pharmacokinetics of acyclovir
after intravenous and oral administration. J Antimicrob
Chemother 1983;12(suppl B):2937. (Level II-3)
46. Soul-Lawton J, Seaber E, On N, Wootton R, Rolan P,
Posner J. Absolute bioavailability and metabolic disposi-
tion of valaciclovir, the L-valyl ester of acyclovir, follow-
ing oral administration to humans. Antimicrob Agents
Chemother 1995;39:27592764. (Level II-3)
47. Frenkel LM, Brown ZA, Bryson YJ, Corey L, Unadkat
JD, Hensleigh PA, et al. Pharmacokinetics of acyclovir in
the term human pregnancy and neonate. Am J Obstet
Gynecol 1991;164:56976. (Level II-2)
48. Pue MA, Benet LZ. Pharmacokinetics of famciclovir in
man. Antiviral Chem Chemother 1993;4(suppl 1):4755.
(Level II-3)
49. Christophers J, Clayton J, Craske J, Ward R, Collins P,
Trowbridge M, et al. Survey of resistance of herpes sim-
plex virus to acyclovir in northwest England. Antimicrob
Agents Chemother 1998;42:86872. (Level II-2)
50. Stranska R, Schuurman R, Nienhuis E, Goedegebuure IW,
Polman M, Weel JF, et al. Survey of acyclovir-resistant
herpes simplex virus in the Netherlands: prevalence and
characterization. J Clin Virol 2005;32:718. (Level II-2)
51. Stone KM, Reiff-Eldridge R, White AD, Cordero JF,
Brown Z, Alexander ER, et al. Pregnancy outcomes fol-
lowing systemic prenatal acyclovir exposure: conclusions
from the international acyclovir pregnancy registry,
19841999. Birth Defects Res A Clin Mol Teratol
2004;70:2017. (Level II-2)
52. Pregnancy outcomes following systemic prenatal acy-
clovir exposure - June 1, 1984June 30, 1993. Centers for
Disease Control and Prevention. MMWR Morb Mortal
Wkly Rep 1993;42:8069. (Level III)
53. Wittek AE, Yeager AS, Au DS, Hensleigh PA.
Asymptomatic shedding of herpes simplex virus from the
cervix and lesion site during pregnancy. Correlation of
antepartum shedding with shedding at delivery. Am J Dis
Child 1984;138:43942. (Level II-3)
54. Arvin AM, Hensleigh PA, Prober CG, Au DS, Yasukawa
LL, Wittek AE, et al. Failure of antepartum maternal cul-
tures to predict the infants risk of exposure to herpes sim-
plex virus at delivery. N Engl J Med 1986;315:796800.
(Level II-3)
55. Cleary KL, Pare E, Stamilio D, Macones GA. Type-spe-
cific screening for asymptomatic herpes infection in preg-
nancy: a decision analysis. BJOG 2005;112:7316.
(Decision analysis)
56. Thung SF, Grobman WA. The cost-effectiveness of rou-
tine antenatal screening for maternal herpes simplex
virus-1 and -2 antibodies. Am J Obstet Gynecol 2005;
192(2):4838. (Cost-effectiveness analysis)
57. Baker D, Brown Z, Hollier LM, Wendel GD Jr, Hulme L,
Griffiths DA, et al. Cost-effectiveness of herpes simplex
virus type 2 serologic testing and antiviral therapy in
pregnancy. Am J Obstet Gynecol 2004;191:207484.
(Cost-effectiveness analysis)
58. Barnabas RV, Carabin H, Garnett GP. The potential role
of suppressive therapy for sex partners in the preven-
tion of neonatal herpes: a health economic analysis.
Sex Transm Infect 2002;78:4259. (Cost-effectiveness
analysis)
59. Rouse DJ, Stringer JS. An appraisal of screening for
maternal type-specific herpes simplex virus antibodies to
prevent neonatal herpes. Am J Obstet Gynecol 2000;
183:4006. (Cost analysis)
60. Peng J, Krause PJ, Kresch M. Neonatal herpes simplex
virus infection after cesarean section with intact amniotic
membranes. J Perinatol 1996;16:3979. (Level III)
61. Roberts SW, Cox SM, Dax J, Wendel GD Jr, Leveno KJ.
Genital herpes during pregnancy: no lesions, no cesarean.
Obstet Gynecol 1995;85:2614. (Level II-2)
62. Kerkering K, Gardella C, Selke S, Krantz E, Corey L,
Wald A. Isolation of herpes simplex virus from the geni-
tal tract during symptomatic recurrence on the buttocks.
Obstet Gynecol 2006;108:94752. (Level II-2)
63. Nahmias AJ, Josey WE, Naib ZM, Freeman MG,
Fernandez RJ, Wheeler JH. Perinatal risk associated with
maternal genital herpes simplex virus infection. Am J
Obstet Gynecol 1971;110:82537. (Level II-3)
64. Majors CA, Towers CV Lewis DF, Garite TJ. Expectant
management of preterm premature rupture of membranes
complicated by active recurrent genital herpes. Am J
Obstet Gynecol 2003;188:15514;discussion 15545.
(Level II-3)
65. Effect of corticosteroids for fetal maturation on perinatal
outcomes, February 28March 2, 1994. National
Institutes of Health. Consensus Development Conference
Statement. Am J Obstet Gynecol 1995;173:24652.
(Level III)
66. Douglas J, Schmidt O, Corey L. Acquisition of neonatal
HSV-1 infection from a paternal source contact. J Pediatr
1983;103:90810. (Level III)
999 PRACTICE BULLETINS
67. Hammerberg O, Watts J, Chernesky M, Luchsinger I,
Rawls W. An outbreak of herpes simplex virus type 1 in
an intensive care nursery. Pediatr Infect Dis 1983;2:
2904. (Level III)
68. Sheffield JS, Fish DN, Hollier LM, Cadematori S, Nobles
BJ, Wendel GD Jr. Acyclovir concentrations in human
breast milk after valacyclovir administration. Am J Obstet
Gynecol 2002;186:1002. (Level II-2)
The MEDLINE database, the Cochrane Library, and
ACOGs own internal resources and documents were used
to conduct a literature search to locate relevant articles pub-
lished between January 1985 and October 2006. The search
was restricted to articles published in the English language.
Priority was given to articles reporting results of original
research, although review articles and commentaries also
were consulted. Abstracts of research presented at sympo-
sia and scientific conferences were not considered adequate
for inclusion in this document. Guidelines published by
organizations or institutions such as the National Institutes
of Health and the American College of Obstetricians and
Gynecologists were reviewed, and additional studies were
located by reviewing bibliographies of identified articles.
When reliable research was not available, expert opinions
from obstetriciangynecologists were used.
Studies were reviewed and evaluated for quality according
to the method outlined by the U.S. Preventive Services Task
Force:
I Evidence obtained from at least one properly
designed randomized controlled trial.
II-1 Evidence obtained from well-designed controlled
trials without randomization.
II-2 Evidence obtained from well-designed cohort or
casecontrol analytic studies, preferably from more
than one center or research group.
II-3 Evidence obtained from multiple time series with or
without the intervention. Dramatic results in uncon-
trolled experiments also could be regarded as this
type of evidence.
III Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees.
Based on the highest level of evidence found in the data,
recommendations are provided and graded according to the
following categories:
Level ARecommendations are based on good and consis-
tent scientific evidence.
Level BRecommendations are based on limited or incon-
sistent scientific evidence.
Level CRecommendations are based primarily on con-
sensus and expert opinion.
Copyright June 2007 by the American College of Obstetri-
cians and Gynecologists. All rights reserved. No part of this
publication may be reproduced, stored in a retrieval system,
posted on the Internet, or transmitted, in any form or by any
means, electronic, mechanical, photocopying, recording, or
otherwise, without prior written permission from the publisher.
Requests for authorization to make photocopies should be
directed to Copyright Clearance Center, 222 Rosewood Drive,
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
The American College of Obstetricians and Gynecologists
409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920
Management of herpes in pregnancy. ACOG Practice Bulletin No. 82.
American College of Obstetricians and Gynecologists. Obstet Gynecol
2007;109:148998.
COMPENDIUM OF SELECTED PUBLICATIONS 1000
CLINICAL MANAGEMENT GUIDELINES FOR
OBSTETRICIANGYNECOLOGISTS
NUMBER 86, OCTOBER 2007
(Replaces Educational Bulletin Number 248, July 1998)
This Practice Bulletin was
developed by the ACOG Com-
mittee on Practice Bulletins
Obstetrics with the assistance
of Neil S. Silverman, MD. The
information is designed to aid
practitioners in making deci-
sions about appropriate obstet-
ric and gynecologic care. These
guidelines should not be con-
strued as dictating an exclusive
course of treatment or proce-
dure. Variations in practice may
be warranted based on the
needs of the individual patient,
resources, and limitations
unique to the institution or type
of practice.
Reaffirmed 2009
Viral Hepatitis in
Pregnancy
Viral hepatitis is one of the most common and potentially serious infections that
can occur in pregnant women. Six forms of viral hepatitis have now been iden-
tified, two of which, hepatitis A and hepatitis B, can be prevented effectively
through vaccination. The purpose of this document is to describe the specific
subtypes of hepatitis, their implications during pregnancy, the risk of perinatal
transmission, and issues related to both treatment and prevention of infection.
Background
Hepatitis A
The hepatitis A virus is a small (27 nm) RNA virus that produces either symp-
tomatic or asymptomatic infection in humans after an average incubation peri-
od of 28 days (range, 1550 days). Hepatitis A virus (HAV) replicates within
the liver and is excreted in bile, with highest viral concentrations late in the incu-
bation period in the feces; this represents the window of greatest infectivity.
In the prevacccine era, approximately one third of cases of acute hepatitis
in the United States were attributable to HAV infection. Person-to-person trans-
mission through fecaloral contamination is the primary means of HAV infec-
tion in the United States, most often in household and extended family settings
(1). Because children usually have asymptomatic or unrecognized infection,
they can play a key role in infecting others. Studies have demonstrated that up
to 40% of adults without an identifiable source of infection had close contact
with a child younger than 6 years (2), which underscores the importance of pri-
mary HAV prevention within families of women of reproductive age.
Poor hygiene and poor sanitation can result in common-source outbreaks
of HAV infection. Food also can be contaminated after cooking, as commonly
occurs in outbreaks associated with HAV-infected food handlers whose hygiene
practices are substandard (3). Depending on conditions, HAV can be stable in
ACOG
PRACTICE
BULLETIN
1001 PRACTICE BULLETINS
the environment for months. Heating foods to above
185F for 1 minute or disinfecting surfaces with a dilute
solution of household bleach can inactivate the virus.
Serious complications of HAV infection are uncom-
mon; the overall casefatality ratio among reported cases
is less than 1%, but reaches 2% among adults older than
50 years. Hepatitis A does not lead to chronic infection,
although 1015% of symptomatic individuals can have
prolonged or relapsing disease lasting up to 6 months (4).
Hepatitis B
Hepatitis B is caused by a small DNA virus. The intact
virus is termed the Dane particle. Hepatitis B virus
(HBV) contains three principal antigens. Hepatitis B sur-
face antigen (HBsAg) is present on the surface of the
virus and circulates freely in the serum in spherical and
filamentous forms. The middle portion of the Dane parti-
cle contains hepatitis B core antigen (HBcAg). The core
antigen is present only in hepatocytes and does not circu-
late in the serum. Hepatitis B e antigen (HBeAg) is encod-
ed by the same portion of the viral genome that codes for
the core antigen. The presence of HBeAg indicates an
extremely high viral inoculum and active virus replication.
Hepatitis B virus is transmitted by parenteral and
sexual contact. Although HBsAg has been detected in a
variety of body fluids, only serum, semen, and saliva
have been proved to be infectious (5, 6). The virus is rel-
atively stable in the environment, can be viable for up to
7 days on surfaces at room temperature, and may cause
transmission via surfaces at concentrations of only
10
2
10
3
virions per milliliter, even if there is no visible
blood (7). Individuals at greatest risk of becoming infec-
ted are those who have multiple sexual partners, inject
drugs percutaneously, or have sexual partners who
engage in these risk-taking behaviors. Sexual contact is
an efficient mechanism for spreading the virus.
Approximately 25% of the frequent sexual contacts of
infected individuals will themselves become infected (8).
All blood donors are screened routinely for HBsAg.
Transmission of HBV by transfusion of blood or blood
products is rare as a result of both donor screening and
blood banking viral inactivation procedures. Recently, it
has been estimated that the risk of transfusion-attribut-
able HBV infection is 1 per 137,000 transfused units of
screened blood (9, 10). In contrast, however, HBV trans-
mission has been reported via patient-to-patient use of
institution-based fingerstick devices for blood sampling,
such as blood glucose meters (11). Appropriate attention
to hygiene and universal precautions is critical within
households and institutions using such devices (12).
The mortality associated with acute hepatitis B is
approximately 1%. Of adult patients who become infec-
ted, 8590% experience complete resolution of their
physical findings and develop protective levels of the
antibody. The other 1015% of patients become chroni-
cally infected. They continue to have detectable serum
levels of HBsAg but are asymptomatic, and most have no
biochemical evidence of hepatic dysfunction. In a small
subgroup (1530%) of those chronically infected, viral
replication continues and is manifested by persistence of
the e antigen and active viral DNA synthesis. These indi-
viduals risk subsequent development of chronic or per-
sistent hepatitis and cirrhosis, and approximately
4,0005,000 die annually of complications of chronic
liver disease, including hepatocellular carcinoma (12, 13).
Hepatitis C
At least six distinct hepatitis C virus (HCV) genotypes
have been identified, with broad geographic variation and
widely ranging prognoses for both disease progression
and response to therapy (14). Among presumably low-
risk volunteer blood donors in developed countries, rates
of HCV seropositivity of 0.51.4% have been reported.
Groups at higher risk for HCV infection include patients
in sexually transmitted disease (STD) clinics (seropreva-
lence, 1.56.2%), hemophiliacs (6486%), and intra-
venous drug users (5686%) (1517).
The principal risk factors for HCV transmission have
been transfusion of blood products and use of intra-
venous drugs. At least 90% of cases of posttransfusion
hepatitis have been traceable to HCV, usually within
510 weeks of the transfusion. Mass screening of the
blood supply for HCV has markedly decreased the risk
of HCV infection to less than 1 per 1,000,000 screened
units of blood. Because the risk of HCV infection from
blood transfusions has decreased, the number of HCV
infections attributable to drug use has significantly
increased, from 20% to at least 60% (18).
Acute HCV infection occurs after an incubation
period of 3060 days. Asymptomatic infection occurs in
75% of patients, and at least 50% of infected individuals
progress to chronic infection, regardless of the mode of
acquisition or severity of initial infection. Chronic HCV
infection also has been associated with an increased risk
of developing both B-cell lymphomas and cryoglobuline-
mia. Although at least 20% of chronic HCV infections
lead to chronic active hepatitis or cirrhosis, whether a
link to hepatocellular carcinoma exists is controversial
and may vary by geographic region (19). Hepatitis C
and HIV share common transmission routes, and con-
comitant infection has been reported to accelerate the
progression and severity of hepatic injury (18).
Hepatitis D
Hepatitis D virus (HDV) is an incomplete viral particle
that causes disease only in the presence of HBV, from
COMPENDIUM OF SELECTED PUBLICATIONS 1002
which it acquires a viral envelope consisting entirely of
excess HBsAg produced by HBV. Infection with HDV
occurs either simultaneously with HBV infection (coin-
fection) or may be acquired after HBV (superinfection).
Transmission is primarily through blood; approximately
2025% of chronic HBV carriers also have evidence of
HDV infection (20, 21).
Chronic hepatitis D produces severe disease more
often than other forms of chronic hepatitis. Of patients
with chronic hepatitis D, 7080% ultimately develop cir-
rhosis and portal hypertension, 15% of whom develop an
unusually rapid progression to cirrhosis within 2 years of
the initial onset of acute illness. Mortality as a result of
hepatic failure approaches 25%. In contrast, only
1530% of patients with chronic hepatitis B virus infec-
tion develop cirrhosis and portal hypertension, and the
disease progression typically is much slower (21).
Hepatitis E
The epidemiologic features of hepatitis E virus (HEV) are
similar to those of hepatitis A. The disease has been
reported only rarely in the United States, and the highest
rates of infection occur in regions of the developing world
where inadequate sanitation promotes transmission of the
virus. Hepatitis E is primarily a waterborne disease; epi-
demics have been reported in areas where fecal contami-
nation of drinking water is common. The ingestion of raw
or undercooked shellfish also has been a source of spo-
radic cases of HEV infection in endemic areas (22).
In general, HEV produces a self-limited viral infec-
tion followed by recovery; the incubation period is 38
weeks, with a mean of 40 days. Among pregnant women,
however, a higher risk of fulminant hepatitis E has been
reported in a number of small series, with maternal mor-
tality rates as high as 20% after infection in the third tri-
mester (22, 23). In one report, HEV infection in women
coinfected with HIV resulted in a 100% mortality rate
(24).
Vaccinations
Hepatitis A
The hepatitis A vaccination is indicated for adults in
groups at increased risk for hepatitis A or its adverse
consequences (25). Medical indications include persons
with chronic liver disease and persons who receive clot-
ting factor concentrates. Behavioral risk populations are
men who have sex with men and persons who use illegal
drugs. Occupational risks include persons working with
HAV-infected primates or with HAV in a research labo-
ratory setting. Other indications are persons traveling to
or working in countries that have high or intermediate
endemicity of hepatitis A (a list of countries is available
at http://www.cdc.gov/travel/diseases.htm) and any per-
son who would like to obtain immunity.
The hepatitis A vaccine is available as both a single-
antigen vaccine and as a combination vaccine (contain-
ing both HAV and HBV antigens). Both vaccines use
inactivated HAV, and the HBV component is a recombi-
nant protein nonviral antigen. There are two HAV vac-
cines available that are given in two doses, either 612
months apart or 618 months apart. The combination
vaccine is given in three doses at 0, 1, and 6 months. The
HAV vaccine is 94100% immunogenic after the first
dose (26) and is highly effective in both reducing disease
incidence and interrupting ongoing epidemics (27, 28).
Immune globulin remains available for postexposure
prophylaxis, although primary vaccine-based prevention
is preferred. Hepatitis A vaccination should still be
administered in addition to immune globulin even in the
context of postexposure prevention. Studies of HAV vac-
cine alone have shown protection against infection in a
limited series (29), although no trials comparing the vac-
cine with immune globulin have been conducted to date.
This strategy of administering HAV vaccine alone for
postexposure prophylaxis in individuals younger than 40
years has recently been proposed by some experts.
Hepatitis B
All individuals with risk factors, particularly health care
workers, should be vaccinated against HBV infection.
Other groups at increased risk include hemodialysis
patients, injection drug users, persons with more than
one sexual partner during the past 3 months or in whom
an STD has been diagnosed recently, clients and staff in
centers for the developmentally delayed, and interna-
tional travelers who will be in high or intermediate
prevalence areas for HBV infection (list of countries at
http://www.cdc.gov/travel/yellowBookCh4-HepB.
aspx#333) (30).
In general, prevaccination testing is not recom-
mended. It may be cost-effective to screen for the anti-
body to HBV in women who belong to groups with a
high risk of infection in order to avoid vaccinating adults
who have had or currently have hepatitis B infection. In
most other low-risk groups, antibody screening before
vaccination probably is not indicated.
Two single antigen vaccines for hepatitis B virus have
been developed (Table 1). Currently available vaccines are
prepared from yeast cultures by using recombinant DNA
technology. They are highly immunogenic and result in
seroconversion in more than 95% of recipients. There is
one combination vaccine available for adults at risk of both
hepatitis A and B virus infection (Twinrix); it contains
recombinant HBsAg and inactivated hepatitis A virus. The
dosage of the hepatitis A component in the combination
1003 PRACTICE BULLETINS
right upper quadrant or epigastric pain. Typical physical
findings include jaundice, upper abdominal tenderness,
and hepatomegaly, although many cases of hepatitis are
anicteric. The patients urine usually is darkened, and the
stool may be gray or acholic. In cases of fulminant
hepatitis, signs of coagulopathy and encephalopathy may
be present.
In patients with hepatitis A or E, clinical manifesta-
tions usually are related temporally to recent travel to an
endemic area or exposure to an infected person.
Similarly, infections with hepatitis B, C, or D typically
ensue after parenteral exposure to contaminated blood or
sexual contact with an infected partner. The evolution of
acute clinical illness in patients with hepatitis D often fol-
lows a biphasic course. In the initial phase of infection,
patients with hepatitis D are indistinguishable from indi-
viduals with acute hepatitis B. Two to four weeks after
apparent resolution of symptoms, patients typically have
a relapse, which usually is of a milder nature and is asso-
ciated with a second episode of elevation in serum
transaminases. At this time serologic assay results for
hepatitis D virus usually are positive.
As noted previously, in some patients with acute
hepatitis B, C, or D, symptomatic infection resolves, and
some become chronic carriers of viral infection.
Although most viral hepatitis carriers initially are asymp-
tomatic, up to one third subsequently develop chronic
active or persistent hepatitis or cirrhosis. Once cirrhosis
ensues, patients have the typical signs of end-stage liver
disease, such as jaundice, muscle wasting, ascites, spider
angioma, palmar erythema, and, ultimately, hepatic
encephalopathy. Hepatitis C is the leading cause of
chronic liver disease in the United States, whereas hepati-
tis B virus is the leading cause worldwide (13, 18).
vaccine is lower than that in the single-antigen hepatitis A
vaccine, allowing it to be administered in a three-dose
schedule (0, 1, and 6 months) instead of the two-dose
schedule used for the single-antigen vaccine. An accelerat-
ed schedule (0, 7, 2130 days, followed by a booster dose
at 12 months) is an option when a rapid immune response
is needed for an occupational or behavioral imminent risk
for hepatitis A and B or for international travel (31).
The vaccine should be administered into the deltoid
muscle. Intragluteal and intradermal injections result in
lower rates of seroconversion. Pregnancy is not a con-
traindication to vaccination. In fact, susceptible pregnant
women who are at risk for HBV infection should be
specifically targeted for vaccination (32).
Unvaccinated individuals or persons known not to
have responded to a complete hepatitis B vaccine series
and who have been exposed to HBV through a discrete,
identifiable exposure to blood or to body fluids that con-
tain blood should receive passive immunization with
hepatitis B immune globulin (HBIG) and start the immu-
nization series. Immunoprophylaxis should be adminis-
tered as soon as possible after exposure (preferably within
24 hours). For sexual exposures, HBIG should not be
administered more than 14 days after exposure (8).
Clinical Considerations and
Recommendations
What are the clinical manifestations of
hepatitis?
The usual subjective symptoms in patients with acute
viral hepatitis are malaise, fatigue, anorexia, nausea, and
Table 1. Recommended Dosages and Schedules of Single-Antigen Hepatitis B Vaccines
Vaccine Age Group Dose Volume No. of Doses Schedule*
Engerix-B
For adult dialysis patients, the Engerix-B dose required is 40 mcg/2.0 mL (use the adult 20 mcg/mL formulation) on a schedule of 0, 1, 2, and 6 months.
For Recombivax HB, a special formulation for dialysis patients is available. The dose is 40 mcg/1.0 mL and it is given on a schedule of 0, 1, and 6 months.
Immunization Action Coalition. Hepatitis A & B vaccines: be sure your patient gets the correct dose! St. Paul (MN): IAC; 2005. Available at:
http://www.immunize.org/catg.d/2081ab.pdf. Retrieved July 20, 2007.
COMPENDIUM OF SELECTED PUBLICATIONS 1004
How is acute hepatitis managed in pregnant
women?
Patients with acute hepatitis should be hospitalized if
they have encephalopathy, coagulopathy, or severe debil-
itation. Nutritional needs should be addressed within the
context of the severity of the disease. Fluid and elec-
trolyte abnormalities should be corrected. If a coagulop-
athy is present, administration of erythrocytes, platelets,
and clotting factors such as fresh frozen plasma or cryo-
precipitate may be necessary. Activity should be limited,
and the patient should be protected from upper abdomi-
nal trauma (32).
Women who are less severely ill may be treated as
outpatients. They should reduce their level of activity,
avoid upper abdominal trauma, and maintain good nutri-
tion. Infected women also should avoid intimate contact
with household members and sexual partners until these
individuals receive appropriate prophylaxis (32).
General Tests
Coincident with the onset of symptoms, patients with
acute hepatitis usually have a marked increase in the
serum concentration of alanine aminotransferase (ALT,
previously known as serum glutamate pyruvate transam-
inase) and aspartate aminotransferase (AST, previously
known as serum glutamic oxaloacetic transaminase). In
addition, the serum bilirubin concentration often is
increased. In patients who are moderately to severely ill,
coagulation abnormalities and hyperammonemia also
may be present (18). Although liver biopsy is rarely indi-
cated in pregnancy, viral hepatitis may be distinguished
histologically from other causes of hepatic injury by its
characteristic pattern of extensive hepatocellular injury
and inflammatory infiltrate. Initial evaluation of the
patient with suspected viral hepatitis should include spe-
cific tests.
Specific Tests
If hepatitis is suspected based on the initial evaluation
and general tests, the type of virus is determined through
laboratory analysis.
Hepatitis A
The diagnosis of acute hepatitis A is confirmed by detect-
ing specific immunoglobulin M (IgM) antibodies to the
virus. A chronic carrier state for this infection does not
exist, but immunoglobulin G (IgG) antibodies to hepati-
tis A virus will persist in patients with either previous
infection or prior vaccination (32, 33).
Hepatitis B
The appearance of HBsAg predates clinical symptoms by
4 weeks on average and remains detectable for 16
weeks (Fig. 1). The chronic carrier state for HBV is
defined by persistence of HBsAg and the absence of
hepatitis B surface IgG antibody (anti-HBs), which is the
protective antibody that defines immunity (Fig. 2). Titers
of anti-HBs (in noncarriers) increase slowly during clin-
Figure 1. Typical serologic course of acute hepatitis B virus infection with recovery. (Centers for Disease Control and Prevention slide
set adapted from Mast EE, Weinbaum CM, Fiore AE, Alter MJ, Bell BP, Finelli L, et al. A comprehensive immunization strategy to elim-
inate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization
Practices [ACIP] part II: immunization of adults. MMWR Recomm Rep 2006;55(RR-16):133; quiz CE14.)
HBeAg Anti-HBe
Symptoms
Total anti-HBc
IgM anti-HBc
HBsAg
Anti-HBs
Weeks after exposure
T
i
t
e
r
0 4 8 12 16 20 24 28 32 36 52 100
1005 PRACTICE BULLETINS
ical recovery and continue to increase for up to 1012
months after HBsAg has been cleared. In most patients
with self-limited acute HBV infection, anti-HBs and
HBsAg do not coexist detectably in serum, and anti-HBs
is seen only after HBsAg has been cleared. The chronic
carrier state usually can be predicted by HBsAg seropos-
itivity for more than 20 weeks (8, 13, 32, 33).
A serologic window has been described for HBV
infection when, despite clinical symptoms, HBsAg is
clearing and undetectable but anti-HBs is not yet
detectable either. In this period, HBV infection can still
be diagnosed by detection of hepatitis B core IgG anti-
body (anti-HBc), which appears 35 weeks after
HBsAg. Hepatitis B core IgG antibody is present only
in the context of natural HBV infection and is not a pro-
tective antibody. It does not distinguish acute resolving
infections from the chronic infection state, which is
done only by persistence or clearance of HBsAg. An
IgM antibody to the hepatitis B core antigen (IgM anti-
HBc) appears during acute or after recent HBV infec-
tion and is present for approximately 6 months. In
contrast, only anti-HBs becomes detectable in serum of
vaccinated individuals. Therefore, the detection of anti-
HBs in the absence of HBsAg and anti-HBc distinguishes
vaccine-mediated immunity from natural infection-based
immunity (where anti-HBc and anti-HBs are both pre-
sent without HBsAg). Hepatitis B core antigen is not
detectable outside of research laboratory assays, and
tests for it should not be ordered as part
of a hepatitis B panel (8, 13, 32, 33). With the variety
of HBV-specific antigens and antibodies identified,
interpretation of hepatitis B serologies is complex
(Table 2).
Hepatitis C
The diagnosis of hepatitis C is confirmed by the identi-
fication of the antibody to hepatitis C virus, via a sec-
ond- or third-generation enzyme immunoassay (ELISA)
(34). The antibody may not be present until 610 weeks
after the onset of clinical illness. Hepatitis C viral RNA
can be detected by polymerase chain reaction assay of
serum soon after infection, as well as in chronic disease.
These other more specific tests for HCV, including
HCV-specific RNA testing and genotyping, are available
to define the specificity of infection, given that there are
small but real false-positive rates associated with anti-
body testing or screening that vary with prevalence or
risk of the disease in the screened populations. Such
DNA-based specific testing usually is best interpreted by
specialists trained in the treatment of hepatitis, to whom
patients with positive serologic antibody test results
should be referred (34). A reference table for the inter-
pretation of these tests is available from the Centers for
Disease Control and Prevention (Table 3).
Hepatitis D
Laboratory tests that may be used to confirm the diag-
nosis of acute hepatitis D are the detection of D antigen
in hepatic tissue or serum and the identification of the
IgM antibody to hepatitis D virus. Hepatitis D antigene-
Figure 2. Progression to chronic hepatitis B virus infection: typical serologic course. (Centers for Disease Control and Prevention slide
set adapted from Mast EE, Weinbaum CM, Fiore AE, Alter MJ, Bell BP, Finelli L, et al. A comprehensive immunization strategy to elim-
inate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization
Practices (ACIP) part II: immunization of adults. MMWR Recomm Rep 2006;55(RR-16):133; quiz CE1-4.
T
i
t
e
r
Acute
(6 months)
HBsAg
Total anti-HBc
IgM anti-HBc
HBeAg Anti-HBe
Chronic
(Years)
Weeks after exposure
0 4 8 12 16 20 24 28 32 36 52
COMPENDIUM OF SELECTED PUBLICATIONS 1006
mia usually persists in patients with chronic hepatitis D
despite the appearance of the IgG antibody to the virus.
Thus, as in hepatitis C and HIV infection, viremia and
end-organ damage can continue despite the presence of
the antibody to the virus (35).
Hepatitis E
The diagnosis of infection with hepatitis E is documented
by the presence of virus-specific antibodies in individuals
with risk factors. The primary risk factor is travel expo-
sure (33).
How are pregnant patients who are presumed
chronic hepatitis carriers treated?
Persons with diagnosed chronic HBV and HCV infec-
tion should be referred for evaluation to a physician
experienced in the management of chronic liver disease.
Diagnosis in the context of pregnancy-specific screening
opens the opportunity for individuals who might other-
wise have not ever been tested to receive appropriate
subspecialty care for counseling and targeted treatment,
usually after delivery. Women who are chronic carriers
of HBV or HCV should inform sexual, household, and
Table 2. Interpretation of Hepatitis B Virus (HBV) Testing
Test Results Interpretation
HBsAg Negative Susceptible
Anti-HBc Negative
Anti-HBs Negative
HBsAg Negative Immune due to natural infection
Anti-HBc Positive
Anti-HBs Positive
HBsAg Negative Immune due to hepatitis B vaccination*
Anti-HBc Negative
Anti-HBs Positive
HBsAg Positive Acutely infected
Anti-HBc Positive
IgM anti-HBc Positive
Anti-HBs Negative
HBsAg Positive Chronically infected
Anti-HBc Positive
IgM anti-HBc Negative
Anti-HBs Negative
HBsAg Negative Four interpretations possible
Anti-HBc Positive
Anti-HBs Negative
*Antibody response (anti-HBs) can be measured quantitatively or qualitatively. A protective antibody response is reported quantitatively as
10 or more milli-international units (10 mIU/mL or less) or qualitatively as positive. Postvaccination testing should be completed 12
months after the third vaccine dose for results to be meaningful.
Four interpretations:
Might be recovering from acute HBV infection
Might be distantly immune and test not sensitive enough to detect very low level of anti-HBs in serum
Might be susceptible with a false-positive anti-HBc
Might be undetectable level of HBsAg present in the serum and the person is actually chronically infected
Definitions
Hepatitis B surface antigen (HBsAg): A serologic marker on the surface of HBV. It can be detected in high levels in serum during acute or
chronic hepatitis. The presence of HBsAg indicates that the person is infectious. The body normally produces antibodies to HBsAg as part
of the normal immune response to infection.
Hepatitis B surface antibody (anti-HBs): The presence of anti-HBs generally is interpreted as indicating recovery and immunity from HBV
infection. Anti-HBs also develops in a person who has been successfully vaccinated against hepatitis B.
Total hepatitis B core antibody (anti-HBc): Appears at the onset of symptoms in acute hepatitis B and persists for life. The presence of anti-
HBc indicates previous or ongoing infection with hepatitis B virus (HBV) in an undefined time frame.
IgM antibody to hepatitis B core antigen (IgM anti-HBc): This antibody appears during acute or recent HBV infection and is present for
approximately 6 months.
Centers for Disease Control and Prevention. Interpretation of the hepatitis B panel. Atlanta (GA): CDC; 2006. Available at: http://www.
cdc.gov/ncidod/diseases/hepatitis/b/Bserology.htm. Retrieved July 11, 2007.
1007 PRACTICE BULLETINS
(13). Approximately 1020% of women who are sero-
positive for HBsAg alone transmit the virus to their
neonates in the absence of neonatal immunoprophylaxis.
In women who are seropositive for both HBsAg and
HBeAg, the frequency of vertical transmission increases
to approximately 90% without neonatal prophylaxis. For
adult-acquired HBV infection, the risk of chronic infec-
tion and its sequelae is only 510%. In contrast, HBV
infection acquired perinatally carries an 8595% risk of
persistence and chronic infection, with a 2530% life-
time risk of serious or fatal liver disease.
In patients with acute hepatitis B, the frequency of
vertical transmission also depends on the time during
gestation that maternal infection occurs. When it occurs
in the first trimester, up to 10% of neonates will be sero-
positive for HBsAg. In women acutely infected in the
third trimester, 8090% of offspring will be infected (13).
needle-sharing contacts of their status and learn about
and use methods to prevent or reduce the risk of trans-
mission of infections to others. All HBsAg-positive lab-
oratory results should be reported to the state or local
health department in accordance with state requirements
for reporting of chronic HBV infection (8, 13).
How can the risk of vertical transmission of
HBV be reduced?
Because hepatitis B virus is highly pathogenic and infec-
tious, perinatal transmission of infection represents the
single largest cause of chronically infected individuals
worldwide. Because risk-factor-based prenatal screening
protocols have been shown to detect at most 60% of
women who are HBV carriers, routine prenatal screen-
ing of all pregnant women with HBsAg is recommended
Table 3. Interpretation of Hepatitis C Virus (HCV) Test Results
If HCV Test Result Is: Interpretation Action
Anti-HCV Screening
Anti-HCV Supplemental Test Result
Additional Testing
Test Result* RIBA
Supplemental anti-HCV
(RIBA)
Positive Not done Not done Positive Past/current Evaluate for chronic
(high s/co ratios
Samples with high signal-to-cutoff (s/co) ratios usually more than 95%) confirm positive, but supplemental serologic testing was not performed. Less than 5 of every
100 test results might represent false-positives; more specific testing should be requested, if indicated.
Single negative HCV RNA result cannot determine infection status; patients might have intermittent viremia.
Centers for Disease Control and Prevention. Reference for interpretation of HCV test results. Atlanta (GA): CDC; 2006. Available at: http://www.cdc.gov/ncidod/
diseases/hepatitis/resource/PDFs/hcv_graph.pdf. Retrieved July 11, 2007.
COMPENDIUM OF SELECTED PUBLICATIONS 1008
The Centers for Disease Control and Prevention rec-
ommends universal active immunization of all infants
born in the United States. The immunization schedule
for infants of women who have been screened and have
negative results should be started preferably before dis-
charge, but by no later than 2 months of age. Preterm
infants weighing less than 2,000 g and born to women
who are HBsAg negative should have their first vaccine
dose delayed until 1 month after birth or hospital dis-
charge (13).
Current guidelines stipulate that infants of women
who are HBsAg positive or whose status is unknown at
the time of delivery also should receive both HBIG and
hepatitis B vaccine within 12 hours of birth given simul-
taneously at different sites intramuscularly. It should
then be followed by two more injections of hepatitis B
vaccine in the first 6 months of life. The physician
responsible for the care of a newborn delivered of a
woman with chronic hepatitis B should be informed of
her carrier status so that the appropriate doses of hepati-
tis B vaccine and HBIG can be given as soon as possible
after delivery (13).
Neonatal immunoprophylaxis will not prevent HBV
infection in newborns who are already infected in utero;
therefore, current research is focusing on the potential
efficacy of antepartum treatment of HBV-infected
women to lower the risk of such infection, particularly in
women who have risk factors for transmission (3639).
In addition, women who did not receive prenatal care
will have unknown HBV status at the time of delivery,
and these women have been shown to have significantly
higher rates of being chronic HBV carriers than women
enrolled in prenatal care (40). The combination of pas-
sive and active immunization has been particularly effec-
tive (8595% efficacy) in reducing the frequency of peri-
natal transmission of hepatitis B virus.
How can transmission of other forms of
hepatitis be prevented?
Hepatitis C virus seroprevalence rates of 0.66.6% have
been reported in study cohorts of pregnant women
worldwide (4144). Vertical HCV transmission rates of
28% have been demonstrated, with maternal viremia
(detectable presence of HCV RNA in blood) an almost
uniform prerequisite for transmission (35, 4547). In
pregnancies among HCV-infected mothers who were
HCV RNA negative, vertical transmission was rare.
Maternal coinfection with HIV significantly increases
the risk of vertical HCV transmission to as much as
44% (45, 47). In a recent cohort study, risk factors
associated with an increased rate of vertical HCV trans-
mission to include higher maternal HCV viral titer, pro-
longed membrane rupture during labor (6 hours or
longer), and use of internal fetal monitoring during
labor were reported (48). If duration of membrane rup-
ture and internal fetal monitoring are confirmed to be
associated with transmission in further investigations,
interventions may be possible to decrease the risk of
transmission.
Currently, no preventive measures are available to
lower the risk of vertical HCV infection of neonates as
there are for HBV. Routine prenatal HCV screening is
not recommended; however, women with significant risk
factors for infection (see the box) should be offered anti-
body screening. Testing for HCV RNA should not be
used for screening purposes.
Vertical transmission of hepatitis D virus has been
documented. Transmission is uncommon, however,
Risk Factors Warranting Hepatitis C
Screening: CDC Guidelines
Individuals who should be screened routinely:
1. Persons who ever injected illegal drugs (even once)
2. Persons notified that they received blood products
before 1987 or from a donor who later tested posi-
tive for hepatitis C virus (HCV)
3. Recipients of transfusions or organ transplants, par-
ticularly if received before July 1992
4. Persons ever on long-term hemodialysis
5. Persons with persistently elevated alanine amino-
transferase (ALT) or other evidence of liver disease
6. Persons seeking evaluation or care for a sexually
transmitted infection, including human immunodefi-
ciency virus
Individuals for whom routine testing is of uncertain
need:
1. Recipients of tissue transplants (eg, cornea, skin,
sperm, ova)
2. Users of intranasal cocaine or other illegal nonin-
jected drugs
3. Persons with a history of tattooing or body piercing
4. Persons with a history of sexually transmitted dis-
eases or multiple sexual partners
5. Long-term steady sex partner of an HCV-infected
individual
Centers for Disease Control and Prevention. Recommendations for
prevention and control of hepatitis C virus (HCV) infection and HCV-
related chronic disease. MMWR 1998;47(RR-19):133 and Centers
for Disease Control and Prevention. Sexually transmitted diseases
treatment guidelines, 2006. MMWR 2006;55(RR-11):194.
1009 PRACTICE BULLETINS
because the measures used to prevent perinatal infection
with hepatitis B virus are almost uniformly effective in
preventing infection by hepatitis D. Vertical transmis-
sion of HEV has been reported, but information is
limited.
Are there special considerations for intra-
partum care in the context of maternal
hepatitis infection?
Between 85% and 95% of cases of perinatal transmis-
sion of HBV occur as a consequence of intrapartum
exposure of the infant to infected blood and genital tract
secretions. The remaining cases result from hematoge-
nous transplacental dissemination and close postnatal
contact between the infant and the infected parent. Risk
factors for intrauterine HBV infection have been report-
ed to include maternal HBeAg seropositivity, history of
threatened preterm labor, higher HBsAg and HBV DNA
titers, and the presence of HBV DNA in villous capillary
endothelial cells (49). Adequate data regarding the risk
of transmission with operative vaginal delivery or inter-
nal fetal monitoring are not available to make recom-
mendations.
The route of delivery has not been shown to influ-
ence the risk of vertical HCV transmission (35, 50).
Cesarean delivery should be performed in HCV-infected
women only for obstetric indications.
What is the safety of invasive prenatal
diagnostic procedures for patients with
chronic hepatitis?
The risk of transmission through amniocentesis appears
to be low for women who are chronically infected with
hepatitis B or hepatitis C, although the number of
exposed cases in the literature is small. Of the 115
women reported to be positive for hepatitis B surface-
antigen who underwent second-trimester amniocentesis,
the rate of neonatal infection was no different than in
women who did not have an amniocentesis. All of the
infants received hepatitis B vaccination and immuno-
prophylaxis beginning at birth (5053). There is only
one series of 22 HCV-positive women reported in the
literature who underwent second-trimester amniocente-
sis. No infants in this series were found to be hepatitis
C RNA positive on postnatal testing. This group includ-
ed one woman with hepatitis C RNA-positive amniotic
fluid (54). Data are insufficient in the literature to assess
the risk of chorionic villus sampling in these women or
to estimate the risk of fetal infection among women
with anterior placentas, those who are HBe antigen pos-
itive, or those with high hepatitis B or hepatitis C viral
loads.
Because of the limited information regarding the risk
of invasive procedures in women chronically infected with
hepatitis B or hepatitis C, it would be prudent to discuss
noninvasive screening options with these women.
Is breastfeeding contraindicated for infants
of women with hepatitis?
In HAV-infected women, breastfeeding is permissible
with appropriate hygienic precautions. Although
immune globulin has been administered to newborns in
specific situations, the efficacy of this practice has not
been established. Breastfeeding is not contraindicated
for women who are HBsAg positive at the time of deliv-
ery. In addition, breastfeeding is not contraindicated in
women chronically infected with HBV if the infant
receives HBIG passive prophylaxis and vaccine active
prophylaxis (13). There are no data from which to make
a recommendation for HBeAg positive patients. In addi-
tion, breastfeeding has not been associated with an
increased risk of neonatal HCV infection (5659) and,
therefore, is not contraindicated in HCV-infected mothers
(58, 59).
Breastfeeding was not detrimental to newborns of
HEV-infected women in one recent series of 93 preg-
nancies. In this cohort, anti-HEV antibody and HEV
RNA were present in clostral samples, but at significant-
ly lower levels than in maternal serum (60).
Immunotherapy
What is the role of specific immunotherapy
in the treatment of chronic hepatitis in
pregnancy?
Hepatitis A
Given the nonchronic and usually self-limited course of
symptomatic HAV infection, no specific antiviral agent
is used for its treatment. The hepatitis A vaccine is not
contraindicated during pregnancy. In populations that
have expected high rates of previous HAV infection, pre-
vaccination testing may be considered to reduce costs by
not vaccinating persons who are already immune.
Prevaccination serologic testing may be cost-effective
for adults who were born in or lived for extended periods
in HAV-endemic areas; adults in certain population groups
(Native Americans, Alaska Natives, and Hispanics); and
adults in groups with a high prevalence of infection (eg,
injection drug users) (25).
Patients who have had close personal or sexual con-
tact with an HAV-infected individual should receive
COMPENDIUM OF SELECTED PUBLICATIONS 1010
postexposure prophylaxis if they have not been immu-
nized. Immune globulin does not pose a risk to either a
pregnant woman or her fetus and should be administered
during pregnancy if indicated. Immune globulin provides
protection through passive antibody transfer. For postex-
posure prophylaxis, a single intramuscular dose of 0.02
mL/kg should be administered as soon as possible after
contact with the infected individual; this confers protec-
tion for up to 3 months at an 8090% efficacy level.
Administration of immune globulin more than 2 weeks
after exposure is not effective in preventing or ameliorat-
ing the severity of hepatitis A (25). The HAV vaccination
series also should be initiated in conjunction with postex-
posure administration of IgG. Although some studies
suggest that HAV vaccine alone also may prevent postex-
posure infection, no comparative trials have been con-
ducted (29). This strategy of administering HAV
vaccine alone for postexposure prophylaxis in individuals
younger than 40 years has been proposed by some experts.
Hepatitis B
No specific therapy is available for treatment of acute
HBV infection. Persons with chronic HBV infection
should be referred for evaluation to a physician experi-
enced in the management of chronic liver disease.
Therapeutic agents have been approved by the FDA
for treatment of chronic HBV infection and can achieve
sustained suppression of HBV replication and remission
of liver disease in some persons (32). One of these
agents, the antiviral agent lamivudine, also has been
shown to be effective, in combination with other med-
ications, for both the treatment of infections with the
human immunodeficiency virus (HIV) and for the inter-
ruption of vertical HIV transmission. Recent research
has demonstrated potential benefit from lamivudine
treatment in decreasing the risk of in utero HBV infec-
tion in women who were HBV carriers during the last
months of pregnancy (37, 39). Other investigators have
studied the use of hepatitis B immune globulin (HBIG)
administered to the mother toward the end of pregnancy
to achieve similar results (36, 38).
Hepatitis C
Optimal obstetric care of women infected with HCV is
limited by the lack of any available prenatal or postnatal
pharmacologic or immunologic measures to decrease the
risk of vertical transmission. Use of antiretroviral treat-
ment to decrease both maternal viral titers and the risk of
neonatal HIV infections (61) raises the question of the
potential for comparable treatment of maternal HCV
infection, given that maternal HCV titer also has been
associated with an increased risk of transmission (44,
46). Recent advances in combination therapy for HCV
infection in nonpregnant adults have made sustained nor-
malization of transaminase levels and clearance of HCV
RNA possible, even in individuals with HCV genotypes
that have a poorer prognosis (62). More recently, the
modification of interferon alfa-2a via a branched-chain
polyethylene glycol moiety has produced a compound,
peginterferon alfa-2a, with prolonged absorption, slower
clearance, and a longer half-life than standard interferon,
allowing once-weekly dosing (63). Randomized trials
have shown peginterferon to be superior to standard
interferon, either alone or in combination with ribavirin,
for the treatment of chronic HCV infection in adults
(64). Even though the use of ribavirin is contraindicated
in pregnancy, interferon has been used safely for the
treatment of T-cell leukemias during pregnancy (65, 66),
and its potential role as an anti-HCV therapy for both
maternal benefit and fetal and neonatal benefit warrants
further study.
How can accidental or occupational
exposures to hepatitis virus be managed?
Accidental exposures are classified as occupational or
nonoccupational for management recommendations.
Guidelines for postexposure prophylaxis of occupational
exposures have been published by the Centers for
Disease Control and Prevention (13, 67, 68) and are
intended for use in settings in which postvaccination
testing is recommended for certain employees and in
which programs are available to implement testing and
follow-up algorithms. There are also specific guidelines
for care of persons with nonoccupational exposure to
HBV through exposure to blood or body fluids (13).
All health care workers who may be exposed to
blood or blood products should be vaccinated against
hepatitis B. The principal mechanism of transmission of
HBV from patient to health care workers is through
injury from a sharp object that is contaminated with
infected blood. Of all the bloodborne transmissible
viruses (including HCV and HIV), HBV exists in high-
est concentrations in blood. Hepatitis B requires much
smaller volumes for transmission and, therefore, can be
injected without hollow-bore needles or deep penetrating
injuries. The risk of infection per injury with HBV-
infected blood is 2030%. Transmission of HBV also
has been reported by mucosal contamination from body
fluid splash exposures.
The risk of health care workers acquiring HCV
infection through workplace exposure to infected blood
is lower than the risk of acquiring HBV (30%) and high-
1011 PRACTICE BULLETINS
er than the risk of acquiring HIV (0.3%) (68, 69).
Standard precautions such as not recapping used needles
has been shown to decrease the risk of workplace injury;
however, recent research has demonstrated that even
practitioners in high-risk subspecialties failed to routinely
practice standard universal precautions (69).
Summary of
Recommendations and
Conclusions
The following recommendations are based on
good and consistent scientific evidence (Level A):
Routine prenatal screening of all pregnant women
by HBsAg testing is recommended.
Newborns born to hepatitis B carriers should receive
combined immunoprophylaxis consisting of HBIG
and hepatitis B vaccine within 12 hours of birth.
Hepatitis B infection is a preventable disease, and
all at-risk individuals, particularly health care work-
ers, should be vaccinated. All infants should receive
the hepatitis B vaccine series as part of the recom-
mended childhood immunization schedule.
Breastfeeding is not contraindicated in women with
HAV infection with appropriate hygienic precau-
tions, in those chronically infected with hepatitis B
if the infant receives HBIG passive prophylaxis and
vaccine active prophylaxis, or in women with HCV
infection.
The following recommendations are based on lim-
ited or inconsistent scientific evidence (Level B):
Routine prenatal HCV screening is not recommend-
ed; however, women with significant risk factors for
infection should be offered antibody screening.
Route of delivery has not been shown to influence
the risk of vertical HCV transmission, and cesarean
delivery should be reserved for obstetric indications
in women with HCV infection.
The following recommendations are based primar-
ily on consensus and expert opinion (Level C):
The risk of transmission of hepatitis B associated
with amniocentesis is low.
Susceptible pregnant women who are at risk for
hepatitis B infections should be specifically targeted
for vaccination.
Proposed Performance
Measure
Percentage of women receiving prenatal care who are
screened for hepatitis B by hepatitis B surface antigen
testing
References
1. Bell BP, Shapiro CN, Alter MJ, Moyer LA, Judson FN,
Moltram K, et al. The diverse patterns of hepatitis A epi-
demiology in the United Statesimplications for vaccina-
tion strategies. J Infect Dis 1998;178:157984. (Level I)
2. Staes CJ, Schlenker TL, Risk I, Cannon KG, Harris H,
Pavia AT, et al. Sources of infection among persons with
acute hepatitis A and no identified risk factors during a
sustained community-wide outbreak. Pediatrics 2000;
106:e54. (Level II-3)
3. Fiore AE. Hepatitis A transmitted by food. Clin Infect Dis
2004;38:70515. (Level III)
4. Glikson M, Galun E, Oren R, Tur-Kaspa R, Shouval D.
Relapsing hepatitis A: review of 14 cases and literature
survey. Medicine 1992;71:1423. (Level III)
5. Alter HJ, Purcell RH, Gerin JL, London WT, Kaplan PM,
McAuliffe VJ, et al. Transmission of hepatitis B to chim-
panzees by hepatitis surface antigen-positive saliva and
semen. Infect Immun 1977;16:92833. (Animal)
6. Bancroft WH, Snitbhan R, Scott RM, Tingpalapong M,
Watson WT, Tanticharoenyos P, et al. Transmission of
hepatitis B virus to gibbons by exposure to human saliva
containing hepatitis B surface antigen. J Infect Dis
1977;135:7985. (Animal)
7. Bond WW, Favero MS, Petersen NJ, Gravelle CR, Ebert
JW, Maynard JE. Survival of hepatitis B virus after drying
and storage for one week. Lancet 1981;1:5501. (Level
III)
8. Mast EE, Margolis HS, Fiore AE, Brink EW, Goldstein
ST, Wang SA, et al. A comprehensive immunization strat-
egy to eliminate transmission of hepatitis B virus infec-
tion in the United States: recommendations of the
Advisory Committee on Immunization Practices (ACIP)
part II: immunization of adults. MMWR 2006;55(RR-
16):133. (Level III)
9. Stramer SL, Glynn SA, Kleinman SH, Strong DM,
Caglioti S, Wright DJ, et al. Detection of HIV-1 and HCV
infections among antibody-negative blood donors by
nucleic-acid amplification testing. National Heart, Lung,
and Blood Institute Nucleic Acid Test Study Group. N
Engl J Med 2004;351:7608. (Level II-3)
10. Schreiber GB, Busch MP, Kleinman SH, Koralitz JJ. The
risk of transfusion-transmitted viral infections. The
Retrovirus Epidemiology Donor Study. N Engl J Med
1996;334:168590. (Level 11-3)
11. American Association of Blood Banks. Transfusion-trans-
mitted diseases. Bethesda (MD): AABB; 2005. Available
COMPENDIUM OF SELECTED PUBLICATIONS 1012
at: http://www.aabb.org/content/About_Blood/Facts_
About_Blood_and_Blood_Banking/fabloodtrans.htm.
Retrieved July 11, 2007. (Level III)
12. Transmission of hepatitis B virus among persons under-
going blood glucose monitoring in long-term-care facili-
tiesMississippi, North Carolina, and Los Angeles
County, California, 2003-2004. Centers for Disease
Control and Prevention (CDC). MMWR Morb Mortal
Wkly Rep 2005;54:2203. (Level II-2)
13. Mast EE, Margolis HS, Fiore AE, Brink EW, Goldstein
ST, Wang SA, et al. A comprehensive immunization strat-
egy to eliminate transmission of hepatitis B virus infec-
tion in the United States: recommendations of the
Advisory Committee on Immunization Practices (ACIP)
part 1: immunization of infants, children, and adolescents.
Advisory Committee on Immunization Practices (ACIP)
[published erratum appears in MMWR Morb Mortal
Wkly Rep 2006;55:1589]. MMWR Recomm Rep
2005;54(RR-16):131. (Level III)
14. van der Poel CL, Cuypers HT, Reesink HW. Hepatitis C
virus six years on. Lancet 1994;344:14759. (Level III)
15. Widell A, Hansson BG, Berntorp E, Moestrup T,
Johansson HP, Hansson H, et al. Antibody to a hepatitis C
virus related protein among patients at high risk for
hepatitis B. Scand J Infect Dis 1991;10:1924. (Level II-
3)
16. Brettler DB, Alter HJ, Dienstag JL, Forsberg AD, Levine
PH. Prevalence of hepatitis C virus antibody in a cohort of
hemophilia patients. Blood 1990;76:2546. (Level II-3)
17. van den Hoek JA, van Haastrecht HJ, Goudsmit J, de Wolf
F, Coutinho RA. Prevalence, incidence, and risk factors of
hepatitis C virus infection among drug users in
Amsterdam. J Infect Dis 1990;162:8236. (Level III)
18. Recommendations for prevention and control of hepatitis
C (virus HCV) infection and HCV-related chronic dis-
ease. Centers for Disease Control and Prevention.
MMWR Recomm Rep 1998;47(RR-19):139. (Level III)
19. Jeffers LJ, Hasan F, De Medina M, Reddy R, Parker T,
Silva M, et al. Prevalence of antibodies to hepatitis C virus
among patients with cryptogenic chronic hepatitis and cir-
rhosis. Hepatology 1992;15:18790. (Level II-3)
20. Hoofnagle JH. Type D (delta) hepatitis [published erratum
in JAMA 1989;261:3552]. JAMA 1989;261:13215.
(Level III)
21. Drobeniuc J, Hutin YJ, Harpaz R, Favorov M, Meinik A,
Iarovoi P, et al. Prevalence of hepatitis B, D and C virus
infections among children and pregnant women in
Moldova: additional evidence supporting the need for rou-
tine hepatitis B vaccination of infants. Epidemiol Infect
1999;123:4637. (Level II-3)
22. Aggarwal R, Krawczynski K. Hepatitis E: an overview
and recent advances in clinical and laboratory research. J
Gastroenterol Hepatol 2000;15:920. (Level III)
23. Hussaini SH, Skidmore SJ, Richardson P, Sherratt LM,
Cooper BT, OGrady JG. Severe hepatitis E infection dur-
ing pregnancy. J Viral Hepat 1997;4:514. (Level III)
24. Singh S, Mohanty A, Joshi YK, Deka D, Mohanty S,
Panda SK. Mother-to-child transmission of hepatitis E
virus infection. Indian J Pediatr 2003;70:379. (Level III)
25. Fiore AE, Wasley A, Bell BP. Prevention of hepatitis A
through active or passive immunization: recommenda-
tions of the Advisory Committee on Immunization
Practices (ACIP). Advisory Committee on Immunization
Practices (ACIP). MMWR Recomm Rep 2006;55(RR-
7):123. (Level III)
26. Clemens R, Safary A, Hepburn A, Roche C, Stanbury WJ,
Andr FE. Clinical experience with an inactivated hepatitis
A vaccine. J Infect Dis 1995;171(suppl 1):S449. (Level III)
27. Zamir C, Rishpon S, Zamir D, Leventhal A, Rimon N,
Ben-Porath E. Control of a community-wide outbreak of
hepatitis A by mass vaccination with inactivated hepatitis
A vaccine. Eur J Clin Microbiol Infect Dis 2001;20:
1857. (Level II-3)
28. Hepatitis A vaccination programs in communities with
high rates of hepatitis A. Centers for Disease Control and
Prevention (CDC). MMWR Morb Mortal Wkly Rep
1997;46:6003. (Level II-3)
29. Sagliocca L, Amoroso P, Stroffolini T, Adamo B, Tosti
ME, Lettieri G, et al. Efficacy of hepatitis A vaccine in
prevention of secondary hepatitis A infection: a ran-
domised trial [published erratum appears in Lancet
1999;353:2078]. Lancet 1999;353:11369. (Level I)
30. Centers for Disease Control and Prevention. Recom-
mended adult immunization schedule: United States,
October 2006September 2007. Atlanta (GA): CDC, 2006.
Available at: http://www.cdc.gov/nip/recs/ adultschedule.
pdf. Retrieved May 16, 2007. (Level III)
31. Connor BA, Blatter MM, Beran J, Zou B, Trofa AF. Rapid
and sustained immune response against hepatitis A and B
achieved with combined vaccine using an accelerated ad-
ministration schedule. J Trav Med 2007;14:915. (Level I)
32. Workowski KA, Berman SM. Sexually transmitted dis-
eases treatment guidelines, 2006. Centers for Disease
Control and Prevention [published erratum appears in
MMWR Morb Mortal Wkly Rep 2006;55:997]. MMWR
Recomm Rep 2006;55(RR-11):194. (Level III)
33. American Academy of Pediatrics. Red book: 2006 report
of the Committee on Infectious Diseases. 27th ed. Elk
Grove Village (IL): AAP; 2006. (Level III)
34. Scott JD, Gretch DR. Molecular diagnostics of hepatitis C
virus infection. JAMA 2007;297:72432. (Level III)
35. Zanetti AR, Tanzi E, Romano L, Zuin G, Minola E,
Vecchi L, et al. Prospective study on mother-to-infant
transmission of hepatitis C virus. Intervirology 1998;
41:20812. (Level II-2)
36. Li XM, Shi MF, Yang YB, Shi ZJ, Hou HY, Shen HM, et
al. Effect of hepatitis B immunoglobulin on interruption
of HBV intrauterine infection. World J Gastroenterol
2004;10:32157. (Level I)
37. Xu WM, Cui YT, Wang L, Yang H, Liang ZQ, Li XM, et
al. Efficacy and safety of lamivudine in late pregnancy for
the prevention of mother-child transmission of hepatitis
B; a multicentre, randomised, double-blind, placebo-
controlled study [abstract]. Hepatology 2004;40(suppl 1):
272A3A. (Level I)
38. Zhu Q, Yu G, Yu H, Lu Q, Gu X, Dong Z, et al. A random-
ized controlled trial on interruption of HBV transmission
in utero. Chinese Med J 2003;116:6857. (Level I)
1013 PRACTICE BULLETINS
39. van Zonneveld M, van Nunen AB, Niesters HG, de Man
RA, Schalm SW, Janssen HL. Lamivudine treatment during
pregnancy to prevent perinatal transmission of hepatitis B
virus infection. J Viral Hepat 2003;10:2947. (Level II-2)
40. Silverman NS, Darby MJ, Ronkin SL, Wapner RJ.
Hepatitis B prevalence in an unregistered prenatal popula-
tion. Implications for neonatal therapy. JAMA 1991;
266:28525. (Level II-3)
41. Silverman NS, Snyder M, Hodinka RL, McGillen P, Knee
G. Detection of hepatitis C virus antibodies and specific
hepatitis C virus ribonucleic acid sequences in cord bloods
from a heterogeneous prenatal population. Am J Obstet
Gynecol 1995;173:1396400. (Level II-3)
42. Bohman VR, Slettler W, Little BB, Wendel GD, Sutor LJ,
Cunningham FG. Seroprevalence and risk factors for
hepatitis C virus antibody in pregnant women. Obstet
Gynecol 1992;80:60913. (Level II-3)
43. Choy Y, Gittens-Williams L, Apuzzio J, Skurnick J,
Zollicoffer C, McGovern PG. Risk factors for hepatitis C
infection among sexually transmitted disease-infected,
inner city obstetric patients. Infect Dis Obstet Gynecol
2003;11:1918. (Level II-3)
44. Okamoto M, Nagata I, Murakami J, Kaji S, Iitsuka T,
Hoschika T, et al. Prospective reevaluation of risk factors
in mother-to-child transmission of hepatitis C virus: high
virus load, vaginal delivery, and negative anti-NS4 anti-
body. J Infect Dis 2000;182:15114. (Level II-2)
45. Ferrero S, Lungaro P, Bruzzone BM, Gotta C, Bentivoglio
G, Ragni N. Prospective study of mother-to-infant trans-
mission of hepatitis C virus: a 10-year survey. Acta Obstet
Gynecol Scand 2003;82:22934. (Level II-2)
46. Tajiri H, Miyoshi Y, Funada S, Etani Y, Abe J, Onodera T,
et al. Prospective study of mother-to-infant transmission
of hepatitis C virus. Pediatr Infect Dis J 2001;20:104.
(Level II-2)
47. Granovsky MO, Minkoff HL, Tess BH, Waters D,
Hatzakis A, Devoid DE, et al. Hepatitis C virus infection
in the mothers and infants cohort study. Pediatrics
1998;102:3559. (Level II-2)
48. Mast EE, Hwang LY, Seto DS, Nolte FS, Nainan OV,
Wurtzel H, et al. Risk factors for perinatal transmission of
hepatitis C virus (HCV) and the natural history of HCV
infection acquired in infancy. J Infect Dis 2005;192:
18809. (Level II-2)
49. Xu DZ, Yan YP, Choi BC, Xu JQ, Men K, Zhang JX, et al.
Risk factors and mechanism of transplacental transmis-
sion of hepatitis B virus: a case-control study. J Med Virol
2002;67:206. (Level II-2)
50. Towers CV, Asrat T, Rumney P. The presence of hepatitis
B surface antigen and deoxyribonucleic acid in amniotic
fluid and cord blood. Am J Obstet Gynecol 2001;
184:15148; discussion 151820. (Level II-2)
51. Alexander JM, Ramus R, Jackson G, Sercely B, Wendel
GD Jr. Risk of hepatitis B transmission after amniocente-
sis in chronic hepatitis B carriers. Infect Dis Obstet
Gynecol 1999;7:2836. (Level III)
52. Grosheide PM, Quartero HW, Schalm SW, Heijtink RA,
Christiaens GC. Early invasive prenatal diagnosis in
HBsAg-positive women. Prenat Diagn 1994;14:5538.
(Level III)
53. Ko TM, Tseng LH, Chang MH, Chen DS, Hsieh FJ,
Chuang SM, et al. Amniocentesis in mothers who are
hepatitis B virus carriers does not expose the infant to an
increased risk of hepatitis B virus infection. Arch Gynecol
Obstet 1994;255;2530. (Level II-2)
54. Delamare C, Carbonne B, Heim N, Berkane N, Petit JC,
Uzan S, et al. Detection of hepatitis C virus RNA (HCV
RNA) in amniotic fluid: a prospective study. J Hepatol
1999;31:41620. (Level II-2)
55. A significant sexbut not elective cesarean section
effect on mother-to-child transmission of hepatitis C virus
infection. J Infect Dis 2005;192:18729. (Level II-2)
56. Kumar RM, Shahul S. Role of breast-feeding in trans-
mission of hepatitis C virus to infants of HCV-infected
mothers. J Hepatol 1009;29:1917. (Level II-2)
57. Lin HH, Kao JH, Hsu HY, Ni YH, Chang MH, Huang SC,
et al. Absence of infection in breast-fed infants born to
hepatitis C virus-infected mothers. J Pediatr 1995;126:
58991. (Level III)
58. American Academy of Pediatrics, American College of
Obstetricians and Gynecologists. Breastfeeding handbook
for physicians. Elk Grove Village (IL): AAP; Washington,
DC: ACOG; 2006. (Level III)
59. Breastfeeding: maternal and infant aspects. ACOG
Committee Opinion No. 361. American College of
Obstetricians and Gynecologists. Obstet Gynecol 2007;
109:47980. (Level III)
60. Chibber RM, Usmani MA, Al-Sibai MH. Should HEV
infected mothers breast feed? Arch Gynecol Obstet
2004;270:1520. (Level II-2)
61. Cooper ER, Chaurat M, Mofenson L, Hanson IC, Pitt J,
Diaz C, et al. Combination antiretroviral strategies for the
treatment of pregnant HIV-1-infected women and preven-
tion of perinatal HIV-1 transmission. Women and Infants
Transmission Study Group. J Acquir Immune Defic Syndr
2002;29:48494. (Level II-2)
62. Poynard T, Marcellin P, Lee SS, Niederau C, Minuk GS,
Ideo G, et al. Randomised trial of interferon alpha2b plus
ribavirin for 48 weeks or for 24 weeks versus interferon
alpha2b plus placebo for 48 weeks for treatment of chron-
ic infection with hepatitis C virus. International Hepatitis
Interventional Therapy Group (IHIT). Lancet 1998;352:
142632. (Level I)
63. Lindsay KL, Trepo C, Heintges T, Shiffman ML, Gordon
SC, Hoefs JC, et al. A randomized, double-blind trial
comparing pegylated interferon alfa-2b to interferon alfa-
2b as initial treatment for chronic hepatitis C. Hepatitis
Interventional Therapy Group. Hepatology 2001;34:
395403. (Level I)
64. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos
G, Goncales FL Jr, et al. Peginterferon alfa-2a plus riba-
virin for chronic hepatitis C virus infection. N Engl J Med
2002;347:97582. (Level I)
65. Hiratsuka M, Minakami H, Koshizuka S, Sato I.
Administration of interferon-alpha during pregnancy:
effects on fetus. J Perinat Med 2000;28:3726. (Level
III)
COMPENDIUM OF SELECTED PUBLICATIONS 1014
66. Crump M, Wang XH, Sermer M, Keating A. Successful
pregnancy and delivery during alpha-interferon therapy
for chronic myeloid leukemia. Am J Hematol 1992;40:
2389. (Level III)
67. Updated U.S. Public Health Service guidelines for the
management of occupational exposures to HBV, HCV,
and HIV and recommendations for postexposure prophy-
laxis. Centers for Disease Control and Prevention.
MMWR Recomm Rep 2001;50 (RR-11):152. (Level III)
68. Panlilio AL, Cardo DM, Grohskopf LA, Heneine W, Ross
CS. Updated U.S. Public Health Service guidelines for the
management of occupational exposures to HIV and rec-
ommendations for postexposure prophylaxis. Centers for
Disease Control and Prevention. MMWR Recomm Rep
2005;54 (RR-9): 117. (Level III)
69. Baffoy-Fayard N, Maugat S, Sapoval M, Cluzel P, Denys
A, Sellier N, et al. Potential exposure to hepatitis C virus
through accidental blood contact in interventional radiol-
ogy. Study Group on Hygiene Practices in Interventional
Radiology. J Vasc Interv Radiol 2003;14:1739. (Level
II-3)
The MEDLINE database, the Cochrane Library, and
ACOGs own internal resources and documents were used
to conduct a literature search to locate relevant articles pub-
lished between January 1985 and February 2007. The search
was restricted to articles published in the English language.
Priority was given to articles reporting results of original
research, although review articles and commentaries also
were consulted. Abstracts of research presented at sympo-
sia and scientific conferences were not considered adequate
for inclusion in this document. Guidelines published by or-
ganizations or institutions such as the National Institutes of
Health and the American College of Obstetricians and
Gynecologists were reviewed, and additional studies were
located by reviewing bibliographies of identified articles.
When reliable research was not available, expert opinions
from obstetriciangynecologists were used.
Studies were reviewed and evaluated for quality according
to the method outlined by the U.S. Preventive Services Task
Force:
I Evidence obtained from at least one properly de-
signed randomized controlled trial.
II-1 Evidence obtained from well-designed controlled
trials without randomization.
II-2 Evidence obtained from well-designed cohort or
casecontrol analytic studies, preferably from more
than one center or research group.
II-3 Evidence obtained from multiple time series with or
without the intervention. Dramatic results in uncon-
trolled experiments also could be regarded as this
type of evidence.
III Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees.
Based on the highest level of evidence found in the data,
recommendations are provided and graded according to the
following categories:
Level ARecommendations are based on good and consis-
tent scientific evidence.
Level BRecommendations are based on limited or incon-
sistent scientific evidence.
Level CRecommendations are based primarily on con-
sensus and expert opinion.
Copyright October 2007 by the American College of
Obstetricians and Gynecologists. All rights reserved. No part of
this publication may be reproduced, stored in a retrieval system,
posted on the Internet, or transmitted, in any form or by any
means, electronic, mechanical, photocopying, recording, or oth-
erwise, without prior written permission from the publisher.
Requests for authorization to make photocopies should be
directed to Copyright Clearance Center, 222 Rosewood Drive,
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
The American College of Obstetricians and Gynecologists
409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920
Viral hepatitis in pregnancy. ACOG Practice Bulletin No. 86. American
College of Obstetricians and Gynecologists. Obstet Gynecol
2007;110:94155.
1015 PRACTICE BULLETINS
CLINICAL MANAGEMENT GUIDELINES FOR
OBSTETRICIANGYNECOLOGISTS
NUMBER 88, DECEMBER 2007
ACOG
PRACTICE
BULLETIN
This Practice Bulletin was
developed by the ACOG Com-
mittee on Practice Bulletins
Obstetrics and the Committee
on Genetics with the assistance
of James Goldberg, MD. The
information is designed to aid
practitioners in making deci-
sions about appropriate obstet-
ric and gynecologic care. These
guidelines should not be con-
strued as dictating an exclusive
course of treatment or proce-
dure. Variations in practice may
be warranted based on the
needs of the individual patient,
resources, and limitations
unique to the institution or type
of practice.
Reaffirmed 2009
Invasive Prenatal Testing
for Aneuploidy
Prenatal diagnosis of fetal chromosomal abnormalities is the most common
indication for invasive prenatal testing. The prevalence of chromosomal abnor-
malities in clinically recognized early pregnancy loss is greater than 50% (1).
Fetuses with aneuploidy account for 611% of all stillbirths and neonatal
deaths (2). Chromosomal abnormalities that are compatible with life but cause
considerable morbidity occur in 0.65% of newborns, and structural chromoso-
mal rearrangements that will eventually affect reproduction occur in 0.2% of
newborns (3). Consequently, screening and diagnostic programs to detect the
most common autosomal trisomies in liveborn infants, including Down syn-
drome, are well established. The purpose of this document is to provide clinical
management guidelines for the prenatal diagnosis of these aneuploidies.
Background
There are many strategies available to screen for chromosomal abnormalities
(4). These incorporate maternal age and a variety of first- and second-trimester
ultrasound and biochemical markers that include nuchal translucency measure-
ment and pregnancy-associated plasma protein A, human chorionic gonad-
otropin, alpha-fetoprotein, estriol, and inhibin levels. All of these approaches
provide an adjusted risk for Down syndrome and trisomy 18. Whereas these
risk figures provide a more accurate risk for Down syndrome and trisomy 18
than maternal age alone, they do not exclude the possibility of an affected fetus
because the test sensitivity is less than 100%, so not all fetuses can be identi-
fied. Studies have shown that many factors influence a womans decision to
undergo an invasive procedure (5). These include feelings about having a child
in whom a chromosomal abnormality has been diagnosed and feelings about
the loss of a normal child as a result of the diagnostic procedure.
COMPENDIUM OF SELECTED PUBLICATIONS 1016
Down syndrome and other trisomies are primarily
the result of meiotic nondisjunction, which increases
with maternal age. Women contemplating screening ver-
sus diagnostic testing for aneuploidy may find it helpful
to compare their adjusted risk after screening with their
age-related risk (Table 1).
Fetuses with aneuploidy may have major anatomic
malformations that often are discovered during an ultra-
sound examination that is performed for another indica-
tion. Abnormalities involving a major organ or structure,
with a few notable exceptions, or the finding of two or
more minor structural abnormalities in the same fetus
indicate increased risk of fetal aneuploidy (6, 7) (Table 2).
There are genetic and nongenetic causes of structural
anomalies. If an aneuploidy is suspected, only a cytoge-
netic analysis of fetal cells can provide a definitive diag-
nosis. In some cases, a fetal karyotype will be sufficient
but, in other situations, adjunct testing such as fluores-
cence in situ hybridization or other genetic testing may
be required to detect chromosomal microdeletions or
duplications or to further characterize marker chromo-
somes or chromosomal rearrangements.
Amniocentesis
Traditional genetic amniocentesis usually is offered
between 15 weeks and 20 weeks of gestation. Many
large, multicenter studies have confirmed the safety of
genetic amniocentesis as well as its cytogenetic diagnos-
tic accuracy (greater than 99%) (8). All of the large col-
laborative studies in which the risk of amniocentesis was
evaluated were performed before the use of high-resolu-
tion concurrent ultrasonography. In more recent studies,
it is suggested that the procedure-related loss rate is as
low as 1 in 300500 and may be even lower with expe-
rienced individuals or centers (9, 10). Complications,
which occur infrequently, include transient vaginal spot-
ting or amniotic fluid leakage in approximately 12% of
all cases and chorioamnionitis in less than 1 in 1,000
cases. The perinatal survival rate in cases of amniotic
fluid leakage after midtrimester amniocentesis is greater
than 90% (11). Needle injuries to the fetus have been
reported but are very rare when amniocentesis is per-
formed under continuous ultrasound guidance. Amniotic
fluid cell culture failure occurs in 0.1% of samples. In
several studies, it has been confirmed that the incidence
of pregnancy loss, blood-contaminated specimens, leak-
ing of amniotic fluid, and the need for more than one
needle puncture are related to the experience of the oper-
ator, the use of small-gauge needles, and ultrasound
guidance (1214).
Early amniocentesis performed from 11 weeks to 13
weeks of gestation has been widely studied, and the tech-
Table 1. Risk Table for Chromosomal Abnormalities By
Maternal Age at Term
Risk for Any
Risk for Chromosome
Age at Term Trisomy 21
Abnormality
Data from Morris JK, Wald NJ, Mutton DE, Alberman E. Comparison of models
of maternal age-specific risk for Down syndrome live births. Prenat Diagn
2003;23:2528.
Risk for any chromosomal abnormality includes the risk for trisomy 21 and tri-
somy 18 in addition to trisomy 13, 47,XXY, 47,XYY, Turner syndrome genotype,
and other clinically significant abnormalities, 47,XXX not included. Data from
Hook EB. Rates of chromosome abnormalities at different maternal ages. Obstet
Gynecol 1981;58:2825.
Assess control in patients taking long-term-control medications to determine whether step-up therapy, step-down therapy, or no change in therapy is indicated.
COMPENDIUM OF SELECTED PUBLICATIONS 1026
indicate that classification of asthma severity and ther-
apy tailored according to asthma severity can result in
excellent infant and maternal outcomes (6, 7).
There are important caveats when interpreting the
study results of asthma in pregnancy. Fewer considerable
adverse associations have been found in the results of
prospective studies, possibly because of better asthma
surveillance and treatment. The excellent maternal and
infant outcomes were achieved at centers that tended to
manage asthma in pregnancy actively. In addition, women
who enroll in research studies tend to be more motivated
and adhere to therapeutic regimens more than the general
public. The lack of more adverse outcomes among
women with severe asthma also may be a function of the
relatively small number of participants in this cohort and
the resulting lack of power to find adverse outcomes that
were statistically significant. Although the results of these
prospective studies are reassuring in their consensus of
good pregnancy outcomes, they do not indicate that asthma
should be considered a benign condition because active
asthma management was a part of these studies and may
have had a positive impact on the outcomes.
Clinical Considerations and
Recommendations
How is asthma diagnosed during pregnancy?
Diagnosis of asthma in a pregnant patient is the same as
that for a nonpregnant patient. Asthma typically includes
characteristic symptoms (wheezing, chest cough, short-
ness of breath, chest tightness), temporal relationships
(fluctuating intensity, worse at night), and triggers (eg,
allergens, exercise, infections). Wheezing on ausculta-
tion would support the diagnosis, but its absence does
not exclude the diagnosis. Ideally, the diagnosis of asthma
would be confirmed by demonstrating airway obstruc-
tion on spirometry that is at least partially reversible
(greater than a 12% increase in FEV
1
after bronchodila-
tor). However, reversible airway obstruction may not be
demonstrable in some patients with asthma. In patients
with a clinical picture consistent with asthma, in whom
reversible airway obstruction cannot be demonstrated, a
trial of asthma therapy is reasonable. In such patients, a
positive response to asthma therapy can be used to diag-
nose asthma during pregnancy.
In patients presenting with new respiratory symp-
toms during pregnancy, the most common differential
diagnosis would be dyspnea of pregnancy. Dyspnea of
pregnancy usually can be differentiated from asthma by
its lack of cough, wheezing, chest tightness, or airway
obstruction. Other differential diagnoses include gastroe-
sophageal reflux, chronic cough from postnasal drip, and
bronchitis.
How should patients with asthma be assessed
during pregnancy?
Clinical evaluation includes subjective assessments and
pulmonary function tests. Because pulmonary function
and asthma severity may change during the course of
pregnancy, routine evaluation of pulmonary function in
pregnant women with persistent asthma is recommended.
For pulmonary function assessment during outpatient vis-
its, spirometry is preferable, but peak expiratory flow
measurement with a peak flow meter also is sufficient.
Patients with worsening symptoms should be evaluated
with peak flow measurement and lung auscultation.
Severity and control of asthma should be assessed in
terms of symptom exacerbation and pulmonary impair-
ment. It is important to identify a history of prior hospi-
talization (especially hospital stays that required intensive
care unit admission or intubation), emergency department
or other unscheduled visits for asthma treatment, or oral
corticosteroid requirements. In patients who are not tak-
ing controllers, it is useful to assess pulmonary impair-
ment based on severity classification (Table 1). Patients
with two or more episodes of symptom exacerbation
requiring the use of oral corticosteroids in the prior
12 months also should be considered to have persistent
asthma. In patients who are taking controllers, it is useful
to assess control (Table 1). Assessing the impairment
domain of control consists of determining the frequency
of daytime symptoms, nocturnal symptoms, activity lim-
itation, frequency of rescue therapy, and FEV
1
. The
assessment in a pregnant patient with asthma also should
include the effect of any prior pregnancies on asthma
severity or control because this may predict the course of
the asthma during subsequent pregnancies.
Can allergy shots be started or continued
during pregnancy?
The use of allergen immunotherapy, or allergy shots,
has been shown to be effective in improving asthma in
patients with allergies (4). In two studies, no adverse
effects of immunotherapy during pregnancy have been
found (22, 23). However, anaphylaxis is a risk of aller-
gen injections, especially early in the course of
immunotherapy when the dose is being escalated, and
anaphylaxis during pregnancy has been associated with
maternal death, fetal death, or both. In a patient who is
receiving a maintenance or near-maintenance dose, not
experiencing adverse reactions to the injections and
apparently deriving clinical benefit, continuation of
immunotherapy is recommended. In such patients, a
1027 PRACTICE BULLETINS
not controlled with the use of medium-dose inhaled cor-
ticosteroids. Alternative add-on therapies are theophylline
or leukotriene receptor antagonists (montelukast, zafir-
lukast). However, the use of long-acting inhaled
2
-ago-
nists is preferred because it has been shown to be a more
effective add-on therapy in nonpregnant patients than
leukotriene receptor antagonists or theophylline. Long-
acting inhaled
2
-agonists have fewer side effects than
theophylline, which has a narrow therapeutic index and
requires serum monitoring, and there are few data on the
use of leukotriene receptor antagonists in humans during
pregnancy. See Table 2 for typical medication dosages.
Because long-acting and short-acting inhaled
2
-agonists
have similar pharmacology and toxicology, long-acting
inhaled
2
-agonists are expected to have a safety profile
similar to that of albuterol. Two long-acting inhaled
2
-agonists are available: 1) salmeterol and 2) formoterol.
Limited observational data exist on their use during preg-
nancy. A step-wise approach to management is advised in
order to achieve control. See the box for specific therapy.
For patients whose symptoms are not well controlled
(Table 1) with the use of medium-dose inhaled corticos-
teroids and long-acting inhaled
2
-agonists, treatment
should be advanced to high-dose inhaled corticosteroids
dose reduction may be considered to further decrease the
chance of anaphylaxis. Riskbenefit considerations do
not usually favor beginning allergen immunotherapy
during pregnancy.
What is appropriate rescue therapy for asthma
during pregnancy?
Inhaled short-acting
2
-agonists are the rescue therapy of
choice for asthma during pregnancy. Inhaled albuterol is
the first-choice, short-acting
2
-agonist for pregnant
women, although other agents also may be appropriate.
In general, patients should use up to two treatments of
inhaled albuterol (two to six puffs) or nebulized albuterol
at 20-minute intervals for most mild to moderate symp-
toms; higher doses can be used for severe symptom exac-
erbation. To avoid maternal and fetal hypoxia, patients
should be counseled to start rescue therapy at home when
they have an exacerbation of symptoms, such as cough-
ing, chest tightness, dyspnea, wheezing, or a 20% decrease
in the PEFR. With a good response (ie, symptoms reduce
or resolve, and the PEFR reaches 80% of personal best)
the patient can continue normal activity. If the patient
does not have a good response or if she notices a
decrease in fetal activity, she should seek medical atten-
tion quickly.
What is first-line controller therapy for asthma
during pregnancy?
For those with mild, intermittent asthma, no controller
therapy is indicated. Use of inhaled corticosteroids is first-
line controller therapy for persistent asthma during preg-
nancy. For patients with mild, persistent asthma, the use of
low-dose inhaled corticosteroids is recommended (see the
box). For patients with moderate persistent asthma or
whose symptoms are not controlled with the use of low-
dose inhaled corticosteroids, the use of medium-dose
inhaled corticosteroids or low-dose inhaled cortico-
steroids and long-acting -agonists are indicated. See
Table 2 for typical inhaled corticosteroid regimens.
Budesonide is the preferred inhaled corticosteroid for use
during pregnancy (4). However, there are no data indicat-
ing that the other inhaled corticosteroid preparations are
unsafe during pregnancy. Therefore, the use of any inhaled
corticosteroids may be continued in patients whose asthma
was well controlled by these agents before pregnancy (4).
What is appropriate add-on controller therapy
for asthma during pregnancy?
Use of long-acting
2
-agonists is the preferred add-on
controller therapy for asthma during pregnancy. This
therapy should be added when patients symptoms are
Step Therapy Medical Management
of Asthma During Pregnancy
Mild Intermittent Asthma
No daily medications, albuterol as needed
Mild Persistent Asthma
PreferredLow-dose inhaled corticosteroid
AlternativeCromolyn, leukotriene receptor antago-
nist, or theophylline (serum level 512 mcg/mL)
Moderate Persistent Asthma
PreferredLow-dose inhaled corticosteroid and
salmeterol or medium-dose inhaled corticosteroid
or (if needed) medium-dose inhaled corticosteroid
and salmeterol
AlternativeLow-dose or (if needed) medium-
dose inhaled corticosteroid and either leukotriene
receptor antagonist or theophylline (serum level
512 mcg/mL)
Severe Persistent Asthma
PreferredHigh-dose inhaled corticosteroid and
salmeterol and (if needed) oral corticosteroid
AlternativeHigh-dose inhaled corticosteroid and
theophylline (serum level 512 mcg/mL) and oral
corticosteroid if needed
COMPENDIUM OF SELECTED PUBLICATIONS 1028
(Table 2) and long-acting inhaled
2
-agonists (salmeterol,
one puff twice daily). Some patients with severe asthma
may require regular oral corticosteroid use to achieve ade-
quate asthma control. For patients whose symptoms are
very poorly controlled (Table 1), a course of oral corticos-
teroids may be necessary to attain control, along with a
step up in therapy, as described previously and in the box.
What nonpharmacologic approaches should
be used for asthma during pregnancy?
Identifying and controlling or avoiding factors, such as
allergens and irritants, that contribute to asthma severity,
particularly tobacco smoke, can lead to improved mater-
nal well-being with less need for medication (4). If gas-
troesophageal reflux is exacerbating the patients asthma,
nonpharmacologic measures, such as elevating the head
of the bed, eating smaller meals, not eating within 23
hours of bedtime, and avoiding triggering foods, may
help. Asthma control is enhanced by ensuring access to
education about asthma, the interrelationships between
asthma and pregnancy, and the skills necessary to man-
age asthma. These skills include self-monitoring, correct
use of inhalers, following a plan for long-term manage-
ment of asthma, and promptly handling signs of worsen-
ing asthma (4). Specific measures to reduce mold, dust
mite exposure, animal dander, cockroaches, and other
environmental triggers may be important. Animal dander
control entails removing the animal from the home or, at
a minimum, keeping the animal out of the patients bed-
room. Cockroaches can be controlled by poison or bait
traps and eliminating exposed food or garbage.
How should asthma therapy be adjusted
during pregnancy?
The step-care therapeutic approach increases the number
and dosage of medications with increasing asthma sever-
ity (see the box). At each step of therapy, medications are
considered to be preferred or alternative based on
efficacy and safety considerations. Patients whose symp-
toms are not optimally responding to treatment should
receive a step up in treatment to more intensive medical
therapy. Once control is achieved and sustained for sev-
eral months, a step-down approach can be considered, but
a change in therapy should be undertaken cautiously and
administered gradually to avoid compromising the stabil-
ity of the asthma control. For some patients, it may be pru-
dent to postpone, until after birth, a reduction of therapy
that is effectively controlling the patients asthma (4).
How should acute asthma be assessed during
pregnancy?
Initial assessment of a pregnant patient presenting with
acute asthma includes obtaining a brief medical history,
performing a physical examination, and examining phys-
iologic measures of airway function and fetal well-being.
Pulmonary physiologic assessment includes measuring
FEV
1
or PEFR and oxygen saturation. Fetal assessment
Table 2. Comparative Daily Doses for Inhaled Corticosteroids*
Corticosteroid Amount Low Dose Medium Dose High Dose
Beclomethasone HFA 40 mcg per puff 26 puffs More than 612 puffs More than 12 puffs
80 mcg per puff 13 puffs More than 36 puffs More than 6 puffs
Budesonide 200 mcg per inhalation 13 puffs More than 36 puffs More than 6 puffs
Flunisolide 250 mcg per puff 24 puffs 48 puffs More than 8 puffs
Fluticasone HFA 44 mcg per puff 26 puffs
110 mcg per puff 2 puffs 24 puffs More than 4 puffs
220 mcg per puff 12 puffs More than 2 puffs
Fluticasone DPI 50 mcg per inhalation 26 puffs
100 mcg per inhalation 13 puffs 35 puffs More than 5 puffs
250 mcg per inhalation 1 puff 2 puffs More than 2 puffs
Mometasone 200 mcg per inhalation 1 puff 2 puffs More than 2 puffs
Triamcinolone 75 mcg per puff 410 puffs 1020 puffs More than 20 puffs
*Total daily puffs is usually divided into a twice-per-day regimen.
Abbreviations: DPI, dry powder inhaler; HFA, hydrofluoroalkane
Adapted from National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program. Expert panel report 3: guide-
lines for the diagnosis and management of asthma. NIH Publication No. 07-4051. Bethesda (MD): NHLBI; 2007. Available at:
http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. Retrieved September 10, 2007.
1029 PRACTICE BULLETINS
depends on the stage of pregnancy, but continuous elec-
tronic fetal monitoring or biophysical profile or both
should be considered if the pregnancy has reached the
stage of fetal viability.
After initial treatment, repeat assessments of the
patient and fetus will determine the need for continuing
care. Patients with FEV
1
or PEFR measurements greater
than or equal to 70% sustained for 60 minutes after last
treatment, no distress, and reassuring fetal status may be
discharged. For an incomplete response (FEV
1
or PEFR
measurements greater than or equal to 50% but less than
70%, mild or moderate symptoms), the disposition (con-
tinued treatment in the emergency department, discharge
home, or hospitalization) will need to be individualized.
For patients with a poor response (FEV
1
or PEFR measure-
ments less than 50%), hospitalization is indicated. For
patients with a poor response and severe symptoms, drowsi-
ness, confusion, or PCO
2
level greater than 42 mm Hg,
intensive care unit admission is indicated and intubation
should be strongly considered.
What should be the discharge regimen after
an acute asthma episode?
Patients discharged after an acute asthmatic episode
should continue treatment with short-acting
2
-agonists,
two to four puffs every 34 hours as needed. Oral corti-
costeroids should be continued at a dose of 4060 mg in
a single dose or two divided doses for 310 days. Inhaled
corticosteroids should be initiated or continued until
review at medical follow-up. Outpatient follow-up
should be arranged within 5 days of the acute visit.
What are considerations for fetal surveillance
in pregnancies complicated by asthma?
Ultrasound examinations and antenatal fetal testing
should be considered for women who have moderate or
severe asthma during pregnancy. First-trimester ultra-
sound dating should be performed, if possible, to facilitate
subsequent evaluations of fetal growth restriction and the
risk of preterm birth. Serial ultrasound examinations to
monitor fetal activity and growth should be considered
(starting at 32 weeks of gestation) for women who have
poorly controlled asthma or moderate-to-severe asthma
and for women recovering from a severe asthma exacer-
bation. All patients should be instructed to be attentive to
fetal activity.
What intrapartum concerns are unique to
pregnant women with asthma?
Asthma medication use should not be discontinued dur-
ing labor and delivery. The patient should be kept hydrated
and should receive adequate analgesia in order to
decrease the risk of bronchospasm. Women who are cur-
rently receiving or recently have taken systemic corti-
costeroids should receive intravenous administration
of corticosteroids (eg, hydrocortisone 100 mg every
8 hours) during labor and for 24 hours after delivery to
prevent adrenal crisis (4).
Cesarean delivery for acute exacerbation of asthma
is rarely needed. Maternal and fetal compromise usually
will respond to aggressive medical management.
However, delivery may benefit the respiratory status of a
patient with unstable asthma who has a mature fetus.
Lumbar anesthesia can reduce oxygen consumption and
minute ventilation during labor (24). Regional anesthe-
sia was reported to incur a 2% incidence of broncho-
spasm (25). Obstetric, anesthetic, and pediatric staff
should communicate to coordinate intrapartum and post-
partum care.
How should women with asthma be counseled
about breastfeeding?
In general, only small amounts of asthma medications
enter breast milk. The National Asthma Education and
Prevention Program found that the use of prednisone,
theophylline, antihistamines, inhaled corticosteroids,
2
-agonists, and cromolyn is not contraindicated for
breastfeeding (4, 26).
Summary of
Recommendations and
Conclusions
The following recommendations and conclusions
are based on limited or inconsistent scientific evi-
dence (Level B):
It is safer for pregnant women with asthma to be
treated with asthma medications than it is for them
to have asthma symptoms and exacerbations.
Clinical evaluation of asthma includes subjective
assessments and pulmonary function tests.
The ultimate goal of asthma therapy in pregnancy is
maintaining adequate oxygenation of the fetus by
preventing hypoxic episodes in the mother.
The step-care therapeutic approach increases the
number and dosage of medications with increasing
asthma severity.
Inhaled corticosteroids are first-line controller ther-
apy for persistent asthma during pregnancy.
COMPENDIUM OF SELECTED PUBLICATIONS 1030
Budesonide is the preferred inhaled corticosteroid
for use during pregnancy.
Inhaled albuterol is recommended rescue therapy
for pregnant women with asthma.
Identifying and controlling or avoiding factors such
as allergens and irritants, particularly tobacco
smoke, can lead to improved maternal well-being
with less need for medication.
Continuation of immunotherapy is recommended in
patients who are at or near a maintenance dose, not
experiencing adverse reactions to the injections, and
apparently deriving clinical benefit.
Use of prednisone, theophylline, antihistamines,
inhaled corticosteroids,
2
-agonists, and cromolyn is
not contraindicated for breastfeeding.
The following recommendations and conclusions
are based primarily on consensus and expert opin-
ion (Level C):
Asthma self-management skills, including self-
monitoring, correct use of inhalers, and following a
plan for long-term management of asthma and
promptly handling signs of worsening asthma,
enhance asthma control.
For pulmonary function assessment of patients dur-
ing outpatient visits, spirometry is preferable, but
peak expiratory flow measurement with a peak flow
meter also is sufficient.
Ultrasound examinations and antenatal fetal testing
should be considered for women who have moder-
ate or severe asthma during pregnancy.
Pregnant patients with asthma, even those with mild
or well-controlled disease, need to be monitored
with PEFR and FEV
1
testing as well as by observing
their symptoms during pregnancy.
Routine evaluation of pulmonary function in preg-
nant women with persistent asthma is recommended.
Because pulmonary function and asthma severity
may change during the course of pregnancy, routine
evaluation of pulmonary function in pregnant
women with persistent asthma is recommended.
Proposed Performance
Measure
The percentage of pregnant patients with persistent asthma
who have undergone pulmonary function testing
References
1. Alexander S, Dodds L, Armson BA. Perinatal outcomes in
women with asthma during pregnancy. Obstet Gynecol
1998;92:43540. (Level II-2)
2. Kwon HL, Belanger K, Bracken MB. Asthma prevalence
among pregnant and childbearing-aged women in the
United States: estimates from national health surveys.
Ann Epidemiol 2003;13:31724. (Level III)
3. Schatz M, Zeiger RS, Hoffman CP. Intrauterine growth is
related to gestational pulmonary function in pregnant
asthmatic women. Kaiser-Permanente Asthma and
Pregnancy Study Group. Chest 1990;98:38992. (Level
II-2)
4. National Heart, Lung, and Blood Institute, National
Asthma Education and Prevention Program. Working
group report on managing asthma during pregnancy: rec-
ommendations for pharmacologic treatmentupdate
2004. NIH Publication No. 05-5236. Bethesda (MD):
NHLBI; 2005. Available at: http://www.nhlbi.nih.gov/
health/prof/lung/asthma/astpreg/astpreg_full.pdf.
Retrieved September 10, 2007. (Level III)
5. Schatz M, Zeiger RS, Hoffman CP, Harden K, Forsythe A,
Chilingar L, et al. Perinatal outcomes in the pregnancies of
asthmatic women: a prospective controlled analysis. Am J
Respir Crit Care Med 1995;151:11704. (Level II-2)
6. Bracken MB, Triche EW, Belanger K, Saftlas A, Beckett
WS, Leaderer BP. Asthma symptoms, severity, and drug
therapy: a prospective study of effects on 2205 pregnan-
cies. Obstet Gynecol 2003;102:73952. (Level II-2)
7. Dombrowski MP, Schatz M, Wise R, Momirova V,
Landon M, Mabie W, et al. Asthma during pregnancy.
National Institute of Child Health and Human
Development MaternalFetal Medicine Units Network
and the National Heart, Lung, and Blood Institute. Obstet
Gynecol 2004;103:512. (Level II-2)
8. Demissie K, Breckenridge MB, Rhoads GG. Infant and
maternal outcomes in the pregnancies of asthmatic
women. Am J Respir Crit Care Med 1998;158:10915.
(Level II-2)
9. Perlow JH, Montgomery D, Morgan MA, Towers CV,
Porto M. Severity of asthma and perinatal outcome. Am J
Obstet Gynecol 1992;167:9637. (Level II-2)
10. Kallen B, Rydhstroem H, Aberg A. Asthma during preg-
nancya population based study. Eur J Epidemiol
2000;16:16771. (Level II-2)
11. Greenberger PA, Patterson R. The outcome of pregnancy
complicated by severe asthma. Allergy Proc 1988;9:
53943. (Level II-3)
12. Bakhireva LN, Schatz M, Chambers CD. Effect of mater-
nal asthma and gestational asthma therapy on fetal growth.
J Asthma 2007;44:7176. (Level III)
13. Towers CV, Briggs GG, Rojas JA. The use of pros-
taglandin E2 in pregnant patients with asthma. Am J
Obstet Gynecol 2004;190:177780; discussion 1780.
(Level II-2)
1031 PRACTICE BULLETINS
14. Schatz M, Dombrowski MP, Wise R, Thom EA, Landon
M, Mabie W, et al. Asthma morbidity during pregnancy
can be predicted by severity classification. J Allergy Clin
Immunol 2003;112:2838. (Level II-2)
15. Stenius-Aarniala B, Piirila P, Teramo K. Asthma and preg-
nancy: a prospective study of 198 pregnancies. Thorax
1988;43:128. (Level II-2)
16. Mihrshahi S, Belousova E, Marks GB, Peat JK.
Pregnancy and birth outcomes in families with asthma.
Childhood Asthma Prevention Team. J Asthma 2003;
40:1817. (Level II-2)
17. Minerbi-Codish I, Fraser D, Avnun L, Glezerman M,
Heimer D. Influence of asthma in pregnancy on labor and
the newborn. Respiration 1998;65:1305. (Level II-2)
18. Stenius-Aarniala BS, Hedman J, Teramo KA. Acute asthma
during pregnancy. Thorax 1996;51:4114. (Level II-2)
19. Jana N, Vasishta K, Saha SC, Khunnu B. Effect of
bronchial asthma on the course of pregnancy, labour and
perinatal outcome. J Obstet Gynaecol 1995;21:22732.
(Level II-2)
20. Triche EW, Saftlas AF, Belanger K, Leaderer BP, Bracken
MB. Association of asthma diagnosis, severity, symptoms,
and treatment with risk of preeclampsia. Obstet Gynecol
2004;104:58593. (Level II-2)
21. Schatz M, Dombrowski MP, Wise R, Momirova V,
Landon M, Mabie W, et al. Spirometry is related to peri-
natal outcomes in pregnant women with asthma. National
Institute of Child Health and Human Development
MaternalFetal Medicine Units Network; National Heart,
Lung, and Blood Institute. Am J Obstet Gynecol 2006;
194:1206. (Level II-2)
22. Metzger WJ, Turner E, Patterson R. The safety of
immunotherapy during pregnancy. J Allergy Clin
Immunol 1978;61:26872. (Level II-3)
23. Shaikh WA. A retrospective study on the safety of
immunotherapy in pregnancy. Clin Exp Allergy 1993;23:
85760. (Level II-2)
24. Hagerdal M, Morgan CW, Sumner AE, Gutsche BB.
Minute ventilation and oxygen consumption during labor
with epidural analgesia. Anesthesiology 1983;59:4257.
(Level II-2)
25. Fung DL. Emergency anesthesia for asthma patients. Clin
Rev Allergy 1985;3:12741. (Level III)
26. Transfer of drugs and other chemicals into human milk.
American Academy of Pediatrics. Pediatrics 2001;108:
77689. (Level III)
The MEDLINE database, the Cochrane Library, and
ACOGs own internal resources and documents were used
to conduct a literature search to locate relevant articles pub-
lished between January 1985 and March 2007. The search
was restricted to articles published in the English language.
Priority was given to articles reporting results of original
research, although review articles and commentaries also
were consulted. Abstracts of research presented at sympo-
sia and scientific conferences were not considered adequate
for inclusion in this document. Guidelines published by
organizations or institutions such as the National Institutes
of Health and the American College of Obstetricians and
Gynecologists were reviewed, and additional studies were
located by reviewing bibliographies of identified articles.
When reliable research was not available, expert opinions
from obstetriciangynecologists were used.
Studies were reviewed and evaluated for quality according
to the method outlined by the U.S. Preventive Services
Task Force:
I Evidence obtained from at least one properly
designed randomized controlled trial.
II-1 Evidence obtained from well-designed controlled
trials without randomization.
II-2 Evidence obtained from well-designed cohort or
casecontrol analytic studies, preferably from more
than one center or research group.
II-3 Evidence obtained from multiple time series with or
without the intervention. Dramatic results in uncon-
trolled experiments also could be regarded as this
type of evidence.
III Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees.
Based on the highest level of evidence found in the data,
recommendations are provided and graded according to the
following categories:
Level ARecommendations are based on good and con-
sistent scientific evidence.
Level BRecommendations are based on limited or incon-
sistent scientific evidence.
Level CRecommendations are based primarily on con-
sensus and expert opinion.
Copyright February 2008 by the American College of Obste-
tricians and Gynecologists. All rights reserved. No part of this
publication may be reproduced, stored in a retrieval system,
posted on the Internet, or transmitted, in any form or by any
means, electronic, mechanical, photocopying, recording, or
otherwise, without prior written permission from the publisher.
Requests for authorization to make photocopies should be
directed to Copyright Clearance Center, 222 Rosewood Drive,
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
The American College of Obstetricians and Gynecologists
409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920
Asthma in pregnancy. ACOG Practice Bulletin No. 90. American
College of Obstetricians and Gynecologists. Obstet Gynecol 2008;
111:45764.
COMPENDIUM OF SELECTED PUBLICATIONS 1032
ACOG
PRACTICE
BULLETIN
CLINICAL MANAGEMENT GUIDELINES FOR
OBSTETRICIANGYNECOLOGISTS
NUMBER 92, APRIL 2008
(Replaces Practice Bulletin Number 87, November 2007)
This Practice Bulletin was
developed by the ACOG Com-
mittee on Practice Bulletins
Obstetrics with the assistance
of Zachary N. Stowe, MD and
Kimberly Ragan, MSW. The
information is designed to aid
practitioners in making deci-
sions about appropriate obstet-
ric and gynecologic care. These
guidelines should not be con-
strued as dictating an exclusive
course of treatment or proce-
dure. Variations in practice may
be warranted based on the
needs of the individual patient,
resources, and limitations
unique to the institution or type
of practice.
Reaffirmed 2009
Use of Psychiatric
Medications During
Pregnancy and Lactation
It is estimated that more than 500,000 pregnancies in the United States each
year involve women who have psychiatric illnesses that either predate or
emerge during pregnancy, and an estimated one third of all pregnant women
are exposed to a psychotropic medication at some point during pregnancy (1).
The use of psychotropic medications is a cause of concern for physicians and
their patients because of the potential teratogenic risk, the risk of perinatal syn-
dromes or neonatal toxicity, and the risk for abnormal postnatal behavioral
development. With the limited information available on the risks of the psy-
chotropic medications, clinical management must incorporate an appraisal of
the clinical consequences of offspring exposure, the potential effect of untreated
maternal psychiatric illness, and the available alternative therapies. The pur-
pose of this document is to present current evidence on the risks and benefits of
treatment for certain psychiatric illnesses during pregnancy.
Background
Advising a pregnant or breastfeeding woman to discontinue medication
exchanges the fetal or neonatal risks of medication exposure for the risks of
untreated maternal illness. Maternal psychiatric illness, if inadequately treated
or untreated, may result in poor compliance with prenatal care, inadequate
nutrition, exposure to additional medication or herbal remedies, increased alco-
hol and tobacco use, deficits in motherinfant bonding, and disruptions within
the family environment (see Table 1). All psychotropic medications studied to
date cross the placenta (1), are present in amniotic fluid (2), and can enter
human breast milk (3). For known teratogens, knowledge of gestational age is
1033 PRACTICE BULLETINS
while breastfeeding also are shown in Table 2. Electronic
resources for information related to the fetal and neona-
tal effects of psychotropic drug therapy in pregnancy and
with breastfeeding include Reprotox (www.reprotox.org)
and TERIS (http://depts.washington.edu/terisweb). Pro-
viding women with patient resources for online informa-
tion that are well referenced is a reasonable option.
helpful in the decision about drug therapy because the
major risk of teratogenesis is during embryogenesis (ie,
during the third through the eighth week of gestation).
The U.S. Food and Drug Administration (FDA) has pro-
vided a system for categorizing individual medications
(see Table 2), although this system has considerable lim-
itations. Categories of risk for neonates from drugs used
(continued)
Table 2. Psychiatric Medications in Pregnancy and Lactation*
Pregnancy Risk American Academy Lactation Risk
Generic Name Trade Name Category
of Pediatrics Rating
Category
Anxiolytic Medications
Benzodiazepines
Alprazolam Xanax D
m
Unknown, of concern L3
Chlordiazepoxide Librium D N/A L3
Clonazepam Klonopin D
m
N/A L3
Clorazepate Tranxene D N/A L3
Diazepam Valium D Unknown, of concern L3, L4 if used chronically
Lorazepam Ativan D
m
Unknown, of concern L3
Oxazepam Serax D N/A L3
Benzodiazepines for Insomnia
Estazolam ProSom X
m
N/A L3
Flurazepam Dalmane X
m
N/A L3
Quazepam Doral X
m
Unknown, of concern L2
Table 1. Impact of Psychiatric Illness on Pregnancy Outcome
Impact on Outcome
Illness Teratogenic Effects Obstetric Neonatal Treatment Options
Anxiety disorders N/A Increased incidence of forceps Decreased developmental Benzodiazepines
deliveries, prolonged labor, scores and inadaptability; Antidepressants
precipitate labor, fetal distress, slowed mental development Psychotherapy
preterm delivery, and at 2 years of age
spontaneous abortion
Major depression N/A Increased incidence of low birth Increased newborn cortisol and Antidepressants
weight, decreased fetal growth, catecholamine levels, infant Psychotherapy
and postnatal complications crying, rates of admission to ECT
neonatal intensive care units
Bipolar disorder N/A See major depression See major depression Lithium
Anticonvulsants
Antipsychotics
ECT
Schizophrenia Congenital malformations, Increased incidence of preterm Increased rates of postnatal Antipsychotics
especially of cardiovascular delivery, low birth weight, death
system small for gestational age,
placental abnormalities, and
antenatal hemorrhage
Abbreviations: ECT, electroconvulsive therapy; N/A, not available (eg, no studies identified)
COMPENDIUM OF SELECTED PUBLICATIONS 1034
Table 2. Psychiatric Medications in Pregnancy and Lactation* (continued)
Pregnancy Risk American Academy Lactation Risk
Generic Name Trade Name Category
of Pediatrics Rating
Category
of Pediatrics Rating
Category
Antidepressants (continued)
Other Antidepressants (continued)
Trazodone Desyrel C
m
Unknown, of concern L2
Venlafaxine Effexor C
m
N/A L3
Antipsychotic Medications
Typical Antipsychotics
Chlorpromazine Thorazine C Unknown, of concern L3
Fluphenazine Prolixin C N/A L3
Haloperidol Haldol C
m
Unknown, of concern L2
Loxapine Loxitane C N/A L4
Perphenazine Trilafon C Unknown, of concern N/A
Pimozide Orap C
m
N/A L4
Thioridazine Mellaril C N/A L4
Thiothixene Navane C N/A L4
Trifluoperazine Stelazine C Unknown, of concern N/A
Atypical Antipsychotics
Aripiprazole Abilify C
m
N/A L3
Clozapine Clozaril B
m
Unknown, of concern L3
Olanzapine Zyprexa C
m
N/A L2
Quetiapine Seroquel C
m
Unknown, of concern L4
Risperidone Risperdal C
m
N/A L3
Ziprasidone
The U.S. Food and Drug Administration classifies drug safety using the following categories: A, controlled studies show no risk; B, no evidence of risk in humans; C,
risk cannot be ruled out; D, positive evidence of risk; X, contraindicated in pregnancy. Risk category adapted from Briggs GG, Freeman RK, Yaffe SJ. Drugs in preg-
nancy and lactation. 7th ed. Philadelphia (PA): Lippincott Williams & Wilkins; 2005. The m subscript is for data taken from the manufacturers package insert.
Lactation risk categories are listed as follows: L1, safest; L2, safer; L3, moderately safe; L4, possibly hazardous; L5, contraindicated. For more information, see Hale TW.
Medications in Mothers Milk. Amaraillo (TX): Pharmasoft Publishing, 2004.
||
Original committee report 1994 listed as compatible, and a correction was later published.
Not listed in Briggs. Risk category taken from Physicians Desk Reference 1992, 1993, 1994, 1996, and 2004.
COMPENDIUM OF SELECTED PUBLICATIONS 1036
depression occur in women between the ages of 25 years
and 44 years (6). Symptoms include depressed or irrita-
ble mood, anhedonia, weight loss or gain, appetite and
sleep changes, loss of energy, feelings of excessive guilt
or worthlessness, psychomotor agitation or retardation
and, in more severe cases, suicidal ideation (7).
Approximately 1016% of pregnant women fulfill diag-
nostic criteria for depression, and up to 70% of pregnant
women report symptoms of depression (6, 810). Many
symptoms of depression overlap with the symptoms of
pregnancy and often are overlooked (6, 11). Of women
taking antidepressants at conception, more than 60%
experienced symptoms of depression during the preg-
nancy (12). In a study of pregnant women taking antide-
pressants before conception, a 68% relapse of depression
was documented in those who discontinued medications
during pregnancy (13) compared with only a 25% relapse
in those who continued antidepressant medications.
Postpartum depression is classified as a major
episode of depression that occurs within the first 4 weeks
postpartum (7) or within the first 6 weeks postpartum
(14). Many women in whom postpartum depression was
diagnosed reported having symptoms of depression dur-
ing pregnancy (9, 1517). These symptoms may be diffi-
cult to differentiate from normal postpartum adaptation.
Survey tools (eg, Edinburgh Postnatal Depression Scale,
Beck Depression Inventory, and the Postpartum
Depression Screening Scale), are widely used to identify
depression during the perinatal period (18). The detection
rate is in the range of 68100% (better for severe depres-
sion) with specificities in the range of 7896% (19).
Untreated maternal depression is associated with an
increase in adverse pregnancy outcomes, including pre-
mature birth, low birthweight infants, fetal growth restric-
tion, and postnatal complications. This association is
stronger when depression occurs in the late second to
early third trimester (20). Newborns of women with
untreated depression during pregnancy cry more and are
more difficult to console (2022). Maternal depression
also is associated with increased life stress, decreased
social support, poor maternal weight gain, smoking, and
alcohol and drug use (23), all of which can adversely
Table 3. Management Issues Associated With Medication Use During Pregnancy and Lactation
Management Issues
Medication Class Birth Defects Pregnancy Delivery Neonatal Lactation Treatment Options
Benzodiazepines Possible increased Ultrasonography for Floppy infant Withdrawal Infant sedation Clonazepam
incidence of cleft facial morphology syndrome syndrome reported Lorazepam
lip or palate Alprazolam
Selective serotonin None confirmed Decreased serum None Neonatal, None Fluoxetine
reuptake inhibitors, concentrations withdrawal Sertraline
selective norepine- across pregnancy syndrome Paroxetine
phrine reuptake Citalopram
inhibitors, and Nortriptyline
tricyclic antidepressants
Lithium Increased Ultrasonography or Intravenous fluids Increased risk for Monitor infant Sustained release
incidence of fetal echocardiography Increased risk for lithium toxicity complete blood lithium
heart defects for heart development lithium toxicity in in infant count, thyroid-
or both mother stimulating
Decreased serum hormone levels,
concentrations and lithium
across pregnancy levels
Antiepileptic Drugs Increased incidence Decreased serum None Neonatal Monitor infant Lamotrigine
of birth defects concentrations across symptoms, complete blood Carbemazepine
pregnancy Vitamin K for count, liver
Folate supplementation, some anti- enzyme levels,
Vitamin K for some epileptic drugs antiepileptic
antiepileptic drugs drug levels
Antipsychotic None Confirmed Avoid anticholinergic None Possible risk for None Haloperidol
Medications medications for neuroleptic
side effects malignant
syndrome and
intestinal
obstruction
1037 PRACTICE BULLETINS
affect infant outcome (2426). Later in life, children of
untreated depressed mothers are more prone to suicidal
behavior, conduct problems, and emotional instability and
more often require psychiatric care (27, 28).
Bipolar Disorder
Bipolar disorder, historically called manicdepressive
disorder, affects between 3.9% and 6.4% of Americans
and affects men and women equally (4, 2931). It com-
monly is characterized by distinct periods of abnormally
and persistently elevated, expansive, or irritable mood
and separate distinct periods of depressed mood or anhe-
donia (7). Women are more likely than men to experience
depressive episodes of bipolar disorder (32), rapid
cycling (33), and mixed episodes (34, 35). Typical onset
of bipolar disorder for women is in the teens or early
twenties.
Rates of postpartum relapse range from 32% (36) to
67% (37). In one study, it was reported that pregnancy had
a protective effect for women with bipolar disorder (38),
but the participants may have had milder illness. Perinatal
episodes of bipolar disorder tend to be depressive (37, 39)
and, when experienced with one pregnancy, are more
likely to recur with subsequent pregnancies (37). There
also is an increased risk of postpartum psychosis as high
as 46% (40, 41).
Anxiety Disorders
Anxiety disorders include panic disorder, obsessive
compulsive disorder (OCD), generalized anxiety disorder
(GAD), posttraumatic stress disorder (PTSD), social anx-
iety disorder, and specific phobias. Collectively, anxiety
disorders are the most commonly occurring psychiatric
disorders, with a prevalence of 18.1% among adults 18
years and older in the United States (42). Panic disorder,
GAD, PTSD, agoraphobia, and specific phobias are two
times more likely to be diagnosed in women than men.
Anxiety and stress during pregnancy are documented as
factors associated with poor obstetric outcomes, includ-
ing spontaneous abortions (43), preterm delivery (44,
45), and delivery complications (46), such as prolonged
labor, precipitate labor, clinical fetal distress, and forceps
deliveries (47). A direct causal relationship has not been
established.
Panic disorder is characterized by recurrent panic
attacks that arise spontaneously in situations that are not
expected to cause anxiety. Most investigators agree that
women are at greatest risk for exacerbation of panic dis-
order during the postpartum period (48, 49). In a recent
study PTSD was reported to be the third most common
psychiatric diagnosis among economically disadvantaged
pregnant women, with a prevalence of 7.7% (50). Women
with PTSD were significantly more likely to have a
comorbid condition, principally major depression or
GAD. Many reports have documented traumatic obstetric
experiences (eg, emergency delivery, miscarriage, and
fetal demise) as precipitants to PTSD-related symptoma-
tology. The incidence of OCD during pregnancy is
unknown. Despite limited formal investigation, most clin-
icians and researchers agree that pregnancy seems to be a
potential trigger of OCD symptom onset, with 39% of the
women in a specialized OCD clinic experiencing symp-
tom onset during pregnancy (51). It generally is accepted
that OCD worsens during the postpartum period.
Schizophrenia-Spectrum Disorders
Schizophrenia is a severe and persistent mental illness
characterized by psychotic symptoms, negative symptoms,
such as flat affect and lack of volition, and significant
occupational and social dysfunction (7). Schizophrenia
occurs in approximately 12% of women, with the most
common age of onset during the childbearing years (52).
A variety of adverse pregnancy outcomes in women
with schizophrenia have been reported, including preterm
delivery, low birth weight infants, small for gestational
age fetuses (53, 54), placental abnormalities and antena-
tal hemorrhage, increased rates of congenital malforma-
tions, especially of the cardiovascular system (55), and a
higher incidence of postnatal death (53). However, in one
study it was found that schizophrenic women were not at
higher risk for specific obstetric complications but were
at greater risk of requiring interventions during delivery,
including labor induction and assisted or cesarean deliv-
ery (56). If left untreated during pregnancy, schizophre-
nia-spectrum disorders can have devastating effects on
both mother and child, with rare reports of maternal self-
mutilation (57, 58), denial of pregnancy resulting in
refusal of prenatal care (59), and infanticide (60, 61).
Clinical Considerations and
Recommendations
What is the evidence regarding the safety
and efficacy of treatment for depression dur-
ing pregnancy?
Most data related to antidepressants in pregnancy are
derived from the use of selective serotonin reuptake
inhibitors (SSRIs) (fluoxetine, sertraline, citalopram, and
paroxetine). Overall, there is limited evidence of terato-
genic effects from the use of antidepressants in pregnancy
or adverse effects from exposure during breastfeeding
(6264). There are two reports from GlaxoSmithKline
COMPENDIUM OF SELECTED PUBLICATIONS 1038
based on a Swedish national registry and a U.S. insur-
ance claims database that have raised concerns about a
1.52-fold increased risk of congenital cardiac malfor-
mations (atrial and ventricular septal defects) associated
with first-trimester paroxetine exposure (www.gskus.com/
news/paroxetine/paxil_letter_e3.pdf). The manufacturer
subsequently changed paroxetines pregnancy FDA cat-
egory from C to D (www.fda.gov/cder/drug/advisory/
paroxetine200512.htm).
More recently, the teratogenic effect of SSRI use
during the first trimester of pregnancy was examined in
two large casecontrol studies from multisite surveil-
lance programs (65, 66). In the National Birth Defects
Prevention Study, no significant associations were
found between SSRI use overall and congenital heart
defects (66). However, an association was found
between SSRI use (particularly paroxetine) during early
pregnancy and anencephaly, craniosynostosis, and
omphalocele. Importantly, these risks were found only
after more than 40 statistical tests were performed. Even
if findings were not the result of chance, the absolute
risks associated with SSRI use identified in this study
were small. For example, a twofold to threefold increase
in birth defects would occur for omphalocele
(1 in 5,000 births), craniosynostosis (1 in 1,800 births)
and anencephaly (1 in 1,000 births). In contrast, in the
Slone Epidemiology Center Birth Defects Study no
increased risk of craniosynostosis, omphalocele, or
heart defects associated with SSRI use overall during
early pregnancy was found (65). An association was
seen between paroxetine and right ventricular outflow
defects. Additionally, sertraline use was associated with
omphalocele and atrial and ventricular septum defects.
A limitation of this study is that the authors conducted
42 comparisons in their analyses for their main hypothe-
ses. Both of these casecontrol studies were limited by
the small number of exposed infants for each individual
malformation. The current data on SSRI exposure dur-
ing early pregnancy provide conflicting data on the risk
for both overall and specific malformations. Some
investigators have found a small increased risk of car-
diac defects, specifically with paroxetine exposure. The
absolute risk is small and generally not greater than two
per 1,000 births; hence, these agents are not considered
major teratogens.
Exposure to SSRIs late in pregnancy has been asso-
ciated with transient neonatal complications, including
jitteriness, mild respiratory distress, transient tachypnea
of the newborn, weak cry, poor tone, and neonatal inten-
sive care unit admission (6771). A more recent FDA
public health advisory highlighted concerns about the
risk of an unconfirmed association of newborn persis-
tent pulmonary hypertension with SSRI use (72)
(www. fda. gov/ cder/ drug/ advi sory/ SSRI_PPHN
200607. htm).
The potential risk of SSRI use in pregnancy must be
considered in the context of the risk of relapse of depres-
sion if treatment is discontinued. Factors associated with
relapse during pregnancy include a long history of
depressive illness (more than 5 years) and a history of
recurrent relapses (more than four episodes) (13).
Therefore, treatment with all SSRIs or selective norepi-
nephrine reuptake inhibitors or both during pregnancy
should be individualized. At this time, paroxetine use in
pregnant women and women planning pregnancy should
be avoided, if possible. Fetal echocardiography should be
considered for women exposed to paroxetine in early
pregnancy. Because abrupt discontinuation of paroxetine
has been associated with withdrawal symptoms, discon-
tinuation of this agent should occur according to the
products prescribing information.
Tricyclic antidepressants (TCAs) have been available
in the United States since 1963 and were widely used by
women during pregnancy and lactation before the intro-
duction of SSRIs. Results from initial studies, which sug-
gested that TCA exposure might be associated with limb
anomalies (7375), have not been confirmed with subse-
quent studies (76, 77). Neonatal neurobehavioral effects
from fetal exposure have not been reported (78).
Acute effects associated with TCA exposure include
case reports of fetal tachycardia (79), neonatal symptoms
such as tachypnea, tachycardia, cyanosis, irritability,
hypertonia, clonus, and spasm (7282), and transient
withdrawal symptoms (83). In more recent studies, a sig-
nificant link between prenatal exposure to TCAs and
perinatal problems has not been documented (64, 8486).
Atypical antidepressants are non-SSRI and non-
TCA antidepressants that work by distinct pharmacody-
namic mechanisms. The atypical antidepressants include
bupropion, duloxetine, mirtazapine, nefazodone, and
venlafaxine. The limited data of fetal exposure to these
antidepressants (70, 8589), do not suggest an increased
risk of fetal anomalies or adverse pregnancy events. In
the one published study of bupropion exposure in 136
patients, a significantly increased risk of spontaneous
abortion, but not an increased risk of major malforma-
tions, was identified (90). In contrast, the bupropion reg-
istry maintained at GlaxoSmithKline has not identified
any increased risk of spontaneous abortion, although
these data have not undergone peer review.
Antidepressant medication is the mainstay of treat-
ment for depression, although considerable data show
that structured psychotherapy, such as interpersonal psy-
chotherapy or cognitive behavioral therapy, are effective
treatments for mild to moderate depression and are bene-
ficial adjuncts to medication. In addition, electroconvul-
sive therapy is an effective treatment for major depression
and is safe to use during pregnancy (91, 92).
1039 PRACTICE BULLETINS
women in whom an unplanned conception occurs while
receiving lithium therapy, the decision to continue or dis-
continue the use of lithium should be in part based on dis-
ease severity, course of the patients illness, and the point
of gestation at the time of exposure.
What is the evidence regarding the safety
and efficacy of the antiepileptic drugs val-
proate and carbamazepine for the treatment
of bipolar disorders during pregnancy?
Several anticonvulsants, including valproate, carba-
mazepine, and lamotrigine, currently are used in the
treatment of bipolar disorder. Data regarding fetal effects
of these drugs are derived primarily from studies of
women with seizures. Whether the underlying pathology
of epilepsy contributes to the teratogenic effect on the
fetus is unclear. Epilepsy may not contribute to the ter-
atogenic effects of antiepileptic drugs based on the
results of a recent study that demonstrated similar rates
of anomalies between infants of women without epi-
lepsy and infants of women with epilepsy but who had
not taken antiepileptic drugs during pregnancy (105).
Prenatal exposure to valproate is associated with a
13.8% risk of neural tube defects, with a corresponding
doseresponse relationship (106113). Other congenital
malformations associated with valproate use include
craniofacial anomalies (114), limb abnormalities (115),
and cardiovascular anomalies (116118). A fetal val-
proate syndrome has been described with features of
fetal growth restriction, facial dysmorphology, and limb
and heart defects (119121). Varying degrees of cognitive
impairment, including mental development delay (122),
autism (123126), and Aspergers syndrome (124), have
been reported with fetal valproate syndrome (124, 127,
128). Acute neonatal risks include hepatotoxicity (129),
coagulopathies (130), neonatal hypoglycemia (131), and
withdrawal symptoms (132).
Carbamazepine exposure in pregnancy is associated
with a fetal carbamazepine syndrome manifest by facial
dysmorphism and fingernail hypoplasia (124, 133136).
It is unclear whether carbamazepine use increases the risk
of fetal neural tube defects or developmental delay (124,
127, 133139). Fetal exposure to lamotrigine has not
been documented to increase the risk of major fetal
anomalies (140145), although there may be an increased
risk of midline facial clefts (0.89% of 564 exposures) as
reported by one pregnancy registry (143), possibly related
to higher daily maternal doses (greater than 200 mg/day)
(145). The reproductive safety of lamotrigine appears to
compare favorably with alternative treatments, but lack-
ing are studies of the effectiveness of this antiepileptic
drug as a mood stabilizer in pregnancy.
What is the evidence regarding the safety
and efficacy of lithium for the treatment of
bipolar disorders during pregnancy?
Use of lithium in pregnancy may be associated with a
small increase in congenital cardiac malformations. The
initial retrospective data suggested that fetal exposure to
lithium was associated with a 400-fold increase in con-
genital heart disease, particularly Ebsteins anomaly (93,
94). A subsequent meta-analysis of the available data
calculated the risk ratio for cardiac malformations to be
1.27.7 and the risk ratio for overall congenital malfor-
mations to be 1.53 (95). In more recent small studies,
limited in their statistical power, the magnitude of early
estimates of teratogenic potential of lithium could not be
confirmed (9698).
Fetal exposure to lithium later in gestation has been
associated with fetal and neonatal cardiac arrhythmias
(99), hypoglycemia, nephrogenic diabetes insipidus
(100), polyhydramnios, reversible changes in thyroid
function (101), premature delivery, and floppy infant syn-
drome similar to that seen with benzodiazepine exposure
(102). Symptoms of neonatal lithium toxicity include
flaccidity, lethargy, and poor suck reflexes, which may
persist for more than 7 days (103). Neurobehavioral
sequelae were not documented in a 5-year follow-up of 60
school-aged children exposed to lithium during gestation
(104).
The physiologic alterations of pregnancy may affect
the absorption, distribution, metabolism and elimination
of lithium, and close monitoring of lithium levels during
pregnancy and postpartum is recommended. The decision
to discontinue lithium therapy in pregnancy because of
fetal risks should be balanced against the maternal risks
of exacerbation of illness. In a recent study, it was re-
ported that abrupt discontinuation of lithium was associ-
ated with a high rate of bipolar relapse among pregnant
women (39). The following treatment guidelines have
been suggested for women with bipolar illness who are
treated with lithium and plan to conceive: 1) in women
who experience mild and infrequent episodes of illness,
treatment with lithium should be gradually tapered before
conception; 2) in women who have more severe episodes
but are only at moderate risk for relapse in the short term,
treatment with lithium should be tapered before concep-
tion but reinstituted after organogenesis; 3) in women
who have especially severe and frequent episodes of ill-
ness, treatment with lithium should be continued
throughout gestation and the patient counseled regarding
reproductive risks (95). Fetal assessment with fetal
echocardiography should be considered in pregnant
women exposed to lithium in the first trimester. For
COMPENDIUM OF SELECTED PUBLICATIONS 1040
In managing bipolar disorders, the use of valproate
and carbamazepine are superior to that of lithium for
patients who experience mixed episodes or rapid cycling
but exhibit limited efficacy in the treatment of bipolar
depression. In contrast, lamotrigine is efficacious in the
prevention of the depressed phase of illness (146, 147).
Lamotrigine is a potential maintenance therapy option for
pregnant women with bipolar disorder because of its pro-
tective effects against bipolar depression, general tolera-
bility, and growing reproductive safety profile relative to
alternative mood stabilizers. Because both valproate and
carbamazepine are associated with adverse effects when
used during pregnancy, their use, if possible should be
avoided especially during the first trimester. The effec-
tiveness of folate supplementation in the prevention of
drug-associated neural tube defects has not been docu-
mented; however, folate supplementation of 4 mg/day
should be offered preconceptionally and for the first
trimester of pregnancy. Prenatal surveillance for congen-
ital anomalies by maternal serum alpha-fetoprotein level
testing, fetal echocardiography, or a detailed ultrasound
examination of the fetal anatomy or a combination of
these procedures should be considered. Whether the use
of antiepileptic drugs such as carbamazepine increase the
risk of neonatal hemorrhage and whether maternal vita-
min K supplementation is effective remains unclear
(148).
What is the evidence regarding the safety and
efficacy of treatment for anxiety disorders
during pregnancy?
Use of benzodiazepines does not appear to carry a sig-
nificant risk of somatic teratogenesis. In early studies of
in utero exposure to diazepam, a benzodiazepine, an
increased risk of oral clefts was reported (149151). In a
subsequent meta-analysis, it was demonstrated that pre-
natal benzodiazepine exposure increased the risk of oral
cleft, although the absolute risk increased by 0.01%,
from 6 in 10,000 to 7 in 10,000 (76). In a recent
casecontrol study of 22,865 infants with congenital
anomalies and 38,151 infants without congenital anom-
alies, an association of congenital anomalies, including
oral clefts with exposure to five different benzodi-
azepines, was not found (152). Similar findings were
documented in a casecontrol study of clonazepam
(153). If discontinuation of benzodiazepine use is con-
sidered during pregnancy, benzodiazepines should not be
abruptly withdrawn.
The data regarding neonatal toxicity and withdrawal
syndromes are well documented, and neonates should be
observed closely in the postpartum period. Floppy infant
syndrome, characterized by hypothermia, lethargy, poor
respiratory effort, and feeding difficulties, is associated
with maternal use of benzodiazepines shortly before
delivery (154162). Neonatal withdrawal syndromes,
characterized by restlessness, hypertonia, hyperreflexia,
tremulousness, apnea, diarrhea, and vomiting, have been
described in infants whose mothers were taking alprazo-
lam (163), chlordiazepoxide (164166), or diazepam
(167, 168). These symptoms have been reported to per-
sist for as long as 3 months postpartum (81).
The long-term neurobehavioral impact of prenatal
benzodiazepine exposure is unclear. The existence of a
benzodiazepine-exposure syndrome, including growth
restriction, dysmorphism, and both mental and psy-
chomotor retardation, in infants exposed prenatally to
benzodiazepines is disputed (169171). In one study, no
differences in the incidence of behavioral abnormalities
at age 8 months or IQ scores at age 4 years were found
among children exposed to chlordiazepoxide during ges-
tation (172).
What is the evidence regarding the safety
and efficacy of treatment for schizophrenia
during pregnancy?
The atypical antipsychotics (eg, clozapine, olanzapine,
quetiapine, risperidone, ziprasidone, and aripiprazole)
have replaced the typical agents as first-line medications
for psychotic disorders (Table 2). The atypical antipsy-
chotics generally are better tolerated and possibly are
more effective in managing the negative symptoms of
schizophrenia. They also are used increasingly for bipo-
lar disorder, obsessivecompulsive disorder, and treat-
ment-resistant depression. The reproductive safety data
regarding the use of atypical antipsychotics remains
extremely limited. In a prospective comparative study of
pregnancy outcomes between groups exposed and
unexposed to atypical antipsychotics, outcomes of 151
pregnancies with exposure to olanzapine, risperidone,
quetiapine, and clozapine demonstrated a higher rate of
low birth weight (10% in the exposed versus 2% in the
nonexposed group) and therapeutic abortions (173).
The typical antipsychotic drugs have a larger repro-
ductive safety profile and include haloperidol, thiori-
dazine, fluphenazine, perphenazine, chlorpromazine, and
trifluoperazine. No significant teratogenic effect has been
documented with chlorpromazine, haloperidol, and per-
phenazine (174176). In a study of 100 women treated
with haloperidol (mean dose of 1.2 mg/day) for hyper-
emesis gravidarum, no differences in gestational dura-
tion, fetal viability, or birth weight were noted (177). In a
large prospective study encompassing approximately
20,000 women treated primarily with phenothiazines for
emesis (178), investigators found no significant associa-
1041 PRACTICE BULLETINS
tion with neonatal survival rates or severe anomalies.
Similar results have been obtained in several retrospec-
tive studies of women treated with trifluoperazine for
repeated abortions and emesis (179, 180). In contrast,
other investigators reported a significant association of
major anomalies with prenatal exposure to phenothiazines
with an aliphatic side chain but not with piperazine or
piperidine class agents (181). Reanalysis of previously
reported data obtained also identified a significant risk of
malformations associated with phenothiazine exposure in
weeks 410 of gestation (182). In clinical neurobehav-
ioral outcome studies encompassing 203 children
exposed to typical antipsychotics during gestation, no
considerable differences have been detected in IQ scores
at 4 years of age (183, 184), although relatively low
antipsychotic doses were used by many women in these
studies.
Fetal and neonatal toxicity reported with exposure to
the typical antipsychotics includes neuroleptic malignant
syndrome (185), dyskinesia (186), extrapyramidal side
effects manifested by heightened muscle tone and
increased rooting and tendon reflexes persisting for sev-
eral months (187), neonatal jaundice (188), and postnatal
intestinal obstruction (189).
Fetuses and infants also may be exposed to drugs
used to manage the extrapyramidal side effects (eg,
diphenhydramine, benztropine, and amantadine). In a
casecontrol study, oral clefts were associated with a sig-
nificantly higher rate of prenatal exposure to diphenhy-
dramine than controls (149). In contrast, in several other
studies diphenhydramine use has not been found to be a
significant risk factor for fetal malformations (190, 191).
Clinical studies of the teratogenic potential of benz-
tropine and amantadine use are lacking.
In summary, typical antipsychotics have been widely
used for more than 40 years, and the available data sug-
gest the risks of use of these agents are minimal with
respect to teratogenic or toxic effects on the fetus. In par-
ticular, use of piperazine phenothiazines (eg, trifluoper-
azine and perphenazine) may have especially limited
teratogenic potential (181). Doses of typical antipsy-
chotics during the peripartum should be kept to a mini-
mum to limit the necessity of utilizing medications to
manage extrapyramidal side effects. There is likewise
little evidence to suggest that the currently available
atypical antipsychotics are associated with elevated
risks for neonatal toxicity or somatic teratogenesis. No
long-term neurobehavioral studies of exposed children
have yet been conducted. Therefore, the routine use of
atypical antipsychotics during pregnancy and lactation
cannot be recommended. In a woman who is taking an
atypical antipsychotic and inadvertently conceives, a
comprehensive riskbenefit assessment may indicate
that continuing therapy with the atypical antipsychotic
(to which the fetus has already been exposed) during
gestation is preferable to switching to therapy with a
typical antipsychotic (to which the fetus has not yet
been exposed).
What is the risk of using psychiatric drugs
while breastfeeding?
Breastfeeding has clear benefits for both mother and
infant and, in making the decision to recommend breast-
feeding, these benefits should be weighed against the
risks to the neonate of medication exposure while breast-
feeding (Table 2). Most medications are transferred
through breast milk, although most are found at very low
levels and likely are not clinically relevant for the
neonate. For women who breastfeed, measuring serum
levels in the neonate is not recommended. Most clinical
laboratory tests lack the sensitivity to detect and measure
the low levels present. However, breastfeeding should be
stopped immediately if a nursing infant develops abnor-
mal symptoms most likely associated with exposure to
the medication. Evaluation of the literature on drug lev-
els in breast milk can facilitate the decision to breastfeed
(192).
In the treatment of depression, published reports
regarding SSRI use and lactation now consist of 173
motherinfant nursing pairs with exposure to sertraline,
fluoxetine, paroxetine, fluvoxamine, and citalopram (193,
194215). In results from studies, it has been shown that,
quantitatively, medication exposure during lactation is
considerably lower than transplacental exposure to these
same SSRIs during gestation (193, 201, 208, 216).
Generally, very low levels of SSRIs are detected in breast
milk. Only a few isolated cases of adverse effects have
been reported, although infant follow-up data are lim-
ited. The package insert for citalopram does report a case
of an infant who experienced a transient apneic episode.
Long-term neurobehavioral studies of infants exposed to
SSRI antidepressants during lactation have not been
conducted.
The TCAs also have been widely used during lacta-
tion. The only adverse event reported to date is respira-
tory depression in a nursing infant exposed to doxepin,
which led to the conclusion that doxepin use should be
avoided but that most TCAs are safe for use during
breastfeeding (217). Data regarding the use of atypical
antidepressants during lactation are limited to the use of
venlafaxine (218) and bupropion (219, 220).
The existing data regarding lithium use and lactation
encompass 10 motherinfant nursing dyads (103,
221225). Adverse events, including lethargy, hypotonia,
hypothermia, cyanosis, and electrocardiogram changes,
COMPENDIUM OF SELECTED PUBLICATIONS 1042
were reported in two of the children in these studies (103,
223). The American Academy of Pediatrics consequently
discourages the use of lithium during lactation (226).
Because dehydration can increase the vulnerability to
lithium toxicity, the hydration status of nursing infants of
mothers taking lithium should be carefully monitored
(102). There are no available reports regarding the long-
term neurobehavioral sequelae of lithium exposure dur-
ing lactation.
Only one adverse event, an infant with thrombocy-
topenia and anemia (227), has been reported in studies
regarding valproate use and lactation, which includes 41
motherinfant nursing dyads (227235). Studies of the
neurobehavioral impact of valproate exposure during lac-
tation have not been conducted. The American Academy
of Pediatrics and the World Health Organization (WHO)
Working Group on Drugs and Human Lactation have
concluded that use of valproate is compatible with breast-
feeding (226, 236). Reported adverse effects of carba-
mazepine in breast milk include transient cholestatic
hepatitis (237, 238) and hyperbilirubinemia (239). The
WHO Working Group on Drugs and Human Lactation
has concluded that use of carbamazepine with breast-
feeding is probably safe (236).
In the management of anxiety disorders, benzodi-
azepine use exhibits lower milk/plasma ratios than other
classes of psychotropics (240, 241). Some investigators
concluded that benzodiazepine use at relatively low doses
does not present a contraindication to nursing (242).
However, infants with an impaired capacity to metabolize
benzodiazepines may exhibit sedation and poor feeding
even with low maternal doses (243).
Of typical antipsychotic medications, chlorpromazine
has been studied in seven breastfeeding infants, none of
whom exhibited developmental deficits at 16-month and
5-year follow-up evaluations (244). However, three
breastfeeding infants in another study, whose mothers
were prescribed both chlorpromazine and haloperidol,
exhibited evidence of developmental delay at 1218
months of age (245).
Resources
American Academy of Pediatrics
Web: www.aap.org
American Psychiatric Association
Web: www.psych.org
National Institutes of Health
Daily medication:
http://dailymed.nlm.nih.gov/dailymed/about.cfm
Lactation medication:
toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Summary of
Recommendations and
Conclusions
The following recommendations and conclusions
are based on good and consistent scientific evi-
dence (Level A):
Lithium exposure in pregnancy may be associated
with a small increase in congenital cardiac malfor-
mations, with a risk ratio of 1.27.7.
Valproate exposure in pregnancy is associated with
an increased risk of fetal anomalies, including neur-
al tube defects, fetal valproate syndrome, and long-
term adverse neurocognitive effects. It should be
avoided in pregnancy, if possible, especially during
the first trimester.
Carbamazepine exposure in pregnancy is associated
with fetal carbamazepine syndrome. It should be
avoided in pregnancy, if possible, especially during
the first trimester.
Maternal benzodiazepine use shortly before delivery
is associated with floppy infant syndrome.
The following recommendations and conclusions
are based on limited or inconsistent scientific evi-
dence (Level B):
Paroxetine use in pregnant women and women plan-
ning pregnancy should be avoided, if possible. Fetal
echocardiography should be considered for women
who are exposed to paroxetine in early pregnancy.
Prenatal benzodiazepine exposure increased the risk
of oral cleft, although the absolute risk increased by
0.01%.
Lamotrigine is a potential maintenance therapy
option for pregnant women with bipolar disorder
because of its protective effects against bipolar
depression, general tolerability, and a growing
reproductive safety profile relative to alternative
mood stabilizers.
Maternal psychiatric illness, if inadequately treated
or untreated, may result in poor compliance with
prenatal care, inadequate nutrition, exposure to
additional medication or herbal remedies, increased
alcohol and tobacco use, deficits in motherinfant
bonding, and disruptions within the family environ-
ment.
1043 PRACTICE BULLETINS
The following recommendations and conclusions
are based primarily on consensus and expert opin-
ion (Level C):
Whenever possible, multidisciplinary management
involving the patients obstetrician, mental health
clinician, primary health care provider, and pediatri-
cian is recommended to facilitate care.
Use of a single medication at a higher dose is
favored over the use of multiple medications for the
treatment of psychiatric illness during pregnancy.
The physiologic alterations of pregnancy may affect
the absorption, distribution, metabolism, and elimi-
nation of lithium, and close monitoring of lithium
levels during pregnancy and postpartum is recom-
mended.
For women who breastfeed, measuring serum levels
in the neonate is not recommended.
Treatment with all SSRIs or selective norepineph-
rine reuptake inhibitors or both during pregnancy
should be individualized.
Fetal assessment with fetal echocardiogram should
be considered in pregnant women exposed to lithi-
um in the first trimester.
References
1. Doering PL, Stewart RB. The extent and character of
drug consumption during pregnancy. JAMA 1978;239:
8436. (Level III)
2. Hostetter A, Ritchie JC, Stowe ZN. Amniotic fluid and
umbilical cord blood concentrations of antidepressants in
three women. Biol Psychiatry 2000;48(10):10324.
(Level III)
3. Newport DJ, Hostetter A, Arnold A, Stowe ZN. The treat-
ment of postpartum depression: minimizing infant expo-
sures. J Clin Psychiatry. 2002;63 (Suppl 7):3144. (Level
III)
4. Kessler RC, McGonagle KA, Zhao S, Nelson CB,
Hughes M, Eshleman S, et al. Lifetime and 12-month
prevalence of DSM-III-R psychiatric disorders in the
United States. Results from the National Comorbidity
Survey. Arch Gen Psychiatry 1994;51:819. (Level II-3)
5. National Institute of Mental Health (US). The numbers
count: mental disorders in America. NIH Publication No.
06-4584. Bethesda (MD): NIMH; 2006. Available at:
http://www. nimh. nih. gov/publicat/numbers. cfm.
Retrieved December 12, 2006. (Level II-3)
6. Weissman M, Olfson M. Depression in women: implica-
tions for health care research. Science 1995;269:
799801. (Level III)
7. American Psychiatric Association. Diagnostic and statis-
tical manual of mental disorders: DSM-IV-TR 4th ed.
text version. Washington, DC: APA; 2000. (Level III)
8. OHara MW, Neunaber DJ, Zekoski EM. Prospective
study of postpartum depression: prevalence, course and
predictive factors. J Abnorm Psychol 1984;93:15871.
(Level II-3)
9. Gotlib IH, Whiffen VE, Mount JH, Milne K, Cordy NI.
Prevalence rates and demographic characteristics associ-
ated with depression in pregnancy and the postpartum. J
Consult Clin Psychol 1989;57:26974. (Level III)
10. Affonso DD, Lovett S, Paul SM, Sheptak S. A standard-
ized interview that differentiates pregnancy and postpar-
tum symptoms from perinatal clinical depression. Birth
1990;17:12130. (Level II-3)
11. Kumar R, Robson K. A prospective study of emotional
disorders in childbearing women. Br J Psychiatry
1984;144:3547. (Level II-3)
12. Hostetter A, Stowe ZN, Strader JR Jr, McLaughlin E,
Llewellyn A. Dose of selective serotonin uptake
inhibitors across pregnancy: clinical implications.
Depress Anxiety 2000;11:517. (Level III-3)
13. Cohen LS, Altshuler LL, Harlow BL, Nonacs R, Newport
DJ, Viguera AC, et al. Relapse of major depression dur-
ing pregnancy in women who maintain or discontinue
antidepressant treatment [published erratum appears in
JAMA 2006;296:170]. JAMA 2006;295:499507. (Level
II-2)
14. Cox J. Postnatal mental disorder: towards ICD-11. World
Psychiatry 2004;3:967. (Level III)
15. Stowe ZN, Hostetter AL, Newport DJ. The onset of post-
partum depression: implications for clinical screening in
obstetrical and primary care. Am J Obstet Gynecol
2005;192:5226. (Level II-3)
16. Watson JP, Elliott SA, Rugg AJ, Brough DI. Psychiatric
disorder in pregnancy and the first postnatal year. Br J
Psychiatry 1984;144:45362. (Level II-3)
17. Evans J, Heron J, Francomb H, Oke S, Golding J. Cohort
study of depressed mood during pregnancy and after
childbirth. BMJ 2001;323:25760. (Level II-2)
18. Cox JL, Holden JM, Sagovsky R. Detection of postnatal
depression. Development of the 10-item Edinburgh
Postnatal Depression Scale. Br J Psychiatry 1987;150:
7826. (Level III)
19. Murray L, Carothers AD. The validation of the
Edinburgh Post-natal Depression Scale on a community
sample. Br J Psychiatry 1990;157:28890. (Level III)
20. Hoffman S, Hatch MC. Depressive symptomatology dur-
ing pregnancy: evidence for an association with decreased
fetal growth in pregnancies of lower social class women.
Health Psychol 2000;19:53543. (Level II-2)
21. Field T, Diego MA, Dieter J, Hernandez-Reif M,
Schanberg S, Kuhn C, et al. Depressed withdrawn and
intrusive mothers effects on their fetuses and neonates.
Infant Behav Dev 2001;24:2739. (Level II-2)
22. Zuckerman B, Bauchner H, Parker S, Cabral H. Maternal
depressive symptoms during pregnancy, and newborn
irritability. J Dev Behav Pediatr 1990;11:1904. (Level
II-3)
COMPENDIUM OF SELECTED PUBLICATIONS 1044
23. Zuckerman B, Amaro H, Bauchner H, Cabral H.
Depressive symptoms during pregnancy: relationship to
poor health behaviors. Am J Obstet Gynecol 1989;160:
110711. (Level II-2)
24. Zuckerman B, Frank DA, Hingson R, Amaro H,
Levenson SM, Kayne H, et al. Effects of maternal mari-
juana and cocaine use on fetal growth. N Engl J Med
1989;320:7628. (Level II-3)
25. Rosett HL, Weiner L, Lee A, Zuckerman B, Dooling E,
Oppenheimer E. Patterns of alcohol consumption and
fetal development. Obstet Gynecol 1983;61:53946.
(Level II-2)
26. Sexton M, Hebel JR. A clinical trial of change in mater-
nal smoking and its effect on birth weight. JAMA 1984;
251:9115. (Level I)
27. Weissman MM, Prusoff BA, Gammon GD, Merikangas
KR, Leckman JF, Kidd KK. Psychopathology in the chil-
dren (ages 618) of depressed and normal parents. J Am
Acad Child Psychiatry 1984;23:7884. (Level II-2)
28. Lyons-Ruth K, Wolfe R, Lyubchik A. Depression and the
parenting of young children: making the case for early
preventive mental health services. Harv Rev Psychiatry
2000;8:14853. (Level III)
29. Judd LL, Akiskal HS. The prevalence and disability of
bipolar spectrum disorders in the US population: re-
analysis of the ECA database taking into account sub-
threshold cases. J Affect Disord 2003;73:12331. (Level
II-3)
30. Kessler RC, Chiu WT, Demler O, Merikangas KR,
Walters EE. Prevalence, severity, and comorbidity of 12-
month DSM-IV disorders in the National Comorbidity
Survey Replication [published erratum appears in Arch
Gen Psychiatry 2005;62:709]. Arch Gen Psychiatry
2005;62:617627. (Level II-3)
31. Robins LN, Helzer JE, Weissman MM, Orvaschel H,
Gruenberg E, Burke JD Jr, et al. Lifetime prevalence of
specific psychiatric disorders in three sites. Arch Gen
Psychiatry 1984;41:94958. (Level II-3)
32. Angst J. The course of affective disorders. II. Typology
of bipolar manic-depressive illness. Arch Psychiatr
Nervenkr 1978;226:6573. (Level III)
33. Yildiz A, Sachs GS. Characteristics of rapid cycling
bipolar-I patients in a bipolar specialty clinic. J Affect
Disord 2004;79:24751. (Level II-3)
34. McElroy SL, Keck PE Jr, Pope HG Jr, Hudson JI, Faedda
GL, Swan AC. Clinical and research implications of the
diagnosis of dysphoric or mixed mania or hypomania.
Am J Psychiatry 1992;149:163344. (Level III)
35. Arnold LM, McElroy SL, Keck PE Jr. The role of gender
in mixed mania. Compr Psychiatry 2000;41:837. (Level
III)
36. Akdeniz F, Vahip S, Pirildar S, Vahip I, Doganer I, Bulut
I. Risk factors associated with childbearing-related
episodes in women with bipolar disorder. Psychopathol-
ogy 2003;36:2348. (Level II-3)
37. Freeman MP, Smith KW, Freeman SA, McElroy SL,
Kmetz GE, Wright R, et al. The impact of reproductive
events on the course of bipolar disorder in women. J Clin
Psychiatry 2002;63:2847. (Level III)
38. Grof P, Robbins W, Alda M, Berghoefer A, Vojtechovsky
M, Nilsson A, et al. Protective effect of pregnancy in
women with lithium-responsive bipolar disorder. J Affect
Disord 2000;61:319. (Level III)
39. Viguera AC, Nonacs R, Cohen LS, Tondo L, Murray A,
Baldessarini RJ. Risk of recurrence of bipolar disorder in
pregnant and nonpregnant women after discontinuing
lithium maintenance. Am J Psychiatry 2000;157:17984.
(Level II-2)
40. Kendall RE, Chalmers JC, Platz C. Epidemiology of
puerperal psychosis [published erratum appears in Br J
Psychiatry 1987;151:135]. Br J Psychiatry 1987;150:
662673. (Level II-2)
41. Marks MN, Wieck A, Checkley SA, Kumar R.
Contribution of psychological and social factors to psy-
chotic and non-psychotic relapse after childbirth in
women with previous histories of affective disorder. J
Affect Disord 1992;24:25363. (Level II-2)
42. Kessler RC, Berglund P, Demler O, Jin R, Merikangas
KR, Walters EE. Lifetime prevalence and age-of-onset
distributions of DSM-IV disorders in the National
Comorbidity Survey Replication [published erratum
appears in Arch Gen Psychiatry 2005;62:768]. Arch Gen
Psychiatry 2005;62:593602. (Level II-3)
43. Boyles SH, Ness RB, Grisso JA, Markovic N,
Bromberger J, CiFelli D. Life event stress and the asso-
ciation with spontaneous abortion in gravid women at an
urban emergency department. Health Psychol 2000;19:
5104. (Level II-2)
44. Berkowitz GS, Kasl SV. The role of psychosocial factors
in spontaneous preterm delivery. J Psychosom Res
1983;27:28390. (Level II-2)
45. Perkin MR, Bland JM, Peacock JL, Anderson HR. The
effect of anxiety and depression during pregnancy on
obstetric complications. Br J Obstet Gynaecol 1993;100:
62934. (Level II-2)
46. Pagel MD, Smilkstein G, Regen H, Montano D.
Psychosocial influences on new born outcomes: a con-
trolled prospective study. Soc Sci Med 1990;30:597604.
(Level II-2)
47. Taylor A, Fisk NM, Glover V. Mode of delivery and
subsequent stress response. Lancet 2000;355:120. (Level
II-2)
48. Northcott CJ, Stein MB. Panic disorder in pregnancy.
J Clin Psychiatry 1994;55:53942. (Level III)
49. Cohen LS, Sichel DA, Dimmock JA, Rosenbaum JF.
Postpartum course in women with preexisting panic dis-
order. J Clin Psychiatry 1994;55:28992. (Level III)
50. Loveland Cook CA, Flick LH, Homan SM, Campbell C,
McSweeney M, Gallagher ME. Posttraumatic stress dis-
order during pregnancy: prevalence, risk factors, and
treatment. Obstet Gynecol 2004;103:7107. (Level II-3)
51. Neziroglu F, Anemone R, Yaryura-Tobias JA. Onset of
obsessive-compulsive disorder in pregnancy. Am J
Psychiatry 1992;149:94750. (Level III)
1045 PRACTICE BULLETINS
52. Goldstein DJ, Corbin LA, Fung MC. Olanzapine-
exposed pregnancies and lactation: early experience.
J Clin Psychopharmacol. 2000;20:399403. (Level III)
53. Bennedsen BE, Mortensen PB, Olesen AV, Henriksen
TB. Preterm birth and intra-uterine growth retardation
among children of women with schizophrenia. Br J
Psychiatry 1999;175:23945. (Level II-2)
54. Nilsson E, Lichtenstein P, Cnattingius S, Murray RM,
Hultman CM. Women with schizophrenia: pregnancy
outcome and infant death among their offspring.
Schizophr Res 2002;58:2219. (Level II-2)
55. Jablensky AV, Morgan V, Zubrick SR, Bower C,
Yellachich LA. Pregnancy, delivery, and neonatal com-
plications in a population cohort of women with schizo-
phrenia and major affective disorders. Am J Psychiatry
2005;162(1):7991. (Level II-2)
56. Bennedsen BE, Mortensen PB, Olesen AV, Henriksen
TB, Frydenberg M. Obstetric complications in women
with schizophrenia. Schizophr Res 2001;47:16775.
(Level II-2)
57. Coons PM, Ascher-Svanum H, Bellis K. Self-amputation
of the female breast. Psychosomatics 1986;27:6678.
(Level III)
58. Yoldas Z, Iscan A, Yoldas T, Ermete L, Akyurek C. A
woman who did her own caesarean section. Lancet
1996;348:135. (Level III)
59. Slayton RI, Soloff PH. Psychotic denial of third-trimester
pregnancy. J Clin Psychiatry 1981;42:4713. (Level III)
60. Bucove AD. A case of prepartum psychosis and infanti-
cide. Psychiatr Q 1968;42:26370. (Level III)
61. Mendlowicz MV, da Silva Filho JF, Gekker M, de
Moraes TM, Rapaport MH, Jean-Louis F. Mothers mur-
dering their newborns in the hospital. Gen Hosp
Psychiatry 2000;22:535. (Level III)
62. Wen SW, Yang Q, Garner P, Fraser W, Olatunbosun O,
Nimrod C, et al. Selective serotonin reuptake inhibitors
and adverse pregnancy outcomes. Am J Obstet Gynecol
2006;194:9616. (Level II-2)
63. Malm H, Klaukka T, Neuvonen PJ. Risks associated with
selective serotonin reuptake inhibitors in pregnancy.
Obstet Gynecol 2005;106:128996. (Level II-2)
64. Einarson TR, Einarson A. Newer antidepressants in preg-
nancy and rates of major malformations: a meta-analysis
of prospective comparative studies. Pharmacoepidemiol
Drug Saf 2005;14:8237. (Meta-analysis)
65. Louik C, Lin AE, Werler MM, Hernandez-Diaz S,
Mitchell AA. First-trimester use of selective serotonin-
reuptake inhibitors and the risk of birth defects. NEJM
2007;356:267583. (Level II-2)
66. Alwan S, Reefhuis J, Rasmussen SA, Olney RS,
Friedman JM. Use of selective serotonin-reuptake
inhibitors in pregnancy and the risk of birth defects.
National Birth Defects Prevention Study. NEJM
2007;356:268492. (Level II-2)
67. Moses-Kolko EL, Bogen D, Perel J, Bregar A, Uhl K,
Levin B, et al. Neonatal signs after late in utero exposure
to serotonin reuptake inhibitors: literature review and
implications for clinical applications. JAMA 2005;
293:237283. (Level III)
68. Chambers CD, Johnson KA, Dick LM, Felix RJ, Jones
KL. Birth outcomes in pregnant women taking fluoxe-
tine. N Engl J Med 1996;335:101015. (Level II-2)
69. Costei AM, Kozer E, Ho T, Ito S, Koren G. Perinatal out-
come following third trimester exposure to paroxetine.
Arch Pediatr Adolesc Med 2002;156:112932. (Level II-2)
70. Kallen B. Neonate characteristics after maternal use of
antidepressants in late pregnancy. Arch Pediatr Adolesc
Med 2004;158:312316. (Level II-2)
71. Zeskind PS, Stephens LE. Maternal selective serotonin
reuptake inhibitor use during pregnancy and newborn
neurobehavior. Pediatrics 2004;113:36875. (Level II-2)
72. Chambers CD, Hernandez-Diaz S, Van Marter LJ, Werler
MM, Louik C, Jones KL, et al. Selective serotonin-reup-
take inhibitors and risk of persistent pulmonary hyper-
tension of the newborn. N Engl J Med 2006;354:57987.
(Level II-2)
73. Barson AJ. Malformed infant. Br Med J 1972;2:45.
(Level III)
74. Elia J, Katz IR, Simpson GM. Teratogenicity of psycho-
therapeutic medications. Psychopharmacol Bull 1987;23:
53186. (Level III)
75. McBride WG. Limb deformities associated with imin-
odibenzyl hydrochloride. Med J Austr 1972;1:492.
(Level III)
76. Altshuler LL, Cohen L, Szuba MP, Burt VK, Gitlin M,
Mintz J. Pharmacologic management of psychiatric ill-
ness during pregnancy: dilemmas and guidelines. Am J
Psychiatry 1996;153:592606. (Level III)
77. McElhatton PR, Garbis HM, Elefant E, Vial T, Bellemin
B, Mastroiacovo P, et al. The outcome of pregnancy in
689 women exposed to therapeutic doses of antidepres-
sants. A collaborative study of the European Network of
Teratology Information Services (ENTIS). Reprod
Toxicol 1996;10:28594. (Level III)
78. Nulman I, Rovet J, Stewart DE, Wolpin J, Gardner HA,
Theis JA et al. Neurodevelopment of children exposed in
utero to antidepressant drugs. N Engl J Med 1997;336:
25862. (Level II-2)
79. Prentice A, Brown R. Fetal tachyarrhythmia and maternal
antidepressant treatment. BMJ 1989;298:190. (Level III)
80. Eggermont E. Withdrawal symptoms in neonates associ-
ated with maternal imipramine therapy. Lancet 1973;2:
680. (Level III)
81. Miller LJ. Clinical strategies for the use of psychotropic
drugs during pregnancy. Psychiatr Med 1991;9:27598.
(Level III)
82. Webster PA. Withdrawal symptoms in neonates associ-
ated with maternal antidepressant therapy. Lancet 1973;
2:3189. (Level III)
83. Misri S, Sivertz K. Tricyclic drugs in pregnancy and lac-
tation: a preliminary report. Int J Psychiatry Med 1991;
21:15771. (Level II-3)
COMPENDIUM OF SELECTED PUBLICATIONS 1046
84. Simon GE, Cunningham ML, Davis RL. Outcomes of
prenatal antidepressant exposure. Am J Psychiatry 2002;
159:205561. (Level II-2)
85. Yaris F, Kadioglu M, Kesim M, Ulku C, Yaris E,
Kalyoncu NI, et al. Newer antidepressants in pregnancy:
prospective outcome of a case series. Reprod Toxicol
2004;19:2358. (Level II-3)
86. Yaris F, Ulku C, Kesim M, Kadioglu M, Unsal M, Dikici
MF, et al. Psychotropic drugs in pregnancy: a case-con-
trol study. Prog Neuropsychopharmacol Biol Psychiatry
2005;29:3338. (Level II-2)
87. Kesim M, Yaris F, Kadioglu M, Yaris E, Kalyoncu NI,
Ulku C. Mirtazapine use in two pregnant women: is it
safe? Teratology 2002;66:204. (Level III)
88. Rohde A, Dembinski J, Dorn C. Mirtazapine (Remergil)
for treatment resistant hyperemesis gravidarum: rescue
of a twin pregnancy. Arch Gynecol Obstet 2003;268:
21921. (Level III)
89. Einarson A, Bonari L, Voyer-Lavigne S, Addis A, Matsui
D, Johnson Y, et al. A multicentre prospective controlled
study to determine the safety of trazodone and nefa-
zodone use during pregnancy. Can J Psychiatry 2003;48:
10610. (Level II-2)
90. Chun-Fai-Chan B, Koren G, Fayez I, Kalra S, Voyer-
Lavigne S, Boshier A, et al. Pregnancy outcome of
women exposed to bupropion during pregnancy: a
prospective comparative study. Am J Obstet Gynecol
2005;192:9326. (Level II-2)
91. Miller LJ. Use of electroconvulsive therapy during preg-
nancy. Hosp Community Psychiatry 1994;45:44450.
(Level III)
92. Rabheru K. The use of electroconvulsive therapy in spe-
cial patient populations. Can J Psychiatry 2001;46:
7109. (Level III)
93. Nora JJ, Nora AH, Toews WH. Lithium, Ebsteins anom-
aly, and other congenital heart defects [letter]. Lancet
1974;2:5945. (Level III)
94. Weinstein MR, Goldfield M. Cardiovascular malforma-
tions with lithium use during pregnancy. Am J Psychiatry
1975;132:52931. (Level III)
95. Cohen LS, Friedman JM, Jefferson JW, Johnson EM,
Weiner ML. A reevaluation of risk of in utero exposure to
lithium [published erratum appears in JAMA 1994;271:
1485]. JAMA 1994;271:14650. (Level III)
96. Kallen B, Tandberg A. Lithium and pregnancy. A cohort
of manic-depressive women. Acta Psychiatr Scand
1983;68:1349. (Level II-2)
97. Jacobson SJ, Jones K, Johnson K, Ceolin L, Kaur P, Sahn
D, et al. Prospective multicentre study of pregnancy out-
come after lithium exposure during first trimester. Lancet
1992;339:5303. (Level II-2)
98. Friedman JM, Polifka JE. Teratogenic effects of drugs: a
resource for clinicians (TERIS). 2nd ed. Baltimore
(MD): Johns Hopkins University Press; 2000. (Level III)
99. Wilson N, Forfar JC, Godman MJ. Atrial flutter in the
newborn resulting from maternal lithium ingestion. Arch
Dis Child 1983;58:5389. (Level III)
100. Mizrahi EM, Hobbs JF, Goldsmith DI. Nephrogenic dia-
betes insipidus in transplacental lithium intoxication.
J Pediatr 1979;94:4935. (Level III)
101. Karlsson K, Lindstedt G, Lundberg PA, Selstam U.
Transplacental lithium poisoning: reversible inhibition of
fetal thyroid [letter]. Lancet 1975;1:1295. (Level III)
102. Llewellyn A, Stowe ZN, Strader JR Jr. The use of lithium
and management of women with bipolar disorder during
pregnancy and lactation. J Clin Psychiatry 1998;59(suppl
6):5764;discussion 65. (Level III)
103. Woody JN, London WL, Wilbanks GD Jr. Lithium toxic-
ity in a newborn. Pediatrics 1971;47:946. (Level III)
104. Schou M. What happened later to the lithium babies? A
follow-up study of children born without malformations.
Acta Psychiatr Scand 1976;54:1937. (Level II-2)
105. Holmes LB, Harvey EA, Coull BA, Huntington KB,
Khoshbin S, Hayes AM. The teratogenicity of anticon-
vulsant drugs. N Engl J Med 2001;344:11328. (Level
11-2)
106. Jager-Roman E, Deichl A, Jakob S, Hartmann AM, Koch
S, Rating D, et al. Fetal growth, major malformations,
and minor anomalies in infants born to women receiving
valproic acid. J Pediatr 1986;108:9971004. (Level II-2)
107. Lindhout D, Schmidt D. In-utero exposure to valproate
and neural tube defects. Lancet 1986;1:13923. (Level
III-3)
108. Spina bifida incidence at birthUnited States,
19831990. Centers for Disease Control (CDC). MMWR
Morb Mortal Wkly Rep 1992;41:497500. (Level II-3)
109. Samren E, van Duijn CM, Koch S, Hiilesmaa VK, Klepel
H, Bardy AH, et al. Maternal use of antiepileptic drugs
and the risk of major congenital malformations: a joint
European prospective study of human teratogenesis asso-
ciated with maternal epilepsy. Epilepsia 1997;38:98190.
(Level II-2)
110. Omtzigt JG, Los FJ, Meiger JW, Lindhout D. The 10, 11-
epoxide-10, 11-diol pathway of carbamazepine in early
pregnancy in maternal serum, urine, and amniotic fluid:
effect of dose, comedication, and relation to outcome of
pregnancy. Ther Drug Monit 1993;15:110. (Level II-3)
111. Samren E, van Duijn CM, Christiaens GC, Hofman A,
Lindhout D. Antiepileptic drug regimens and major con-
genital abnormalities in the offspring. Ann Neurol 1999;
46:73946. (Level II-2)
112. Canger R, Battino D, Canevini MP, Fumarola C,
Guidolin L, Vignoli A, et al. Malformations in offspring
of women with epilepsy: a prospective study. Epilepsia
1999;40:12316. (Level II-2)
113. Kaneko S, Battino D, Andermann E, Wada K, Kan R,
Takeda A, et al. Congenital malformations due to anti-
epileptic drugs. Epilepsy Res 1999;33:14558. (Level II-2)
114. Paulson GW, Paulson RB. Teratogenic effects of anticon-
vulsants. Arch Neurol 1981;38:1403. (Level III)
115. Rodriguez-Pinilla E, Arroyo I, Fondevilla J, Garcia MJ,
Martinez-Frias ML. Prenatal exposure to valproic acid
during pregnancy and limb deficiencies: a case-control
study. Am J Med Genet 2000;90:37681. (Level II-2)
1047 PRACTICE BULLETINS
116. Dalens B, Raynaud EJ, Gaulme J. Teratogenicity of val-
proic acid. J Pediatr 1980:97:3323. (Level III)
117. Koch S, Jager-Roman E, Rating D, Helge H. Possible ter-
atogenic effect of valproate during pregnancy. J Pediatr
1983;103:10078. (Level III)
118. Sodhi P, Poddar B, Parmar V. Fatal cardiac malformation
in fetal valproate syndrome. Indian J Pediatr 2001;68:
98990. (Level III)
119. Winter RM, Donnai D, Burn J, Tucker SM. Fetal val-
proate syndrome: is there a recognisable phenotype?
J Med Genet 1987;24:6925. (Level III)
120. Ardinger HH, Atkin JF, Blackston RD, Elsas LJ, Clarren
SK, Livingstone S, et al. Verification of the fetal val-
proate syndrome phenotype. Am J Med Genet 1988;29:
17185. (Level III)
121. Martinez-Frias ML. Clinical manifestation of prenatal
exposure to valproic acid using case reports and epi-
demiologic information. Am J Med Genet 1990;37:
27782. (Level III)
122. Kozma C. Valproic acid embryopathy: report of two sib-
lings with further expansion of the phenotypic abnormal-
ities and a review of the literature. Am J Med Genet
2001;98:16875. (Level III)
123. Williams PG, Hersh JH. A male with fetal valproate syn-
drome and autism. Dev Med Child Neurol 1997;39:
6324. (Level III)
124. Moore SJ, Turnpenny P, Quinn A, Glover S, Lloyd DJ,
Montgomery T, et al. A clinical study of 57 children with
fetal anticonvulsant syndromes. J Med Genet 2000;37:
48997. (Level III)
125. Bescoby-Chambers N, Forster P, Bates G. Foetal val-
proate syndrome and autism: additional evidence of an
association [letter]. Dev Med Child Neurol 2001;43:847.
(Level III)
126. Williams G, King J, Cunningham M, Stephan M, Kerr B,
Hersh JH. Fetal valproate syndrome and autism: addi-
tional evidence of an association. Dev Med Child Neurol
2001;43:2026. (Level III)
127. Gaily E, Kantola-Sorsa E, Granstrom ML. Specific cog-
nitive dysfunction in children with epileptic mothers.
Dev Med Child Neurol 1990;32:40314. (Level II-2)
128. Adab N, Jacoby A, Smith D, Chadwick D. Additional
educational needs in children born to mothers with
epilepsy. J Neurol Neurosurg Psychiatry 2001;70:1521.
(Level II-2)
129. Kennedy D, Koren G. Valproic acid use in psychiatry:
issues in treating women of reproductive age. J Psychiatry
Neurosci 1998;23:2238. (Level III)
130. Mountain KR, Hirsch J, Gallus AS. Neonatal coagulation
defect due to anticonvulsant drug treatment in pregnancy.
Lancet 1970;1:2658. (Level II-3)
131. Thisted E, Ebbesen F. Malformations, withdrawal mani-
festations, and hypoglycaemia after exposure to valproate
in utero. Arch Dis Child 1993;69:28891. (Level III)
132. Ebbesen F, Joergensen A, Hoseth E, Kaad PH, Moeller
M, Holsteen V, et al. Neonatal hypoglycaemia and with-
drawal symptoms after exposure in utero to valproate.
Arch Dis Child Fetal Neonatal Ed 2000;83:F1249.
(Level II-2)
133. Jones KL, Lacro RV, Johnson KA, Adams J. Pattern of
malformations in the children of women treated with car-
bamazepine during pregnancy. N Engl J Med 1989;
320:16616. (Level II-3)
134. Scolnik D, Nulman I, Rovet J, Gladstone D, Czuchta D,
Gardner HA, et al. Neurodevelopment of children
exposed in utero to phenytoin and carbamazepine
monotherapy [published erratum appears in JAMA 1994;
271:1745]. JAMA 1994;271:76770. (Level II-2)
135. Wide K, Winbladh B, Tomson T, Sars-Zimmer K,
Berggren E. Psychomotor development and minor anom-
alies in children exposed to antiepileptic drugs in utero: a
prospective population-based study [published erratum
appears in Dev Med Child Neurol 2000;42:356]. Dev
Med Child Neurol 2000;42:8792. (Level II-2)
136. Ornoy A, Cohen E. Outcome of children born to epilep-
tic mothers treated with carbamazepine during preg-
nancy. Arch Dis Child 1996;75:51720. (Level II-2)
137. Gaily E, Granstrom ML, Liukkonen E. Oxcarbazepine in
the treatment of epilepsy in children and adolescents with
intellectual disability. J Intellect Disabil Res. 1998;42
(suppl 1):415. (Level III)
138. Van der Pol MC, Hadders-Algra M, Huisjes MJ, Touwen
BC. Antiepileptic medication in pregnancy: late effects
on the childrens central nervous system development.
Am J Obstet Gynecol 1991;164:1218. (Level II-2)
139. Matalon S, Schechtman S, Goldzweig G, Ornoy A. The
teratogenic effect of carbamazepine: a meta-analysis of
1255 exposures. Reprod Toxicol 2002;16:917. (Meta-
analysis)
140. Vajda FJ, OBrien TJ, Hitchcock A, Graham J, Lander C.
The Australian registry of anti-epileptic drugs in preg-
nancy: experience after 30 months. J Clin Neurosci 2003;
10:5439. (Level II-2)
141. Sabers A, Dam M, A-Rogvi-Hansen B, Boas J, Sidenius
P, Laue Friis M, et al. Epilepsy and pregnancy: lamotrig-
ine as main drug used. Acta Neurol Scand 2004;109:
913. (Level III)
142. Cunnington M, Tennis P. Lamotrigine and the risk of
malformations in pregnancy. International Lamotrigine
Pregnancy Registry Scientific Advisory Committee.
Neurology 2005;64:95560. (Level III)
143. Holmes LB, Wyszynski DF. North American antiepilep-
tic drug pregnancy registry. Epilepsia 2004;45:1465. (Level
III)
144. Meador KJ, Baker GA, Finnell RH, Kalayjian LA,
Liporace JD, Loring DW, et al. In utero antiepileptic drug
exposure: fetal death and malformations. NEAD Study
Group. Neurology 2006;67:40712. (Level II-2)
145. Morrow J, Russell A, Guthrie E, Parsons L, Robertson I,
Waddell R, et al. Malformation risks of antiepileptic
drugs in pregnancy: a prospective study from the UK
Epilepsy and Pregnancy Register. J Neurol Neurosurg
Psychiatry 2006;77:1938. (Level II-2)
COMPENDIUM OF SELECTED PUBLICATIONS 1048
146. Baldessarini RJ, Faedda GL, Hennen J. Risk of mania
with antidepressants. Arch Pediatr Adolesc Med 2005;
159:298. (Level III)
147. Newport DJ, Viguera AC, Beach AJ, Ritchie JC, Cohen
LS, Stowe ZN. Lithium placental passage and obstetrical
outcome: implications for clinical management during
late pregnancy. Am J Psychiatry 2005;162:216270.
(Level III)
148. Choulika S, Grabowski E, Holmes LB. Is antenatal vita-
min K prophylaxis needed for pregnant women taking
anticonvulsants? Am J Obstet Gynecol 2004;190:8823.
(Level II-2)
149. Saxen I. Cleft palate and maternal diphenhydramine
intake [letter]. Lancet 1974;1:4078. (Level III)
150. Aarkog D. Association between maternal intake of
diazepam and oral clefts [letter]. The Lancet 1975;2:921.
(Level II-2)
151. Saxen I. Associations between oral clefts and drugs taken
during pregnancy. Int J Epidemiol 1975;4:3744. (Level
II-2)
152. Eros E, Czeizel AE, Rockenbauer M, Sorensen HT,
Olsen J. A population-based case-control teratologic study
of nitrazepam, medazepam, tofisopam, alprazolum and
clonazepam treatment during pregnancy. Euro J Obstet,
Gynecol Reprod Biol 2002;101:14754. (Level II-2)
153. Lin AE, Peller AJ, Westgate MN, Houde K, Franz A,
Holmes LB. Clonazepam use in pregnancy and the risk
of malformations. Birth Defects Res A Clin Mol Teratol
2004;70:5346. (Level III-3)
154. Haram K. Floppy infant syndrome and maternal
diazepam. Lancet 1977;2:6123. (Level III)
155. Speight AN. Floppy-infant syndrome and maternal
diazepam and/or nitrazepam. Lancet 1977;2:878. (Level
III)
156. Woods DL, Malan AF. Side-effects of maternal diazepam
on the newborn infant. S Afr Med J 1978;54:636. (Level
III)
157. Kriel RL, Cloyd J. Clonazepam and pregnancy. Ann
Neurol 1982;11:544. (Level III)
158. McAuley DM, ONeill MP, Moore J, Dundee JW.
Lorazepam premedication for labour. Br J Obstet
Gynaecol 1982;89:14954. (Level I)
159. Erkkola R, Kero P, Kanto J, Aaltonen L. Severe abuse of
psychotropic drugs during pregnancy with good perinatal
outcome. Ann Clin Res 1983;15:8891. (Level III)
160. Fisher JB, Edgren BE, Mammel MC, Coleman JM.
Neonatal apnea associated with maternal clonazepam
therapy: a case report. Obstet Gynecol. 1985;66(suppl):
34s35s. (Level III)
161. Sanchis A, Rosique D, Catala J. Adverse effects of mater-
nal lorazepam on neonates. DICP 1991;25:11378.
(Level III)
162. Whitelaw AG, Cummings AJ, McFadyen IR. Effect of
maternal lorazepam on the neonate. Br Med J (Clin Res
Ed) 1981;282:11068. (Level II-2)
163. Barry WS, St Clair S. Exposure to benzodiazepines in
utero. Lancet 1987;1:14367. (Level III)
164. Bitnun S. Possible effect of chlordiazepoxide on the
fetus. Can Med Assoc J 1969;100:351. (Level III)
165. Stirrat GM, Edington PT, Berry DJ. Transplacental pas-
sage of chlordiazepoxide [letter]. Br Med J 1974;2:729.
(Level III)
166. Athinarayanan P, Pierog SH, Nigam SK, Glass L.
Chloriazepoxide withdrawal in the neonate. Am J Obstet
Gynecol 1976;124:2123. (Level III)
167. Mazzi E. Possible neonatal diazepam withdrawal: a case
report. Am J Obstet Gynecol 1977;129:5867. (Level III)
168. Backes CR, Cordero L. Withdrawal symptoms in the
neonate from presumptive intrauterine exposure to
diazepam: report of case. J Am Osteopath Assoc 1980;
79:5845. (Level III)
169. Laegreid L, Olegard R, Wahlstrom J, Conradi N.
Abnormalities in children exposed to benzodiazepines in
utero. Lancet 1987;1:108109. (Level III)
170. Gerhardsson M, Alfredsson L. In utero exposure to ben-
zodiazepines [letter]. Lancet 1987:628. (Level III)
171. Winter RM. In-utero exposure to benzodiazepines [let-
ter]. Lancet 1987;1:627. (Level III)
172. Hartz SC, Heinonen OP, Shapiro S, Siskind V, Slone D.
Antenatal exposure to meprobamate and chlordiazepox-
ide in relation to malformations, mental development,
and childhood mortality. N Engl J Med 1975;292:7268.
(Level II-2)
173. McKenna K, Koren G, Tetelbaum M, Wilton L, Shakir S,
Diav-Citrin O, et al. Pregnancy outcome of women using
atypical antipsychotic drugs: a prospective comparative
study. J Clin Psychiatry 2005;66:4449;quiz 546. (Level
III-3)
174. Goldberg HL, DiMascio A. Psychotropic drugs in preg-
nancy. In: Lipton MA, DiMascio A, Killam KF, editors.
Psychopharmacology: a generation of progress. New York
(NY): Raven Press; 1978. p.104755. (Level III)
175. Hill RM, Stern L. Drugs in pregnancy: effects on the
fetus and newborn. Drugs 1979;17:18297. (Level III)
176. Nurnberg HG, Prudic J. Guidelines for treatment of psy-
chosis during pregnancy. Hosp Community Psychiatry
1984;35:6771. (Level III)
177. Van Waes A, Van de Velde E. Safety evaluation of
haloperidol in the treatment of hyperemesis gravidarum.
J Clin Pharmacol 1969;9:2247. (Level II-2)
178. Miklovich L, van den Berg BJ. An evaluation of the ter-
atogenicity of certain antinauseant drugs. Am J Obstet
Gynecol 1976;125:2448. (Level II-2)
179. Moriarty AJ, Nance NR. Trifluoperazine and pregnancy
[letter]. Can Med Assoc J 1963;88:3756. (Level III)
180. Rawlings WJ. Use of medroxyprogesterone in the treat-
ment of recurrent abortion. Med J Aust 1963;50:1834.
(Level III)
181. Rumeau-Rouquette C, Goujard J, Huel G. Possible ter-
atogenic effect of phenothiazines in human beings.
Teratology 1977;15:5764. (Level II-2)
1049 PRACTICE BULLETINS
182. Edlund MJ, Craig TJ. Antipsychotic drug use and birth
defects: an epidemiologic reassessment. Compr Psychiatry
1984;25:327. (Level II-2)
183. Kris EB. Children of mothers maintained on pharma-
cotherapy during pregnancy and postpartum. Curr Ther
Res Clin Exp 1965;7:7859. (Level III)
184. Slone D, Siskind V, Heinonen OP, Monson RR, Kaufman
DW, Shapiro S. Antenatal exposure to the phenothiazines
in relation to congenital malformations, perinatal mortal-
ity rate, birth weight, and intelligence quotient score. Am
J Obstet Gynecol. 1977;128:4868. (Level II-2)
185. James ME. Neuroleptic malignant syndrome in preg-
nancy. Psychosomatics 1988;29:11922. (Level III)
186. Collins KO, Comer JB. Maternal haloperidol therapy
associated with dyskinesia in a newborn. Am J Health
Syst Pharm 2003;60:22535. (Level III)
187. Hill RM, Desmond MM, Kay JL. Extrapyramidal dys-
function in an infant of a schizophrenic mother. J Pediatr
1966;69:58995. (Level III)
188. Scokel PW 3rd, Jones WN. Infant jaundice after phe-
nothiazine drugs for labor: an enigma. Obstet Gynecol
1962;20:1247. (Level II-2)
189. Falterman CG, Richardson CJ. Small left colon syn-
drome associated with maternal ingestion of psycho-
tropic drugs. J Pediatr 1980;97:30810. (Level III)
190. Heinonen OP, Shapiro S, Slone D. Birth defects and
drugs in pregnancy. Littleton (MA): Publishing Sciences
Group; 1977. (Level III)
191. Nelson MM, Forfar JO. Associations between drugs
administered during pregnancy and congenital abnormal-
ities of the fetus. Br Med J 1971;1:5237. (Level III)
192. Hale TW. Medications in Mothers Milk. Amaraillo (TX):
Pharmasoft Publishing, 2004. (Level III)
193. Stowe ZN, Owens MJ, Landry JC, Kilts CD, Ely T,
Llewellyn A, et al. Sertraline and desmethylsertraline in
human breast milk and nursing infants. Am J Psychiatry
1997;154:125560. (Level II-3)
194. Altshuler LL, Burt VK, McMullen M, Hendrick V.
Breastfeeding and sertraline: a 24-hour analysis. J Clin
Psychiatry 1995;56:2435. (Level III)
195. Epperson CN, Anderson GM, McDougle CJ. Sertraline
and breast-feeding. N Engl J Med 1997;336:118990.
(Level III)
196. Kristensen JH, Ilett KF, Dusci LJ, Hackett LP, Yapp P,
Wojnar-Horton RE, et al. Distribution and excretion of
sertraline and N-desmethylsertraline in human milk. Br J
Clin Pharmacol 1998;45:4537. (Level III)
197. Mammen O, Perel JM, Wheeler S. Antidepressants and
breast-feeding. Am J Psychiatry 1997;154:11745. (Level
III)
198. Wisner KL, Perel JM, Blumer J. Serum sertraline and N-
desmethylsertraline levels in breast-feeding mother-
infant pairs. Am J Psychiatry 1998;155:6902. (Level III)
199. Birnbaum CS, Cohen LS, Bailey JW, Grush LR,
Robertson LM, Stowe ZN. Serum concentrations of anti-
depressants and benzodiazepines in nursing infants: a
case series. Pediatrics 1999;104(1):e11. (Level III)
200. Dodd S, Buist A, Norman TR. Antidepressants and
breast-feeding: a review of the literature. Paediatr Drugs
2000;2:18392. (Level III)
201. Stowe ZN, Cohen LS, Hostetter A, Ritchie JC, Owens
MJ, Nemeroff CB. Paroxetine in human breast milk and
nursing infants. Am J Psychiatry 2000;157:1859. (Level
II-3)
202. Epperson N, Czarkowski KA, Ward-OBrien D, Weiss E,
Gueorguieva R, Jatlow P, et al. Maternal sertraline treat-
ment and serotonin transport in breast-feeding mother-
infant pairs. Am J Psychiatry 2001;158:16317. (Level
II-3)
203. Hendrick V, Fukuchi A, Altshuler L, Widawski M,
Wertheimer A, Brunhuber MV. Use of sertraline, paroxe-
tine and fluvoxamine by nursing women. Br J Psychiatr
2001;179:1636. (Level II-3)
204. Burch KJ, Wells BG. Fluoxetine/norfluoxetine concen-
trations in human milk. Pediatrics 1992;89:6767. (Level
III)
205. Lester BM, Cucca J, Andreozzi L, Flanagan P, Oh W.
Possible association between fluoxetine hydrochloride
and colic in an infant. J Am Acad Child Adolesc Psych-
iatry 1993;32:12535. (Level III)
206. Taddio A, Ito S, Koren G. Excretion of fluoxetine and its
metabolite, norfluoxetine, in human breast milk. J Clin
Pharmacol 1996;36:427. (Level II-3)
207. Yoshida K, Kumar RC, Smith B, Craggs M. Psychotropic
drugs in breast milk: no evidence for adverse effects on
prepulse modulation of startle reflex or on cognitive level
in infants. Dev Psychobiol 1998;32:24956. (Level II-2)
208. Cohen LS, Heller V, Bailey JW, Grush L, Ablon JS,
Bouffard SM. Birth outcomes following prenatal expo-
sure to fluoxetine. Biol Psychiatry 2000;48:9961000.
(Level II-2)
209. Spigset O, Carleborg L, Norstrom A, Sandlund M.
Paroxetine level in breast milk. J Clin Psychiatry 1996;
57:39. (Level III)
210. Ohman R, Hagg S, Carleborg L, Spigset O. Excretion of
paroxetine into breast milk. J Clin Psychiatry 1999;60:
51923. (Level III)
211. Wright S, Dawling S, Ashford JJ. Excretion of fluvox-
amine in breast milk. British Journal of Clinical Phar-
macology 1991;31(2):209. (Level III)
212. Piontek CM, Wisner KL, Perel JM, Peindl KS. Serum
fluvoxamine levels in breastfed infants. J Clin Psychiatry
2001;62:1113. (Level III)
213. Jensen PN, Olesen OV, Bertelsen A, Linnet K.
Citalopram and desmethylcitalopram concentrations in
breast milk and in serum of mother and infant. Ther Drug
Monit 1997;19:2369. (Level III)
214. Spigset O, Carieborg L, Ohman R, Norstrom A.
Excretion of citalopram in breast milk. Br J Clin Phar-
macol 1997;44:2958. (Level III)
COMPENDIUM OF SELECTED PUBLICATIONS 1050
215. Schmidt K, Olesen OV, Jensen PN. Citalopram and
breast-feeding: serum concentration and side effects in
the infant. Biol Psychiatry 2000;47:1645. (Level III)
216. Stowe ZN, Hostetter AL, Owens MJ, Ritchie JC,
Sternberg K, Cohen LS, et al. The pharmacokinetics of
sertraline excretion into human breast milk: determinants
of infant serum concentrations. J Clin Psychiatry 2003;
64:7380. (Level III)
217. Matheson I, Pande H, Alertsen AR. Respiratory depres-
sion caused by N-desmethyldoxepin in breast milk. Lancet
1985;2:1124. (Level III)
218. Ilett KF, Hackett LP, Dusci LJ, Roberts MJ, Kristensen
JH, Paech M, et al. Distribution and excretion of venla-
faxine and O-desmethylvenlafaxine in human milk. Br J
Clin Pharmacol 1998;45:45962. (Level III)
219. Briggs GG, Samson JH, Ambrose PJ, Schroeder DH.
Excretion of bupropion in breast milk. Ann Pharmacother
1993;27:4313. (Level III)
220. Baab SW, Peindl KS, Piontek CM, Wisner KL. Serum
bupropion levels in 2 breastfeeding mother-infant pairs.
J Clin Psychiatry 2002;63:9101. (Level III)
221. Weinstein MR, Goldfield M. Lithium carbonate treat-
ment during pregnancy; report of a case. Dis Nerv Syst
1969;30:82832. (Level III)
222. Fries H. Lithium in pregnancy. Lancet 1970;1:1233. (Level
III)
223. Tunnessen WW Jr, Hertz CG. Toxic effects of lithium in
newborn infants: a commentary. J Pediatr 1972;81:
8047. (Level III)
224. Schou M, Amdisen A. Lithium and pregnancy. 3.: lithium
ingestion by children breast-fed by women on lithium
treatment. BMJ 1973;2:138. (Level III)
225. Sykes PA, Quarrie J, Alexander FW. Lithium carbonate
and breast-feeding [letter]. BMJ 1976;2:1299. (Level III)
226. Transfer of drugs and other chemicals into human milk.
American Academy of Pediatrics Committee on Drugs.
Pediatrics 2001;108:77689. (Level III)
227. Stahl MM, Neiderud J, Vinge E. Thrombocytopenic pur-
pura and anemia in a breast-fed infant whose mother was
treated with valproic acid. J Pediatr 1997;130:10013.
(Level III)
228. Alexander FW. Sodium valproate and pregnancy. Arch
Dis Child 1979;54:2401. (Level III)
229. Dickinson RG, Harland RC, Lynn RK, Smith WB,
Gerber N. Transmission of valproic acid (Depakene)
across the placenta: half-life of the drug in mother and
baby. J Pediatr 1979;94:8325. (Level III)
230. Nau H, Rating D, Koch S, Hauser I, Helge H. Valproic
acid and its metabolites: placental transfer, neonatal
pharmacokinetics, transfer via mothers milk and clinical
status in neonates of epileptic mothers. J Pharmacol Exp
Ther 1981;219:76877. (Level II-3)
231. Bardy AH, Teramo K, Hiilesmaa VK. Apparent plasma
clearances of phenytoin, phenobarbitone, primidone, and
carbamazepine during pregnancy: results of the
Prospective Helsinki Study. In: Janz D, Dam M, Richens
A, Bossi L, Helge H, Schmidt D, editors. Epilepsy, preg-
nancy, and the child. New York (NY): Raven Press; 1982.
p.1415. (Level III-3)
232. von Unruh GE, Froescher W, Hoffmann F, Niesen M.
Valproic acid in breast milk: how much is really there?
Ther Drug Monit 1984;6:2726. (Level III)
233. Tsuru N, Maeda T, Tsuruoka M. Three cases of delivery
under sodium valproateplacental transfer, milk transfer
and probable teratogenicity of sodium valproate. Jpn J
Psychiatry Neurol 1988;42:8996. (Level III)
234. Wisner KL, Perel JM. Serum levels of valproate and car-
bamazepine in breastfeeding mother-infant pairs. J Clin
Psychopharmacol 1998;18:1679. (Level III)
235. Piontek CM, Baab S, Peindl KS, Wisner KL. Serum val-
proate levels in 6 breastfeeding mother-infant pairs.
J Clin Psychiatry 2000;61:1702. (Level III)
236. Bennett PN, editor. Drugs and human lactation. 2nd ed.
New York (NY): Elsevier; 1996. (Level III)
237. Frey B, Braegger CP, Ghelfi D. Neonatal cholestatic
hepatitis from carbamazepine exposure during pregnancy
and breast feeding. Ann Pharmacother 2002;36:6447.
(Level III)
238. Frey B, Schubiger G, Musy JP. Transient cholestatic
hepatitis in a neonate associated with carbamazepine
exposure during pregnancy and breast-feeding. Eur J
Pediatr 1990;150:1368. (Level III)
239. Merlob P, Mor N, Litwin A. Transient hepatic dysfunc-
tion in an infant of an epileptic mother treated with car-
bamazepine during pregnancy and breastfeeding. Ann
Pharmacother 1992;26:15635. (Level III)
240. Wretlind M. Excretion of oxazepam in breast milk. Eur J
Clin Pharmacol 1987;33:20910. (Level III)
241. Summerfield RJ, Nielsen MS. Excretion of lorazepam
into breast milk. Br J Anaesth 1985;57:10423. (Level
III)
242. Buist A, Norman TR, Dennerstein L. Breastfeeding and
the use of psychotropic medication: a review. J Affect
Disord 1990;19:197206. (Level III)
243. Wesson DR, Camber S, Harkey M, Smith DE. Diazepam
and desmethyldiazepam in breast milk. J Psychoactive
Drugs 1985;17(1):5556. (Level III)
244. Kris EB, Carmichael DM. Chlorpromazine maintenance
therapy during pregnancy and confinement. Psychiatr Q
1957;31:6905. (Level III)
245. Yoshida K, Smith B, Craggs M, Kumar R. Neuroleptic
drugs in breast-milk: a study of pharmacokinetics and of
possible adverse effects in breast-fed infants. Psychol
Med 1998;28:8191. (Level II-2)
1051 PRACTICE BULLETINS
The MEDLINE database, the Cochrane Library, and
ACOGs own internal resources and documents were used
to conduct a literature search to locate relevant articles pub-
lished between January 1985 and June 2007. The search
was restricted to articles published in the English language.
Priority was given to articles reporting results of original
research, although review articles and commentaries also
were consulted. Abstracts of research presented at sympo-
sia and scientific conferences were not considered adequate
for inclusion in this document. Guidelines published by
organizations or institutions such as the National Institutes
of Health and the American College of Obstetricians and
Gynecologists were reviewed, and additional studies were
located by reviewing bibliographies of identified articles.
When reliable research was not available, expert opinions
from obstetriciangynecologists were used.
Studies were reviewed and evaluated for quality according
to the method outlined by the U.S. Preventive Services Task
Force:
I Evidence obtained from at least one properly
designed randomized controlled trial.
II-1 Evidence obtained from well-designed controlled
trials without randomization.
II-2 Evidence obtained from well-designed cohort or
casecontrol analytic studies, preferably from more
than one center or research group.
II-3 Evidence obtained from multiple time series with or
without the intervention. Dramatic results in uncon-
trolled experiments also could be regarded as this
type of evidence.
III Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees.
Based on the highest level of evidence found in the data,
recommendations are provided and graded according to the
following categories:
Level ARecommendations are based on good and consis-
tent scientific evidence.
Level BRecommendations are based on limited or incon-
sistent scientific evidence.
Level CRecommendations are based primarily on con-
sensus and expert opinion.
Copyright April 2008 by the American College of Obstetri-
cians and Gynecologists. All rights reserved. No part of this
publication may be reproduced, stored in a retrieval system,
posted on the Internet, or transmitted, in any form or by any
means, electronic, mechanical, photocopying, recording, or
otherwise, without prior written permission from the publisher.
Requests for authorization to make photocopies should be
directed to Copyright Clearance Center, 222 Rosewood Drive,
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
The American College of Obstetricians and Gynecologists
409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920
Use of psychiatric medications during pregnancy and lactation. ACOG
Practice Bulletin No. 92. American College of Obstetricians and Gyne-
cologists. Obstet Gynecol 2008;111:100120.
COMPENDIUM OF SELECTED PUBLICATIONS 1052
CLINICAL MANAGEMENT GUIDELINES FOR OBSTETRICIANGYNECOLOGISTS
NUMBER 95, JULY 2008
This Practice Bulletin was devel-
oped by the ACOG Committee on
Practice BulletinsObstetrics with
the assistance of Maureen Malee,
PhD, MD. The information is
designed to aid practitioners in
making decisions about appropriate
obstetric and gynecologic care.
These guidelines should not be con-
strued as dictating an exclusive
course of treatment or procedure.
Variations in practice may be war-
ranted based on the needs of the
individual patient, resources, and
limitations unique to the institution
or type of practice.
Anemia in Pregnancy
Anemia, the most common hematologic abnormality, is a reduction in the con-
centration of erythrocytes or hemoglobin in blood. The two most common causes
of anemia in pregnancy and the puerperium are iron deficiency and acute blood
loss. Iron requirements increase during pregnancy, and a failure to maintain
sufficient levels of iron may result in adverse maternalfetal consequences. The
purpose of this document is to provide a brief overview of the causes of anemia
in pregnancy, review iron requirements, and provide recommendations for
screening and clinical management of anemia during pregnancy.
Background
Classification
The definition of anemia recommended by the Centers for Disease Control and
Prevention is a hemoglobin (Hgb) or hematocrit (Hct) value less than the fifth
percentile of the distribution of Hgb or Hct in a healthy reference population
based on the stage of pregnancy. Classification derived from an iron-supple-
mented population lists the following levels as anemic: Hgb (g/dL) and Hct
(percentage) levels below 11 g/dL and 33%, respectively, in the first trimester;
10.5 g/dL and 32%, respectively, in the second trimester; and 11 g/dL and 33%,
respectively, in the third trimester (1).
Anemias may be categorized by the underlying causative mechanism, red
blood cell morphology, or by whether they are inherited or acquired (see the
boxes). A mechanistic approach categorizes anemias caused by decreased red
blood cell production, increased red blood cell destruction, and blood loss.
Decreased production may result from a lack of nutrients, such as iron, vitamin
B
12
, or folate. This lack may be a result of dietary deficiency, malabsorption, or
bleeding. Bone marrow disorders or suppression, hormone deficiencies, and
chronic disease or infection also may lead to decreased production. Hemolytic
anemias are associated with increased destruction.
ACOG
PRACTICE
BULLETIN
THE AMERICAN COLLEGE OF
OBSTETRICIANS AND
GYNECOLOGISTS
WOMENS HEALTH CARE PHYSICIANS
1053 PRACTICE BULLETINS
Anemias also may be classified by cell size. In con-
temporary practice, this typically is done by an automated
cell counter. Macrocytic anemias are associated with a
mean corpuscular volume (MCV) greater than 100 fL.
Reticulocytosis also may cause an increased MCV. A
common cause of macrocytic anemia is folate deficiency.
Microcytic anemias are associated with an MCV less than
80 fL. The most common cause of microcytic anemia is
iron deficiency. Another common cause of microcytic
anemia in certain ethnic groups is hemoglobinopathy (2).
Anemia in Pregnancy
Pregnancy is associated with physiologic changes that
may complicate the diagnosis of hematologic disorders.
There is an increased iron requirement during pregnancy
because blood volume expands by approximately 50%
Anemia Classification
Acquired
Deficiency anemia (eg, iron, vitamin B
12
, folate)
Hemorrhagic anemia
Anemia of chronic disease
Acquired hemolytic anemia
Aplastic anemia
Inherited
Thalassemias
Sickle cell anemia
Hemoglobinopathies (other than sickle cell anemia)
Inherited hemolytic anemias
Anemias Classified by Mean Corpuscular Volume
Microcytic (MCV less than 80 fL)
Iron deficiency anemia
Thalassemias
Anemia of chronic disease
Sideroblastic anemia
Anemia associated with copper deficiency
Anemia associated with lead poisoning
Normocytic (MCV 80100 fL)
Hemorrhagic anemia
Early iron deficiency anemia
Anemia of chronic disease
Anemia associated with bone marrow suppression
Anemia associated with chronic renal insufficiency
Anemia associated with endocrine dysfunction
Autoimmune hemolytic anemia
Anemia associated with hypothyroidism or
hypopituitarism
Hereditary spherocytosis
Hemolytic anemia associated with paroxysmal
nocturnal hemoglobinuria
Macrocytic (MCV greater than 100 fL)
Folic acid deficiency anemia
Anemia associated with vitamin B
12
deficiency
Drug-induced hemolytic anemia (eg, zidovudine)
Anemia associated with reticulocytosis
Anemia associated with liver disease
Anemia associated with ethanol abuse
Anemia associated with acute myelodysplastic
syndrome
Abbreviation: MCV, mean corpuscular volume
Anemias Characterized by Mechanism
Decreased red blood cell production
Iron deficiency anemia
Anemia associated with vitamin B
12
deficiency
Folic acid deficiency anemia
Anemia associated with bone marrow disorders
Anemia associated with bone marrow suppression
Anemia associated with low levels of erythropoietin
Anemia associated with hypothyroidism
Increased red blood cell destruction
Inherited hemolytic anemias
Sickle cell anemia
Thalassemia major
Hereditary spherocytosis
Acquired hemolytic anemias
Autoimmune hemolytic anemia
Hemolytic anemia associated with thrombotic
thrombocytopenic purpura
Hemolytic anemia associated with hemolytic
uremic syndrome
Hemolytic anemia associated with malaria
Hemorrhagic anemia
COMPENDIUM OF SELECTED PUBLICATIONS 1054
(1,000 mL), and total red blood cell mass expands by
approximately 25% (300 mL) during a singleton gesta-
tion (3). The greater expansion in plasma typically is
reflected by decreases in Hgb and Hct levels.
The total amount of iron in the body is determined
by intake, loss, and storage (4). There are approximately
2.3 g of total body iron in women. Additional iron stores
during pregnancy (approximately 1 g) support this increased
red blood cell mass, the fetus and placenta, and the antici-
pated blood loss accompanying a vaginal delivery. When
there is adequate iron to meet needs, more than 70% is
classified as functional iron, and the remainder as storage
iron. Of the functional iron, more than 80% is found in
the red blood cell mass as hemoglobin, with the remain-
der in myoglobin and in respiratory enzymes (5).
Iron Deficiency Anemia
Iron deficiency can be defined as abnormal values on
biochemical test results, increases in hemoglobin con-
centrations of more than 1 g/dL after iron treatment, or
absent bone marrow iron stores as determined by a bone
marrow iron smear (1). The spectrum of iron deficiency
ranges from iron depletion, when stored iron is low, to
iron deficient erythropoiesis, when both stored and trans-
port iron are low, to iron deficiency anemia, when stored,
transport, and functional iron are low (6).
Measurements of serum Hgb concentration or Hct
are the primary screening tests for identifying anemia
but are nonspecific for identifying iron deficiency.
Normal iron indices are listed in Table 1. Laboratory test
results characteristic of iron deficiency anemia are a
microcytic, hypochromic anemia with evidence of
depleted iron stores, low plasma iron levels, high total
iron-binding capacity, low serum ferritin levels, and
increased levels of free erythrocyte protoporphyrin.
Measurement of ferritin levels has the highest sensi-
tivity and specificity for diagnosing iron deficiency in
anemic patients (7). Levels of less than 1015 micro-
grams/L confirm iron-deficiency anemia. The Centers for
Disease Control and Prevention recommends screening
for iron deficiency anemia in pregnant women and uni-
versal iron supplementation to meet the iron requirements
of pregnancy except in the presence of certain genetic dis-
orders, such as hemochromatosis (1, 8). The rationale is
that treatment maintains maternal iron stores and may be
beneficial for neonatal iron stores. The typical diet con-
fers 15 mg of elemental iron per day. The recommended
daily dietary allowance of ferrous iron during pregnancy
is 27 mg, which is present in most prenatal vitamins (8).
Available iron supplements are listed in Table 2. Perinatal
iron supplementation is important because the typical
American diet and endogenous stores are insufficient
sources for the increased iron requirements during preg-
nancy. Sustained-release or enteric-coated preparations
dissolve poorly and may be less effective.
Prevalence, Etiologies, and Risk Factors
A national study of anemia in pregnancy in the United
States found a prevalence of 21.55 per 1,000 women
when anemia was defined as a hemoglobin concentration
less than 10 g/dL (9). The prevalence of anemia in preg-
nancy in non-Hispanic black women (35.38 per 1,000
women) was two times higher than that of non-Hispanic
white women (18.02 per 1,000 women) (9). Teenaged
mothers had the highest prevalence of anemia in preg-
nancy of all races (9). Prevalence data specific to iron
deficiency anemia in pregnancy are limited (10). A
recent report estimates that in a low income, mostly
minority population, rates of iron deficiency anemia are
1.8% in the first trimester, 8.2% in the second trimester,
and 27.4% in the third trimester (11).
In reproductive-aged women of all races, risk fac-
tors for iron deficiency anemia include a diet poor in
iron-rich foods, such as clams, oysters, liver, beef,
shrimp, turkey, enriched breakfast cereals, beans, and
lentils; a diet poor in iron absorption enhancers, such as
orange juice, grapefruit, strawberries, broccoli, and pep-
pers; a diet rich in foods that diminish iron absorption,
such as dairy products, soy products, spinach, coffee,
and tea; pica (eating nonfood substances such as clay or
laundry starch); gastrointestinal disease affecting
Table 1. Normal Iron Indices in Pregnancy
Test Normal Value
Plasma iron level 40175 micrograms/dL
Plasma total iron-binding capacity 216400 micrograms/dL
Transferrin saturation 1660%
Serum ferritin level More than 10 micrograms/dL
Free erythrocyte protoporphyrin level Less than 3 micrograms/g
Table 2. Iron Supplements
Preparation Dose
Ferrous fumarate 106 mg elemental iron per 325 mg tablet
Ferrous sulfate 65 mg elemental iron per 325 mg tablet
Ferrous gluconate 34 mg elemental iron per 300 mg tablet
Iron dextran 50 mg elemental iron per milliliter,
intramuscularly or intravenously
Ferric gluconate 12.5 mg iron per milliliter,
intravenously only
Iron sucrose 20 mg iron per milliliter, intravenously only
1055 PRACTICE BULLETINS
absorption; heavy menses; short interpregnancy interval;
and blood loss at delivery exceeding that of an uncom-
plicated vaginal delivery.
Iron deficiency anemia during pregnancy has been
associated with an increased risk of low birth weight,
preterm delivery, and perinatal mortality (11, 12). In
addition, there may be an association between maternal
iron deficiency anemia and postpartum depression, with
poor results in mental and psychomotor performance
testing in offspring (1315).
Macrocytic Anemia
Macrocytic anemia may be megaloblastic or nonmega-
loblastic. Causes of megaloblastic anemia include folate
and vitamin B
12
deficiency and pernicious anemia. Causes
of nonmegaloblastic anemia include alcoholism, liver dis-
ease, myelodysplasia, aplastic anemia, hypothyroidism,
and an increased reticulocyte count. Macrocytic anemia is
characterized by an MCV greater than 100 fL. Levels
greater than 115 fL are almost exclusively seen in patients
with folic acid or vitamin B
12
deficiencies. The diagnosis
may be confirmed by measurement of serum folic acid or
vitamin B
12
levels. Measurement of red cell folate also has
been proposed (16). In the United States, macrocytic ane-
mia beginning during pregnancy is overwhelmingly
caused by folic acid deficiency. It is associated with diets
lacking fresh leafy vegetables, legumes, or animal pro-
teins. During pregnancy, folic acid requirements increase
from 50 micrograms to 400 micrograms per day.
Treatment of pregnancy-induced folic acid deficiency
should include a nutritious diet and folic acid and iron sup-
plementation. Treatment with 1 mg of folic acid, adminis-
tered orally, each day typically produces an appropriate
response. Macrocytic anemia in pregnancy caused by vit-
amin B
12
(cyanocobalamin) deficiency may be encoun-
tered in women who have had a partial or total gastric
resection or in women with Crohn disease. Women who
have had a total gastrectomy require 1,000 micrograms of
vitamin B
12
, intramuscularly, at monthly intervals.
Clinical Considerations and
Recommendations
Who should be screened for anemia during
pregnancy?
All pregnant women should be screened for anemia dur-
ing pregnancy. Those with iron deficiency anemia should
be treated with supplemental iron, in addition to prenatal
vitamins. Patients with anemia other than iron deficiency
anemia should be further evaluated.
When should evaluation of an asymptomatic
patient with mild anemia be considered?
Asymptomatic women who meet the criteria for anemia
(Hct levels less than 33% in the first and third trimesters
and less than 32% in the second trimester) should be
evaluated. Living at a high altitude and tobacco abuse
cause a generalized upward shift in Hgb and Hct levels,
and adjustments for these potential confounders may be
appropriate (1719). Hemoglobin and Hct levels are
lower in African-American women compared with white
women, even after correction for income (20, 21). Thus,
applying the same criteria to all women could inappro-
priately classify almost 30% of African-American
women as iron deficient. For African-American adults,
the Institute of Medicine recommends lowering the cut-
off levels for Hgb and Hct by 0.8 g/dL and 2%, respec-
tively (21, 22).
How should asymptomatic pregnant women
with mild to moderate anemia be evaluated?
The initial evaluation of pregnant women with mild to
moderate anemia may include a medical history, physical
examination, and measurements of the complete blood
count, red blood cell indices, serum iron levels, and fer-
ritin levels. Examination of a peripheral smear is helpful
for the diagnosis of hemolytic or parasitic disease. In cer-
tain ethnic groups, an Hgb electrophoresis is indicated (2).
Using biochemical tests, iron deficiency anemia is defined
by results of abnormal values for levels of serum ferritin,
transferrin saturation, and levels of free erythrocyte proto-
porphyrin, along with low Hgb or Hct levels (see Table 1
and Table 3). In practice, the diagnosis of mild to moder-
ate iron deficiency anemia is often presumptive. In
patients without evidence of causes of anemia other than
iron deficiency, it may be reasonable to empirically initi-
ate iron therapy without first obtaining iron test results.
When pregnant women with moderate iron deficiency
anemia are given adequate iron therapy, reticulocytosis
may be observed 710 days after iron therapy, followed by
an increase in Hgb and Hct levels in subsequent weeks.
Failure to respond to iron therapy should prompt further
investigation and may suggest an incorrect diagnosis,
coexisting disease, malabsorption (sometimes caused by
the use of enteric-coated tablets or concomitant use of
antacids), noncompliance, or blood loss.
Are there benefits of iron supplementation
for patients who are not anemic?
Iron supplementation decreases the prevalence of mater-
nal anemia at delivery (23). However, it is unclear
COMPENDIUM OF SELECTED PUBLICATIONS 1056
whether iron supplementation in well-nourished preg-
nant women who are not anemic affects perinatal out-
comes. There is little evidence that iron supplementation
results in morbidity beyond gastrointestinal symptoms,
except in patients with hemochromatosis or certain other
genetic disorders.
When should transfusion be considered in
the antepartum or preoperative patient?
Transfusions of red cells seldom are indicated unless
hypovolemia from blood loss coexists or an operative
delivery must be performed on a patient with anemia.
The need for transfusion in women with antepartum
complications can be predicted in only 24% of those
who ultimately require blood products (24). The most
common diagnoses associated with transfusion include
trauma caused by instrumented delivery, uterine atony,
placenta previa, retained products of conception, placen-
tal abruption, and coagulopathy (eg, the syndrome of
hemolysis, elevated liver enzymes, and low platelet
count [HELLP]). The presence of these diagnoses in a
patient with anemia should prompt consideration of
transfusion, particularly in the presence of unstable vital
signs (24).
Severe anemia with maternal Hgb levels less than 6
g/dL has been associated with abnormal fetal oxygena-
tion, resulting in nonreassuring fetal heart rate patterns,
reduced amniotic fluid volume, fetal cerebral vasodilata-
tion, and fetal death (25, 26). Thus, maternal transfusion
should be considered for fetal indications in cases of
severe anemia.
When should parenteral iron be used in
pregnant patients? Is there a role for
erythropoietin?
Parenteral iron is used in the rare patient who cannot
tolerate or will not take modest doses of oral iron.
Patients with a malabsorption syndrome and severe iron
deficiency anemia may benefit from parenteral therapy.
Anaphylactic reactions have been reported in 1% of
patients receiving parenteral iron dextran. In comparison
with patients who take iron dextran, patients who take
ferrous sucrose have fewer allergic reactions (8.7 versus
3.3 allergic events per 1,000,000 doses) and a signifi-
cantly lower fatality rate (31 versus 0, P <.001) (27).
In a recent randomized trial of the use of oral versus
intravenous iron sucrose for postpartum anemia,
women treated with intravenous iron had significantly
higher Hgb levels on days 5 and 14 than women
treated with an oral supplement. However, by day 40,
there was no significant difference between the Hgb
levels of the two groups (28). Thus, in most clinical
circumstances, oral preparations are appropriate and
sufficient.
Few studies have examined the role of erythropoi-
etin in pregnant patients with anemia. In a randomized,
controlled trial that examined the time to reach the tar-
geted Hgb value and changes in efficacy measurements,
including reticulocyte count and Hct levels, the use of
both parenteral iron and parenteral iron plus erythropoi-
etin improved measured parameters. However, the use
of adjuvant erythropoietin alone was associated with
a significantly shorter time to the targeted hemoglobin
level and improved indices (reticulocyte count, Hct lev-
els) in less than 2 weeks after treatment was initiated.
No differences in maternalfetal safety parameters were
reported (29). In contrast, a randomized trial of women
with postpartum anemia showed no additional benefit
of the use of erythropoietin and iron versus iron alone
(30).
Is there a role for autologous transfusion?
Case reports suggest a role for autologous transfusion in
patients with diagnoses placing them at high risk of
symptomatic blood loss, such as placenta previa.
Suggested criteria for consideration of autologous dona-
tion include an Hct level greater than 32% at 32 weeks
of gestation (31). However, autologous transfusions
rarely are performed, and the inability to predict the
eventual need for transfusion has led to the conclusion
that they are not cost-effective (32).
Table 3. Biochemical Tests for Diagnosis of Anemia
Results Indicating Results Indicating Results Indicating
Test Iron Deficiency Anemia Thalassemia Anemia of Chronic Disease
Iron level Decreased level Normal Decreased level
Total iron-binding capacity Increased capacity Normal Decreased capacity
Ferritin level Decreased level Normal Increased level
Iron/total iron-binding capacity Less than 18% Normal More than 18%
1057 PRACTICE BULLETINS
Summary of
Recommendations and
Conclusions
The following conclusion is based on good and
consistent scientific evidence (Level A):
Iron supplementation decreases the prevalence of
maternal anemia at delivery.
The following recommendation and conclusions
are based on limited or inconsistent scientific data
(Level B):
Iron deficiency anemia during pregnancy has been
associated with an increased risk of low birth
weight, preterm delivery, and perinatal mortality.
Severe anemia with maternal Hgb levels less than
6 g/dL has been associated with abnormal fetal oxy-
genation resulting in nonreassuring fetal heart rate
patterns, reduced amniotic fluid volume, fetal cere-
bral vasodilatation, and fetal death. Thus, maternal
transfusion should be considered for fetal indications.
The following recommendations are based pri-
marily on consensus and expert opinion (Level
C):
All pregnant women should be screened for anemia,
and those with iron deficiency anemia should be
treated with supplemental iron, in addition to prena-
tal vitamins.
Patients with anemia other than iron deficiency ane-
mia should be further evaluated.
Failure to respond to iron therapy should prompt fur-
ther investigation and may suggest an incorrect diag-
nosis, coexisting disease, malabsorption (sometimes
caused by the use of enteric-coated tablets or concomi-
tant use of antacids), noncompliance, or blood loss.
Proposed Performance
Measure
Percentage of pregnant patients with iron deficiency ane-
mia treated with supplemental iron in addition to prena-
tal vitamins
References
1. Recommendations to prevent and control iron deficiency
in the United States. Centers for Disease Control and
Prevention. MMWR Recomm Rep 1998;47(RR-3):129.
(Level III)
2. Angastiniotis M, Modell B. Global epidemiology of
hemoglobin disorders. Ann N Y Acad Sci 1998;850:
25169. (Level II-3)
3. Pitkin RM. Nutritional influences during pregnancy. Med
Clin North Am 1977;61:315. (Level III)
4. Bothwell TH. Overview and mechanisms of iron regula-
tion. Nutr Rev 1995;53:23745. (Level III)
5. Bothwell TH, Charlton RW. Iron deficiency in women.
Washington, DC: The Nutrition Foundation; 1981. (Level
III)
6. Baynes RD. Iron deficiency. In: Brock JH, Halliday JW,
Pippard MJ, Powell LW, editors. Iron metabolism in
health and disease. Philadelphia (PA): W.B. Saunders;
1994. p.189225. (Level III)
7. Ontario Association of Medical Laboratories. Guidelines
for the use of serum tests for iron deficiency. Guidelines
for Clinical Laboratory Practice CLP 002. North York
(ON): OAML; 1995. Available at: http://www.oaml.com/
PDF/CLP002.pdf. Retrieved April 4, 2008. (Level III)
8. Institute of Medicine (US). Dietary reference intakes for
vitamin A, vitamin K, arsenic, boron, chromium, copper,
iodine, iron, manganese, molybdenum, nickel, silicon,
vanadium, and zinc. Washington, DC: National Academy
Press 2002. (Level III)
9. Adebisi OY, Strayhorn G. Anemia in pregnancy and race
in the United States: blacks at risk. Fam Med 2005;37:
65562. (Level III)
10. Agency for Healthcare Research and Quality. Screening
for iron deficiency anemia in childhood and pregnancy:
update of the 1996 U.S. Preventive Task Force review.
AHRQ Publication No. 06-0590-EF-1. Rockville (MD):
AHRQ; 2006. (Level III)
11. Scholl TO. Iron status during pregnancy: setting the stage
for mother and infant. Am J Clin Nutr 2005;81:
1218S22S. (Level III)
12. Rasmussen K. Is there a causal relationship between iron
deficiency or iron-deficiency anemia and weight at birth,
length of gestation and perinatal mortality? J Nutr
2001;131:590S,601S; discussion 601S603S. (Level III)
13. Tamura T, Goldenberg RL, Hou J, Johnston KE, Cliver
SP, Ramey SL et al. Cord serum ferritin concentrations
and mental and psychomotor development of children at
five years of age. J Pediatr 2002;140:16570. (Level II-2)
14. Corwin EJ, Murray-Kolb LE, Beard JL. Low hemoglobin
level is a risk factor for postpartum depression. J Nutr
2003;133:413942. (Level II-3)
15. Perez EM, Hendricks MK, Beard JL, Murray-Kolb LE,
Berg A, Tomlinson M, et al. Mother-infant interactions
and infant development are altered by maternal iron defi-
ciency anemia. J Nutr 2005;135:8505. (Level I)
16. Snow CF. Laboratory diagnosis of vitamin B12 and folate
deficiency: a guide for the primary care physician. Arch
Intern Med 1999;159:128998. (Level III)
17. CDC criteria for anemia in children and childbearing-aged
women. Centers for Disease Control (CDC). MMWR
Morb Mortal Wkly Rep 1989;38:4004. (Level III)
COMPENDIUM OF SELECTED PUBLICATIONS 1058
18. Dirren H, Logman MH, Barclay DV, Freire WB. Altitude
correction for hemoglobin. Eur J Clin Nutr 1994;48:
62532. (Level II-3)
19. Nordenberg D, Yip R, Binkin NJ. The effect of cigarette
smoking on hemoglobin levels and anemia screening.
JAMA 1990;264:15569. (Level II-2)
20. Johnson-Spear MA, Yip R. Hemoglobin difference
between black and white women with comparable iron
status: justification for race-specific anemia criteria. Am J
Clin Nutr 1994;60:11721. (Level III)
21. Perry GS, Byers T, Yip R, Margen S. Iron nutrition does
not account for the hemoglobin differences between
blacks and whites. J Nutr 1992;122:141724. (Level II-3)
22. Institute of Medicine (US). Iron deficiency anemia: rec-
ommended guidelines for the prevention, detection, and
management among U.S. children and women of child-
bearing age. Washington, DC: National Academy Press;
1993. (Level III)
23. Pena-Rosas JP, Viteri FE. Effects of routine oral iron sup-
plementation with or without folic acid for women during
pregnancy. Cochrane Database of Systematic Reviews
2006, Issue 3. Art. No.: CD004736. DOI: 10.1002/
14651858.CD004736.pub2. (Level III)
24. Sherman SJ, Greenspoon JS, Nelson JM, Paul RH.
Obstetric hemorrhage and blood utilization. J Reprod
Med 1993;38:92934. (Level II-2)
25. Carles G, Tobal N, Raynal P, Herault S, Beucher G, Marret
H, et al. Doppler assessment of the fetal cerebral hemody-
namic response to moderate or severe maternal anemia.
Am J Obstet Gynecol 2003;188:7949. (Level II-3)
26. Sifakis S, Pharmakides G. Anemia in pregnancy. Ann N Y
Acad Sci 2000;900:12536. (Level III)
27. Faich G, Strobos J. Sodium ferric gluconate complex in
sucrose: safer intravenous iron therapy than iron dextrans.
Am J Kidney Dis 1999;33:46470. (Level III)
28. Bhandal N, Russell R. Intravenous versus oral iron ther-
apy for postpartum anaemia. BJOG 2006;113:124852.
(Level I)
29. Breymann C, Visca E, Huch R, Huch A. Efficacy and safe-
ty of intravenously administered iron sucrose with and
without adjuvant recombinant human erythropoietin for the
treatment of resistant iron-deficiency anemia during preg-
nancy. Am J Obstet Gynecol 2001;184:6627. (Level I)
30. Wagstrom E, Akesson A, Van Rooijen M, Larson B,
Bremme K. Erythropoietin and intravenous iron therapy
in postpartum anaemia. Acta Obstet Gynecol Scand
2007;86: 95762. (Level I)
31. Toedt ME. Feasibility of autologous blood donation in
patients with placenta previa. J Fam Pract 1999;48:
21921. (Level II-3)
32. Etchason J, Petz L, Keeler E, Calhoun L, Kleinman S,
Snider C, et al. The cost effectiveness of preoperative
autologous blood donations. N Engl J Med 1995;332:
71924. (Level III)
The MEDLINE database, the Cochrane Library, and
ACOGs own internal resources and documents were used
to conduct a literature search to locate relevant articles pub-
lished between January 1985 and September 2007. The
search was restricted to articles published in the English lan-
guage. Priority was given to articles reporting results of
original research, although review articles and commentar-
ies also were consulted. Abstracts of research presented at
symposia and scientific conferences were not considered
adequate for inclusion in this document. Guidelines pub-
lished by organizations or institutions such as the National
Institutes of Health and the American College of Obstetri-
cians and Gynecologists were reviewed, and additional
studies were located by reviewing bibliographies of identi-
fied articles. When reliable research was not available,
expert opinions from obstetriciangynecologists were used.
Studies were reviewed and evaluated for quality according
to the method outlined by the U.S. Preventive Services
Task Force:
I Evidence obtained from at least one properly
designed randomized controlled trial.
II-1 Evidence obtained from well-designed controlled
trials without randomization.
II-2 Evidence obtained from well-designed cohort or
casecontrol analytic studies, preferably from more
than one center or research group.
II-3 Evidence obtained from multiple time series with or
without the intervention. Dramatic results in uncon-
trolled experiments also could be regarded as this
type of evidence.
III Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees.
Based on the highest level of evidence found in the data,
recommendations are provided and graded according to the
following categories:
Level ARecommendations are based on good and con-
sistent scientific evidence.
Level BRecommendations are based on limited or incon-
sistent scientific evidence.
Level CRecommendations are based primarily on con-
sensus and expert opinion.
Copyright July 2008 by the American College of Obstetri-
cians and Gynecologists. All rights reserved. No part of this
publication may be reproduced, stored in a retrieval system,
posted on the Internet, or transmitted, in any form or by any
means, electronic, mechanical, photocopying, recording, or
otherwise, without prior written permission from the publisher.
Requests for authorization to make photocopies should be
directed to Copyright Clearance Center, 222 Rosewood Drive,
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
The American College of Obstetricians and Gynecologists
409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920
Anemia in pregnancy. ACOG Practice Bulletin No. 95. American
College of Obstetricians and Gynecologists. Obstet Gynecol 2008;112:
2017.
1059 PRACTICE BULLETINS
CLINICAL MANAGEMENT GUIDELINES FOR OBSTETRICIANGYNECOLOGISTS
NUMBER 97, SEPTEMBER 2008
Replaces Educational Bulletin Number 230, November 1996
This Practice Bulletin was devel-
oped by the ACOG Committee on
Practice BulletinsObstetrics with
the assistance of William N.P.
Herbert, MD, and Thomas Peng,
MD. The information is designed to
aid practitioners in making deci-
sions about appropriate obstetric
and gynecologic care. These guide-
lines should not be construed as
dictating an exclusive course of
treatment or procedure. Variations
in practice may be warranted based
on the needs of the individual
patient, resources, and limitations
unique to the institution or type of
practice.
Fetal Lung Maturity
Respiratory difficulties are common in neonates born with immature lung
development. Assessment of fetal lung maturity is an important component in
determining the timing of delivery in certain patients who experience compli-
cations during pregnancy. Enhancement of fetal pulmonary function with the
use of antenatal steroids and the administration of surfactant lessens the preva-
lence and severity of neonatal respiratory distress syndrome (RDS) and its
sequelae. However, RDS remains a major clinical issue. Commonly used tests
to determine fetal lung maturity are reviewed in this Practice Bulletin.
Background
The status of fetal lung maturation can assist the clinician in determining when
delivery should occur. Testing for fetal lung maturity should not be performed,
and is contraindicated, when delivery is mandated for fetal or maternal indica-
tions. Conversely, a mature fetal lung maturity test result before 39 weeks of
gestation, in the absence of appropriate clinical circumstances, is not an indi-
cation for delivery. Respiratory distress syndrome, intraventricular hemorrhage,
necrotizing enterocolitis, and other complications have been reported in pre-
mature newborns delivered with mature lecithin (phosphatidylcholine)/sphin-
gomyelin ratios or the presence of phosphatidylglycerol (1, 2).
Indications for Assessing Fetal Maturity
To prevent iatrogenic prematurity, fetal pulmonary maturity should be con-
firmed before scheduled delivery at less than 39 weeks of gestation unless fetal
maturity can be inferred from any of the following historic criteria:
Ultrasound measurement at less than 20 weeks of gestation supports ges-
tational age of 39 weeks or greater.
Fetal heart tones have been documented as present for 30 weeks by
Doppler ultrasonography.
ACOG
PRACTICE
BULLETIN
THE AMERICAN COLLEGE OF
OBSTETRICIANS AND
GYNECOLOGISTS
WOMENS HEALTH CARE PHYSICIANS
COMPENDIUM OF SELECTED PUBLICATIONS 1060
It has been 36 weeks since a positive serum or urine
human chorionic gonadotropin pregnancy test result.
If any of these criteria confirms a gestational age of
39 weeks or more, it is appropriate to schedule delivery at
that time. Ultrasonography may be considered to confirm
menstrual dates if there is a gestational age agreement
within 1 week by crownrump measurements obtained in
the first trimester or within 10 days by an average of mul-
tiple fetal biometric measurements (eg, crownrump
length, biparietal diameter, head and abdominal circum-
ference, and femur length) obtained in the second
trimester (up to 20 weeks of gestation).
The risk of RDS is increased significantly in infants
born by electively scheduled cesarean delivery between
37
0
7 weeks and 38
6
7 weeks of gestation (3). In a retro-
spective study of 1,284 elective cesarean deliveries, RDS
was diagnosed at a rate of 25 per 1,000 live births when
cesarean delivery occurred between 37
0
7 weeks and 38
6
7
weeks of gestation, versus a significantly lower rate of
RDS, 7 per 1,000 with cesarean delivery after 39
0
7
weeks of gestation. Neonatal RDS with vaginal deliver-
ies did not vary (34/1000) across these gestational ages.
Physiology and Pathophysiology
Fetal Lung Development
The development of the pulmonary system begins
approximately 3 weeks after conception and continues
well into childhood. From approximately 1624 weeks
of gestation, early bronchioles develop, and the epithe-
lium vascularizes and differentiates. It is in the alveolar
phase of pulmonary development, which begins at
approximately 2223 weeks of gestation, that subse-
quent bronchiolar division occurs such that thin spheri-
cal saccules known as alveoli develop. The concomitant
proliferation of capillaries around these alveoli makes
effective gas exchange possible after delivery.
The alveoli are lined by type II pneumocytes, which
produce phospholipids that are packaged into lamellar
bodies. Surfactant is the name given to a group of sur-
face-active phospholipid compounds that can be
released from these lamellar bodies and reduce the sur-
face tension within the alveolar spaces. Maintaining a
low surface tension within the alveoli allows the sacs to
remain expanded, which permits continuous and maxi-
mal effective gas exchange. During the latter portion of
pregnancy, fetal respiratory activity permits the passage
of surfactant into the amniotic fluid where its quantity or
function can be evaluated. The most prominent of these
surfactant compounds is lecithin, which generally
appears earlier in gestation than another component of
surfactant, phosphatidylglycerol.
Respiratory Distress Syndrome
A deficiency in the quantity of surfactant in premature
infants leads to higher surface tension within the alveoli,
causing alveolar collapse and difficult gas exchange. The
result is neonatal hypoxia, with further worsening of pul-
monary status manifested by acidosis and increased
shunting within the lungs. Signs of RDS include neona-
tal tachypnea, grunting, inspiratory thoracic retractions,
and cyanosis, often occurring within several hours of
birth.
Other complications associated with RDS include
necrotizing enterocolitis, patent ductus arteriosus, intra-
ventricular hemorrhage, and infection. Some survivors
will experience bronchopulmonary dysplasia, or chronic
lung disease.
Fetal Lung Maturity Tests
Laboratory tests measure either the concentration of par-
ticular components of pulmonary surfactant (biochemi-
cal tests) or the surface-active effects of these phospho-
lipids (biophysical tests). Common biochemical tests
include measuring the lecithin/sphingomyelin ratio and
determining the presence of phosphatidylglycerol.
Biophysical tests include fluorescence polarization.
Lamellar body counts also are generally available. Less
frequently used tests include foam stability index and
optical density of amniotic fluid at 650 nm.
Commonly used fetal lung maturity tests include
fluorescence polarization (TDx-FLM II), lecithin/sphin-
gomyelin ratio, phosphatidylglycerol presence, and
lamellar body counts. No test has been conclusively
shown to be superior, and each requires its own standard
to define the risk of neonatal RDS. Comparisons
between the different tests have shown varying results. A
comparison of lecithin/sphingomyelin ratio to lamellar
body counts in 833 neonates born within 72 hours of
fetal lung maturity testing (prevalence of RDS was 12%)
noted that both tests had similar sensitivity (proportion
of immature test result in neonates with RDS) of 81.8%
and 88.9%, respectively, and negative predictive values
(probability of no RDS with a mature fetal lung maturity
test result) 96.8% and 97.7%, respectively (4).
Comparisons of lamellar body counts (cutoff greater
than 50,000) and TDx-FLM II assay results (greater than
55 mg/g) also demonstrated similar test characteristics in
sensitivity (92% and 83%, respectively) and negative
predictive values (99% and 98%, respectively) (5).
Studies comparing lecithin/sphingomyelin ratios with
TDx-FLM II assay results demonstrate that both tests
yield high sensitivity for RDS and high negative predic-
tive values. Neonates of 109 pregnant women were
delivered within 72 hours of the fetal lung maturity test,
1061 PRACTICE BULLETINS
and RDS was diagnosed in 9 (8%) (6). In this study, using
cutoff values of 45 mg/g for TDx-FLM II assay results and
2 for lecithin/sphingomyelin ratios, the sensitivity and
negative predictive values were 100% for both tests (6).
A multiinstitutional study compared test character-
istics of lecithin/sphingomyelin ratio, phosphatidylglyc-
erol presence, lamellar body counts, and TDx-FLM II
assays. The investigators found that characteristics were
similar in a population of 220 neonates delivered within
48 hours of testing (7). Cutoff values were lecithin/
sphingomyelin ratios of 2.5, phosphatidylglycerol pres-
ence greater than 0.5, TDx-FLM II assay results greater
than 40 mg/g, and lamellar body counts greater than
30,000. Of the 13 (6%) neonates diagnosed with RDS,
the lecithin/sphingomyelin ratios were falsely reassuring
(greater than 2.5) in five, as were the TDx-FLM II assay
results, phosphatidylglycerol presence measurements,
and lamellar body counts in one amniotic fluid sample.
As noted by the authors, a probability risk of RDS that
takes into account the fetal gestation may be more help-
ful than a cutoff value to define mature versus immature
neonatal lung function.
Ideally, laboratories should develop their own refer-
ence standards for fetal lung maturity testing, but few
have a sufficient number of amniotic fluid samples and
outcomes for such internal evaluations. The predictive
values of fetal lung maturity tests will vary with the
prevalence of RDS in the population sampled. In addi-
tion, it should be noted that there is a risk of RDS even
with a positive mature fetal lung maturity test result and
that this risk varies by gestational age (79).
Fluorescence Polarization
Fetal lung maturity testing using fluorescence polariza-
tion is based on competitive binding of a fluorescent
probe to albumin and surfactant. When the probe is
bound to albumin, net polarization values are high; when
bound to surfactant, polarization values are low. In amni-
otic fluid samples, the fluorescence polarization mea-
sured by an automated analyzer reflects the ratio of
surfactant to albumin, a value that correlates with lung
maturity. Recent modifications of this concept provide a
simple, automated, rapid test that is widely available,
varies minimally between laboratories, and requires only
a small volume of amniotic fluid (typically 1 mL). In the
recently modified commercial version of this assay
(TDx-FLM II), values above 55 mg surfactant per 1 g
albumin are considered mature (10); values below 40 mg
surfactant per 1 g albumin are considered immature; and
values between 40 mg surfactant per 1 g albumin and 54
mg surfactant per 1 g albumin are considered indetermi-
nate. In a retrospective analysis of 185 samples (15 with
RDS and 170 without RDS), a cutoff value of greater
than or equal to 45 mg/g yielded a sensitivity of 100%
(95% confidence interval [CI], 82100%), specificity
(proportion of mature result in a neonate without RDS) of
84% (95% CI, 7889%) (11). The assay compares favor-
ably with other direct tests, but blood and meconium con-
tamination interfere with its interpretation (Table 1).
Lecithin/Sphingomyelin Ratio
The lecithin/sphingomyelin ratio measures the ratio of
lecithin to sphingomyelin in amniotic fluid. As gesta-
tional age advances, the concentration of lecithin
increases, whereas the concentration of sphingomyelin
remains relatively constant. Reporting results in a ratio
takes into account the increasing amniotic fluid volume
as gestational age progresses.
Determination of the lecithin/sphingomyelin ratio
involves thin-layer chromatography after organic solvent
extraction. A value of 2 is the commonly accepted stan-
dard indicating pulmonary maturity in the fetus,
although laboratories may define a different ratio to indi-
cate fetal lung maturity.
Compared with newer tests, popularity of the
lecithin/sphingomyelin ratio has diminished substantially
in recent years. The technique is more costly, has a longer
turnaround time (average of 56 hours), and requires
highly trained personnel. Blood and meconium contami-
nation can interfere with test interpretation (Table 1).
Phosphatidylglycerol Presence
Phosphatidylglycerol is a minor constituent of surfac-
tant. Because phosphatidylglycerol enhances the spread
of phospholipids on the alveolar surface, its presence
indicates a more advanced state of fetal pulmonary
maturity. Phosphatidylglycerol can be determined using
thin-layer chromatography as an extension of the
lecithin/sphingomyelin ratio. In addition, a slide-aggluti-
nation test has been developed using antisera specific for
phosphatidylglycerol. This test can be performed quickly
and generally is not affected by the presence of blood,
meconium, or other contaminants. Its relatively late
appearance in pregnancy means that its false-postive rate
(proportion of neonates without RDS with an immature
FLM test result) for RDS is high. Older studies noted that
when phosphatidylglycerol was present, the risk of RDS
was very low (less than 1%). When phosphatidylglycerol
was absent, the risk of RDS was in the range of 25%,
which is poorly predictive of occurrence of RDS (12).
Lamellar Body Counts
Surfactant is stored within type II pneumocytes in the
form of lamellar bodies. These bodies are actively
COMPENDIUM OF SELECTED PUBLICATIONS 1062
secreted into the alveoli space and hence into the amni-
otic fluid. The similarity of lamellar body size to that of
platelets permits the use of a standard hematologic
counter to determine lamellar body concentrations. Such
counting is simple, rapid, inexpensive, and reliably pre-
dictive of pulmonary maturity. However, there are no
clearly established protocols, consistent instrumentation,
guidelines, or consensus on cutoff values for a lamellar
body count that predicts absence of RDS.
Neonatal RDS may be reduced by acceptance of a
higher threshold, a higher lamellar body count. In a
cohort study of 527 neonates, two cutoff values, a lamel-
lar body count of greater than 30,000 and a count of
greater than 50,000, were defined as indicating pul-
monary maturity (13). Neonatal intensive care unit
admissions, neonatal respiratory assistance, and overall
neonatal complications were less frequent with a cutoff
value of greater than 50,000. A similar study of 80 preg-
nancies documented a negative predictive value of 93%
when a cutoff value for maturity of lamellar body counts
of greater than 50,000 was used (14). Meconium conta-
mination may marginally increase the lamellar body
count, and blood contamination can lead to falsely
increased lamellar body counts because of platelet cont-
amination (Table 1) (4, 15). If testing is not performed
rapidly, coagulation will reduce the lamellar body count.
Interpretation of Tests and Testing
Strategies
As shown in Table 1, the negative predictive value for
mature neonatal lung function is high, and if one of these
test results for fetal lung maturity is positive, RDS is
Table 1. Commonly Used Direct Tests of Fetal Lung Maturity
Typical Predictive
Value (%)
Mature Immature
Blood Meconium
Time and Negative Positive
Range in complexity: 1+ indicates procedure is simple, procedure is available all the time, procedure time is short, and personnel effort is not intensive; 4+ indicates
procedure is complex or difficult, time consuming, and, therefore, frequently not available at all times.
Positive predictive value is the probability of neonatal respiratory distress syndrome when the fetal lung maturity test result is immature.
The manufacturer has reformulated the product and revised the testing procedure. Currently, the threshold for maturity is 55; with the original assay, it was 70.
1063 PRACTICE BULLETINS
unlikely. The main value for fetal lung maturity testing is
predicting the absence of RDS. An immature test result
for fetal lung maturity is less reliable in predicting the
presence of RDS.
Fetal lung maturity testing traditionally has been
based on the result alone, not taking into account the ges-
tational age of the fetus. More recently, it has been
recognized that the probability of neonatal RDS is
dependent on both the fetal lung maturity test result and
the gestational age at which the fetal lung maturity test
was performed (7, 8, 16, 17). The prevalence of RDS
within a population will alter the positive predictive
value of the fetal lung maturity test results. Nonetheless,
combining test results and gestational age improves the
clinicians ability to counsel patients about perinatal
management and the neonatal risks, including the risk of
RDS, with elective delivery. Another factor in choosing
which amniotic fluid test to perform is the effect of var-
ious contaminants on test results (Table 1).
Clinical Considerations and
Recommendations
What are the complications of third-trimester
amniocentesis?
Complications from third-trimester amniocentesis for
fetal lung maturity are uncommon when performed with
ultrasound guidance (18, 19). One study of 562 amnio-
centeses documented a 0.7% rate of complications, which
included one each of preterm labor, premature rupture of
membranes, placental abruption, and fetalmaternal hem-
orrhage (18). None of the complications required urgent
delivery. One study documented complications requiring
urgent delivery on the day of amniocentesis in 6 patients
(0.7%) from 913 amniocenteses for fetal lung maturity.
Complications were isolated events but included three
fetal heart rate abnormalities and one each of placental
bleeding, placental abruption, and uterine rupture.
Is there a gestational age below which there
is no utility of fetal lung maturity testing?
Before 32 weeks of gestation, fetal lung maturity testing
generally is not indicated because most test results will
indicate immaturity. Thus, delivery is indicated at this ges-
tational age only for specific maternal or fetal indications.
What is the impact of corticosteroid adminis-
tration on fetal lung maturity test results?
Corticosteroid administration significantly reduces the
incidence of RDS but may not have an impact on the
results of fetal lung maturity testing (20, 21). In a cohort
study of pregnant patients with hypertension and similar
gestational ages at the time of amniocenteses for fetal
lung maturity, 34 patients were treated with betametha-
sone before amniocentesis and 34 were not treated.
Amniocentesis for fetal lung maturity occurred within 5
days of the corticosteroid administration. Compared with
no corticosteroid exposure, patients with hypertension
who were treated with corticosteroids had significantly
higher values for lecithin/sphingomyelin ratios and
lamellar body counts, but no difference in phosphatidyl-
glycerol presence. (21). No such increases in lecithin/
sphingomyelin ratios were noted in a subset of patients
enrolled in a study of dexamethasone versus placebo for
fetal lung maturation. No difference in the lecithin/sphin-
gomyelin ratio was found in the amniotic fluid obtained a
week after dexamethasone administration in 25 women
compared with the placebo group of 20 women (20).
In a patient with a twin pregnancy, should
fetal lung maturity testing be performed for
each fetus?
Information concerning pulmonary maturation and test-
ing in twin pregnancies is mixed. Studies have reported
that values of fetal maturity test results in twin pregnan-
cies are higher compared with those in singleton preg-
nancies at similar gestations (22, 23). In a study of 27
twin pregnancies and 143 singleton pregnancies, the
higher values of TDx FLM assay results were noted in
the twin pregnancies after 31 weeks of gestation (23).
Other studies have found no difference (24).
In twin pregnancies, data are not clear as to whether
assessing fetal lung maturity in one twin is sufficient or
whether assessing both twins is necessary to predict the
risk of neonatal RDS. Several studies suggest good corre-
lation of fetal lung maturity assay values between both
Table 2. Fetal Lung Maturity Testing in Twin Gestations
Amniocentesis to Test
Gestational Age Fetal Lung Maturity
30
0
732
6
7 weeks of gestation Both twins
33
0
735
6
7 weeks of gestation
Concordant gender Either twin
Discordant gender and discordant Either twin
weight less than 10% or greater than
20%
Discordant gender and discordant One twin (prefer
weight 1020% nonpresenting or male)
Greater than 35
6
7 weeks of gestation Either twin
Data from Mackenzie MW. Predicting concordance of biochemical lung matur-
ity in the preterm twin gestation. J Matern Fetal Neonat Med 2002;12:508.
COMPENDIUM OF SELECTED PUBLICATIONS 1064
twins with correlation coefficients of 0.830.86 (25, 26).
The correlation was not affected by the presenting versus
nonpresenting twin, by gender discordance, or by birth-
weight discordance (26). Discordant values (one twin
with a fetal lung maturity value in the mature range and
the other twin with a fetal lung maturity value in the
immature range) appear to occur more frequently at earli-
er gestational ages (26, 27). Many of these reports used
the lecithin/sphingomyelin ratio for fetal lung maturity
testing, which, because of larger differences in interlabo-
ratory and intralaboratory variation, may have contributed
to the varying results in concordance. These data suggest
that amniocentesis of both twins be performed when the
gestation is between 30
0
7 weeks and 32
6
7 weeks of gesta-
tion. Amniocentesis of one twin appears to be sufficient
when gestation is greater than 32
6
7 weeks (27) (Table 2).
Before elective delivery, fetal lung maturity testing
in twins with well defined gestational ages of 38
0
7 weeks
or greater may not be necessary. A descriptive study of
126 twins electively delivered without fetal lung testing
noted five pregnancies in which one or both twins were
diagnosed with RDS (28). For all five, delivery occurred
at less than 38
0
7 weeks of gestation. Of the 47 twin preg-
nancies delivered at 38
0
7 weeks or greater, one infant
was affected by transient tachypnea of the newborn.
How do abnormal amniotic fluid volumes
(hydramnios, oligohydramnios) affect fetal
lung maturity test results?
Very few studies have addressed this question. Based on
the results of one clinical study, the effect of amniotic
fluid volume on the results of fetal lung maturity testing
appears to be minimal. In a study of patients with oligo-
hydramnios (an amniotic fluid index of 5 cm or less), the
lecithin/sphingomyelin ratios, phosphatidylglycerol
presence, and lamellar body counts were similar to con-
trols of similar gestation but with a normal amniotic
fluid index. However, in patients with polyhydramnios
(an amniotic fluid index greater than 25), the
lecithin/sphingomyelin ratios, lamellar body counts, and
phosphatidylglycerol presence were lower compared
with the control group (29).
Are results of fetal lung maturity tests
performed on samples collected vaginally
reliable?
Studies comparing results of fetal lung maturity tests of
amniotic fluid collected vaginally with those collected
by transabdominal amniocentesis demonstrated that
when results from fluid collected vaginally are mature,
the results are reliable (30, 31). In a study of 16 patients
with preterm premature rupture of membranes, amniotic
fluid was collected both vaginally and by transabdomi-
nal amniocentesis within twelve hours of each other.
Twelve samples collected by transabdominal amniocen-
tesis indicated mature lung development compared with
four samples collected vaginally. Results of a TDx-FLM
assay were lower in the fluid collected vaginally then
fluid collected by transabdominal amniocentesis, but
when the assay of the fluid collected vaginally was
mature, it was always confirmed by results of the fluid
collected by transabdominal amniocentesis (31).
Compared with transabdominal amniocentesis, fluid col-
lected vaginally for fetal lung maturity testing yields
higher specificity (100%) and positive predictive value
(100%) but had lower sensitivity (42%) and negative
predictive value (36%) for neonatal RDS.
How does blood and meconium contamina-
tion affect fetal lung maturity test results?
Contamination of amniotic fluid with blood appears to
increase the number of falsely immature fetal lung matu-
rity test results. With an in vitro system, increasing
aliquots of blood added to samples of amniotic fluid pro-
duced fetal lung maturity test results that were less
mature (32). Table 1 lists the effects of various sub-
stances on the reliability of interpretation of tests of fetal
lung maturity.
How are results interpreted in the presence
of diabetes mellitus? Are there additional
tests that may be helpful?
In general, the same threshold values for fetal lung maturi-
ty tests that predict low risk of neonatal RDS in pregnan-
cies of women who are not diabetic apply to pregnancies
of women who are diabetic, whether the woman has ges-
tational diabetes mellitus or pregestational diabetes melli-
tus. Most studies have evaluated the performance of
lecithin/sphingomyelin ratios, tests for the presence of
phosphatidylglycerol, and TDx-FLM and TDx-FLM II
assays. The manufacturer of TDx-FLM II assays recom-
mends a value of 55 mg/g or higher as compatible with a
mature lung profile. In a series of 45 pregnant women
with diabetes mellitus who gave birth within 72 hours of
the performance of a fetal lung maturity test, 40 had
fetuses with a mature profile (TDx-FLM II value was
equal to 55 mg/g or greater), and no neonatal RDS
occurred (17). The remaining five had fetuses with an
indeterminate profile (TDx-FLM II value between 40
mg/g and 55 mg/g), and one had RDS. Therefore, testing
with fluorescence polarization (TDx-FLM II), using a
defined mature profile of a value of 55 mg/g or greater, is
appropriate for the determination of risk of neonatal RDS
in pregnant women with diabetes mellitus.
1065 PRACTICE BULLETINS
Similar findings were noted with the older version of
the fluorescence polarization test, TDx-FLM, in which val-
ues greater than 70 mg/g in amniotic fluid obtained by
amniocentesis were associated with a very low risk of
neonatal RDS (33, 34). In one series of 182 pregnant
women with diabetes mellitus, five neonates born within 4
days of the amniocentesis experienced severe RDS. The
TDx-FLM values of these five neonates ranged from 1859
mg/g. Mild RDS, requiring hood oxygenation, occurred in
three neonates with fetal lung maturity values of 47, 74, and
81 mg/g (33). In another series of 121 pregnant women
with diabetes mellitus who gave birth within 72 hours of
fetal lung maturity testing, one neonate had RDS with a
TDx-FLM value of 7.2 mg/g. No RDS was noted when the
value was 70 mg/g or greater (108 patients) (34).
Evaluation of lecithin/sphingomyelin ratios and tests
for the presence of phosphatidylglycerol in an older study
of pregnant women with and without diabetes mellitus
confirmed that a mature lecithin/sphingomyelin ratio pre-
dicted very low risk of neonatal RDS in both populations
(1.6% and 1.8%, respectively), and when phosphatidyl-
glycerol was present, no RDS was identified in either
group (35).
The effect of diabetes mellitus or glucose control on
the development of a mature phospholipid profile in amni-
otic fluid is unclear (36). Some reports indicate a delay in
production of phosphatidylglycerol in fetuses of pregnant
women with diabetes mellitus (37, 38) and a higher pro-
portion of immature profiles in women with poorly con-
trolled compared with well controlled diabetes mellitus
(39). Others report no difference in phospholipid profiles
between patients with diabetes mellitus and patients with-
out diabetes mellitus (40, 41). There is more of a consensus
that the extent of glycemic control is related to the timing
of pulmonary maturation and fetal lung maturity testing.
In pregnant women with diabetes mellitus and good
glycemic control, amniocentesis for fetal lung maturity
testing is not indicated before scheduled delivery at or
beyond 39 weeks of gestation. It has been suggested that
with the rare risk of RDS in pregnant women with well-
controlled diabetes mellitus, amniocentesis for fetal lung
maturity may be eliminated in women with a well-dated
pregnancy at or beyond 38 weeks of gestation (42). In
patients with diabetes mellitus and poor glucose control,
fetal lung maturity testing is recommended if delivery is
contemplated at less than 39 weeks of gestation.
How is an immature or indeterminate test
result managed? What is the interval for
repeat testing?
If the test results following the first amniocentesis are
immature, individual circumstances can guide decision
making. The risks of untoward fetal or maternal outcome
if the pregnancy continues and the results of the testing
(very immature or indeterminate) can be helpful in such
situations. With an indeterminate test result, the practi-
tioner should consider incorporation of the gestational
age of the fetus into the interpretation of the fetal lung
maturity value and risk of neonatal RDS.
For borderline lecithin/sphingomyelin ratios
(1.81.9), the risk of neonatal morbidity and mortality if
delivered within 72 hours of the test appear significant.
In a group of 63 pregnancies at a gestation of 2736
weeks delivered within 72 hours of the fetal lung matu-
rity test, there was a 13% neonatal morbidity rate and 3%
neonatal mortality rate when the lecithin/sphingomyelin
ratio was 1.8 compared with a 3% morbidity rate and no
mortality when the lecithin/sphingomyelin ratio was 1.9.
All the major neonatal morbidity occurred in gestations
less than 3234 weeks (43). Increased risk of RDS was
noted with TDx-FLM II results in the indeterminate zone
(4055 mg/g), with proportional increases in the risk of
RDS as fetal gestation decreased (16).
No consensus exists as to whether repeat testing is
required or when to perform a repeat test when the fetal
lung maturity test is either immature or indeterminate.
TDx-FLM II results derived from two sequential amnio-
centeses in a group of 85 pregnant women documented
that as fetal gestation progresses, the increase in the
value of TDx-FLM II results appear to be constant,
increasing approximately 14.4 plus or minus 9.9 mg/g
(95% CI, 12.316.5) per week over a broad range of ges-
tations (3138 weeks of gestation) (44). This may pro-
vide guidance on whether repeat testing is necessary and
when to consider repeat testing.
Summary of
Recommendations and
Conclusions
The following recommendations and conclusions
are based on limited or inconsistent scientific evi-
dence (Level B:)
Testing for fetal lung maturity should not be per-
formed, and is contraindicated, when delivery is
mandated for fetal or maternal indications.
Fetal pulmonary maturity should be confirmed
before scheduled delivery at less than 39 weeks of
gestation unless fetal maturity can be inferred from
historic criteria.
The probability of neonatal RDS is dependent on
both the fetal lung maturity test result and the gesta-
COMPENDIUM OF SELECTED PUBLICATIONS 1066
tional age at which the fetal lung maturity test was
performed.
Fluorescence polarization assays (TDx FLM II)
using a defined mature profile of 55 mg/g or greater
is appropriate for the determination of risk of neona-
tal RDS in pregnancies of women with diabetes
mellitus.
Fetal lung maturity test results from amniotic fluid
collected vaginally compared with those from fluid
collected by transabdominal amniocentesis demon-
strate that when results from fluid collected vaginally
are mature, the results are reliable.
Complications from third-trimester amniocentesis
for fetal lung maturity are uncommon when per-
formed with ultrasound guidance.
The following conclusions are based primarily on
consensus and expert opinion (Level C):
In general, the same threshold values for fetal lung
maturity tests that predict low risk of neonatal RDS
in pregnancies of women who do not have diabetes
mellitus apply to pregnancies of women who have
diabetes mellitus, whether it is gestational diabetes
mellitus or pregestational diabetes mellitus.
Data suggest that amniocentesis of both twins be
performed when the gestation is between 30
0
7
weeks and 32
6
7 weeks of gestation. Amniocentesis
of one twin appears to be sufficient when gestation
is greater than 32
6
7 weeks.
Prior to elective delivery, fetal lung maturity testing
in twins with well defined gestational ages at 38
0
7
weeks or greater may not be necessary.
Proposed Performance
Measure
Documentation of discussion or performance of fetal
lung maturity testing in elective cesarean deliveries at a
gestation less than 39
0
7 weeks
References
1. Wigton TR, Tamura RK, Wickstrom E, Atkins V, Deddish
R, Socol ML. Neonatal morbidity after preterm delivery
in the presence of documented lung maturity. Am J Obstet
Gynecol 1993;169:9515. (Level III)
2. Ghidini A, Hicks C, Lapinski RH, Lockwood CJ. Morbid-
ity in the preterm infant with mature lung indices. Am J
Perinatol 1997;14:758. (Level II-3)
3. Zanardo V, Simbi AK, Franzoi M, Solda G, Salvadori A,
Trevisanuto D. Neonatal respiratory morbidity risk and
mode of delivery at term: influence of timing of elective
caesarean delivery. Acta Paediatr 2004;93:6437. (Level
II-2)
4. Neerhof MG, Haney EI, Silver RK, Ashwood ER, Lee IS,
Piazze JJ. Lamellar body counts compared with traditional
phospholipid analysis as an assay for evaluating fetal lung
maturity. Obstet Gynecol 2001;97:3059. (Level II-3)
5. Haymond S, Luzzi VI, Parvin CA, Gronowski AM. A
direct comparison between lamellar body counts and flu-
orescent polarization methods for predicting respiratory
distress syndrome. Am J Clin Pathol 2006;126:8949.
(Level II-3)
6. Winn-McMillan T, Karon BS. Comparison of the TDx-
FLM II and lecithin to sphingomyelin ratio assays in pre-
dicting fetal lung maturity. Am J Obstet Gynecol 2005;
193:77882. (Level II-3)
7. Karcher R, Sykes E, Batton D, Uddin Z, Ross G,
Hockman E, et al. Gestational age-specific predicted risk
of neonatal respiratory distress syndrome using lamellar
body count and surfactant-to-albumin ratio in amniotic
fluid. Am J Obstet Gynecol 2005;193:16804. (Level II-3)
8. Parvin CA, Kaplan LA, Chapman JF, McManamon TG,
Gronowski AM. Predicting respiratory distress syndrome
using gestational age and fetal lung maturity by fluores-
cent polarization. Am J Obstet Gynecol 2005;192:
199207. (Level III)
9. Pinette MG, Blackstone J, Wax JR, Cartin A. Fetal lung
maturity indicesa plea for gestational age-specific inter-
pretation: a case report and discussion. Am J Obstet
Gynecol 2002;187:17212. (Level III)
10. Kesselman EJ, Figueroa R, Garry D, Maulik D. The use-
fulness of the TDx/TDxFLx fetal lung maturity II assay in
the initial evaluation of fetal lung maturity. Am J Obstet
Gynecol 2003;188:12202. (Level II-3)
11. Fantz CR, Powell C, Karon B, Parvin CA, Hankins K,
Dayal M, et al. Assessment of the diagnostic accuracy of
the TDx-FLM II to predict fetal lung maturity. Clin Chem
2002;48:7615. (Level II-3)
12. Field NT, Gilbert WM. Current status of amniotic fluid
tests of fetal maturity. Clin Obstet Gynecol 1997;40:
36686. (Level III)
13. Ventolini G, Neiger R, Hood DL, Belcastro MR. Changes
in the threshold of fetal lung maturity testing and neo-
natal outcome of infants delivered electively before
39 weeks gestation: implications and cost-effectiveness.
J Perinatol 2006;26:2647. (Level II-3)
14. Khazardoost S, Yahyazadeh H, Borna S, Sohrabvand F,
Yahyazadeh N, Amini E. Amniotic fluid lamellar body
count and its sensitivity and specificity in evaluating of
fetal lung maturity. J Obstet Gynaecol 2005;25:2579.
(Level II-3)
15. Torday JS, Rehan VK. Testing for fetal lung maturation: a
biochemical window to the developing fetus. Clin Lab
Med 2003;23:36183. (Level III)
16. Kaplan LA, Chapman JF, Bock JL, Santa Maria E, Clejan
S, Huddleston DJ, et al. Prediction of respiratory distress
1067 PRACTICE BULLETINS
syndrome using the Abbott FLM-II amniotic fluid assay.
Clin Chim Acta 2002;326:618. (Level III)
17. Melanson SE, Jarolim P, McElrath TF, Berg A,
Tanasijevic MJ. Fetal lung maturity testing in diabetic
mothers. Lab Med 2007;38:5535. (Level III)
18. Gordon MC, Narula K, OShaughnessy R, Barth WH Jr.
Complications of third-trimester amniocentesis using con-
tinuous ultrasound guidance. Obstet Gynecol 2002;99:
2559. (Level II-3)
19. Stark CM, Smith RS, Lagrandeur RM, Batton DG, Lorenz
RP. Need for urgent delivery after third-trimester amnio-
centesis. Obstet Gynecol 2000;95:4850. (Level II-3)
20. Farrell PM, Engle MJ, Zachman RD, Curet LB, Morrison
JC, Rao AV, et al. Amniotic fluid phospholipids after
maternal administration of dexamethasone. Am J Obstet
Gynecol 1983;145:48490. (Level II-2)
21. Piazze JJ, Maranghi L, Nigro G, Rizzo G, Cosmi EV,
Anceschi MM. The effect of glucocorticoid therapy on
fetal lung maturity indices in hypertensive pregnancies.
Obstet Gynecol 1998;92:2205. (Level II-2)
22. Leveno KJ, Quirk JG, Whalley PJ, Herbert WN, Trubey
R. Fetal lung maturation in twin gestation. Am J Obstet
Gynecol 1984;148:40511. (Level III)
23. McElrath TF, Norwitz ER, Robinson JN, Tanasijevic MJ,
Lieberman ES. Differences in TDx fetal lung maturity
assay values between twin and singleton gestations. Am J
Obstet Gynecol 2000;182:11102. (Level II-3)
24. Winn HN, Romero R, Roberts A, Liu H, Hobbins JC.
Comparison of fetal lung maturation in preterm singleton
and twin pregnancies. Am J Perinatol 1992;9:3268.
(Level II-3)
25. Spellacy WN, Cruz AC, Buhi WC, Birk SA. Amniotic
fluid L/S ratio in twin gestation. Obstet Gynecol
1977;50:6870. (Level II-3)
26. Whitworth NS, Magann EF, Morrison JC. Evaluation of
fetal lung maturity in diamniotic twins. Am J Obstet
Gynecol 1999;180:143841. (Level II-3)
27. Mackenzie MW. Predicting concordance of biochemical
lung maturity in the preterm twin gestation. J Matern Fetal
Neonatal Med 2002;12:508. (Level II-3)
28. Chasen ST, Madden A, Chervenak FA. Cesarean delivery
of twins and neonatal respiratory disorders. Am J Obstet
Gynecol 1999;181:10526. (Level II-3)
29. Piazze JJ, Maranghi L, Cosmi EV, Anceschi MM. The
effect of polyhydramnios and oligohydramnios on fetal
lung maturity indexes. Am J Perinatol 1998;15:24952.
(Level II-2)
30. Edwards RK, Duff P, Ross KC. Amniotic fluid indices of
fetal pulmonary maturity with preterm premature rupture of
membranes. Obstet Gynecol 2000;96:1025. (Level II-3)
31. Cleary-Goldman J, Connolly T, Chelmow D, Malone F.
Accuracy of the TDx-FLM assay of amniotic fluid: a
comparison of vaginal pool samples with amniocentesis. J
Matern Fetal Neonatal Med 2002;11:3747. (Level
II-3)
32. Carlan SJ, Gearity D, OBrien WF. The effect of maternal
blood contamination on the TDx-FLM II assay. Am J
Perinatol 1997;14:4914. (Level III)
33. Livingston EG, Herbert WN, Hage ML, Chapman JF,
Stubbs TM. Use of the TDx-FLM assay in evaluating fetal
lung maturity in an insulin-dependent diabetic population.
The Diabetes and Fetal Maturity Study Group. Obstet
Gynecol 1995;86:8269. (Level II-3)
34. Del Valle GO, Adair CD, Ramos EE, Gaudier FL,
Sanchez-Ramos L, Morales R. Interpretation of the TDx-
FLM fluorescence polarization assay in pregnancies com-
plicated by diabetes mellitus. Am J Perinatol
1997;14:2414. (Level II-3)
35. Curet LB, Tsao FH, Zachman RD, Olson RW, Henderson
PA. Phosphatidylglycerol, lecithin/sphingomyelin ratio
and respiratory distress syndrome in diabetic and non-dia-
betic pregnancies. Int J Gynaecol Obstet 1989;30: 1058.
(Level II-2)
36. Langer O. The controversy surrounding fetal lung maturi-
ty in diabetes in pregnancy: a re-evaluation. J Matern
Fetal Neonatal Med 2002;12:42832. (Level III)
37. Piper JM, Xenakis EM, Langer O. Delayed appearance of
pulmonary maturation markers is associated with poor
glucose control in diabetic pregnancies. J Matern Fetal
Med 1998;7:14853. (Level II-2)
38. Moore TR. A comparison of amniotic fluid fetal pul-
monary phospholipids in normal and diabetic pregnancy.
Am J Obstet Gynecol 2002;186:64150. (Level II-2)
39. Piper JM, Langer O. Does maternal diabetes delay fetal
pulmonary maturity? Am J Obstet Gynecol 1993;168:
7836. (Level II-2)
40. Berkowitz K, Reyes C, Saadat P, Kjos SL. Fetal lung mat-
uration. Comparison of biochemical indices in gestational
diabetic and nondiabetic pregnancies. J Reprod Med
1997;42:793800. (Level II-2)
41. Piazze JJ, Anceschi MM, Maranghi L, Brancato V,
Marchiani E, Cosmi EV. Fetal lung maturity in pregnan-
cies complicated by insulin-dependent and gestational
diabetes: a matched cohort study. Eur J Obstet Gynecol
Reprod Biol 1999;83:14550. (Level II-2)
42. Piper JM. Lung maturation in diabetes in pregnancy: if and
when to test. Semin Perinatol 2002;26:2069. (Level III)
43. Burkhart AE, Towers CV, Rumney PJ, Lewis DF.
Neonatal outcome when delivery follows a borderline
immature lecithin to sphingomyelin ratio. J Perinatol
2000;20:15760. (Level III)
44. Bildirici I, Moga CN, Gronowski AM, Sadovsky Y. The
mean weekly increment of amniotic fluid TDx-FLM II
ratio is constant during the latter part of pregnancy. Am J
Obstet Gynecol 2005;193:168590. (Level III)
COMPENDIUM OF SELECTED PUBLICATIONS 1068
The MEDLINE database, the Cochrane Library, and
ACOGs own internal resources and documents were used
to conduct a literature search to locate relevant articles pub-
lished between January 1985 and October 2007. The search
was restricted to articles published in the English language.
Priority was given to articles reporting results of original re-
search, although review articles and commentaries also
were consulted. Abstracts of research presented at symposia
and scientific conferences were not considered adequate for
inclusion in this document. Guidelines published by organi-
zations or institutions such as the National Institutes of
Health and the American College of Obstetricians and Gy-
necologists were reviewed, and additional studies were
located by reviewing bibliographies of identified articles.
When reliable research was not available, expert opinions
from obstetriciangynecologists were used.
Studies were reviewed and evaluated for quality according
to the method outlined by the U.S. Preventive Services
Task Force:
I Evidence obtained from at least one properly
designed randomized controlled trial.
II-1 Evidence obtained from well-designed controlled
trials without randomization.
II-2 Evidence obtained from well-designed cohort or
casecontrol analytic studies, preferably from more
than one center or research group.
II-3 Evidence obtained from multiple time series with or
without the intervention. Dramatic results in uncon-
trolled experiments also could be regarded as this
type of evidence.
III Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees.
Based on the highest level of evidence found in the data,
recommendations are provided and graded according to the
following categories:
Level ARecommendations are based on good and con-
sistent scientific evidence.
Level BRecommendations are based on limited or incon-
sistent scientific evidence.
Level CRecommendations are based primarily on con-
sensus and expert opinion.
Copyright September 2008 by the American College of
Obstetricians and Gynecologists. All rights reserved. No part of
this publication may be reproduced, stored in a retrieval system,
posted on the Internet, or transmitted, in any form or by any
means, electronic, mechanical, photocopying, recording, or
otherwise, without prior written permission from the publisher.
Requests for authorization to make photocopies should be
directed to Copyright Clearance Center, 222 Rosewood Drive,
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
The American College of Obstetricians and Gynecologists
409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920
Fetal lung maturity. ACOG Practice Bulletin No. 97. American College
of Obstetricians and Gynecologists. Obstet Gynecol 2008;112:
71726.
1069 PRACTICE BULLETINS
CLINICAL MANAGEMENT GUIDELINES FOR OBSTETRICIANGYNECOLOGISTS
NUMBER 100, FEBRUARY 2009
This Practice Bulletin was devel-
oped by the ACOG Committee on
Practice BulletinsObstetrics with
the assistance of Lauren A. Plante,
MD, MPH. The information is
designed to aid practitioners in
making decisions about appropriate
obstetric and gynecologic care.
These guidelines should not be con-
strued as dictating an exclusive
course of treatment or procedure.
Variations in practice may be war-
ranted based on the needs of the
individual patient, resources, and
limitations unique to the institution
or type of practice.
ACOG
PRACTICE
BULLETIN
THE AMERICAN COLLEGE OF
OBSTETRICIANS AND
GYNECOLOGISTS
WOMENS HEALTH CARE PHYSICIANS
Critical Care in Pregnancy
Critical care in pregnancy is a field that remains unevenly researched. Although
there is a body of evidence to guide many recommendations in critical care,
limited research specifically addresses obstetric critical care. The purpose of
this document is to review the available evidence, propose strategies for care,
and highlight the need for additional research. Much of the review will, of
necessity, focus on general principles of critical care, extrapolating where pos-
sible to obstetric critical care.
Background
Recent case series suggest that between 0.1% and 0.8% of obstetric patients are
admitted to a traditional intensive care unit (ICU) (19). Among this popula-
tion, the risk of death ranges from 2% to 11%. Although survival is better than
that in an unselected population, mortality is substantially higher than the
maternal mortality ratio in the developed world. In addition, approximately
12% of pregnant women receive critical care outside of a traditional ICU, but
within a specialized obstetric care unit (10, 11). Therefore, overall estimates
suggest that 13% of pregnant women require critical care services in the
United States each year, approximately 40,000120,000 women (based on 4
million births per year) (12).
Techniques for Critical Care
Competence in a number of core procedural skills is necessary for any physi-
cian practicing in critical care. Except in very large maternity centers, there is
little opportunity to develop or maintain these skills, although alternative means
may be available. Some techniques can be performed under supervision in other
settings (eg, airway techniques under anesthesiologists supervision in the oper-
ating room), others can be rehearsed through electronic resources or online
(electrocardiogram interpretation), and still others lend themselves to task train-
ing through medical simulation.
COMPENDIUM OF SELECTED PUBLICATIONS 1070
Organization of Critical Care
In an open ICU, any physician can write orders or per-
form procedures; management or consultation by a qual-
ified intensive care physician is not mandatory. In a
closed ICU, only the critical care attending physician or
house staff can write orders and manage patient care.
The hybrid or transitional model allows all physicians to
write orders but requires an on-site critical care physi-
cian to provide consultation, conduct rounds, or co-man-
age all patient care. Additional terminology classifies
ICU physician staffing as high-intensity (closed ICU or
mandatory intensivist consultation) or low-intensity
(optional intensivist) (13). High-intensity ICU physician
staffing is associated with lower ICU mortality, lower
hospital mortality, and decreased length of stay in both
the ICU and the hospital, compared with low intensity
ICU physician staffing (13). Although there are limited
data specifically addressing the critical care obstetric
patient, it seems reasonable that these findings would
apply to this population as well (14, 15).
Critical care requires a multidisciplinary approach
to achieve the best outcomes (16). The usual ICU team
includes physicians, nurses, pharmacists, and respiratory
therapists. In critical care obstetrics, the team also should
include obstetricians or maternalfetal medicine subspe-
cialists, obstetric nurses, and neonatologists.
The obstetrician transferring a patient to an ICU
must be familiar with the types of units available at the
institution, such as a general medicalsurgical ICU or a
specialty unit for cardiothoracic or neurologic or neuro-
surgical care as well as the role of the obstetrician with-
in each unit (17).
There are three levels of adult critical care described
by the American College of Critical Care Medicine, with
Level I delivering the highest level of care. Alternatives
to traditional ICU care include intermediate-care or
high-dependency units such as post-ICU step-down units,
telemetry units for cardiac patients, and units for patients
requiring long-term ventilator use (10, 11, 18).
Admission to Intensive Care
Because ICU beds are a scarce resource, ICU admission
should be reserved for those patients who are likely to
benefit. Most obstetric patients will be admitted under
the objective parameters triage model. In this model,
specific criteria trigger ICU admission, regardless of
diagnosis. These triggers were achieved by consensus, in
response to the review by the Joint Commission (for-
merly the Joint Commission on Accreditation of
Healthcare Organizations), and are acknowledged to be
largely arbitrary. They include specific abnormalities in
vital signs, laboratory values, and imaging and physical
findings. Admission criteria for nonpregnant patients are
listed in the box Objective Parameters Model for
Admission of Nonpregnant Patients to an Intensive Care
Unit. A description of changes to normal laboratory val-
ues during pregnancy is provided in the box Key
Laboratory Values That are Different in Pregnancy.
Considerations in Transfer
The care of any pregnant woman requiring ICU services
should be managed in a facility with obstetric adult ICU
and neonatal ICU capability. Standard guidelines for
perinatal transfer have been published by the American
College of Obstetricians and Gynecologists and the
American Academy of Pediatrics and follow federal
Emergency Medical Treatment and Labor Act guidelines
(19). These guidelines generally recommend antenatal
rather than neonatal transfer and describe the responsi-
bilities of the referring and receiving hospitals. In the
event that maternal transport is unsafe or impossible,
alternative arrangements for neonatal transport may be
necessary. In patients where imminent delivery is
expected, transfer should be held until after delivery.
The mimimal monitoring required for a critically ill
patient during transport includes continuous pulse
oximetry and electrocardiography as well as regular
assessment of vital signs (19, 20). All critically ill patients
must have secure venous access before transport.
Patients who already have arterial or central lines or
other invasive monitoring devices in place should have
those monitored as well. Women who are mechanically
ventilated must have the endotracheal tube position con-
firmed and secured before transport and must be
assessed for adequacy of oxygenation and ventilation.
There are no data to guide obstetric monitoring dur-
ing transport of the critically ill obstetric patient. Fetal
and tocodynamic monitoring during transport is likely
feasible but of unproven utility (21). In some circum-
stances, identifying fetal compromise in transit may
allow for advance preparation for intervention, including
delivery, by the receiving institution. Simple measures,
such as left uterine displacement and supplemental oxy-
gen, should be applied routinely during transport.
Clinical Considerations and
Recommendations
What are the findings in a pregnant or
postpartum woman that might prompt ICU
admission?
Patients should be transferred to an ICU if they need cir-
culatory or pulmonary support. An obstetric service
should adopt site-specific guidelines for transfer based
1071 PRACTICE BULLETINS
Objective Parameters Model for Admission of
Nonpregnant Patients to an Intensive Care Unit
Vital Signs
Heart rate of less than 40 beats per minute or
greater than 150 beats per minute
Blood pressure of less than 80 mm Hg systolic (or
20 mm Hg below the patients usual blood pressure)
Mean arterial pressure of less than 60 mm Hg
Blood pressure of greater than 120 mm Hg diastolic
Respiratory rate of greater than 35 per minute
Laboratory Values
Serum sodium level of less than 110 mEq/L or
greater than 170 mEq/L
Serum potassium level of less than 2 or greater than
7 mEq/L
PaO
2
of less than 50 mm Hg
pH level of less than 7.1 or greater than 7.7
Serum calcium level of greater than 15 mg/dL
Serum glucose level of greater than 800 mg/dL
Toxic drug level in a hemodynamically or neurologi-
cally compromised patient
Imaging
Cerebrovascular hemorrhage, contusion, or sub-
arachnoid hemorrhage with altered mental status or
focal neurologic findings
Ruptured viscus or esophageal varices with hemody-
namic instability
Dissecting aortic aneurysm
Electrocardiography
Myocardial infarction with complex arrhythmia,
hemodynamic instability, or congestive heart failure
Sustained ventricular tachycardia or ventricular fibril-
lation
Complete heart block with hemodynamic instability
Physical Findings
Airway obstruction
Anuria
Burns of greater than 10% of body surface area
Cardiac tamponade
Coma
Continuous seizures
Cyanosis
Unequal pupils (unconscious patient)
Guidelines for intensive care unit admission, discharge, and triage.
Task Force of the American College of Critical Care Medicine,
Society of Critical Care. Crit Care Med 1999;27:6338.
Key Laboratory Values That are
Different in Pregnancy
Hemodynamic Variables
Increased cardiac output
Decreased systemic vascular resistance
Decreased blood pressure
Increased heart rate
Decreased pulmonary vascular resistance
Respiratory Variables
Decreased functional residual capacity
Increased minute ventilation
Laboratory Variables
Increased PAO
2
and PaO
2
Decreased PaCO
2
Decreased serum bicarbonate (HCO
3
)
Decreased hemoglobin and hematocrit levels
Increased white blood cell count
Decreased protein S levels
Decreased coagulation factors XI and XIII levels
Increased coagulation factors I, VII, VIII, IX, and
X levels
Increased fibrinogen levels
Increased D-dimer levels
Increased erythrocyte sedimentation rate
Decreased serum creatinine levels
Decreased blood urea nitrogen level (BUN)
Decreased uric acid level
Increased alkaline phosphatase level
Increased aldosterone level
Increased serum cortisol, free cortisol, cortisol-bind-
ing globulin, and adrenocorticotropic hormone level
Increased insulin level
Decreased fasting blood glucose level
Increased triglyceride level
Increased cholesterol, low-density lipoprotein, and
high-density lipoprotein levels
Data from Gabbe SG, Niebyl JR, Simpson JL, Galan H, Goetzl L,
Jauniaux ER, et al, editors. Obstetrics: normal and problem preg-
nancies. 5th ed. Philadelphia (PA): Churchill Livingstone Elsevier;
2007.
COMPENDIUM OF SELECTED PUBLICATIONS 1072
on the level of care required. These guidelines also
should define and distinguish between levels of care that
can be provided on the labor floor or, if applicable, the
obstetric intermediate care unit.
Hemorrhage and hypertension are the most common
causes of ICU admission in obstetric patients (17, 9,
2236). Most of these patients typically require relative-
ly simple interventions, monitoring, and supportive care.
Approximately 2030% of obstetric ICU patients
have nonobstetric causes for an ICU admission, such as
sepsis (1, 5, 7, 11). Early goal-directed therapy for sep-
sis should not be delayed until the admission to the ICU
but should begin as soon as septic shock is diagnosed
(3739). The patient should be stabilized, intravenous
access maintained, urine output and fluid volume man-
aged, and antibiotics started for treatment of sepsis.
Broad-spectrum antibiotic therapy should be started
within 1 hour of the diagnosis of severe sepsis or septic
shock (37). Cultures, including blood cultures, should be
obtained, but should not delay initiating antibiotics. Fetal
resuscitation in utero through maternal oxygen therapy
and circulatory support is preferable to cesarean delivery
for nonreassuring fetal heart rate patterns in most cases.
Approximately 75% of obstetric ICU patients admitted
to the ICU are postpartum (5, 6, 25). This may be due to
specific postpartum causes, such as postpartum hemor-
rhage, or to ascertainment bias; obstetricians may be less
willing to transfer or intensivists less willing to accept a
patient whose fetus must still be considered in care plan-
ning. The process of transport itself is risky for a critically
ill patient, who requires ongoing monitoring and mainte-
nance while in transport. In a viable pregnancy, fetal moni-
toring during transport between obstetric units and the ICU
may be prudent, especially if the patient is in labor (20).
Admission to the ICU is dependent on levels of care
available on a local level. Patients needing the following
procedures should be treated in a critical care unit:
1. Respiratory support, including airway maintenance
and endotracheal intubation
2. Treatment of pneumothorax
3. Cardiovascular support, including treatment with
pressors
4. Pulmonary artery catheterization (insertion, mainte-
nance, and interpretation)
5. Abnormal electrocardiographic findings requiring
intervention, including cardioversion or defibrillation
interpretation
What is the obstetriciangynecologists role
in the transfer of a patient to a critical care
unit?
When obstetric patients are transferred to the ICU, the
obstetricians role will depend on the ICU model (open
or closed) and the patients status (antepartum or post-
partum). Regardless of the primary caregiver, patient
care decisions must be made collaboratively between the
intensivist, obstetrician, and neonatologist, and should
involve the patient, her family, or both.
Obstetric input in the care of the postpartum ICU
patient may include evaluation of vaginal or intraabdom-
inal bleeding, evaluation of obstetric sources of infec-
tion, duration of specific therapies, such as magnesium
for eclampsia prophylaxis, and feasibility of breast-feed-
ing, especially compatibility of various medications with
breast-feeding. There may be issues related to surgical
interventions, including reexploration of the abdomen,
or reclosure of abdominal or vaginal incisions. Under
some circumstances, the obsterician and the neonatolo-
gist also will need to advocate for bringing together the
critically ill mother and her baby.
Multidisciplinary care is essential for the critically
ill obstetric patient. When a pregnant patient is trans-
ferred to the ICU, members of the care team should
assess the anticipated course of her condition or disease,
including possible complications, and set parameters for
delivery, if appropriate. The plan should be clear to the
medical team and to the patients family, and to the
patient herself if she is able to understand. Because the
riskbenefit calculation for a given intervention may
change as pregnancy progresses, it is important to reeval-
uate the care plan on a regular basis.
The plan for delivery should be made long before
delivery is imminent, and it must include decisions about
preferred location for delivery, preferred mode of deliv-
ery (vaginal versus cesarean), need for analgesia or anes-
thesia, and access to pediatricians. It also must include
an alternative plan or set of plans in the event that the
original plan cannot be followed.
If postpartum ICU admission is necessary, the
patient and her family may have questions regarding the
obstetric events that precipitated transfer even when
obstetric care has been optimal. Anger, dissatisfaction, or
legal action often follow a perceived bad outcome; in the
case of a postpartum complication or condition requiring
critical care, the obstetrician may bear the brunt of these
questions. Although a full discussion about disclosure
and review of adverse events is beyond the scope of this
document, resources are available to assist the obstetri-
cian through this stressful time (40).
How should care be organized when a
laboring patient needs critical care?
If a laboring patient requires critical care services, it is
important to determine the optimal setting for her care.
1073 PRACTICE BULLETINS
If the fetus is pre-viable or the duration of ICU services
is anticipated to be lengthy, the labor floor is unlikely to
be the best option. However during active labor, the labor
unit may be the best choice if adequate maternal support
can be provided. Advantages of vaginal delivery in the
ICU include the availability of critical care interventions
and staff. Disadvantages include lack of space to conduct
a vaginal delivery and to accommodate pediatric person-
nel and equipment, and unfamiliarity of critical care per-
sonnel with obstetric interventions and management.
Factors that will affect this decision include the degree of
patient instability, interventions required, staffing and
expertise available, anticipated duration of ICU stay, and
probability of delivery.
Delivery in the ICU is associated with an increased
likelihood of operative vaginal delivery. In part, this is
because patients with translaryngeal intubation cannot
close the glottis to push; therefore, an assisted second
stage of labor may be required. In addition, ICU patients
often have underlying cardiac or neurologic processes
where an assisted second stage of labor is recommended.
Adequate analgesia is required, although assessment of
pain may be complicated by altered mental status or intu-
bation. Regional analgesia is preferred but may not be
possible because of coagulopathy, hemodynamic instabil-
ity, or difficulties with patient positioning. Parenteral nar-
cotics can be used instead of regional analgesia but are
less effective in preventing pain; suboptimally treated pain
may result in hemodynamic derangements that must be
anticipated and treated.
Cesarean delivery in the ICU is complex and has
significant disadvantages compared with procedures per-
formed in a traditional operating room. These disadvan-
tages include inadequate space for anesthetic, surgical,
and neonatal resuscitation equipment and attendant per-
sonnel unfamiliar with the operation. In addition, ICUs
have the highest rates of health care associated infections
in a hospital, so the risk of nosocomial infection with
drug-resistant organisms is increased (41, 42). Cesarean
delivery in the ICU should be restricted to cases in which
transport to the operating room or delivery room cannot
be achieved safely or expeditiously, or to a perimortem
procedure.
Are there special fetal considerations in the
care of a pregnant woman in a critical care
setting (eg, assessment of gestational age,
fetal monitoring, or complications related to
medications)?
Establishment of gestational age is crucial to determine
whether the fetus is of gestational age sufficient to
ensure a good chance of survival after birth. When pos-
sible, prenatal care records should be obtained to estab-
lish the most accurate dating criteria. In the event that
gestational age remains uncertain, prompt ultrasound
evaluation should establish the best possible estimate
with documentation of the potential range of uncertainty.
Use of obstetric medications may pose particular
challenges in the critically ill patient; known side effects
must be carefully monitored and riskbenefit ratios should
be assessed in each individual situation. Examples of
common drug-related side effects include tachycardia and
decreased blood pressure with beta-agonists, effects on
platelet function and renal perfusion with indomethacin,
and negative inotropic effects on cardiac function with
magnesium. If preterm delivery may be necessary, a
course of antenatal corticosteroids should be given to pro-
mote fetal lung maturity in fetuses between 24 weeks of
gestation and 34 weeks of gestation, and are not con-
traindicated in an ICU setting even in the setting of sepsis.
Pregnancy often modifies drug effects or serum lev-
els. Drugs that cross the placenta may have fetal effects;
for example, sedative or parasympatholytic drugs can
affect the fetal heart rate tracing. However, necessary
medications should not be withheld from a pregnant
woman because of fetal concerns. Additionally, neces-
sary imaging studies should not be withheld out of
potential concern for fetal status, although attempts
should be made to limit fetal radiation exposure during
diagnostic testing.
Fetal surveillance often is used when a pregnant
patient is admitted to the ICU. Because fetal heart rate
monitoring reflects uteroplacental perfusion and mater-
nal acidbase status, changes in baseline variability or
the new onset of decelerations may serve as an early
warning system for derangements in maternal end-organ
status. Changes in fetal monitoring should prompt
reassessment of maternal mean arterial pressure, hypox-
ia, acidemia, or compression of the inferior vena cava by
the gravid uterus. Correction of these factors may result
in improvement of the tracing and every attempt should
be made at intrauterine fetal resuscitation.
Is intraoperative fetal monitoring needed for
a pregnant patient?
Although there are no data to allow for a specific recom-
mendation regarding fetal monitoring for nonobstetric
surgery, it is important for physicians to obtain obstetric
consultation before performing nonobstetric surgery.
Obstetricians are uniquely qualified to discuss aspects of
maternal physiology and anatomy that may affect intra-
operative maternalfetal well-being. The decision to use
fetal monitoring should be individualized and, if used,
may be based on gestational age, type of surgery, and
COMPENDIUM OF SELECTED PUBLICATIONS 1074
facilities available. Ultimately, each case warrants a team
approach (anesthesia, obstetrics, and surgery) for opti-
mal maternal and fetal safety.
When is perimortem caesarean delivery
appropriate?
Although there are no clear guidelines regarding peri-
mortem cesarean delivery, fetal survival is unlikely if
more than 1520 minutes have passed since the loss of
maternal vital signs. There are insufficient data on which
to base conclusions regarding the appropriateness of
cesarean delivery when efforts at resuscitation have
failed. Based on isolated case reports, cesarean delivery
should be considered for both maternal and fetal benefit
approximately 4 minutes after a woman has experienced
cardiopulmonary arrest in the third trimester (43, 44).
Summary of
Recommendations and
Conclusions
The following conclusions are based on good and
consistent scientific evidence (Level A):
Pregnancy changes normal laboratory values and
physiologic parameters.
Approximately 75% of obstetric ICU patients are
admitted to the unit postpartum.
Hemorrhage and hypertension are the most common
causes of admission from obstetric services to inten-
sive care.
The following recommendations are based on lim-
ited or inconsistent scientific evidence (Level B):
Cesarean delivery in the ICU should be restricted to
cases in which transport to the operating room or
delivery room cannot be achieved safely or expedi-
tiously, or to a perimortem procedure.
Treatment of sepsis should not await admission to
an ICU but should begin as soon as septic shock is
diagnosed.
The following recommendations and conclusions
are based primarily on consensus and expert opin-
ion (Level C):
High-intensity ICU physician staffing is associated
with lower ICU mortality rates, lower hospital mor-
tality rates, and decreased length of stay in both the
ICU and a hospital, compared with models in which
intensivist consultation is optional.
Decisions about care for a pregnant patient in the ICU
should be made collaboratively with the intensivist,
obstetrician, specialty nurses, and neonatologist.
The care of any pregnant woman requiring ICU ser-
vices should be managed in a facility with obstetric
adult ICU and neonatal ICU capability.
Necessary medications should not be withheld from
a pregnant woman because of fetal concerns.
Necessary imaging studies should not be withheld
out of potential concern for fetal status, although
attempts should be made to limit fetal radiation
exposure during diagnostic testing.
Proposed Performance
Measure
Percentage of pregnant or postpartum patients in the ICU
who have documented involvement of an obstetrician
gynecologist
References
1. Panchal S, Arria AM, Labhsetwar SA. Maternal mortality
during hospital admission for delivery: a retrospective
analysis using a state-maintained database. Anesth Analg
2001;93:13441. (Level II-2)
2. Keizer JL, Zwart JJ, Meerman RH, Harinck BI, Feuth
HD, van Roosmalen J. Obstetric intensive care admis-
sions: a 12-year review in a tertiary care centre. Eur J
Obstet Gynecol Reprod Biol 2006;128:1526. (Level III)
3. Umo-Etuk J, Lumley J, Holdcroft A. Critically ill parturi-
ent women and admission to intensive care: a 5-year
review. Int J Obstet Anesth 1996;5:7984. (Level III)
4. Hazelgrove JF, Price C, Pappachan VJ, Smith GB.
Multicenter study of obstetric admissions to 14 intensive
care units in southern England. Crit Care Med 2001;29:
7705. (II-3)
5. Lapinsky SE, Kruczynski K, Seaward GR, Farine D,
Grossman RF. Critical care management of the obstetric
patient. Can J Anaesth 1997;44:3259. (Level III)
6. Selo-Ojeme DO, Omosaiye M, Battacharjee P, Kadir RA.
Risk factors for obstetric admissions to the intensive care
unit in a tertiary hospital: a case-control study. Arch
Gynecol Obstet 2005;272:20710. (Level II-2)
7. Munnur U, Karnad DR, Bandi VD, Lapsia V, Suresh MS,
Ramshesh P, et al. Critically ill obstetric patients in an
American and an Indian public hospital: comparison of
case-mix, organ dysfunction, intensive care requirements,
and outcomes. Intensive Care Med 2005;31:108794.
(Level II-3)
1075 PRACTICE BULLETINS
8. Brace V, Penney G, Hall M. Quantifying severe maternal
morbidity: a Scottish population study. BJOG 2004;111:
4814. (Level II-2)
9. Heinonen S, Tyrvainen E, Saarikoski S, Ruokonen E. Need
for maternal critical care in obstetrics: a population-based
analysis. Int J Obstet Anesth 2002;11:2604. (Level III)
10. Ryan M, Hamilton V, Bowen M, McKenna P. The role of
a high-dependency unit in a regional obstetric hospital.
Anaesthesia 2000;55:11558. (Level III)
11. Zeeman GG, Wendel GD Jr, Cunningham FG. A blueprint
for obstetric critical care. Am J Obstet Gynecol 2003;
188:5326. (Level III)
12. Martin JA, Hamilton BE, Sutton PD, Ventura SJ,
Menacker F, Kirmeyer S, et al. Births: final data for 2005.
Natl Vital Stat Rep 2007;56:1103. (Level II-3)
13. Pronovost PJ, Angus DC, Dorman T, Robinson KA,
Dremsizov TT, Young TL. Physician staffing patterns and
clinical outcomes in critically ill patients: a systematic
review. JAMA 2002;288:215162. (Level III)
14. Jenkins TM, Troiano NH, Graves CR, Baird SM, Boehm
FH. Mechanical ventilation in an obstetric population:
characteristics and delivery rates. Am J Obstet Gynecol
2003;188:54952. (Level III)
15. Plante LA. Mechanical ventilation in an obstetric popula-
tion. Am J Obstet Gynecol 2003;189:1516. (Level III)
16. Brilli RJ, Spevetz A, Branson RD, Campbell GM, Cohen
H, Dasta JF, et al. Critical care delivery in the intensive
care unit: defining clinical roles and the best practice
model. American College of Critical Care Medicine
Task Force on Models of Critical Care Delivery. The
American College of Critical Care Medicine Guidelines
for the Definition of an Intensivist and the Practice of
Critical Care Medicine. Crit Care Med 2001;29:200719.
(Level III)
17. Chang SY, Multz AS, Hall JB. Critical care organization.
Crit Care Clin 2005;21:4353, viii. (Level III)
18. Nasraway SA, Cohen IL, Dennis RC, Howenstein MA,
Nikas DK, Warren J, et al. Guidelines on admission and
discharge for adult intermediate care units. American
College of Critical Care Medicine of the Society of
Critical Care Medicine. Crit Care Med 1998;26:60710.
(Level III)
19. American Academy of Pediatrics, American College of
Obstetricians and Gynecologists. Guidelines for perinatal
care. 6th ed. Elk Grove Village (IL): AAP; Washington,
DC: ACOG; 2007. (Level III)
20. Warren J, Fromm RE Jr, Orr RA, Rotello LC, Horst HM.
Guidelines for the inter- and intrahospital transport of crit-
ically ill patients. American College of Critical Care
Medicine. Crit Care Med 2004;32:25662. (Level III)
21. Elliott JP, Trujillo R. Fetal monitoring during emergency
obstetric transport. Am J Obstet Gynecol 1987;157:
2457. (Level III)
22. Afessa B, Green B, Delke I, Koch K. Systemic inflamma-
tory response syndrome, organ failure, and outcome in
critically ill obstetric patients treated in an ICU. Chest
2001;120:12717. (Level III)
23. Bouvier-Colle MH, Salanave B, Ancel PY, Varnoux N,
Fernandez H, Papiernik E, et al. Obstetric patients treated
in intensive care units and maternal mortality. Regional
Teams for the Survey. Eur J Obstet Gynecol Reprod Biol
1996;65:1215. (Level III)
24. Collop NA, Sahn SA. Critical illness in pregnancy. An
analysis of 20 patients admitted to a medical intensive
care unit. Chest 1993;103:154852. (Level III)
25. Gilbert TT, Smulian JC, Martin AA, Ananth CV, Scorza
W, Scardella AT. Obstetric admissions to the intensive
care unit: outcomes and severity of illness. Critical Care
Obstetric Team. Obstet Gynecol 2003;102:897903.
(Level II-3)
26. Graham SG, Luxton MC. The requirement for intensive
care support for the pregnant population. Anaesthesia
1989;44:5814. (Level III)
27. Karnad DR, Guntupalli KK. Critical illness and pregnancy:
review of a global problem. Crit Care Clin 2004;20:555
76, vii. (Level III)
28. Kilpatrick SJ, Matthay MA. Obstetric patients requiring
critical care. A five-year review. Chest 1992;101:140712.
(Level III)
29. Kwee A, Bots ML, Visser GH, Bruinse HW. Emergency
peripartum hysterectomy: a prospective study in the
Netherlands. Eur J Obstet Gynecol Reprod Biol 2006;
124:18792. (Level III)
30. Mabie WC, Sibai BM. Treatment in an obstetric intensive
care unit. Am J Obstet Gynecol 1990;162:14. (Level III)
31. Mahutte NG, Murphy-Kaulbeck L, Le Q, Solomon J,
Benjamin A, Boyd ME. Obstetric admissions to the inten-
sive care unit. Obstet Gynecol 1999;94:2636. (Level III)
32. Monaco TJ Jr, Spielman FJ, Katz VL. Pregnant patients in
the intensive care unit: a descriptive analysis. South Med
J 1993;86:4147. (Level III)
33. Say L, Pattinson RC, Gulmezoglu AM. WHO systematic
review of maternal morbidity and mortality: the preva-
lence of severe acute maternal morbidity (near miss).
Reprod Health 2004;1:3. (Level III)
34. Soubra SH, Guntupalli KK. Critical illness in pregnancy:
an overview. Crit Care Med 2005;33:S24855. (Level III)
35. Wen SW, Huang L, Liston R, Heaman M, Baskett T,
Rusen ID, et al. Severe maternal morbidity in Canada,
1991-2001. Maternal Health Study Group, Canadian
Perinatal Surveillance System. CMAJ 2005;173:75964.
(Level II-2)
36. Zhang WH, Alexander S, Bouvier-Colle MH, Macfarlane
A. Incidence of severe pre-eclampsia, postpartum haem-
orrhage and sepsis as a surrogate marker for severe mater-
nal morbidity in a European population-based study: the
MOMS-B survey. MOMS-B Group. BJOG 2005;112:
8996. (Level II-3)
37. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM,
Jaeschke R, et al. Surviving Sepsis Campaign: interna-
tional guidelines for management of severe sepsis and
septic shock: 2008. International Surviving Sepsis
Campaign Guidelines Committee. Crit Care Med 2008;
36:296327. (Level III)
COMPENDIUM OF SELECTED PUBLICATIONS 1076
38. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A,
Knoblich B, et al. Early goal-directed therapy in the treat-
ment of severe sepsis and septic shock. Early Goal-
Directed Therapy Collaborative Group. N Engl J Med
2001;345:136877. (Level I)
39. Guinn DA, Abel DE, Tomlinson MW. Early goal directed
therapy for sepsis during pregnancy. Obstet Gynecol Clin
North Am 2007;34:45979, xi. (Level III)
40. Disclosure and discussion of adverse events. ACOG
Committee Opinion No. 380. American College of
Obstetricians and Gynecologists. Obstet Gynecol 2007;
110:9578. (Level III)
41. Weber DJ, Sickbert-Bennett EE, Brown V, Rutala WA.
Comparison of hospitalwide surveillance and targeted
intensive care unit surveillance of healthcare-associated
infections. Infect Control Hosp Epidemiol 2007;28:
13616. (Level II-3)
42. Edwards JR, Peterson KD, Andrus ML, Tolson JS,
Goulding JS, Dudeck MA, et al. National Healthcare
Safety Network (NHSN) Report, data summary for 2006,
issued June 2007. NHSN Facilities. Am J Infect Control
2007;35:290301. (Level II-3)
43. Katz VL, Dotters DJ, Droegemueller W. Perimortem
cesarean delivery. Obstet Gynecol 1986;68:5716. (Level
III)
44. Katz V, Balderston K, DeFreest M. Perimortem cesarean
delivery: were our assumptions correct? Am J Obstet
Gynecol 2005;192:1916-20; discussion 19201. (Level III)
The MEDLINE database, the Cochrane Library, and
ACOGs own internal resources and documents were used
to conduct a literature search to locate relevant articles pub-
lished between January 1985 and January 2008. The search
was restricted to articles published in the English language.
Priority was given to articles reporting results of original
research, although review articles and commentaries also
were consulted. Abstracts of research presented at symposia
and scientific conferences were not considered adequate for
inclusion in this document. Guidelines published by organi-
zations or institutions such as the National Institutes of
Health and the American College of Obstetricians and
Gynecologists were reviewed, and additional studies were
located by reviewing bibliographies of identified articles.
When reliable research was not available, expert opinions
from obstetriciangynecologists were used.
Studies were reviewed and evaluated for quality according
to the method outlined by the U.S. Preventive Services
Task Force:
I Evidence obtained from at least one properly
designed randomized controlled trial.
II-1 Evidence obtained from well-designed controlled
trials without randomization.
II-2 Evidence obtained from well-designed cohort or
casecontrol analytic studies, preferably from more
than one center or research group.
II-3 Evidence obtained from multiple time series with or
without the intervention. Dramatic results in uncon-
trolled experiments also could be regarded as this
type of evidence.
III Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees.
Based on the highest level of evidence found in the data,
recommendations are provided and graded according to the
following categories:
Level ARecommendations are based on good and con-
sistent scientific evidence.
Level BRecommendations are based on limited or incon-
sistent scientific evidence.
Level CRecommendations are based primarily on con-
sensus and expert opinion.
Copyright February 2009 by the American College of
Obstetricians and Gynecologists. All rights reserved. No part of
this publication may be reproduced, stored in a retrieval system,
posted on the Internet, or transmitted, in any form or by any
means, electronic, mechanical, photocopying, recording, or
otherwise, without prior written permission from the publisher.
Requests for authorization to make photocopies should be
directed to Copyright Clearance Center, 222 Rosewood Drive,
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
The American College of Obstetricians and Gynecologists
409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920
Critical care in pregnancy. ACOG Practice Bulletin No. 100. American
College of Obstetricians and Gynecologists. Obstet Gynecol 2009;
113:44350.
1077 PRACTICE BULLETINS
CLINICAL MANAGEMENT GUIDELINES FOR OBSTETRICIANGYNECOLOGISTS
NUMBER 101, FEBRUARY 2009
This Practice Bulletin was devel-
oped by the ACOG Committee
on Practice BulletinsObstetrics
with the assistance of Alfred Z.
Abuhamad, MD. The information
is designed to aid practitioners in
making decisions about appropriate
obstetric and gynecologic care.
These guidelines should not be con-
strued as dictating an exclusive
course of treatment or procedure.
Variations in practice may be war-
ranted based on the needs of the
individual patient, resources, and
limitations unique to the institution
or type of practice.
ACOG
PRACTICE
BULLETIN
THE AMERICAN COLLEGE OF
OBSTETRICIANS AND
GYNECOLOGISTS
WOMENS HEALTH CARE PHYSICIANS
Ultrasonography in
Pregnancy
Most women have at least one ultrasound examination during pregnancy. The
purpose of this document is to present evidence regarding the methodology
of, indications for, benefits of, and risks associated with obstetric ultrasonog-
raphy in specific clinical situations. Portions of this document were developed
collaboratively with the American College of Radiology and the American
Institute of Ultrasound in Medicine. The sections that address physician quali-
fications and responsibilities, documentation, quality control, infection control,
and patient safety contain recommendations from the American College of
Obstetricians and Gynecologists.
Background
Instrumentation
Ultrasound examination should be conducted with real-time scanners, using a
transabdominal or a transvaginal approach or both. Real-time ultrasonography
is necessary to confirm the presence of fetal life through observation of cardiac
activity and active movement. The choice of transducer frequency is a trade-off
between beam penetration and resolution. With modern equipment, abdominal
transducers with frequencies ranging from 3 MHz to 5 MHz allow sufficient
penetration in most patients while providing adequate resolution. A lower-fre-
quency transducer (22.25 MHz) may be needed to provide adequate penetra-
tion for abdominal imaging in an obese patient. During early pregnancy, an
abdominal transducer with a frequency of 5 MHz or a transvaginal transducer
with a frequency of 510 MHz or higher may provide superior resolution while
still allowing adequate penetration. A method for storing the images also is
required. The equipment should be serviced at regular intervals according to the
manufacturers recommendations.
COMPENDIUM OF SELECTED PUBLICATIONS 1078
Essential Elements of Standard
Examination of Fetal Anatomy
Head, Face and Neck*
Cerebellum
Choroid plexus
Cisterna magna
Lateral cerebral ventricles
Midline falx
Cavum septi pellucidi
Upper lip
ChestHeart (The basic cardiac examination includes
a four-chamber view of the fetal heart. As part of the
cardiac screening examination, an attempt should be
made, if technically feasible, to view the outflow
tracts.)
Abdomen
Stomach (presence, size, and situs)
Kidneys
Bladder
Umbilical cord insertion site into the fetal abdomen
Umbilical cord vessel number
SpineCervical, thoracic, lumbar, and sacral spine
ExtremitiesLegs and arms (presence or absence)
SexMedically indicated in low-risk pregnancies
only for the evaluation of multiple gestations
*A measurement of the nuchal fold may be helpful during a specific
age interval to suggest an increased risk of aneuploidy.
American College of Radiology. ACR practice guideline for the per-
formance of obstetrical ultrasound. In: ACR practice guidelines and
technical standards, 2007. Reston (VA): ACR; 2007. p. 10251033.
Types of Examinations
The American College of Obstetricians and Gynecolo-
gists uses the terms standard (also called basic), lim-
ited, and specialized (also called detailed) to describe
various types of ultrasound examinations performed dur-
ing the second or third trimesters. First-trimester ultra-
sound examination is distinct and is discussed separately.
Standard Examination
Ultrasonography is an accurate method of determining ges-
tational age, fetal number, viability, and placental location.
A standard obstetric ultrasound examination in the second
or third trimester includes an evaluation of fetal presenta-
tion, amniotic fluid volume, cardiac activity, placental posi-
tion, fetal biometry, and fetal number, plus an anatomic
survey. The maternal cervix and adnexa should be exam-
ined as clinically appropriate when technically feasible.
Fetal anatomy, as described in this document, may
be assessed adequately by ultrasonography after approx-
imately 18 weeks of gestation. It may be possible to doc-
ument normal structures before this time, although some
structures can be difficult to visualize because of fetal
size, position, and movement; maternal abdominal scars;
and increased maternal abdominal wall thickness. A sec-
ond- or third-trimester ultrasound examination may pose
technical limitations for an anatomic evaluation because
of suboptimal imaging. When this occurs, the report of
the ultrasound examination should document the nature
of this technical limitation. A follow-up examination
may be helpful. The essential elements of a standard
examination of fetal anatomy are listed in the box.
Limited Examination
A limited examination does not replace a standard exami-
nation and is performed when a specific question requires
investigation. For example, a limited examination in the
second or third trimester could be performed to confirm
fetal heart activity in a patient experiencing vaginal bleed-
ing or to establish fetal presentation in a laboring patient.
A limited examination also may be performed in any
trimester to evaluate interval growth, estimate amniotic
fluid volume, evaluate the cervix, and assess the presence
of cardiac activity.
Specialized Examination
A detailed or targeted anatomic examination is per-
formed when an anomaly is suspected on the basis of
history, laboratory abnormalities, or the results of either
the limited or standard examination. Other specialized
examinations might include fetal Doppler ultrasonogra-
phy, biophysical profile, amniotic fluid assessment, fetal
echocardiography, or additional biometric measure-
ments. Specialized examinations are performed by an
operator with experience and expertise in such ultra-
sonography who determines the components of the
examination on a case-by-case basis.
First-Trimester Ultrasound Examination
Indications. A first-trimester ultrasound examination is
an ultrasound examination performed before 13 weeks
and 6 days of gestation. Indications for performing first-
trimester ultrasound examinations are listed in the box.
Imaging Parameters. Scanning in the first trimester
may be performed either transabdominally or transvagi-
nally. If a transabdominal examination is not definitive,
a transvaginal scan or transperineal scan should be per-
1079 PRACTICE BULLETINS
Indications for First-Trimester Ultrasonography
To confirm the presence of an intrauterine
pregnancy
To evaluate a suspected ectopic pregnancy
To evaluate vaginal bleeding
To evaluate pelvic pain
To estimate gestational age
To diagnosis or evaluate multiple gestations
To confirm cardiac activity
As adjunct to chorionic villus sampling,
embryo transfer, or localization and removal
of an intrauterine device
To assess for certain fetal anomalies, such as
anencephaly, in patients at high risk
To evaluate maternal pelvic or adnexal masses or
uterine abnormalities
To screen for fetal aneuploidy
To evaluate suspected hydatidiform mole
American College of Radiology. ACR practice guideline for the per-
formance of obstetrical ultrasound. In: ACR practice guidelines and
technical standards, 2007. Reston (VA): ACR; 2007. p. 10251033.
formed whenever possible. The following factors should
be considered during the examination.
The uterus, including the cervix, and adnexa should
be evaluated for the presence of a gestational sac. If a
gestational sac is seen, its location should be docu-
mented. The gestational sac should be evaluated for the
presence or absence of a yolk sac or embryo, and the
crownrump length should be recorded, when possible.
The crownrump length is a more accurate indicator of
gestational (menstrual) age than is mean gestational sac
diameter. However, the mean gestational sac diameter
may be recorded when an embryo is not identified.
Caution should be used in presumptively diagnosing a
gestational sac in the absence of a definite embryo or
yolk sac. Without these findings, intrauterine fluid col-
lection could represent a pseudogestational sac associated
with an ectopic pregnancy.
Presence or absence of cardiac activity should be
reported. With transvaginal scans, cardiac motion should
be observed when the embryo is 5 mm or greater in
length. An embryo should be visible by transvaginal
ultrasonography with a mean gestational sac diameter of
20 mm or greater. If an embryo less than 5 mm in length
is seen without cardiac activity, a subsequent scan at a
later time may be needed to assess the presence or
absence of cardiac activity. Fetal number should be
reported. Amnionicity and chorionicity should be docu-
mented for all multiple gestations when possible.
Embryonic or fetal anatomy should be assessed accord-
ing to gestational age.
The uterus, including adnexal structures, should be
evaluated. The presence, location, and size of adnexal
masses should be recorded. The presence of leiomyomas
should be recorded, and measurements of the largest or
any potentially clinically significant leiomyomas may
be recorded. The cul-de-sac should be evaluated for the
presence or absence of fluid.
For patients who desire an assessment of their indi-
vidual risk of fetal aneuploidy, a standardized measure-
ment of the nuchal translucency during a specific age
interval is necessary. Nuchal translucency measurements
should be used (in conjunction with serum biochemistry)
to determine the risk of Down syndrome, trisomy 13, tri-
somy 18, or other anatomic abnormalities, such as heart
defects. In this setting, it is important that the practitioner
measure the nuchal translucency according to estab-
lished guidelines for measurement. In addition, a quality
assessment program is recommended to ensure accurate
results. Organizations currently providing guidelines and
ongoing quality assessment include the Nuchal
Translucency Quality Review program of the Maternal
Fetal Medicine Foundation and the program sponsored
by the Fetal Medicine Foundation.
Second- and Third-Trimester
Ultrasound Examination
Indications. Ultrasonography can be of benefit in many
situations in the second and third trimesters. Indications
for second- and third-trimester ultrasonography are listed
in the box.
Imaging Parameters for a Standard Fetal Examin-
ation. Fetal cardiac activity, fetal number, and fetal pre-
sentation should be reported. Any abnormal heart rates
or rhythms should be reported. Multiple gestations
require the documentation of additional information:
chorionicity, amnionicity, comparison of fetal sizes, esti-
mation of amniotic fluid volume (increased, decreased,
or normal) on each side of the membrane, and fetal gen-
italia (when visualized).
Ultrasonography can detect abnormalities in amni-
otic fluid volume. An estimate of amniotic fluid volume
should be reported. Although it is acceptable for experi-
enced examiners to qualitatively estimate amniotic fluid
volume, semiquantitative methods also have been des-
cribed for this purpose (eg, amniotic fluid index, single
deepest pocket, two-diameter pocket).
COMPENDIUM OF SELECTED PUBLICATIONS 1080
Indications for Second- and Third-Trimester
Ultrasonography
Estimation of gestational age
Evaluation of fetal growth
Evaluation of vaginal bleeding
Evaluation of cervical insufficiency
Evaluation of abdominal and pelvic pain
Determination of fetal presentation
Evaluation of suspected multiple gestation
Adjunct to amniocentesis or other procedure
Significant discrepancy between uterine size and
clinical dates
Evaluation of pelvic mass
Examination of suspected hydatidiform mole
Adjunct to cervical cerclage placement
Evaluation of suspected ectopic pregnancy
Evaluation of suspected fetal death
Evaluation of suspected uterine abnormality
Evaluation for fetal well-being
Evaluation of suspected amniotic fluid abnormalities
Evaluation of suspected placental abruption
Adjunct to external cephalic version
Evaluation for premature rupture of membranes or
premature labor
Evaluation for abnormal biochemical markers
Follow-up evaluation of a fetal anomaly
Follow-up evaluation of placental location for
suspected placenta previa
Evaluation for those with a history of previous
congenital anomaly
Evaluation of fetal condition in late registrants for
prenatal care
To assess findings that may increase the risk of
aneuploidy
To screen for fetal anomalies
American College of Radiology. ACR practice guideline for the per-
formance of obstetrical ultrasound. In: ACR practice guidelines and
technical standards, 2007. Reston (VA): ACR; 2007. p. 10251033.
The placental location, appearance, and relationship
to the internal cervical os should be recorded. It is rec-
ognized that apparent placental position early in preg-
nancy may not correlate well with its location at the time
of delivery. Therefore, if a low-lying placenta or placenta
previa is suspected early in gestation, verification in the
third trimester by repeat ultrasonography is indicated.
Transabdominal, transperineal, or transvaginal views
may be helpful in assessing cervical length or visualiz-
ing the internal cervical os and its relationship to the pla-
centa. Transvaginal or transperineal ultrasonography
may be considered if the cervix appears shortened.
Gestational age is most accurately determined in the
first half of pregnancy. First-trimester crownrump
measurement is the most accurate means for ultrasound
dating of pregnancy. Beyond this period, a variety of
ultrasound parameters, such as biparietal diameter,
abdominal circumference, and femoral diaphysis length,
can be used to estimate gestational age. However, the
variability of gestational age estimations increases with
advancing pregnancy. Significant discrepancies between
gestational age and fetal measurements may suggest the
possibility of a fetal growth abnormality, intrauterine
growth restriction, or macrosomia. The pregnancy should
not be redated after a date has been calculated from an
accurate earlier scan that is available for comparison.
Biparietal diameter is measured at the level of the
thalami and cavum septi pellucidi. The cerebellar hemi-
spheres should not be visible in this scanning plane. The
measurement is taken from the outer edge of the proxi-
mal skull to the inner edge of the distal skull. The head
shape may be flattened (dolichocephaly) or rounded
(brachycephaly) as a normal variant. Under these cir-
cumstances, measurement of the head circumference
may be more reliable than measurement of the biparietal
diameter for estimating gestational age. Head circumfer-
ence is measured at the same level as the biparietal diam-
eter, around the outer perimeter of the calvaria. This
measurement is not affected by head shape.
Femoral diaphysis length can be reliably used after
14 weeks of gestation. The long axis of the femoral shaft
is most accurately measured with the beam of insonation
being perpendicular to the shaft, excluding the distal
femoral epiphysis.
Abdominal circumference or average abdominal
diameter should be determined at the skin line on a true
transverse view at the level of the junction of the umbil-
ical vein, portal sinus, and fetal stomach when visible.
Abdominal circumference or average abdominal diame-
ter measurement is used with other biometric parameters
to estimate fetal weight and may allow detection of
intrauterine growth restriction or macrosomia.
Fetal weight can be estimated by obtaining mea-
surements such as the biparietal diameter, head circum-
ference, abdominal circumference or average abdominal
diameter, and femoral diaphysis length. Results from
various prediction models can be compared with fetal
1081 PRACTICE BULLETINS
weight percentiles from published nomograms. If previ-
ous studies have been performed, appropriateness of
growth also should be reported. Scans for growth evalu-
ation are typically performed at least 24 weeks apart.
A shorter scan interval may result in confusion as to
whether anatomic changes are caused by growth or
by variations in the measurement technique itself.
Currently, even the best fetal weight prediction methods
can yield errors as high as plus or minus 15%. This vari-
ability can be influenced by factors such as the nature
of the patient population, the number and types of
ana-tomic parameters being measured, technical factors
that affect the resolution of ultrasound images, and the
weight range being studied.
Evaluation of the uterus, adnexal structures, and
cervix should be performed when appropriate. The pres-
ence, location, and size of adnexal masses and the pres-
ence of at least the largest and potentially clinically
significant leiomyomas may be recorded. It may not be
possible to image the normal maternal ovaries during the
second and third trimesters.
Three-Dimensional Ultrasonography
Three-dimensional ultrasonography provides an advance
in imaging technology. With three-dimensional ultra-
sonography, the volume of a target anatomic region can be
acquired. The acquired volume then can be displayed in
three orthogonal two-dimensional planes, representing
the sagittal, transverse, and coronal planes of a reference
two-dimensional image within the volume. The volume
also can be displayed in its rendered format, which depicts
the topographic anatomy of the acquired volume. The
technical advantages of three-dimensional ultrasonogra-
phy include its ability to acquire and manipulate an infinite
number of planes and to display ultrasound planes tradi-
tionally inaccessible by two-dimensional ultrasonography.
Despite these technical advantages, proof of a clinical
advantage of three-dimensional ultrasonography in prena-
tal diagnosis in general is still lacking. Potential areas of
promise include fetal facial anomalies, neural tube
defects, and skeletal malformations where three-dimen-
sional ultrasonography may be helpful in diagnosis as an
adjunct to, but not a replacement for, two-dimensional
ultrasonography (1). Until clinical evidence shows a clear
advantage to conventional two-dimensional ultrasonogra-
phy, three-dimensional ultrasonography is not considered
a required modality at this time.
Ultrasound Facility Accreditation
The American Institute of Ultrasound in Medicine and
the American College of Radiology offer ultrasound
facility accreditation. This process involves review of
submitted ultrasound case studies, equipment use and
maintenance, report generation, storage of images, and
ultrasonographer and physician qualifications. Practices,
not individuals, may be accredited in ultrasonography for
obstetrics, gynecology, or both. Practices that receive
ultrasound accreditation have been shown to improve
compliance with published standards and guidelines for
the performance of obstetric ultrasound examinations (2).
Physicians who perform, evaluate, and interpret
diagnostic obstetric ultrasound examinations should be
licensed medical practitioners with an understanding of
the indications for such imaging studies, the expected
content of a complete obstetric ultrasound examination,
and a familiarity with the limitations of ultrasound imag-
ing. They should be familiar with the anatomy, physiol-
ogy, and pathophysiology of the pelvis, the pregnant
uterus, and the fetus. These physicians should have
undergone specific training in obstetric ultrasonography
either during or since their residency training and should
be able to document this training. Completion of an
approved residency in obstetrics and gynecology with
documentation of obstetric ultrasound experience and
training with certification by the American Board of
Obstetrics and Gynecology is evidence of the necessary
and appropriate training.
Physicians are responsible for the quality and accu-
racy of ultrasound examinations performed in their names,
regardless of whether they personally produced the
images. Physicians also are responsible for the quality of
the documentation of examinations and the quality con-
trol and safety of the environments and the procedures.
Documentation and Quality Assurance
Adequate documentation is essential for high-quality
patient care. There should be a record of the ultrasound
examination and its interpretation. Ideally, quality con-
trol is accomplished through careful record keeping of
obstetric ultrasound examination results, reliable archiv-
ing of reports and images, and clinical correlation with
clinical outcomes. The ultimate quality standard of any
imaging study is to correlate the study findings with clin-
ical outcomes. Any practice active in obstetric ultra-
sonography should maintain such records and make
every effort to correlate imaging results with ultimate
clinical outcome data.
Patient Safety
Ultrasonography is safe for the fetus when used appropri-
ately and when medical information about a pregnancy
is needed; however, ultrasound energy delivered to the
fetus cannot be assumed to be completely innocuous,
and the possibility exists that such biological effects may
COMPENDIUM OF SELECTED PUBLICATIONS 1082
be identified in the future (3). Ultrasonography should be
performed only when there is a valid medical indication,
and the lowest possible ultrasound exposure setting
should be used to gain the necessary diagnostic informa-
tion under the as-low-as-reasonably achievable principle
(4). Diagnostic levels of ultrasonography can produce
physical effects, such as mechanical vibrations (referred
to as cavitation) or an increase in tissue temperature
under laboratory conditions.
Although there is no reliable evidence of physical
harm to human fetuses from diagnostic ultrasound imag-
ing using current technology, public health experts, clin-
icians, and industry representatives agree that casual use
of ultrasonography, especially during pregnancy, should
be avoided. The use of either two-dimensional or three-
dimensional ultrasonography only to view the fetus,
obtain a picture of the fetus, or determine the fetal sex
without a medical indication is inappropriate and con-
trary to responsible medical practice. Viewed in this
light, exposing the fetus to ultrasonography with no
anticipation of medical benefit is not justified (57). The
U.S. Food and Drug Administration views the promo-
tion, sale, or lease of ultrasound equipment for making
keepsake fetal videos as an unapproved use of a med-
ical device. Use of ultrasonography without a physi-
cians order may be a violation of state or local laws or
regulations regarding the use of a prescription medical
device (8). Thus, ultrasonography should be used in a
prudent manner to provide medical benefit to the patient.
Cleaning and Sterilization
Use of ultrasound transducers, like any instrument used
on a patient, presents the possibility of microbial trans-
mission if not properly cleaned after each patients use.
Transabdominal ultrasonography is not completely free
of this risk, although the risk is substantially lower than
it is for transvaginal ultrasonography. Transabdominal
ultrasound transducers may be adequately cleansed
between patients simply by wiping with a disposable
antiseptic paper towelette. Transvaginal ultrasound
transducers should always be covered with a single-use
disposable latex or nonlatex cover. However, disposable
protective covers are not without risk of rupture or
defect, and it is recommended that transvaginal ultra-
sound transducers undergo high-level disinfection
between each use. Steps involved in cleaning transvagi-
nal ultrasound transducers include using running water
or a damp soft cloth to remove any residual gel or debris
from the probe, followed by high-level disinfection with
chemical agents (9, 10). The U.S. Food and Drug
Administration has published a list of approved high-
level disinfectants for use in processing reusable medical
devices (11). For all chemical disinfectants, precautions
must be taken to protect workers and patients from the
toxicity of the disinfectant. Practitioners should consult
the labels of proprietary products for specific instruc-
tions as well as instrument manufacturers regarding the
compatibility of these agents with probes.
Clinical Considerations and
Recommendations
Should all patients be offered ultrasonogra-
phy, and what is the sensitivity of ultrasound
for detecting fetal anomalies?
Ultrasonography can be used to diagnose many major
fetal anomalies. It has been suggested that all patients be
offered routine ultrasound screening, given that 90% of
infants with congenital anomalies are born to women
with no risk factors (12). Significant controversy exists
with regard to the sensitivity of routine ultrasonography
in detecting fetal anomalies (1315). In a review of 36
studies involving more than 900,000 fetuses, an overall
sensitivity of 40.4% for detecting fetal anomalies was
noted, with a range of 13.382.4% (16). Studies on this
subject vary with regard to the definition of major versus
minor fetal anomalies, the level of risk in the study pop-
ulation (high risk versus low risk), the expertise of the
operators (tertiary versus nontertiary centers) and the
ascertainment of anomalies. In general, studies per-
formed at tertiary centers showed a higher detection rate
for fetal anomalies (15, 17). Sensitivity tends to be higher
for defects of the central nervous system and urinary
tract than for the heart and great vessels (18). When an
ultrasound examination is performed, patients should be
counseled about the limitations of ultrasonography. This
should include a discussion of the sensitivity of the
examination for the detection of abnormalities and
potential false-positive findings.
Prenatal ultrasonography may reduce the rate of
perinatal mortality, primarily through pregnancy termi-
nation for prenatally diagnosed congenital malforma-
tions, but does not appear to reduce the rate of perinatal
morbidity. Ultrasonography provides more accurate esti-
mation of gestational age, which prevents unnecessary
labor inductions for postterm pregnancy (19). Screening
detects multiple gestations, congenital anomalies, and
intrauterine growth restriction, but direct health benefits
from having this knowledge currently are unproven (20).
Despite the limitations of the evidence, given the detec-
tion rate of more than 80% for fetal anomalies in some
experienced centers, the benefits and limitations of ultra-
sonography should be discussed with all patients.
1083 PRACTICE BULLETINS
However, if a patient requests ultrasonography, it is rea-
sonable to honor the request. The decision ultimately
rests with the physician and patient jointly.
What gestational age represents the optimal
time for an obstetric ultrasound examination?
Ideally, all women should be offered aneuploidy screen-
ing before 20 weeks of gestation, regardless of maternal
age (21). For women presenting before 14 weeks of ges-
tation, the option for first-trimester screening is available,
which may include ultrasonography for nuchal translu-
cency measurement. Ultrasonography in the context of a
nuchal translucency measurement provides accurate dat-
ing of pregnancy and a very effective screening test for
Down syndrome and trisomy 18 when combined with
maternal age and serum markers (pregnancy-associated
plasma protein A and free or total -hCG) (22). However,
a complete anatomic assessment is not possible before 14
weeks of gestation.
In the absence of specific indications, ultrasound
examination between 1820 weeks of gestation allows for
a reasonable survey of fetal anatomy and an accurate esti-
mation of gestational age. At 1820 weeks of gestation,
anatomically complex organs, such as the fetal heart and
brain, can be imaged with sufficient clarity to allow detec-
tion of many major malformations at a time when termi-
nation of pregnancy may still be an option. Therefore, the
optimal timing for a single ultrasound examination in the
absence of specific indications for a first-trimester exam-
ination is at 1820 weeks of gestation.
Should routine measurement of cervical
length be included in ultrasonography?
The value of routine cervical length measurement in low-
risk pregnancies has not been established; therefore, this
practice currently is not recommended. Although there is
an association between short cervix and preterm delivery,
there are no data to support routine screening for all
women. An effective screening protocol for assessing risk
of preterm birth that combines cervical measurements
and other risk factors has not been developed (2325).
For certain pregnant women at high risk, serial evaluation
of the cervical length may identify those at increased risk
of primary or recurrent preterm birth.
How and when is ultrasonography used to
adjust gestational age?
In general, ultrasound-established dates should take pref-
erence over menstrual dates when the discrepancy is
greater than 7 days in the first trimester and greater than
10 days in the second trimester. Ultrasonography may be
considered to confirm menstrual dates if there is a gesta-
tional age agreement within 1 week by crownrump mea-
surements obtained in the first trimester or within 10 days
by an average of multiple fetal biometric measurements
obtained in the second trimester (up to 20 weeks of gesta-
tion). Reassigning gestational age in the third trimester
should be done with caution because the accur-acy of
ultrasonography is within 34 weeks. Before 6 weeks of
gestation, dating can be done by measurement of the ges-
tational sac, which is visible as early as 4 weeks of gesta-
tion and certainly by the fifth week of gestation. The mean
sac diameter, which is the average of three measurements
of the gestational sac, can accurately estimate gestational
age (mean sac diameter [mm] + 30 = gestational age
[days]) (26). Maximum embryo length at 610 weeks of
gestation and crownrump length, which represents the
maximum length of the fetus from the top of the head to
the rump region, are the most accurate at determining ges-
tational age (27). When the crownrump length exceeds
60 mm, dating of pregnancy can be accomplished by other
biometric parameters, such as measurement of the bipari-
etal diameter, head circumference, femur length, and
abdominal circumference. The head circumference is the
most predictive parameter of gestational age between
1422 weeks of gestation because it predicts gestational
age by 3.4 days (28). Combining various parameters
improves the prediction of gestational age slightly over the
use of head circumference measurement alone (28).
Formulas derived from singleton data can be used to
determine gestational age in twins and triplets (28). In the
third trimester, the best single measurement of gestational
age based on fetal biometry is the femur length. However,
reported accuracy of femur length ranges from 1 week in
the second trimester to 34 weeks at term (29, 30).
Guidelines for assignment of gestational age when a dis-
crepancy exists between menstrual and ultrasound-estab-
lished dates vary in different ultrasound units.
How is amniotic fluid volume evaluated
using ultrasonography?
Several techniques have been proposed for the estimation
of amniotic fluid during the ultrasound examination,
including a subjective assessment, single deepest pocket,
and amniotic fluid index (AFI). The technique of subjec-
tive assessment includes comparing the echo-free areas in
the uterus with the areas occupied by the fetus and pla-
centa. This technique showed good intraobserver and
interobserver agreements among experienced examiners
(31) but does not allow for dissemination of criteria for use
by less experienced operators. Furthermore, this technique
does not allow for a longitudinal assessment of trends
in amniotic fluid estimation. The single deepest pocket
COMPENDIUM OF SELECTED PUBLICATIONS 1084
technique involves finding the single largest pocket of
amniotic fluid on ultrasonography, free of cord and fetal
parts, and then measuring either the greatest vertical
dimension or the greatest vertical and horizontal dimen-
sions with the ultrasound transducer perpendicular to the
floor. The AFI technique is based on the division of the
uterus into four quadrants and measuring the deepest verti-
cal pocket of fluid in each quadrant and then adding the
four measurements together. Most ultrasonographers mea-
sure pockets of fluid that are free of cord and fetal parts.
The term oligohydramnios refers to decreased
amniotic fluid volume relative to gestational age.
Oligohy-dramnios is associated with genitourinary
abnormalities in the fetus, premature rupture of mem-
branes, uteroplacental insufficiency, and postterm preg-
nancy. Oligohy-dramnios has been linked to increased
rates of perinatal morbidity and mortality (32).
Oligohydramnios is described in various ways. Two
acceptable definitions are 1) an AFI less than 5 cm or 2)
a maximum deepest vertical pocket of less than 2 cm. In
a randomized clinical trial, the use of amniotic fluid index
compared with single deepest pocket technique during
antepartum surveillance was associated with significantly
higher rates of suspected oligohydramnios, which led to
increased interventions without a demonstrable benefit
(33). Recent studies suggest that AFI is a weaker predic-
tor of perinatal outcome than has been classically sug-
gested (34).
The term polyhydramnios or hydramnios refers to
increased amniotic fluid volume relative to gestational
age. Hydramnios often is idiopathic but can be associated
with gestational and pregestational diabetes, isoimmu-
nization, fetal structural and chromosomal abnormali-
ties, fetal infections, multiple gestations with twintwin
transfusion syndrome, or fetalmaternal hemorrhage.
Idiopathic hydramnios, which represents 5060% of
cases of hydramnios, has been linked to fetal macroso-
mia and an increase in adverse pregnancy outcome (35).
Hydramnios commonly is described by an AFI greater
than or equal to 24 cm or a maximum deepest vertical
pocket of equal to or greater than 8 cm.
How may ultrasonography be used to detect
fetal chromosome abnormalities in the second
trimester?
A second-trimester specialized ultrasound examination,
often called a genetic ultrasound examination, may be
targeted to detect fetal aneuploidy. Individual second-
trimester ultrasound markers, such as echogenic bowel,
intracardiac echogenic focus, short femur or humerus, and
dilated renal pelvis, have a low sensitivity and specificity
for Down syndrome, particularly when used to screen a
low-risk population (36). Studies indicate that the highest
detection rate is achieved with a systematic combination
of markers and gross anomalies, such as thickened
nuchal fold or cardiac defects (37, 38). Studies done in
high-risk populations have reported detection rates of
approximately 5075% in the second trimester, albeit
with a high false-positive rate (39). If no abnormal ultra-
sound markers are identified after carefully performed
ultrasonography, the a priori risk of Down syndrome in a
patient at high risk may be reduced (40). This approach
has not been adequately studied in women at low risk.
With the current limitations of ultrasonography,
ultrasound evaluation is not recommended as a primary
screening modality for Down syndrome and other chro-
mosomal abnormalities. A major limitation of the use of
second-trimester ultrasound markers has been the lack of
standardization in measurements and definitions of what
constitutes abnormal findings. Identification of an
echogenic intracardiac focus or echogenic bowel in a
fetus is based on a subjective assessment of the operator.
Furthermore, studies that defined the lower limits of fetal
long bone measurements for ultrasonography in screen-
ing for Down syndrome have primarily relied on a high-
risk referral population. At this time, risk adjustment
based on second-trimester ultrasound markers should be
limited to individuals with expertise in this area.
How is ultrasonography used to detect
disturbances in fetal growth?
Ultrasonography is helpful in detecting fetal growth dis-
turbances. Four standard fetal measurements generally
are obtained as part of any complete obstetric ultrasound
examination after the first trimester: 1) fetal abdominal
circumference, 2) head circumference, 3) biparietal
diameter, and 4) femur length (41). Fetal morphologic
parameters can be converted to fetal weight estimates
using published formulas and tables (42). Contemporary
ultrasound equipment calculates and displays an esti-
mate of fetal weight on the basis of these formulas.
Although all of the published formulas for estimating
fetal weight show a good correlation with birth weight,
the variability of the estimate generally is plus or minus
1620% (2 standard deviations) (41). If the estimated
fetal weight is below the 10th percentile, further evalua-
tion should be considered for intrauterine growth restric-
tion (43). Similarly, if the estimated fetal weight is more
than 4,000 g or 4,500 g, evaluation should be considered
for fetal macrosomia (44).
Serial ultrasound measurements are of considerable
clinical value in confirming or excluding the diagnosis
and assessing the progression and severity of growth dis-
turbances. Serial ultrasonography to determine the rate
1085 PRACTICE BULLETINS
of growth should be obtained approximately every 24
weeks. Measurements at shorter intervals (less than 2
weeks) may overlap and cause interpretation errors.
Summary of
Recommendations and
Conclusions
The following conclusions are based on good and
consistent evidence (Level A):
Ultrasound examination is an accurate method of
determining gestational age, fetal number, viability,
and placental location.
Gestational age is most accurately determined in the
first half of pregnancy.
Ultrasonography can be used in the diagnosis of
many major fetal anomalies.
Ultrasonography is safe for the fetus when used
appropriately.
The following conclusions are based on limited or
inconsistent evidence (Level B):
Ultrasonography is helpful in detecting fetal growth
disturbances.
Ultrasonography can detect abnormalities in amni-
otic fluid volume.
The following conclusion and recommendation
are based primarily on consensus and expert opin-
ion (Level C):
The optimal timing for a single ultrasound examina-
tion in the absence of specific indications for a first-
trimester examination is at 1820 weeks of gestation.
The benefits and limitations of ultrasonography
should be discussed with all patients.
Proposed Performance
Measure
Documentation of the discussion of the benefits and lim-
itations of ultrasonography
References
1. Goncalves LF, Lee W, Espinoza J, Romero R. Three- and
4-dimensional ultrasound in obstetric practice: does it
help? J Ultrasound Med 2005;24:1599624. (Level III)
2. Abuhamad AZ, Benacerraf BR, Woletz P, Burke BL. The
accreditation of ultrasound practices: impact on compli-
ance with minimum performance guidelines. J Ultra-
sound Med 2004;23:10239. (Level II-3)
3. Abramowicz JS, Fowlkes JB, Skelly AC, Stratmeyer ME,
Ziskin MC. Conclusions regarding epidemiology for
obstetric ultrasound. J Ultrasound Med 2008;27:63744.
(Level III)
4. American Institute of Ultrasound in Medicine. Medical
ultrasound safety. Laurel (MD): AIUM; 1994; reapproved
2002. (Level III)
5. Stark CR, Orleans M, Haverkamp AD, Murphy J. Short-
and long-term risks after exposure to diagnostic ultra-
sound in utero. Obstet Gynecol 1984;63:194200. (Level
II-2)
6. Lyons EA, Dyke C, Toms M, Cheang M. In utero expo-
sure to diagnostic ultrasound: a 6-year follow-up.
Radiology 1988;166:68790. (Level II-2)
7. American Institute of Ultrasound in Medicine. Prudent
Use. Laurel (MD): AIUM; 1999; reapproved 2005. (Level
III)
8. Rados C. FDA cautions against ultrasound keepsake
images. FDA Consum 2004;38:126. (Level III)
9. American Institute of Ultrasound in Medicine. Guidel-
ines for cleaning and preparing endocavitary ultrasound
transducers between patients. Laurel (MD): AIUM; 2000.
(Level III)
10. Centers for Disease Control and Prevention. Sterilization
or disinfection of medical devices. Atlanta (GA): CDC;
2002. Available at: http://www.cdc.gov/ncidod/dhqp/
bp_sterilization_medDevices.html. Retrieved June 9,
2008. (Level III)
11. Food and Drug Administration (US). FDA-cleared steri-
lants and high level disinfectants with general claims for
processing reusable medical and dental devices -
September 28, 2006. Rockville (MD): FDA; 2006.
Available at: http://www.fda.gov/cdrh/ode/germlab.html.
Retrieved June 9, 2008. (Level III)
12. Long G, Sprigg A. A comparative study of routine versus
selective fetal anomaly ultrasound scanning. J Med Screen
1998;5:610. (Level III)
13. Ewigman BG, Crane JP, Frigoletto FD, LeFevre ML, Bain
RP, McNellis D. Effect of prenatal ultrasound screening
on perinatal outcome. RADIUS Study Group. N Engl J
Med 1993;329:8217. (Level I)
14. Saari-Kemppainen A, Karjalainen O, Ylostalo P,
Heinonen OP. Fetal anomalies in a controlled one-stage
ultrasound screening trial. A report from the Helsinki
Ultrasound Trial. J Perinat Med 1994;22:27989. (Level I)
15. Grandjean H, Larroque D, Levi S. The performance of
routine ultrasonographic screening of pregnancies in the
Eurofetus Study. Am J Obstet Gynecol 1999;181:44654.
(Level II-2)
16. Levi S. Ultrasound in prenatal diagnosis: polemics around
routine ultrasound screening for second trimester fetal
malformations. Prenat Diagn 2002;22:28595. (Level III)
COMPENDIUM OF SELECTED PUBLICATIONS 1086
17. Crane JP, LeFevre ML, Winborn RC, Evans JK, Ewigman
BG, Bain RP, et al. A randomized trial of prenatal ultra-
sonographic screening: impact on the detection, manage-
ment, and outcome of anomalous fetuses. The RADIUS
Study Group. Am J Obstet Gynecol 1994;171:3929.
(Level I)
18. Grandjean H, Larroque D, Levi S. Sensitivity of routine
ultrasound screening of pregnancies in the Eurofetus data-
base. The Eurofetus Team. Ann N Y Acad Sci 1998;
847:11824. (Level II-3)
19. Eik-Nes SH, Salvesen KA, Okland O, Vatten LJ. Routine
ultrasound fetal examination in pregnancy: the Alesund
randomized controlled trial. Ultrasound Obstet Gynecol
2000;15:4738. (Level I)
20. Woolf SH. The accuracy and effectiveness of routine pop-
ulation screening with mammography, prostate-specific
antigen, and prenatal ultrasound: a review of published
scientific evidence. Int J Technol Assess Health Care
2001;17:275304. (Level III)
21. American College of Obstetricians and Gynecologists.
Invasive Prenatal Testing for Aneuploidy. ACOG Practice
Bulletin 88. Washington, DC: ACOG; 2007. (Level III)
22. Malone FD, Canick JA, Ball RH, Nyberg DA, Comstock
CH, Bukowski R, et al. First-trimester or second-trimester
screening, or both, for Downs syndrome. First- and
Second-Trimester Evaluation of Risk (FASTER)
Research Consortium. N Engl J Med 2005;353:200111.
(Level II-1)
23. Spong CY. Prediction and prevention of recurrent sponta-
neous preterm birth. Obstet Gynecol 2007;110:40515.
(Level III)
24. Iams JD, Goldenberg RL, Mercer BM, Moawad AH, Meis
PJ, Das AF, et al. The preterm prediction study: can low-
risk women destined for spontaneous preterm birth be
identified? National Institute of Child Health and Human
Development Maternal-Fetal Medicine Units Network.
Am J Obstet Gynecol 2001;184:6525. (Level II-3)
25. Conoscenti G, Meir YJ, DOttavio G, Rustico MA,
Pinzano R, Fischer-Tamaro L, et al. Does cervical length
at 13-15 weeks gestation predict preterm delivery in an
unselected population? Ultrasound Obstet Gynecol
2003;21:12834. (Level II-2)
26. Nyberg DA, Mack LA, Laing FC, Patten RM. Distinguish-
ing normal from abnormal gestational sac growth in early
pregnancy. J Ultrasound Med 1987;6:237. (Level II-3)
27. Wisser J, Dirschedl P, Krone S. Estimation of gestational
age by transvaginal sonographic measurement of greatest
embryonic length in dated human embryos. Ultrasound
Obstet Gynecol 1994;4:45762. (Level III)
28. Chervenak FA, Skupski DW, Romero R, Myers MK,
Smith-Levitin M, Rosenwaks Z, et al. How accurate is
fetal biometry in the assessment of fetal age? Am J Obstet
Gynecol 1998;178:67887. (Level II-3)
29. Stebbins B, Jaffe R. Fetal biometry and gestational age
estimation. In: Jaffe R, Bui TH, editors. Textbook of fetal
ultrasound. New York (NY): Parthenon Publishing; 1999.
p. 4757. (Level III)
30. Pierce BT, Hancock EG, Kovac CM, Napolitano PG,
Hume RF Jr, Calhoun BC. Influence of gestational age
and maternal height on fetal femur length calculations.
Obstet Gynecol 2001;97:7426. (Level II-3)
31. Goldstein RB, Filly RA. Sonographic estimation of amni-
otic fluid volume. Subjective assessment versus pocket
measurements. J Ultrasound Med 1988;7:3639. (Level
III)
32. Baron C, Morgan MA, Garite TJ. The impact of amniotic
fluid volume assessed intrapartum on perinatal outcome.
Am J Obstet Gynecol 1995;173:16774. (Level II-3)
33. Chauhan SP, Doherty DD, Magann EF, Cahanding F,
Moreno F, Klausen JH. Amniotic fluid index vs single
deepest pocket technique during modified biophysical
profile: a randomized clinical trial. Am J Obstet Gynecol
2004;191:6617; discussion 6678. (Level I)
34. Ott WJ. Reevaluation of the relationship between amniot-
ic fluid volume and perinatal outcome. Am J Obstet
Gynecol 2005;192:18039; discussion 1809. (Level II-2)
35. Magann EF, Chauhan SP, Doherty DA, Lutgendorf MA,
Magann MI, Morrison JC. A review of idiopathic
hydramnios and pregnancy outcomes. Obstet Gynecol
Surv 2007;62:795802. (Level III)
36. Smith-Bindman R, Hosmer W, Feldstein VA, Deeks JJ,
Goldberg JD. Second-trimester ultrasound to detect fetus-
es with Down syndrome: a meta-analysis. JAMA
2001;285:104455. (Level III)
37. Vintzileos AM, Campbell WA, Rodis JF, Guzman ER,
Smulian JC, Knuppel RA. The use of second-trimester
genetic sonogram in guiding clinical management of
patients at increased risk for fetal trisomy 21. Obstet
Gynecol 1996;87:94852. (Level III)
38. Bromley B, Benacerraf BR. The genetic sonogram scor-
ing index. Semin Perinatol 2003;27:1249. (Level III)
39. Bahado-Singh RO, Oz UA, Mendilcioglu I, Mahoney MJ.
The mid-trimester genetic sonogram. Semin Perinatol
2005;29:20914. (Level III)
40. Yeo L, Vintzileos AM. The use of genetic sonography to
reduce the need for amniocentesis in women at high-risk
for Down syndrome. Semin Perinatol 2003;27:1529.
(Level III)
41. Hadlock FP, Deter RL, Harrist RB, Park SK. Estimating
fetal age: computer-assisted analysis of multiple fetal
growth parameters. Radiology 1984;152:497501. (Level
II-3)
42. Shepard MJ, Richards VA, Berkowitz RL, Warsof SL,
Hobbins JC. An evaluation of two equations for predict-
ing fetal weight by ultrasound. Am J Obstet Gynecol
1982; 142:4754. (Level III)
43. American College of Obstetricians and Gynecologists.
Intrauterine Growth Restriction. ACOG Practice Bulletin
12. Washington, DC: ACOG; 2000. (Level III)
44. American College of Obstetricians and Gynecologists.
Fetal macrosomia. ACOG Practice Bulletin 22.
Washington, DC: ACOG; 2000. (Level III)
1087 PRACTICE BULLETINS
The MEDLINE database, the Cochrane Library, and
ACOGs own internal resources and documents were used
to conduct a literature search to locate relevant articles pub-
lished between January 1985 and April 2008. The search
was restricted to articles published in the English language.
Priority was given to articles reporting results of original
research, although review articles and commentaries also
were consulted. Abstracts of research presented at symposia
and scientific conferences were not considered adequate for
inclusion in this document. Guidelines published by organi-
zations or institutions such as the National Institutes of
Health and the American College of Obstetricians and
Gynecologists were reviewed, and additional studies were
located by reviewing bibliographies of identified articles.
When reliable research was not available, expert opinions
from obstetriciangynecologists were used.
Studies were reviewed and evaluated for quality according
to the method outlined by the U.S. Preventive Services
Task Force:
I Evidence obtained from at least one properly
designed randomized controlled trial.
II-1 Evidence obtained from well-designed controlled
trials without randomization.
II-2 Evidence obtained from well-designed cohort or
casecontrol analytic studies, preferably from more
than one center or research group.
II-3 Evidence obtained from multiple time series with or
without the intervention. Dramatic results in uncon-
trolled experiments also could be regarded as this
type of evidence.
III Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees.
Based on the highest level of evidence found in the data,
recommendations are provided and graded according to the
following categories:
Level ARecommendations are based on good and con-
sistent scientific evidence.
Level BRecommendations are based on limited or incon-
sistent scientific evidence.
Level CRecommendations are based primarily on con-
sensus and expert opinion.
Copyright February 2009 by the American College of
Obstetricians and Gynecologists. All rights reserved. No part of
this publication may be reproduced, stored in a retrieval system,
posted on the Internet, or transmitted, in any form or by any
means, electronic, mechanical, photocopying, recording, or
otherwise, without prior written permission from the publisher.
Requests for authorization to make photocopies should be
directed to Copyright Clearance Center, 222 Rosewood Drive,
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
The American College of Obstetricians and Gynecologists
409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920
Ultrasonography in pregnancy. ACOG Practice Bulletin No. 101.
American College of Obstetricians and Gynecologists. Obstet
Gynecol 2009;113:45161.
COMPENDIUM OF SELECTED PUBLICATIONS 1088
CLINICAL MANAGEMENT GUIDELINES FOR OBSTETRICIANGYNECOLOGISTS
NUMBER 102, MARCH 2009
(Replaces Committee Opinion Number 383, October 2007)
This Practice Bulletin was devel-
oped by the ACOG Committee on
Practice BulletinsObstetrics with
the assistance of Ruth C. Fretts,
MD. The information is designed to
aid practitioners in making deci-
sions about appropriate obstetric
and gynecologic care. These guide-
lines should not be construed as
dictating an exclusive course of
treatment or procedure. Variations
in practice may be warranted based
on the needs of the individual
patient, resources, and limitations
unique to the institution or type of
practice.
ACOG
PRACTICE
BULLETIN
THE AMERICAN COLLEGE OF
OBSTETRICIANS AND
GYNECOLOGISTS
WOMENS HEALTH CARE PHYSICIANS
Management of Stillbirth
Stillbirth is one of the most common adverse pregnancy outcomes, complicat-
ing 1 in 160 deliveries in the United States. Approximately 25,000 stillbirths
at 20 weeks or greater of gestation are reported annually (1). The purpose
of this bulletin is to review the current information on stillbirth, including
definitions and management, the evaluation of a stillbirth, and strategies for
prevention.
Background
Definition
The United States National Center for Health Statistics defines fetal death as
the delivery of a fetus showing no signs of life as indicated by the absence of
breathing, heart beats, pulsation of the umbilical cord, or definite movements of
voluntary muscles (2). There is not complete uniformity among states with
regard to birth weight and gestational age criteria for reporting fetal deaths.
However, the suggested requirement is to report fetal deaths at 20 weeks or
greater of gestation (if the gestational age is known), or a weight greater than
or equal to 350 grams if the gestational age is not known (3). The cutoff of 350
grams is the 50th percentile for weight at 20 weeks of gestation.
The term stillbirth is preferred among parent groups, and more recent
research efforts have begun using this term in place of fetal death. Therefore, in
this document, the term stillbirth is used. It must be emphasized that the crite-
ria for stillbirth do not imply a point of viability and were chosen to facilitate
uniform data collection.
In the United States, fetal losses related to terminations of pregnancy for
lethal fetal anomalies and inductions of labor for previable premature rupture
of membranes are specifically excluded from the stillbirth statistics and are
classified as terminations of pregnancy.
1089 PRACTICE BULLETINS
Table 1. Commonly Reported Maternal Risk Factors and Causes for Stillbirth
Developed Countries Developing Countries
Congenital and karyotypic anomalies Obstructed and prolonged labor and associated asphyxia, infection,
and birth injury
Growth restriction and placental abnormalities Infection especially syphilis and gram-negative infections
Medical diseases such as diabetes, systemic lupus erythematosus, Hypertensive disease and complications of preeclampsia and eclampsia
renal disease, thyroid disorders, and cholestasis of pregnancy
Congenital anomalies
Hypertensive disease and preeclampsia
Poor nutritional status
Infection such as human parvovirus B19, syphilis, streptococcal infection,
Malaria
and listeria
Sickle cell disease
Smoking
Multiple gestation
Reproduced with permission by the International Federation of Gynecology and Obstetrics (FIGO) from: McClure EM, Nalubamba-Phiri M, Goldenberg RL. Stillbirth in
developing countries. Intl J Gynecol Obstet 2006;94(2):8290.
Frequency of Occurrence
In 2004, the stillbirth rate in the United States was 6.2
per 1,000 births, down from 6.4 per 1,000 births in 2002
(1). Since 1990, the rate of early stillbirth (2027 weeks)
has remained stable at approximately 3.2 per 1,000
births, while the rate of late stillbirth (28 weeks or
greater) has decreased from 4.3 to 3.1 per 1,000 births.
Risk Factors
In developed countries, the most prevalent risk factors
associated with stillbirth are non-Hispanic black race,
nulliparity, advanced maternal age, and obesity (see
Table 1 for additional risk factors). From a public health
perspective, obesity, smoking, and drug and alcohol use
are common potentially modifiable risk factors for
adverse pregnancy outcome.
Racial Factors
In the United States, Hispanic, Asian, and Native American
women, and non-Hispanic white women all have stillbirth
rates of less than 6 per 1,000. In contrast, stillbirth rates
have been consistently and significantly higher in non-
Hispanic black women at a rate of 11.25 per 1,000 (1). The
reason for this health care disparity is multifactorial and
the subject of ongoing research. Higher rates of stillbirth
persist among non-Hispanic black women with adequate
prenatal care; this has been attributed to higher rates of dia-
betes mellitus, hypertension, placental abruption, and pre-
mature rupture of membranes (4, 5).
Comorbidities
Hypertension and diabetes are two of the most common
medical comorbid pregnancy conditions (6). Population-
based studies demonstrated a twofold to fivefold
increase in the risk of stillbirth among women with
pregestational diabetes (7, 8). However, with preconcep-
tion care and optimal glycemic control, the risk of
perinatal death may be reduced (9, 10). Patients with a
personal history or family history of thromboembolism
or multiple inherited or acquired thrombophilias appear
to have an increased risk of stillbirth, but there is no evi-
dence that screening an unselected population is either
clinically effective or cost-effective (11). Other reported
medical risk factors for stillbirth in the United States are
described in Table 2.
Obesity
Obesity is defined as a prepregnancy body mass index
(BMI) (defined as weight in kilograms divided by height
in meters squared) of 30 or greater and is the fastest
growing health problem in the United States (12).
Obesity in pregnancy is associated with an increased risk
of both early fetal loss and stillbirth (13). In a national
database, the risk of stillbirth was 5.5/1,000 for nonobese
mothers, 8/1,000 for those with a BMI of 3039.9 and
11/1,000 for women with a BMI greater than 40.0 (14).
There is some evidence that the obesity-related stillbirth
risk increases with gestational age. In one study, the haz-
ard ratio for stillbirth increased from 2.1 at 2836 weeks
to 4.6 at 40 weeks of gestation (15). The reason for this
association is likely multifactorial, but obesity is associ-
ated with a fivefold increase in stillbirth associated with
placental dysfunction. Obesity remains an independent
risk factor for stillbirth even after controlling for smok-
ing, gestational diabetes, and preeclampsia. (1618).
Multiple Gestations
The stillbirth rate among multiple gestations is four times
higher than among singletons (19.6 per 1,000) (19). Higher
rates are due both to complications specific to multiple ges-
tation (such as twintwin transfusion syndrome), as well as
COMPENDIUM OF SELECTED PUBLICATIONS 1090
Table 2. Estimates of Maternal Risk Factors and Risk of Stillbirth
Condition Prevalence Estimated rate of stillbirth OR*
All pregnancies 6.4/1000 1.0
Low-risk pregnancies 80% 4.05.5/1000 0.86
Hypertensive disorders
Chronic hypertension 6%10% 625/1000 1.52.7
Pregnancy-induced hypertension
Mild 5.8%7.7% 951/1000 1.24.0
Severe 1.3%3.3% 1229/1000 1.84.4
Diabetes
Treated with diet 2.5%5% 610/1000 1.22.2
Treated with insulin 2.4% 635/1000 1.77.0
SLE <1% 40150/1000 620
Renal disease <1% 15200/1000 2.230
Thyroid disorders 0.2%2% 1220/1000 2.23.0
Thrombophilia 1%5% 1840/1000 2.85.0
Cholestasis of pregnancy <0.1% 1230/1000 1.84.4
Smoking >10 cigarettes 10%20% 1015/1000 1.73.0
Obesity (prepregnancy)
BMI 2529.9 kg/m
2
21% 1215/1000 1.92.7
BMI >30 20% 1318/1000 2.12.8
Low educational attainment (<12 y vs. 12 y+) 30% 1013/1000 1.62.0
Previous growth-restricted infant (<10%) 6.7% 1230/1000 24.6
Previous stillbirth 0.5%1.0% 920/1000 1.43.2
Multiple gestation
Twins 2.7% 12/1000 1.02.8
Triplets 0.14% 34/1000 2.83.7
Advanced maternal age (reference <35 y)
3539 y 15%18% 1114/1000 1.82.2
40 y+ 2% 1121/1000 1.83.3
Black women compared with white women 15% 1214/1000 2.02.2
*OR of the factor present compared to the risk factor absent.
Reprinted from Am J Obstet Gynecol, 193, Fretts R, Etiology and prevention of stillbirth, 192335, 2005, with permission from Elsevier.
to increased risks of common complications such as
advanced maternal age, fetal abnormalities, and growth
restriction.
Maternal Age Older Than 35 years
Older maternal age is associated with an increased risk of
stillbirth in both nulliparous and multiparous women (9,
20). A significant proportion of perinatal deaths seen in
older women are related to lethal congenital and chromo-
somal anomalies. The introduction of population-based
screening for chromosomal abnormalities has contributed
to lower rates of this type of perinatal demise (21). Large-
scale studies suggest that an increased risk of unexplained
stillbirth late in pregnancy persists in older women, even
after controlling for risk factors such as hypertension, dia-
betes, placenta previa, and multiple gestation (20, 22, 23).
In addition, there appears to be an interaction between first
birth and advanced maternal age that places primiparous
older women at an increased risk (20). Based on one study,
the estimated risk of stillbirth is 1 in 116 in a 40-year-old
nulliparous woman after 37 weeks of gestation, compared
with 1 in 304 in a multiparous woman of the same age (20).
1091 PRACTICE BULLETINS
Past Obstetric History
Women with previous pregnancy complications, such as
preterm delivery, growth restriction, or preeclampsia, are
at increased risk of stillbirth in subsequent pregnancies
(24). The relationship is strongest for explained stillbirth
and there also is a persistent 1.7-fold to 2-fold increase in
unexplained stillbirth associated with these pregnancy
complications. In addition, the risk of subsequent still
birth is twice as high for women with a prior live born,
growth restricted infant delivered before 32 weeks of ges-
tation than for women with a prior stillbirth (25). The rela-
tionship between prior cesarean delivery and subsequent
stillbirth remains controversial. This association has not
been confirmed in three large studies from the United
States (2628). In the largest of these studies, the unex-
plained fetal death rates at term for women with and with-
out a previous cesarean delivery were 0.8 and 0.7 per 1,000
births, respectively (27). In contrast, in two large studies
from the United Kingdom, previous cesarean delivery was
associated with an increased rate of explained (29) and
unexplained stillbirth (24) with an increased odds ratio of
1.5 for all causes of subsequent stillbirth.
Potential Causes of Stillbirth
The study of specific causes of stillbirth has been ham-
pered by the lack of uniform protocols for evaluating and
classifying stillbirths and by decreasing autopsy rates. In
most cases, fetal death certificates are filled out before a
full postnatal investigation, and amended death certifi-
cates are rarely filed when additional information from
the stillbirth evaluation emerges. In any specific case, it
may be difficult to assign a definite cause to a stillbirth.
A significant proportion of stillbirths remain unex-
plained even after a thorough evaluation (22, 23).
Fetal Growth Restriction
Fetal growth restriction is associated with a significant
increase in the risk of stillbirth with the most severely
affected fetuses (weight less than the 2.5th percentile)
being at the greatest risk (30). The cumulative risk of
fetal death is approximately 1.5% at fetal weights less
than the 10th percentile, increasing to a risk of 2.5% at
less than the 5th percentile for gestational age (31, 32).
Fetal growth restriction is associated with some fetal
aneuplodies, fetal infection, maternal smoking, hyper-
tension, autoimmune disease, obesity, and diabetes.
Placental Abruption
Placental abruption is another common cause of still-
birth. If abruption occurs in the preterm fetus, it is more
likely to cause stillbirth. The rates of abruption appear to
be increasing (33). Maternal cocaine and other illicit
drug use, smoking, hypertension, and preeclampsia are
all significant contributors to abruption and stillbirth
(3437). Fetomaternal hemorrhage in the absence of pla-
cental abruption is a rare cause of stillbirth and occurs
mainly in unusual scenarios, such as chorioangioma or
choriocarcinoma.
Chromosomal and Genetic
Abnormalities
An abnormal karyotype can be found in approximately
813% of stillbirths (3840). The rate of karyotypic abnor-
malities exceeds 20% in fetuses with anatomic abnormali-
ties or in those with growth restriction, but the rate of
chromosomal anomalies found in normally formed fetuses
was found to be 4.6% in one large series (40). If an abnor-
mal karyotype is found in association with stillbirth, the
most common abnormalities are monosomy X (23%), tri-
somy 21 (23%), trisomy 18 (21%), and trisomy 13 (8%).
Confined placental mosaicism also has been associated
with an increased risk of stillbirth, but currently is not part
of standard testing (41). Karyotypic analysis underesti-
mates the contribution of genetic abnormalities to stillbirth
because in up to 50% of karyotype attempts cell culture is
unsuccesful (39). One strategy to increase the yield of cell
culture is to perform an amniocentesis before the delivery.
This is typically performed after the woman has had an
opportunity to process the death of her baby and after an
epidural is placed. In a large Dutch study, invasive testing
had a much greater tissue culture rate (85%) than fetal tis-
sue sampling after birth (28%) (40). In addition, routine
assessments for single gene defects and microdeletions cur-
rently are not recommended because of uncertainty of the
role of these genetic anomalies. However, it is likely that no
single-gene defect is likely to be responsible for a signifi-
cant proportion of stillbirth. Genetic evaluation for specific
abnormalities should be guided by the clinical history and
detected fetal abnormalities. Approximately 20% of still-
born fetuses have dysmorphic features or skeletal abnor-
malities and 1520% have a major malformation (38, 42).
Infection
In developed countries, most stillbirths related to infec-
tion occur in the premature fetus. It has been estimated
that infection is implicated in up to 19% of stillbirths at
less than 28 weeks of gestation, but only 2% of stillbirths
at term (43). There is considerable variation in the
reported proportion of stillbirths related to infection due
in part to differences in classification methods.
Pathogens that are causally associated with stillbirth,
include parvovirus, cytomegalovirus, Listeria monocyto-
genes, and syphilis. In the developing world, malaria is a
significant preventable cause of stillbirth.
COMPENDIUM OF SELECTED PUBLICATIONS 1092
Cord Events
Although many stillbirths are attributed to a cord acci-
dent, this diagnosis should be made with caution. Cord
abnormalities, including a nuchal cord, are found in
approximately 30% of normal births and may be an inci-
dental finding (44). In order to attribute a stillbirth to a
cord accident there should be evidence of obstruction or
circulatory compromise on umbilical cord examination.
In addition, other causes of stillbirth should be excluded.
Management
Sensitivity is needed when discussing evaluation of a still-
born fetus with the family. In discussing options, clinicians
should refer to the fetus by name, if one was given. Grief-
stricken parents may be reluctant to consent to evaluation or
autopsy examination, and some may have religious or cul-
tural objections. Parents should be informed about the rea-
sons for autopsy, procedures (eg, the face usually is not
disfigured) and potential costs. Even though the bereaved
parents may not want the information initially, health care
providers should emphasize that results of the evaluation
may be useful to the patient and her family in planning
future pregnancies. If the family objects to a standard autop-
sy, they should be informed of the potential value of less
invasive methods of evaluation, including the use of pho-
tographs, X-ray imaging, ultrasonography, magnetic reso-
nance imaging, and tissue sampling (blood or skin). These
methods may help to identify a syndrome or chromosomal
abnormality even without full autopsy data. Syndrome
identification may delineate etiologic and pathogenetic fac-
tors that could have predictive significance for recurrence
risk and the risk of other associated anomalies (45).
After a stillbirth or neonatal death, proper manage-
ment includes obtaining a complete perinatal and family
history, performing a physical examination of the fetus
(with documentation by description and photography, if
possible), and obtaining laboratory studies (see Fig. 1). To
ascertain the etiology and provide appropriate counseling
to the family, clinicalpathologic correlation is best accom-
plished by a team comprising obstetricians, pediatricians
or neonatologists, pathologists, and geneticists. Initial eval-
uation by a geneticist or pathologist may help the team
coordinate the evaluation and the needed follow-up.
Clinical Considerations
What are the essential components of an
evaluation of a fetal death?
The most important tests in the evaluation of a stillbirth
are fetal autopsy; examination of the placenta, cord, and
membranes; and karyotype evaluation. An algorithm for
Figure. 1. Flow chart for fetal and placental evaluation
Inspect fetus and placenta:
Weight, head circumference, and length of fetus
Weight of placenta
Photographs of fetus and placenta
Frontal and profile photographs of whole body, face, extremi-
ties, palms, and any abnormalities
Document finding and abnormalities
Obtain consent from parents for cytologic specimens:
Obtain cytologic specimens with sterile techniques and
instruments
Acceptable cytologic specimens (at least one)
Amniotic fluid obtained by amniocentesis at time of
prenatal diagnosis of demise: particularly valuable if
delivery is not expected imminently
Placental block (1 1) cm taken from below the cord
insertion site on the unfixed placenta
Umbilical cord segment (1.5 cm)
Internal fetal tissue specimen, such as costochondral
junction or patella; skin is not recommended
Place specimens in a sterile tissue culture medium of lactated
Ringers solution and keep at room temperature when trans-
ported to cytology laboratory
Obtain parental consent for fetal autopsy
Fetal autopsy and placental
pathology (may include
fetal whole-body X-ray)
If no consent is given for
autopsy, send placenta
alone for pathology
evaluation is given in Figure 1. Specific aspects of the
evaluation are outlined as follows and in Table 3.
Examination of the Stillborn Fetus
The general examination of the stillborn fetus should be
done promptly, noting any dysmorphic features and
obtaining measurements of weight, length, and head cir-
cumference (4648). Foot length may be especially useful
before 23 weeks of gestation to ascertain gestational age.
Photographs of the whole body (unclothed); frontal and
profile views of the face, extremities, and palms; and
close-up photographs of specific abnormalities are vital
for subsequent review and consultation with a specialist,
particularly if no geneticist is available at the institution.
Even if parents have declined an autopsy, a description of
any obvious abnormalities of the stillborn fetus should be
1093 PRACTICE BULLETINS
Table 3. Alternatives to a Complete Autopsy
Examination Strengths and Limitations
Placental examination and external examination by a perinatal Will be more likely to identify syndromes, congenital abnormality, and
pathologist (generally includes measurements of the baby, X-rays, timing of death as well as growth abnormalities. Will be able to
and photographs) detect placental and cord infections
Will miss fetal infections and internal congenital and CNS anomalies
Placental examination and external examination by a perinatal Same as above but will be more likely to identify fetal infections
pathologist, and selected biopsies (this generally includes measurements
of the baby, X-rays, and photographs)
Gross and microscopic placental examination and external and internal Allows the baby to be returned to the family with all of the organs.
examination of the fetus by a perinatal pathologist, organs are left with Will miss central nervous system pathology, but will detect internal
the body, and the brain is not examined (this generally includes congenital abnormalities and be able to assess the role of infection
measurements of the baby, X-rays, and photographs)
Head sparing autopsy Benefits of full autopsy, may miss some CNS pathology
MRI (plus or minus directed needle biopsy) May be very useful when the family requires burial intact in a timely
manner. MRI is good in the identification of CNS pathology, but other
abnormalities such as cardiac abnormalities are more likely to be
missed. Infections will not be diagnosed unless additional needle
biopsies are considered. This strategy has not been compared with
traditional autopsy
Ultrasound Best done while in utero, but can be done after birth. The head, kidney,
or abdomen can be evaluated, but only static images of the heart can
be seen. Not as good as MRI for the brain, but may be able to provide
some useful information if a previous fetal radiologic survey was not
performed. Limited by the degree of maceration, and does not assess
role of infection in the fetal death
Abbreviations: CNS, central nervous system; MRI, magnetic resonance imaging
included in the medical record. Measurements may be
accomplished by the obstetrician, pathologist, or other
specialist, such as a neonatologist, depending on the insti-
tutional protocol.
Autopsy as well as examination of the placenta should
be offered. This is especially true when dysmorphic fea-
tures, inconsistent growth measurements, anomalies,
hydrops, or growth restriction are present. Parents should
be given the opportunity to hold the baby and perform cul-
tural or religious activities, such as baptism, before the
autopsy. Whole-body X-ray with anteriorposterior and
lateral views may reveal an unrecognized skeletal abnor-
mality or further define a grossly apparent deformity.
When a full autopsy is performed, it should follow
published guidelines for perinatal autopsy (49, 50). The
pathologist should be aware of the clinical history and
suspected genetic diagnoses, as well as any necessary tis-
sue collection that needs to be performed for additional
analyses.
Examination of the Placenta
Gross and microscopic examination of the placenta is an
essential component of the evaluation of any stillbirth
and should include an examination of the membranes
and umbilical cord that may corroborate autopsy find-
ings. Even if the family declines fetal autopsy, histolog-
ic study of the placenta usually is acceptable and can be
valuable in identifying underlying etiologies (51, 52).
Fetal Laboratory Studies
Karyotypic analyses are of sufficient yield that it should
be performed in all cases of stillbirth after appropriate
parental permission is obtained (40). If chromosomal
culture is not successful, in situ hybridization can be
used to detect common chromosomal abnormalities.
Chromosomal information is particularly valuable if the
fetus displays dysmorphic features, inconsistent growth
measurements, anomalies, hydrops, or growth restric-
tion. Fetal karyotype also is important if a parent carries
a balanced chromosomal rearrangement (eg, transloca-
tion or inversion) or has a mosaic karyotype. Samples of
amniotic fluid, umbilical cord, fetal tissue, or placenta
may be obtained for chromosomal and any other relevant
tests. Amniocentesis for fetal karyotyping has the high-
est yield and is particularly valuable if delivery is not
expected imminently (40).
After delivery, the most viable tissue generally is the
placenta or segment of umbilical cord closest to the pla-
centa, followed by fetal cartilage obtained from the cos-
tochondral junction or patella (see Fig. 1) (5355).
COMPENDIUM OF SELECTED PUBLICATIONS 1094
Appropriate history and physical findings should be sent
to the laboratory for the laboratory personnel to choose
any appropriate cytogenetic tests.
The Wisconsin Stillbirth Service program estimated
that the real cost of a stillbirth assessment was approxi-
mately $1,450 in 2001 (56). The most significant infor-
mation gained was a change in the estimated risk of
recurrent stillbirth (42% of cases). Other consequences
were a change in the recommendations for subsequent
pregnancies with respect to prenatal diagnosis (in 22%)
and preconception management (in 1%).
Maternal Evaluation
A thorough maternal history should be taken looking
for known conditions or symptoms suggestive of those
that have been associated with stillbirth (Table 4). In
addition to obstetric history, including exposures
(eg, medications and viral infections), a family history
with a three-generation pedigree, if possible, should be
reviewed. Any pertinent information in the maternal or
paternal pedigree should be documented and investi-
gated further. Relevant original medical records and doc-
umentation should be obtained whenever possible. The
gestational age by last menstrual period, maternal exam-
inations, laboratory data, and ultrasound examination
should be recorded for correlation with the physical
examination of the neonate. Possible nongenetic causes,
such as infection, placental abruption, and umbilical
cord abnormality also should be considered.
Investigation for fetalmaternal hemorrhage should be
conducted shortly after the diagnosis of the demise (57).
Maternal testing for lupus anticoagulant, anticardiolipin
antibodies, human parvovirus B19 immunoglobulin G and
immunoglobulin M antibodies and thyroid stimulating
hormone may provide information that could affect future
pregnancy management (5860). In cases with severe
placental pathology, significant growth restriction, or in
the setting of a family or personal history of thrombosis,
factor V Leiden mutation, prothrombin mutation,
antithrombin III level, MTHFR gene mutation, protein C
activity, and protein S activity may provide information
that could affect future pregnancy management (5860).
However, routine testing for thrombophilias is contro-
vesial and may lead to unnecessary interventions.
What are the options for management of the
current pregnancy after confirmation of a
diagnosis of fetal death?
Methods of Delivery
The method and timing of delivery after a fetal death
depends on the gestational age at which the death occur-
red, on the maternal history of a previous uterine scar, and
maternal preference. Although most patients will desire
prompt delivery, the timing of delivery is not critical;
coagulopathies are associated with prolonged fetal reten-
tion and are uncommon. In the second trimester, dilation
and evacuation can be offered if an experienced provider
is available, although patients should be counseled that
dilation and evacuation may limit efficacy of autopsy for
the detection of macroscopic fetal abnormalities.
Labor induction is appropriate at later gestational
ages, if second trimester dilation and evacuation is
unavailable, or based on patient preference. Much of the
data for management of fetal demise has been extrapo-
lated fromrandomized trials of management of second
trimester pregnancy termination. Before 28 weeks of
gestation, vaginal misoprostol appears to be the most
efficient method of induction, regardless of cervical
Bishop score (61, 62), although high-dose oxytocin infu-
sion also is an acceptable choice (63, 64). Typical
dosages for misoprostol use are 200400 mcg vaginally
every 412 hours. After 28 weeks of gestation, induction
of labor should be managed according to usual obstetric
protocols. Cesarean delivery for fetal demise should be
reserved for unusual circumstances because it is associ-
ated with potential maternal morbid-ity without any fetal
benefit.
Several studies have evaluated the use of misopros-
tol at a dosage of 400 mcg every 6 hours in women with
a stillbirth between 24 and 28 weeks of gestation and a
prior uterine scar (65, 66). Available evidence from ran-
domized trials supports the use of vaginal misoprostol as
a medical treatment to terminate nonviable pregnancies
before 24 weeks of gestation (67). Further research is
required to assess effectiveness and safety, optimal route
of administration, and dose.
In patients after 28 weeks of gestation, cervical
ripening with a transcervical Foley catheter has been
associated with uterine rupture rates comparable to spon-
taneous labor (68) and this may be a helpful adjunct in
patients with an unfavorable cervical examination.
Therefore, based on limited data in patients with a prior
low transverse cesarean delivery, trial of labor remains a
favorable option. There are limited data to guide clinical
practice in a patient with a prior classical cesarean deliv-
ery, and the delivery plan should be individualized.
What support services and clinical counseling
should be offered to the patient with a fetal
death?
Patient support should include emotional support and
clear communication of test results. Referral to a bereave-
ment counselor, religious leader, peer support group, or
1095 PRACTICE BULLETINS
Table 4. Elements of the Stillbirth Evaluation
Key Components Details Comments
Patient history Family history
Recurrent spontaneous abortions
Venous thromboembolism or pulmonary embolism
Congenital anomaly or abnormal karyotype
Hereditary condition or syndrome
Developmental delay
Consanguinity
Maternal history
Prior venous thromboembolism or pulmonary embolism
Diabetes mellitus
Chronic hypertension
Thrombophilia
Systemic lupus erythematosus
Autoimmune disease
Epilepsy
Severe anemia
Heart disease
Tobacco, alcohol, drug or medication abuse
Obstetric history
Recurrent miscarriages
Previous child with anomaly, hereditary condition, or
growth restriction
Previous gestational hypertension or preeclampsia
Previous gestational diabetes mellitus
Previous placental abruption
Previous fetal demise
Current pregnancy
Maternal age
Gestational age at fetal death
Medical conditions complicating pregnancy
Hypertension
Gestational diabetes mellitus
Systemic lupus erythematosus
Cholestasis
Pregnancy weight gain and body mass index
Complications of multifetal gestation, such as
twintwin transfusion syndrome, twin reversed
arterial perfusion syndrome, and discordant growth
Placental abruption
Abdominal trauma
Preterm labor or rupture of membranes
Gestational age at onset of prenatal care
Abnormalities seen on an ultrasound image
Infections or chorioamnionitis
(continued)
COMPENDIUM OF SELECTED PUBLICATIONS 1096
Table 4. Elements of the Stillbirth Evaluation (continued)
Key Components Details Comments
Fetal autopsy If patient declines, external evaluation by a trained Provides important information in approximately
perinatal pathologist. Other options include photographs, 30% of cases
X-ray imaging, ultrasonography, magnetic resonance
imaging, and sampling of tissues, such as blood or skin.
Fetal karyotype Amniocentesis before delivery provides the greatest Abnormalities found approximately 8%
yield (84%). Umbilical cord proximal to placenta if
amniocentesis declined (30%). Fluorescence in situ
hybridization may be useful if fetal cells cannot be cultured.
Placental examination Includes evaluation for signs of viral or bacterial infection. Provides additional information in 30% of cases.
Discuss available tests with pathologist. Infection is more common in preterm stillbirth
(19% versus 2% at term)
Maternal evaluation at time Complete blood count Routine testing for thrombophilias is controversial
of demise
Fetalmaternal hemorrhage screen: KleihauerBetke
and may lead to unnecessary interventions.
test or comparable test for fetal cells in maternal
Consider in cases with severe placental pathology
circulation
and or growth restriction, or in the setting of a
Human parvovirus B-19 immunoglobulin G and
personal or family history of thromboembolic
immunoglobulin M antibody
disease.
Syphilis
Lupus anticoagulant
Anticardiolipin antibodies
Thyroid-stimulating hormone
Thrombophilia (selected cases only)
Factor V Leiden
Prothrombin gene mutation
Antithrombin III
Fasting homocysteine
Postpartum Protein S and protein C activity (selected cases)
Parental karyotype (if appropriate)
In selected cases Indirect Coombs test If not performed previously in pregnancy.
Glucose screening (oral glucose tolerance test, In the large for gestational age baby
hemoglobin A1C)
Toxicology screen In cases of placental abruption or when drug use is
suspected
Unproven benefit Antinuclear antibody test Many times is an incidental finding and may lead
to unnecessary interventions
Serology for toxoplasmosis, rubella, cytomegalovirus, Rarely helpful, infection causing death is made by
herpes simplex virus history and examining the baby, placenta,
and cord
Developing technology Comparative genomic hybridization The value of these has not yet been established
Testing for single-gene mutations
Testing for confined placental mosaicism and nucleic
acid-based testing for infection
mental health professional may be advisable for manage-
ment of grief and depression. Feelings of guilt or anger in
parents who have experienced a perinatal death are com-
mon and may be magnified when there is an abnormal
child or a genetic defect. However, some parents may
welcome discussion and find relief in autopsy results. The
results of the tests are important even when no specific
diagnosis is identified (69). The results of the autopsy,
placental examination, laboratory tests, and cytogenetic
studies should be communicated to the involved clini-
cians and to the family of the deceased infant in a timely
manner. If there was no growth of the fetal chromosomes
1097 PRACTICE BULLETINS
(or these were not obtained), further consultation with a
genetics or maternalfetal medicine subspecialist is
advised to discuss the need for parental chromosomal
testing. A copy of the results of the tests and a list of diag-
noses excluded should be provided to the patients.
For the patient with a history of an unex-
plained fetal death in a previous pregnancy,
how should clinical management be altered
in subsequent pregnancies?
Recurrence Counseling
Counseling can be hampered by insufficient information
regarding the etiology of the prior stillbirth. In many
cases, the prior stillbirth may be unexplained despite a
thorough evaluation. In patients in whom complete eval-
uation for previous stillbirth was not done, evaluation
should be completed with parental permission. When
specific risks are identified, the risk of recurrence may be
quantifiable. In low-risk women with unexplained still-
birth, the risk of recurrence stillbirth after 20 weeks is
estimated at 7.810.5/1,000 with most of this risk occur-
ring before 37 weeks of gestation. The risk of recurrent
stillbirth after 37 weeks is very low at 1.8/1,000. In com-
parison, women with a history of a live birth complicated
by preterm fetal growth restriction have a stillbirth rate
of 21.8/1,000 in a subsequent pregnancy (25). Rates of
recurrent fetal loss are higher in women with medical
complications such as diabetes or hypertension or in
those with obstetric problems with a significant recur-
rence risk, such as placental abruption. Despite reassur-
ances, the patient is likely to be anxious and to require
ongoing support.
Antepartum Surveillance
There is little evidence-based data to guide the treating
clinician in the antepartum surveillance of a patient who
had a prior unexplained stillbirth. In patients with a histo-
ry of stillbirth, antepartum testing may be initiated at
3234 weeks of gestation. However, this approach is asso-
ciated with potential morbidity and cost: rates of delivery
for abnormal or equivocal testing were 16.3% at or before
39 weeks of gestation and 1% before 36 weeks of gesta-
tion. Similarly, the authors of one study estimate that ante-
natal testing before 37 weeks of gestation results in a 1.5%
rate of iatrogenic prematurity for intervention based on
false- positive test results (70). The excess risk of infant
mortality due to late preterm birth is 8.8/1,000 at 3233
weeks of gestation and 3/1,000 at 3436 weeks of gesta-
tion (71), and this must be considered in any strategy that
may lead to iatrogenic late preterm birth.
Fetal Kick Counting
Multiple studies have demonstrated that women who
report decreased fetal movement are at increased risk for
adverse perinatal outcome (72). Although fetal kick
counting is an inexpensive test of fetal well being, the
effectiveness in preventing stillbirth is uncertain (73).
Timing of Delivery
The decision to proceed with early delivery to prevent
stillbirth must incorporate an understanding of the
increased risks of maternal and neonatal complications
compared with the potential benefits. Deliveries before
39 weeks of gestation are associated with an increased
risk of admission to neonatal special care units for respi-
ratory complications and other neonatal morbidities.
Details of pregnancy for women with a prior stillbirth are
listed in the box.
Summary of
Recommendations and
Conclusions
The following recommendations and conclusions
are based on good and consistent scientific
evidence. (Level A)
In low-risk women with unexplained stillbirth the
risk of recurrence stillbirth after 20 weeks of gesta-
tion is estimated at 7.810.5/1,000 with most of this
risk occurring before 37 weeks of gestation.
The most prevalent risk factors associated with still-
birth are non-Hispanic black race, nulliparity,
advanced maternal age, and obesity (Table 1).
The risk of subsequent still birth is twice as high for
women with a prior live born, growth restricted
infant delivered before 32 weeks of gestation than
for women with a prior stillbirth.
Amniocentesis for fetal karyotyping has the highest
yield and is particularly valuable if delivery is not
expected imminently.
The following recommendations and conclusions
are based primarily on limited or inconsistent
scientific evidence (Level B):
In the second trimester, dilation and evacuation can
be offered. Labor induction also is appropriate at
later gestational ages, if second trimester dilation
and evacuation is unavailable, or based on patient
preference.
COMPENDIUM OF SELECTED PUBLICATIONS 1098
Management of Subsequent Pregnancy
After Stillbirth
Preconception or initial prenatal visit
Detailed medical and obstetric history
Evaluation and workup of previous stillbirth
Determination of recurrence risk
Smoking cessation
Weight loss in obese women (preconception only)
Genetic counseling if family genetic condition exists
Diabetes screen
Thrombophilia workup: antiphospholipid antibodies
(only if specifically indicated)
Support and reassurance
First trimester
Dating ultrasonography
First-trimester screen: pregnancy-associated plasma
protein A, human chorionic gonadotropin, and nuchal
translucency*
Support and reassurance
Second trimester
Fetal ultrasonographic anatomic survey at 1820
weeks of gestation
Maternal serum screening (Quadruple) or single marker
alpha fetoprotein if first trimester screening*
Support and reassurance
Third trimester
Ultrasonographic screening for fetal growth restriction
after 28 weeks of gestation
Kick counts starting at 28 weeks of gestation
Antepartum fetal surveillance starting at 32 weeks of
gestation or 12 weeks earlier than prior stillbirth
Support and reassurance
Delivery
Elective induction at 39 weeks of gestation
Delivery before 39 weeks of gestation only with docu-
mented fetal lung maturity by amniocentesis
*Provides risk modification but does not alter management
(Adapted from Reddy UM. Prediction and prevention of recurrent
stillbirth. Obstet Gynecol 2007;110:115164.)
Induction of labor with vaginal misoprostol is safe
and effective in patients with a prior cesarean deliv-
ery with a low transverse uterine scar before 28
weeks of gestation.
The following recommendations and conclusions
are based primarily on consensus and expert
opinion (Level C):
The most important tests in the evaluation of a still-
birth are fetal autopsy; examination of the placenta,
cord, and membranes; and karyotype evaluation.
Patient support should include emotional support
and clear communication of test results. Referral to
a bereavement counselor, religious leader, peer sup-
port group, or mental health professional may be
advisable for management of grief and depression.
Performance Measure
The percentage of stillbirths for which placental evalua-
tion was performed and autopsy was offered
References
1. MacDorman MF, Munson ML, Kirmeyer S. Fetal and
perinatal mortality, United States, 2004. Natl Vital Stat
Rep 2007;56:119. (Level II-3)
2. National Center for Health Statistics. State definitions
and reporting requirements for live births, fetal deaths,
and induced terminations of pregnancy. 1997 revision.
Hyattsville (MD): NCHS; 1997. Available at: http://www.
cdc.gov/nchs/data/misc/itop97.pdf. Retrieved November
19, 2008. (Level II-3)
3. National Center for Health Statistics. Model state vital
statistics act and regulations. 1992 revision. Hyattsville
(MD): NCHS; 1994. Available at: http://www.cdc.gov/
nchs/data/misc/mvsact92b.pdf. Retrieved December 3,
2008. (Level III)
4. Healy AJ, Malone FD, Sullivan LM, Porter TF, Luthy
DA, Comstock CH, et al. Early access to prenatal care:
implications for racial disparity in perinatal mortality.
FASTER Trial Research Consortium. Obstet Gynecol
2006;107: 62531. (Level II-2)
5. Vintzileos AM, Ananth CV, Smulian JC, Scorza WE,
Knuppel RA. Prenatal care and black-white fetal death
disparity in the United States: heterogeneity by high-risk
conditions. Obstet Gynecol 2002;99:4839. (Level II-3
6. Martin JA, Hamilton BE, Sutton PD, Ventura SJ,
Menacker F, Kirmeyer S, et al. Births: final data for 2005.
Centers for Disease Control and Prevention National
Center for Health Statistics National Vital Statistics
System. Natl Vital Stat Rep 2007;56:1103. (Level II-3)
1099 PRACTICE BULLETINS
7. Casson IF, Clarke CA, Howard CV, McKendrick O,
Pennycook S, Pharoah PO, et al. Outcomes of pregnancy
in insulin dependent diabetic women: results of a five year
population cohort study. BMJ 1997;315:2758. (Level II-3)
8. Dunne F, Brydon P, Smith K, Gee H. Pregnancy in women
with Type 2 diabetes: 12 years outcome data 19902002.
Diabet Med 2003;20:7348. (Level II-3)
9. Fretts RC, Schmittdiel J, McLean FH, Usher RH,
Goldman MB. Increased maternal age and the risk of fetal
death. N Engl J Med 1995;333:953-7. (Level II-3)
10. Karlsson K, Kjellmer I. The outcome of diabetic pregnan-
cies in relation to the mothers blood sugar level. Am J
Obstet Gynecol 1972;112:21320. (Level II-3)
11. Wu O, Robertson L, Twaddle S, Lowe GD, Clark P,
Greaves M, et al. Screening for thrombophilia in high-risk
situations: systematic review and cost-effectiveness analy-
sis. The Thrombosis: Risk and Economic Assessment of
Thrombophilia Screening (TREATS) study. Health
Technol Assess 2006;10:1110. (Level III)
12. Hedley AA, Ogden CL, Johnson CL, Carroll MD, Curtin
LR, Flegal KM. Prevalence of overweight and obesity
among US children, adolescents, and adults, 19992002.
JAMA 2004;291:284750. (Level II-3)
13. Catalano PM. Management of obesity in pregnancy.
Obstet Gynecol 2007;109:41933. (Level II-3)
14. Salihu HM, Dunlop AL, Hedayatzadeh M, Alio AP, Kirby
RS, Alexander GR. Extreme obesity and risk of stillbirth
among black and white gravidas. Obstet Gynecol
2007;110:5527. (Level II-3)
15. Nohr EA, Bech BH, Davies MJ, Frydenberg M,
Henriksen TB, Olsen J. Prepregnancy obesity and fetal
death: a study within the Danish National Birth Cohort.
Obstet Gynecol 2005;106:2509. (Level II-2)
16. Cnattingius S, Bergstrom R, Lipworth L, Kramer MS.
Prepregnancy weight and the risk of adverse pregnancy
outcomes. N Engl J Med 1998;338:14752. (Level II-3)
17. Cnattingius S, Lambe M. Trends in smoking and over-
weight during pregnancy: prevalence, risks of pregnancy
complications, and adverse pregnancy outcomes. Semin
Perinatol 2002;26:28695. (Level III)
18. Stephansson O, Dickman PW, Johansson A, Cnattingius
S. Maternal weight, pregnancy weight gain, and the risk
of antepartum stillbirth. Am J Obstet Gynecol 2001;
184:4639. (Level II-2)
19. Bell R, Glinianaia SV, Rankin J, Wright C, Pearce MS,
Parker L. Changing patterns of perinatal death, 1982-
2000: a retrospective cohort study. Arch Dis Child Fetal
Neonatal Ed 2004;89:F5316. (Level II-3)
20. Reddy UM, Ko CW, Willinger M. Maternal age and the
risk of stillbirth throughout pregnancy in the United States.
Am J Obstet Gynecol 2006;195:76470. (Level II-3)
21. Liu S, Joseph KS, Kramer MS, Allen AC, Sauve R, Rusen
ID, et al. Relationship of prenatal diagnosis and pregnancy
termination to overall infant mortality in Canada. Fetal and
Infant Health Study Group of the Canadian Perinatal
Surveillance System. JAMA 2002;287:15617. (Level II-3)
22. Froen JF, Arnestad M, Frey K, Vege A, Saugstad OD,
Stray-Pedersen B. Risk factors for sudden intrauterine
unexplained death: epidemiologic characteristics of sin-
gleton cases in Oslo, Norway, 1986-1995. Am J Obstet
Gynecol 2001;184:694702. (Level II-3)
23. Huang DY, Usher RH, Kramer MS, Yang H, Morin L,
Fretts RC. Determinants of unexplained antepartum fetal
deaths. Obstet Gynecol 2000;95:21521. (Level II-3)
24. Smith GC, Shah I, White IR, Pell JP, Dobbie R. Previous
preeclampsia, preterm delivery, and delivery of a small for
gestational age infant and the risk of unexplained stillbirth
in the second pregnancy: a retrospective cohort study,
Scotland, 19922001. Am J Epidemiol 2007;165:194
202. (Level II-3)
25. Surkan PJ, Stephansson O, Dickman PW, Cnattingius S.
Previous preterm and small-for-gestational-age births and
the subsequent risk of stillbirth. N Engl J Med
2004;350:77785. (Level II-2)
26. Salihu HM, Sharma PP, Kristensen S, Blot C, Alio AP,
Ananth CV, et al. Risk of stillbirth following a cesarean
delivery: black-white disparity. Obstet Gynecol
2006;107:38390. (Level III)
27. Bahtiyar MO, Julien S, Robinson JN, Lumey L, Zybert P,
Copel JA, et al. Prior cesarean delivery is not associated
with an increased risk of stillbirth in a subsequent preg-
nancy: analysis of U.S. perinatal mortality data, 1995-
1997. Am J Obstet Gynecol 2006;195:13738. (Level II-
3)
28. Landon MB, Hauth JC, Leveno KJ, Spong CY,
Leindecker S, Varner MW, et al. Maternal and perinatal
outcomes associated with a trial of labor after prior
cesarean delivery. National Institute of Child Health and
Human Development Maternal-Fetal Medicine Units
Network. N Engl J Med 2004;351:25819. (Level II-2)
29. Gray R, Quigley MA, Hockley C, Kurinczuk JJ, Goldacre
M, Brocklehurst P. Caesarean delivery and risk of still-
birth in subsequent pregnancy: a retrospective cohort
study in an English population. BJOG 2007;114:26470.
(Level II-3)
30. Clausson B, Gardosi J, Francis A, Cnattingius S. Perinatal
outcome in SGA births defined by customised versus pop-
ulation-based birthweight standards. BJOG 2001;108:
8304. (Level II-3)
31. Getahun D, Ananth CV, Kinzler WL. Risk factors for
antepartum and intrapartum stillbirth: a population-based
study. Am J Obstet Gynecol 2007;196:499507. (Level II-
3)
32. Ego A, Subtil D, Grange G, Thiebaugeorges O, Senat MV,
Vayssiere C, et al. Customized versus population-based
birth weight standards for identifying growth restricted
infants: a French multicenter study. Am J Obstet Gynecol
2006;194:10429. (Level II-3)
33. Ananth CV, Smulian JC, Demissie K, Vintzileos AM,
Knuppel RA. Placental abruption among singleton and
twin births in the United States: risk factor profiles. Am J
Epidemiol 2001;153:7718. (Level II-3)
34. Hoskins IA, Friedman DM, Frieden FJ, Ordorica SA,
Young BK. Relationship between antepartum cocaine
COMPENDIUM OF SELECTED PUBLICATIONS 1100
abuse, abnormal umbilical artery Doppler velocimetry,
and placental abruption. Obstet Gynecol 1991;78:27982.
(Level II-2)
35. Hulse GK, Milne E, English DR, Holman CD. Assessing
the relationship between maternal cocaine use and abrup-
tio placentae. Addiction 1997;92:154751. (Level III)
36. Kramer MS, Usher RH, Pollack R, Boyd M, Usher S.
Etiologic determinants of abruptio placentae. Obstet
Gynecol 1997;89:2216. (Level II-3)
37. Ananth CV, Oyelese Y, Yeo L, Pradhan A, Vintzileos AM.
Placental abruption in the United States, 1979 through
2001: temporal trends and potential determinants. Am J
Obstet Gynecol 2005;192:1918. (Level II-3)
38. Pauli RM, Reiser CA, Lebovitz RM, Kirkpatrick SJ.
Wisconsin Stillbirth Service Program: I. Establishment
and assessment of a community-based program for etio-
logic investigation of intrauterine deaths. Am J Med Genet
1994;50:11634. (Level III)
39. Laury A, Sanchez-Lara PA, Pepkowitz S, Graham JM Jr.
A study of 534 fetal pathology cases from prenatal diag-
nosis referrals analyzed from 1989 through 2000. Am J
Med Genet A 2007;143A:310720. (Level III)
40. Korteweg FJ, Bouman K, Erwich JJ, Timmer A, Veeger
NJ, Ravise JM, et al. Cytogenetic analysis after evaluation
of 750 fetal deaths: proposal for diagnostic workup.
Obstet Gynecol 2008;111:86574. (Level III)
41. Kalousek DK, Barrett I. Confined placental mosaicism
and stillbirth. Pediatr Pathol 1994;14:1519. (Level III)
42. Pauli RM, Reiser CA. Wisconsin Stillbirth Service
Program: II. Analysis of diagnoses and diagnostic cate-
gories in the first 1,000 referrals. Am J Med Genet 1994;
50:13553. (Level III)
43. Copper RL, Goldenberg RL, DuBard MB, Davis RO.
Risk factors for fetal death in white, black, and Hispanic
women. Collaborative Group on Preterm Birth Preven-
tion. Obstet Gynecol 1994;84:4905. (Level II-3)
44. Spellacy WN, Gravem H, Fisch RO. The umbilical cord
complications of true knots, nuchal coils, and cords
around the body. Report from the collaborative study of
cerebral palsy. Am J Obstet Gynecol 1966;94:113642.
(Level III)
45. Leppig KA, Werler MM, Cann CI, Cook CA, Holmes LB.
Predictive value of minor anomalies. I. Association with
major malformations. J Pediatr 1987;110:5317. (Level III)
46. Reed GB, Claireaux AE, Cockburn F, editors. Diseases of
the fetus and newborn: pathology, imaging, genetics and
management. London (UK): Chapan & Hall Medical;
1995. (Level III)
47. Stocker JT, Dehner LP, editors. Pediatric pathology. 2nd
ed. Philadelphia (PA): Lippincott Williams & Wilkins;
2001. (Level III)
48. Naeye RL. Disorders of the placenta, fetus, and neonate:
diagnosis and clinical significance. St. Louis (MO): Mosby
Year Book; 1992. (Level III)
49. Valdes-Depena M, Huff DS. Perinatal autopsy manual.
Washington, DC: Armed Forces Institute of Pathology;
1983. (Level III)
50. Bove KE. Practice guidelines for autopsy pathology: the
perinatal and pediatric autopsy. Autopsy Committee of the
College of American Pathologists. Arch Pathol Lab Med
1997;121:36876. (Level III)
51. Benirschke K, Kaufmann P. Pathology of the human pla-
centa. 4th ed. New York (NY): Springer; 2000. (Level III)
52. Genest DR. Estimating the time of death in stillborn fetus-
es: II. Histologic evaluation of the placenta; a study of 71
stillborns. Obstet Gynecol 1992;80:58592. (Level III)
53. Smith A, Bannatyne P, Russell P, Ellwood D, den Dulk G.
Cytogenetic studies in perinatal death. Aust N Z J Obstet
Gynaecol 1990;30:20610. (Level III)
54. Baena N, Guitart M, Ferreres JC, Gabau E, Corona M,
Mellado F, et al. Fetal and placenta chromosome constitu-
tion in 237 pregnancy losses. Ann Genet 2001;44:838.
(Level III)
55. Gelman-Kohan Z, Rosensaft J, Ben-Hur H, Haber A,
Chemke J. Cytogenetic analysis of fetal chondrocytes: a
comparative study. Prenat Diagn 1996;16:1658. (Level
III)
56. Michalski ST, Porter J, Pauli RM. Costs and conse-
quences of comprehensive stillbirth assessment. Am J
Obstet Gynecol 2002;186:102734. (Level III)
57. Biankin SA, Arbuckle SM, Graf NS. Autopsy findings in
a series of five cases of fetomaternal haemorrhages.
Pathology 2003;35:31924. (Level III)
58. Fretts RC. Etiology and prevention of stillbirth. Am J
Obstet Gynecol 2005;193:192335. (Level III)
59. Leduc L, Farine D, Armson BA, Brunner M, Crane J,
Delisle MF, et al. Stillbirth and bereavement: guidelines
for stillbirth investigation. Maternal-Fetal Medicine
Committee; Clinical Practice Obstetrics Committee. J
Obstet Gynaecol Can 2006;28:54052. (Level III)
60. Alonso A, Soto I, Urgelles MF, Corte JR, Rodriguez MJ,
Pinto CR. Acquired and inherited thrombophilia in
women with unexplained fetal losses. Am J Obstet
Gynecol 2002;187:133742. (Level II-3)
61. Dickinson JE, Evans SF. The optimization of intravaginal
misoprostol dosing schedules in second-trimester preg-
nancy termination [published erratum appears in Am J
Obstet Gynecol 2005;193:597]. Am J Obstet Gynecol
2002;186:470-4. (Level I)
62. Tang OS, Lau WN, Chan CC, Ho PC. A prospective ran-
domised comparison of sublingual and vaginal misopros-
tol in second trimester termination of pregnancy. BJOG
2004;111:10015. (Level I)
63. Toaff R, Ayalon D, Gogol G. Clinical use of high concen-
tration oxytocin drip. Obstet Gynecol 1971;37:11220.
(Level II-3)
64. Winkler CL, Gray SE, Hauth JC, Owen J, Tucker JM.
Mid-second-trimester labor induction: concentrated oxy-
tocin compared with prostaglandin E2 vaginal supposito-
ries. Obstet Gynecol 1991;77:297300. (Level II-3)
65. Dickinson JE. Misoprostol for second-trimester pregnan-
cy termination in women with a prior cesarean delivery.
Obstet Gynecol 2005;105:3526. (Level II-2)
1101 PRACTICE BULLETINS
66. Daskalakis GJ, Mesogitis SA, Papantoniou NE,
Moulopoulos GG, Papapanagiotou AA, Antsaklis AJ.
Misoprostol for second trimester pregnancy termination
in women with prior caesarean section. BJOG 2005;
112:979. (Level II-2)
67. Neilson JP, Hickey M, Vazquez J. Medical treatment for
early fetal death (less than 24 weeks). Cochrane Data-
base of Systematic Reviews 2006, Issue 3. Art. No.:
CD002253. DOI: 10.1002/14651858.CD002253.pub3.
(Level 1)
68. Bujold E, Blackwell SC, Gauthier RJ. Cervical ripening
with transcervical foley catheter and the risk of uterine
rupture. Obstet Gynecol 2004;103:1823. (Level II-2)
69. Rushton DI. Prognostic role of the perinatal postmortem.
Br J Hosp Med 1994;52:4504. (Level III)
70. Miller DA, Rabello YA, Paul RH. The modified biophysi-
cal profile: antepartum testing in the 1990s. Am J Obstet
Gynecol 1996;174:8127. (Level II-3)
71. Kramer MS, Demissie K, Yang H, Platt RW, Sauve R,
Liston R. The contribution of mild and moderate preterm
birth to infant mortality. Fetal and Infant Health Study
Group of the Canadian Perinatal Surveillance System.
JAMA 2000;284:8439. (Level II-3)
72. Froen JF. A kick from withinfetal movement counting
and the cancelled progress in antenatal care. J Perinat Med
2004;32:1324. (Level III)
73. Grant A, Elbourne D, Valentin L, Alexander S. Routine
formal fetal movement counting and risk of antepartum
late death in normally formed singletons. Lancet 1989;
2:3459. (Level I)
The MEDLINE database, the Cochrane Library, and
ACOGs own internal resources and documents were used
to conduct a literature search to locate relevant articles pub-
lished between January 1985 and April 2008. The search
was restricted to articles published in the English language.
Priority was given to articles reporting results of original
research, although review articles and commentaries also
were consulted. Abstracts of research presented at symposia
and scientific conferences were not considered adequate for
inclusion in this document. Guidelines published by organi-
zations or institutions such as the National Institutes of
Health and the American College of Obstetricians and
Gynecologists were reviewed, and additional studies were
located by reviewing bibliographies of identified articles.
When reliable research was not available, expert opinions
from obstetriciangynecologists were used.
Studies were reviewed and evaluated for quality according
to the method outlined by the U.S. Preventive Services
Task Force:
I Evidence obtained from at least one properly
designed randomized controlled trial.
II-1 Evidence obtained from well-designed controlled
trials without randomization.
II-2 Evidence obtained from well-designed cohort or
casecontrol analytic studies, preferably from more
than one center or research group.
II-3 Evidence obtained from multiple time series with or
without the intervention. Dramatic results in uncon-
trolled experiments also could be regarded as this
type of evidence.
III Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees.
Based on the highest level of evidence found in the data,
recommendations are provided and graded according to the
following categories:
Level ARecommendations are based on good and con-
sistent scientific evidence.
Level BRecommendations are based on limited or incon-
sistent scientific evidence.
Level CRecommendations are based primarily on con-
sensus and expert opinion.
Copyright March 2009 by the American College of
Obstetricians and Gynecologists. All rights reserved. No part of
this publication may be reproduced, stored in a retrieval system,
posted on the Internet, or transmitted, in any form or by any
means, electronic, mechanical, photocopying, recording, or
otherwise, without prior written permission from the publisher.
Requests for authorization to make photocopies should be
directed to Copyright Clearance Center, 222 Rosewood Drive,
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
The American College of Obstetricians and Gynecologists
409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920
Management of stillbirth. ACOG Practice Bulletin No. 102. American
College of Obstetricians and Gynecologists. Obstet Gynecol 2009;
113:74861.
COMPENDIUM OF SELECTED PUBLICATIONS 1102
CLINICAL MANAGEMENT GUIDELINES FOR OBSTETRICIANGYNECOLOGISTS
NUMBER 105, JUNE 2009
This Practice Bulletin was devel-
oped by the ACOG Committee on
Practice BulletinsObstetrics with
the assistance of Michelle A.
Kominiarek, MD. The information
is designed to aid practitioners in
making decisions about appropriate
obstetric and gynecologic care.
These guidelines should not be con-
strued as dictating an exclusive
course of treatment or procedure.
Variations in practice may be war-
ranted based on the needs of the
individual patient, resources, and
limitations unique to the institution
or type of practice.
ACOG
PRACTICE
BULLETIN
THE AMERICAN COLLEGE OF
OBSTETRICIANS AND
GYNECOLOGISTS
WOMENS HEALTH CARE PHYSICIANS
Bariatric Surgery and
Pregnancy
As the rate of obesity increases, it is becoming more common for providers of
womens health care to encounter patients who are either contemplating or have
had operative procedures for weight loss, also known as bariatric surgery. The
counseling and management of patients who become pregnant after bariatric
surgery can be complex. Although pregnancy outcomes generally have been
favorable after bariatric surgery, nutritional and surgical complications can
occur and some of these complications can result in adverse perinatal outcomes.
The purpose of this Practice Bulletin is to provide a summary of the risks of
obesity in pregnancy, review the available literature regarding outcomes of preg-
nancy after bariatric surgery, and provide recommendations for the care of the
patient during her pregnancy and delivery after bariatric surgery.
Background
Incidence
Obesity is an epidemic in the United States66% of adults were either over-
weight or obese in 2004 (1). The prevalence of maternal obesity, defined as a
body mass index (BMI) of 30 or more in the United States has been reported
to range from 10% to 36% (26). BMI is calculated as weight in kilograms
divided by height in meters squared. The prevalence of adult obesity increased
dramatically (from 16% to 26%) in the past decade, with 30 states reporting
prevalences greater than 25% (7, 8). Furthermore, the prevalence of obesity in
reproductive-aged women (2039 years) was 29% in 2004, affecting a greater
proportion of Mexican American (36%) and non-Hispanic black (50%) women
(1). A prepregnancy BMI of more than 30 or a prepregnancy weight of more
than 200 lbs can be used to stratify risk during pregnancy (2, 9, 10). In a pop-
ulation-based study of obesity trends in the United States, there was a 70%
increase in prepregnancy obesity from 1994 to 2003 (11).
1103 PRACTICE BULLETINS
Maternal Effects of Obesity on Pregnancy
Obesity is associated with reduced fertility primarily as a
result of oligo-ovulation and anovulation (12). Therefore,
obese women are less likely to respond to ovulation
induction, even with higher doses of gonadotropins (13,
14).
In pregnancy, additional risks occur in obese patients.
The increased risks for gestational diabetes, preeclamp-
sia, cesarean delivery, and infectious morbidity associated
with obesity are well established (6, 1518). In addition,
operative morbidity increases as a result of difficulty in
establishment of and recovery from regional and general
anesthesia (19, 20), prolonged operating times, increased
blood loss (21), and thromboembolism (22). Obese
patients also are less likely to have a successful vaginal
birth after cesarean delivery (2326). Although obese
patients have a higher incidence of preterm birth for
maternal or fetal indications, they are less likely to have
spontaneous preterm labor (2729). Obese patients are
more likely to be admitted earlier in labor, need labor
induction, require more oxytocin, and have longer labor
(30).
Fetal and Neonatal Effects of Obesity
in Pregnancy
Maternal obesity can have effects on the fetus, including
increased risks of congenital anomalies, growth abnor-
malities, miscarriage, and stillbirth (3134). The most
common types of obesity-associated birth defects are
related to the neural tube, cardiac systems, and facial
clefting, even after controlling for diabetes (35, 36). In
addition, increased body mass impairs visualization of
ultrasound images and can compromise prenatal diagno-
sis of fetal anomalies, such as neural tube or cardiac
defects (37, 38). However, increased maternal BMI does
not appear to compromise fetal weight estimations (39).
Although some studies have reported an increase in
small for gestational age infants, most studies report an
increase in large for gestational age and macrosomic
infants among women who are obese during pregnancy
(40, 41). The risk for stillbirth is 2.14.3-fold greater in
obese compared with normal weight women (5, 42). The
pathophysiology behind the increased risk for birth
defects and stillbirth in this population is not known.
Maternal obesity also has been associated with an
increase in subsequent childhood obesity (43, 44).
Bariatric Surgery
Nonsurgical approaches to weight loss include behavioral
changes, diet, exercise, and pharmacotherapy. Bariatric
surgery, first performed in the 1960s, may be available to
patients with a BMI of 40 or more or those with a BMI of
35 or more and other comorbidities. Bariatric surgery is
the most effective therapy available for morbid obesity
and results in improvement or complete resolution of
comorbidities and improved quality of life (45, 46).
Two primary approaches to bariatric surgery weight
loss are restrictive and a combination of restrictive and mal-
absorptive operations. The types of procedures commonly
performed today include the Roux-en-Y gastric bypass (a
combination of restrictive and malabsorptive effect) and
adjustable gastric banding (restrictive). The Roux-en-Y
gastric bypass creates a roux limb (or straight limb) con-
nected to the gastric pouch and the Y portion is down-
stream as the enteroenterostomy. The proximal stomach
is separated from the remaining part of the stomach with
staples. In the banding procedure, a fluid-filled band is
placed around the stomach near the fundus, reducing func-
tional stomach volume. Both techniques can be performed
by laparoscopy or laparotomy. Vertical banded gastro-
plasty (restrictive) and biliopancreatic diversion (malab-
sorptive) are now less commonly used, and jejunoileal
bypass (purely malabsorptive) is no longer performed.
The number of bariatric surgical procedures per-
formed annually has dramatically increased from 12,480
in 1998 to 113,500 in 2005 (47). The majority of these
patients are female (more than 80%) and one half of the
bariatric procedures in 2004 were performed in repro-
ductive-aged women with a mean age of 40 years (48,
49). Bariatric surgery also is being used increasingly to
treat adolescents with morbid obesity (50).
Effect of Surgery on Future Fertility
Rapid weight loss follows bariatric surgery, resulting in
improvement of conditions such as polycystic ovary syn-
drome, anovulation, and irregular menses, thus leading to
higher fertility rates (5154). However, bariatric surgery
should not be considered a treatment for infertility (55).
Several studies have discussed the potential for com-
promised absorption of oral contraceptives (OCPs) after
bariatric surgery (56, 57), given the number of unintended
pregnancies that occurred after the procedures. There
may be decreased absorption of OCPs as a result of the
anatomic and physiologic alterations from malabsorptive
surgery (58, 59). The effect of bariatric surgery on mis-
carriage rates is difficult to evaluate because of small
numbers in studies (51, 53, 54, 60).
Effect of Surgery on Maternal
Morbidity and Mortality
Weight loss outside of pregnancy, whether achieved via
surgical or nonsurgical methods, has been shown to be
the most effective intervention to improve medical
comorbidities, especially diabetes and hypertension (45,
COMPENDIUM OF SELECTED PUBLICATIONS 1104
46). However, in the studies of pregnancy after bariatric
surgery many patients are still obese, with a reported
prevalence as high as 80% in one series (6163). The pos-
sibility of continued obesity after surgery is important to
consider when interpreting studies about this population.
In a study comparing 298 women who had bariatric
surgery to the general obstetric population of 158,912
women, patients who had bariatric surgery were more
likely to have had a prior cesarean delivery (15.4% versus
10.5%, P=0.006), develop gestational diabetes (9.4% ver-
sus 5.0%, P<0.001), and give birth via cesarean delivery
(25.2% versus 12.2%, P<0.001) (64). In one study com-
paring pregnancies before and after a Roux-en-Y gastric
bypass, the rate of hypertension (including chronic and
gestational hypertension and preeclampsia) (45.6% ver-
sus 8.7%, P<0.001) was decreased after surgery (65).
Similarly, the occurrence of pregestational diabetes was
decreased (OR, 0.42; 95% CI, 0.260.67) after bariatric
surgery of several types (66). A systematic review of preg-
nancy after bariatric surgery also described decreased
rates of gestational diabetes and preeclampsia (67).
Average weight gain during pregnancy also was
decreased in several studies after bariatric surgery (62,
65, 6871). Although preterm premature rupture of mem-
branes was increased in patients after bariatric surgery
compared with the general population (64), preterm
delivery in other studies with more similar control
groups was unchanged (62, 63, 66). One study reported
higher cesarean delivery rates after bariatric surgery com-
pared with rates for nonobese women who had not
undergone bariatric surgery (61.5% versus 36.2%,
P< 0.05). In this study, cesarean delivery rates for women
after bariatric surgery compared with obese (46.5%) and
severely obese controls (43.5%) was not significantly
different (71). The increase in cesarean delivery after
bariatric surgery may be attributed to previous cesarean
deliveries in this obese population (66).
Several case reports and small studies have identi-
fied significant late complications of previous bariatric
surgery that have occurred during pregnancy, including
maternal intestinal obstruction and gastrointestinal hem-
orrhage (61, 63, 69, 71-74). Exploratory surgery during
pregnancy may be required to treat these complications
from bariatric surgery. Maternal deaths have been reported
(75, 76). There should be a high index of suspicion for
gastrointestinal surgical complications when pregnant
women who have had these procedures present with sig-
nificant abdominal symptoms.
Effect of Surgery on Fetal and Infant
Morbidity and Mortality
The number of congenital anomalies after bariatric
surgery is not increased compared with the general pop-
ulation (64, 77). Some reports suggest a trend towards
lower mean birth weights indicating more appropriately
grown infants, fewer large for gestational age infants,
and more small for gestational age infants (53, 60, 65,
66, 6971). After bariatric surgery, maternal weight gain
during pregnancy is likely a predictor of birth weight (68,
78). Macro-somia (birth weight greater than 4,000 g)
also was decreased after Roux-en-Y gastric bypass (70,
71, 79). Pre-vious bariatric surgery is not associated with
an increase in perinatal death (60, 64, 65). The data are
limited on other neonatal outcomes.
Clinical Considerations and
Recommendations
How should contraception and preconception
be approached in patients after bariatric
surgery?
Contraception and preconception counseling should be a
component of the overall counseling for any reproductive-
aged woman undergoing bariatric surgery. Contraceptive
counseling is especially important for adolescents
because pregnancy rates after bariatric surgery are double
the rate in the general adolescent population (12.8% versus
6.4%) (80). In addition, because there is an increased risk
of oral contraception failure after bariatric surgery with a
significant malabsorption component, nonoral adminis-
tration of hormonal contraception should be considered
in these patients (55).
Some authorities have recommended waiting 1224
months after bariatric surgery before conceiving so that
the fetus is not exposed to a rapid maternal weight loss
environment and so that the patient can achieve full
weight loss goals (81). Should pregnancy occur before
this recommended time frame, closer surveillance of
maternal weight and nutritional status may be beneficial.
Use of ultrasound for serial monitoring of fetal growth
also may be useful and should be considered.
What are effective strategies for addressing
nutritional status during pregnancy in
women who have had bariatric surgery?
The most common nutritional deficiencies after Roux-
en-Y gastric bypass surgery are of protein, iron, vitamin
B
12
, folate, vitamin D, and calcium. Several groups have
recommended a broad evaluation for micronutrient defi-
ciencies at the beginning of pregnancy for women who
have had bariatric surgery, and it should be considered
(79, 8284). If there is a proven deficit, then appropriate
treatment should be instituted and monitored. In the
1105 PRACTICE BULLETINS
absence of a deficiency, monitoring the blood count,
iron, ferritin, calcium, and vitamin D levels every trimes-
ter may be considered.
Beginning supplementation with oral forms is
appropriate, but parenteral forms should be considered if
laboratory studies do not improve. It is not known if
women require higher doses of folic acid (greater than
0.4 mg/d) after weight loss surgery to decrease the risk
of birth defects. Only 1459% of postoperative bariatric
surgery patients continue to take the prescribed multivi-
tamin supplement long-term; therefore, patients without
appropriate preconception care may not have adequate
supplement levels at the start of pregnancy (85, 86). The
daily recommendation for protein intake of 60 g is the
same regardless of bariatric surgery status (9). Limited
evidence shows that caloric and protein restriction dur-
ing pregnancy may impair fetal growth and is of no ben-
efit in reducing other pregnancy comorbidities (87).
Consequently, even if patients continue to be overweight
after bariatric surgery, there is no recommendation for
caloric restriction during pregnancy.
Several studies have suggested that women who
become pregnant after bariatric surgery should take a
prenatal vitamin in addition to a multivitamin (79, 88). It
should be noted that an excess of vitamin A consumption
during pregnancy is associated with birth defects, so sup-
plemental dosages of vitamin A should be limited to
5,000 international units per day during pregnancy.
Consultation with a nutritionist after conception may
help the patient adhere to dietary regimens and to cope
with the physiologic changes of pregnancy. One study
reported that if the bariatric surgery team monitored the
patient throughout the pregnancy, the weight gain was
optimal and similar to the Institute of Medicine (IOM)
recommendations (9.2 plus or minus 8.4 kg), compared
with patients who were not seen at all, not seen until
after the first trimester (poor weight gain of 4.8 plus or
minus 9.0 kg), or seen only in the first trimester (exces-
sive weight gain of 13.0 plus or minus 9.7 kg, P=0.009)
(68). Close surveillance should continue postpartum
because there are several case reports of nutritional defi-
ciencies in infants who were breast-fed by women who
had under-gone bariatric procedures (89, 90).
Nutrient deficiencies also can occur after restrictive
surgical procedures (eg, adjustable gastric banding pro-
cedure). Patients may experience decreased food intake,
intolerance to certain foods, or both because the gastric
opening is narrowed after such procedures. Several
authors have described active band management
whereby fluid from the gastric band is removed or less-
ened during a pregnancy allowing for less gastric con-
striction and an increase in oral intake (62, 63, 69, 91).
Removing fluid from the gastric band also has been
described to relieve nausea and vomiting during the first
trimester (62, 63, 70, 91). There is no consensus on the
management of patients during pregnancy who have
undergone an adjustable gastric banding procedure, but
early consultation with a bariatric surgeon is recom-
mended.
Are there special considerations in the
antenatal period for women who have had
bariatric surgery?
In pregnancy, there may be a delay in the diagnosis of
bariatric-related operative complications. These compli-
cations include anastomotic leaks, bowel obstructions,
internal hernias, ventral hernias, band erosion, and band
migration. All gastrointestinal problems such as nausea,
vomiting, and abdominal pain, which occur commonly
during pregnancy, should be thoroughly evaluated in
patients who have had bariatric surgery. Early involve-
ment of the bariatric surgeon in evaluating abdominal
pain is critical because the underlying pathology may
relate to the weight loss surgery.
Dumping syndrome can occur after gastric bypass
procedures. It is related to the ingestion of refined sugars
or high glycemic carbohydrates that the stomach rapidly
empties into the small intestine. Fluid shifts from the
intravascular compartment into the bowel lumen result in
small-bowel distention. Symptoms include abdominal
cramps, bloating, nausea, vomiting, and diarrhea.
Hyperinsulinemia and consequent hypoglycemia can
occur later, resulting in tachycardia, palpitations, anxi-
ety, and diaphoresis. Patients with dumping syndrome
may not tolerate the 50-g glucose solution commonly
administered at 2428 weeks of gestation to screen for
gestational diabetes. Alternative measures to screen for
gestational diabetes should be considered for patients
who have undergone malabsorptive-type surgery. One
proposed alternative is home glucose monitoring (fasting
and 2-hour postprandial blood sugar) for approximately
1 week during the 2428 weeks of gestation (73, 92).
Other concerns for patients who have had bariatric
surgery relate to medication dosages. After operations
such as the Roux-en-Y gastric bypass, the absorptive
surface of the intestine is decreased, leading to decreased
time for absorption. Extended-release preparations are
not recommended in these patients; instead oral solu-
tions or rapid release formulations are preferred (93). In
addition, the gastric pouch is smaller and bariatric sur-
geons have cautioned against using nonsteroidal
anti-inflammatory drugs postpartum to avoid gastric
ulceration (94, 95). In using medications in which a ther-
apeutic drug level is critical, testing drug levels may be
necessary to ensure a therapeutic effect.
COMPENDIUM OF SELECTED PUBLICATIONS 1106
Are there special considerations during labor
and delivery for women who have had
bariatric surgery?
Bariatric surgery should not alter the course of labor and
delivery, and as such does not significantly affect its man-
agement. However, many patients remain obese after
bariatric procedures and, as with obese women without
bariatric surgery, may be admitted earlier in labor, need
labor induction, require more oxytocin, and have longer
labor (30). Cesarean delivery rates are higher after
bariatric surgery, as high as 62% in one study (65, 66, 71,
79, 88). Similarly, in one study, even after controlling for
confounders (previous cesarean delivery, obesity, and fetal
macrosomia), bariatric surgery was found to be an inde-
pendent risk factor for cesarean delivery (64). There is no
known physiologic reason for performing more cesarean
deliveries in women who have had bariatric surgery.
Therefore, the bariatric surgery itself should not be con-
sidered an indication for a cesarean delivery. If a patient
has had extensive and complicated abdominal surgery
from weight loss procedures, prelabor consultation with a
bariatric surgeon should be considered.
Summary of
Recommendations and
Conclusions
The following conclusions and recommendations
are based on limited or inconsistent scientific evi-
dence (Level B:)
Contraceptive counseling is important for adoles-
cents because pregnancy rates after bariatric surgery
are double the rate in the general adolescent popu-
lation.
Because there is an increased risk of oral contracep-
tion failure after bariatric surgery with a significant
malabsorption component, nonoral administration
of hormonal contraception should be considered in
these patients.
In using medications in which a therapeutic drug
level is critical, testing drug levels may be necessary
to ensure a therapeutic effect.
The following conclusions and recommendations
are based primarily on consensus and expert opin-
ion (Level C):
There should be a high index of suspicion for gastro-
intestinal surgical complications when pregnant
women who have had these procedures present with
significant abdominal symptoms.
Bariatric surgery should not be considered a treat-
ment for infertility.
Bariatric surgery should not be considered an indi-
cation for cesarean delivery.
There is no consensus on the management of
patients during pregnancy who have had an
adjustable gastric banding procedure, but early con-
sultation with a bariatric surgeon is recommended.
Alternative testing for gestational diabetes should be
considered for those patients with a malabsorptive-
type surgery.
Consultation with a nutritionist after conception
may help the patient adhere to dietary regimens and
cope with the physiologic changes of pregnancy.
A broad evaluation for micronutrient deficiencies at
the beginning of pregnancy for women who have
had bariatric surgery should be considered.
Proposed Performance
Measure
Documentation of counseling about weight gain and
nutrition in pregnancy
References
1. Ogden CL, Carroll MD, Curtin LR, McDowell MA,
Tabak CJ, Flegal KM. Prevalence of overweight and obe-
sity in the United States, 1999-2004. JAMA 2006;295:
154955. (Level II-3)
2. Ehrenberg HM, Dierker L, Milluzzi C, Mercer BM.
Prevalence of maternal obesity in an urban center. Am J
Obstet Gynecol 2002;187:118993. (Level II-3)
3. Ogunyemi D, Hullett S, Leeper J, Risk A. Prepregnancy
body mass index, weight gain during pregnancy, and peri-
natal outcome in a rural black population. J Matern Fetal
Med 1998;7:1903. (Level II-3)
4. Baeten JM, Bukusi EA, Lambe M. Pregnancy complica-
tions and outcomes among overweight and obese nul-
liparous women. Am J Public Health 2001;91:43640.
(Level II-3)
5. Cnattingius S, Bergstrom R, Lipworth L, Kramer MS.
Prepregnancy weight and the risk of adverse pregnancy
outcomes. N Engl J Med 1998;338:14752. (Level II-2)
6. Young TK, Woodmansee B. Factors that are associated
with cesarean delivery in a large private practice: the
importance of prepregnancy body mass index and weight
gain. Am J Obstet Gynecol 2002;187:3128; discussion
31820. (Level II-3)
1107 PRACTICE BULLETINS
7. Centers for Disease Control and Prevention. Behavioral
Risk Factor Surveillance System Survey Data. Atlanta
(GA): CDC; 1997. Available at http://apps.nccd.cdc.gov/
BRFSS. Retrieved March 24, 2009. (Level III)
8. Centers for Disease Control and Prevention. Behavioral
Risk Factor Surveillance System Survey Data. Atlanta
(GA): CDC; 2007. Available at: http://apps.nccd.cdc.gov/
BRFSS. Retrieved March 24, 2009. (Level III)
9. Institute of Medicine (US). Assessment of gestational
weight gain. In: Nutrition during pregnancy. Washington
(DC): National Academy Press; 1990. p. 6395. (Level III)
10. Lu GC, Rouse DJ, DuBard M, Cliver S, Kimberlin D,
Hauth JC. The effect of the increasing prevalence of
maternal obesity on perinatal morbidity. Am J Obstet
Gynecol 2001;185:8459. (Level II-3)
11. Kim SY, Dietz PM, England L, Morrow B, Callaghan
WM. Trends in pre-pregnancy obesity in nine states,
19932003. Obesity 2007;15:98693. (Level II-3)
12. Pathi A, Esen U, Hildreth A. A comparison of complica-
tions of pregnancy and delivery in morbidly obese and
non-obese women. J Obstet Gynaecol 2006;26:52730.
(Level II-3)
13. Pasquali R, Pelusi C, Genghini S, Cacciari M, Gambineri
A. Obesity and reproductive disorders in women. Hum
Reprod Update 2003;9:35972. (Level III)
14. Dokras A, Baredziak L, Blaine J, Syrop C, VanVoorhis BJ,
Sparks A. Obstetric outcomes after in vitro fertilization in
obese and morbidly obese women. Obstet Gynecol
2006;108:619. (Level II-2)
15. Chu SY, Callaghan WM, Kim SY, Schmid CH, Lau J,
England LJ, et al. Maternal obesity and risk of gestational
diabetes mellitus. Diabetes Care 2007;30:20706. (Meta-
analysis)
16. OBrien TE, Ray JG, Chan WS. Maternal body mass
index and the risk of preeclampsia: a systematic overview.
Epid 2003;14:36874.
17. Vermillion ST, Lamoutte C, Soper DE, Verdeja A. Wound
infection after cesarean: effect of subcutaneous tissue
thickness. Obstet Gynecol 2000;95:9236. (Level II-2)
18. Myles TD, Gooch J, Santolaya J. Obesity as an indepen-
dent risk factor for infectious morbidity in patients who
undergo cesarean delivery. Obstet Gynecol 2002;100:
95964. (Level II-3)
19. Perlow JH, Morgan MA. Massive maternal obesity and
perioperative cesarean morbidity. Am J Obstet Gynecol
1994;170:5605. (Level II-3)
20. Hood DD, Dewan DM. Anesthetic and obstetric outcome
in morbidly obese parturients. Anesthesiology 1993;79:
12108. (Level II-2)
21. Naef RW 3rd, Chauhan SP, Chevalier SP, Roberts WE,
Meydrech EF, Morrison JC. Prediction of hemorrhage at
cesarean delivery. Obstet Gynecol 1994;83:9236. (Level
II-2)
22. James AH, Jamison MG, Brancazio LR, Myers ER.
Venous thromboembolism during pregnancy and the post-
partum period: incidence, risk factors, and mortality. Am
J Obstet Gynecol 2006;194:13115. (Level II-3)
23. Durnwald CP, Ehrenberg HM, Mercer BM. The impact of
maternal obesity and weight gain on vaginal birth after
cesarean section success. Am J Obstet Gynecol 2004;
191:9547. (Level II-3)
24. Goodall PT, Ahn JT, Chapa JB, Hibbard JU. Obesity as a
risk factor for failed trial of labor in patients with previous
cesarean delivery. Am J Obstet Gynecol 2005;192:
14236. (Level II-3)
25. Edwards RK, Harnsberger DS, Johnson IM, Treloar RW,
Cruz AC. Deciding on route of delivery for obese women
with a prior cesarean delivery. Am J Obstet Gynecol
2003;189:3859; discussion 38990. (Level II-3)
26. Hibbard JU, Gilbert S, Landon MB, Hauth JC, Leveno
KJ, Spong CY, et al. Trial of labor or repeat cesarean
delivery in women with morbid obesity and previous
cesarean delivery. National Institute of Child Health and
Human Development Maternal-Fetal Medicine Units
Network. Obstet Gynecol 2006;108:12533. (Level II-2)
27. Smith GC, Shah I, Pell JP, Crossley JA, Dobbie R.
Maternal obesity in early pregnancy and risk of sponta-
neous and elective preterm deliveries: a retrospective
cohort study. Am J Public Health 2007;97:15762. (Level
II-2)
28. Salihu HM, Lynch O, Alio AP, Liu J. Obesity subtypes
and risk of spontaneous versus medically indicated
preterm births in singletons and twins. Am J Epidemiol
2008;168:1320. (Level II-3)
29. Ehrenberg HM, Iams JD, Goldenberg RL, Newman RB,
Weiner SJ, Sibai BM, Caritis SN, Miodovnik M,
Dombrowski MP, for the Eunice Kennedy Shriver
National Institute of Child Health and Human Develop-
ment Maternal-Fetal Medicine Units Network. Maternal
obesity, uterine activity, and the risk of spontaneous
preterm birth. Obstet Gynecol 2009;113:4852.
30. Vahratian A, Zhang J, Troendle JF, Savitz DA, Siega-Riz
AM. Maternal prepregnancy overweight and obesity and
the pattern of labor progression in term nulliparous
women. Obstet Gynecol 2004;104:94351. (Level II-3)
31. Waller DK, Mills JL, Simpson JL, Cunningham GC,
Conley MR, Lassman MR, et al. Are obese women at
higher risk for producing malformed offspring? Am J
Obstet Gynecol 1994;170:5418. (Level II-2)
32. Shaw GM, Velie EM, Schaffer D. Risk of neural tube
defect-affected pregnancies among obese women. JAMA
1996;275:10936. (Level III)
33. Lashen H, Fear K, Sturdee DW. Obesity is associated with
increased risk of first trimester and recurrent miscarriage:
matched case-control study. Hum Reprod 2004;19:
16446. (Level II-2)
34. Waller DK, Shaw GM, Rasmussen SA, Hobbs CA,
Canfield MA, Siega-Riz AM, et al. Prepregnancy obesity
as a risk factor for structural birth defects. National Birth
Defects Prevention Study. Arch Pediatr Adolesc Med
2007;161:74550. (Level II-2)
35. Rasmussen SA, Chu SY, Kim SY, Schmid CH, Lau J.
Maternal obesity and the risk of neural tube defects: a
metaanalysis. Am J Obstet Gynecol 2008;198:61119.
(Meta-analysis)
COMPENDIUM OF SELECTED PUBLICATIONS 1108
36. Stothard KJ, Tennant PWG, Bell R, Rankin J. Maternal
overweight and obesity and the risk of congenital anom-
alies: a systemic review and meta-analysis. JAMA 2009;
301:63650. (Meta-analysis)
37. Wolfe HM, Sokol RJ, Martier SM, Zador IE. Maternal
obesity: a potential source of error in sonographic prenatal
diagnosis. Obstet Gynecol 1990;76:33942. (Level II-3)
38. Hendler I, Blackwell SC, Bujold E, Treadwell MC, Wolfe
HM, Sokol RJ, et al. The impact of maternal obesity on
midtrimester sonographic visualization of fetal cardiac
and craniospinal structures. Int J Obes Relat Metab Disord
2004;28:160711. (Level II-3)
39. Field NT, Piper JM, Langer O. The effect of maternal obe-
sity on the accuracy of fetal weight estimation. Obstet
Gynecol 1995;86:1027. (Level II-3)
40. Larsen CE, Serdula MK, Sullivan KM. Macrosomia:
influence of maternal overweight among a low-income
population. Am J Obstet Gynecol 1990;162:4904. (Level
II-3)
41. Bianco AT, Smilen SW, Davis Y, Lopez S, Lapinski R,
Lockwood CJ. Pregnancy outcome and weight gain rec-
ommendations for the morbidly obese woman. Obstet
Gynecol 1998;91:97102. (Level II-3)
42. Stephansson O, Dickman PW, Johansson A, Cnattingius
S. Maternal weight, pregnancy weight gain, and the risk
of antepartum stillbirth. Am J Obstet Gynecol 2001;184:
4639. (Level II-3)
43. Whitaker RC. Predicting preschooler obesity at birth: the
role of maternal obesity in early pregnancy. Pediatrics
2004;114:e2936. (Level II-3)
44. Salsberry PJ, Reagan PB. Taking the long view: the pre-
natal environment and early adolescent overweight. Res
Nurs Health 2007;30:297307. (Level II-3)
45. Buchwald H, Avidor Y, Braunwald E, Jensen MD, Pories
W, Fahrbach K, et al. Bariatric surgery: a systematic
review and meta-analysis [published erratum appears in
JAMA 2005;293:1728]. JAMA 2004;292:172437. (Meta-
analysis)
46. Colquitt JL, Clegg AJ, Loveman E, Royle P, Sidhu MK.
Surgery for morbid obesity. Cochrane Database of
Systematic Reviews 2005, Issue 4. Art. No.: CD003641.
DOI: 10.1002/14651858.CD003641.pub2. (Level III)
47. Maggard MA, Yermilov I, Li Z, Maglione M, Newberry S,
Suttorp M. Pregnancy and fertility following bariatric
surgery. JAMA 2008;300:228696. (Meta-analysis)
48. Davis MM, Slish K, Chao C, Cabana MD. National trends
in bariatric surgery, 1996-2002. Arch Surg 2006;141:
714; discussion 75. (Level III)
49. National Center for Health Statistics. Health, United
States, 2007: with chartbook on trends in the health of
Americans. Hyattsville (MD): NCHS; 2007. Available at:
http://www.cdc.gov/nchs/data/hus/hus07.pdf. Retrieved
February 18, 2009. (Level III)
50. Tsai WS, Inge TH, Burd RS. Bariatric surgery in adoles-
cents: recent national trends in use and in-hospital out-
come. Arch Pediatr Adolesc Med 2007;161:21721.
(Level II-3)
51. Teitelman M, Grotegut CA, Williams NN, Lewis JD. The
impact of bariatric surgery on menstrual patterns. Obes
Surg 2006;16:145763. (Level III)
52. Eid GM, Cottam DR, Velcu LM, Mattar SG, Korytkowski
MT, Gosman G, et al. Effective treatment of polycystic
ovarian syndrome with Roux-en-Y gastric bypass. Surg
Obes Relat Dis 2005;1:7780. (Level III)
53. Deitel M, Stone E, Kassam HA, Wilk EJ, Sutherland DJ.
Gynecologic-obstetric changes after loss of massive
excess weight following bariatric surgery. J Am Coll Nutr
1988;7:14753. (Level III)
54. Bilenka B, Ben-Shlomo I, Cozacov C, Gold CH, Zohar S.
Fertility, miscarriage and pregnancy after vertical banded
gastroplasty operation for morbid obesity. Acta Obstet
Gynecol Scand 1995;74:424. (Level III)
55. Merhi ZO. Weight loss by bariatric surgery and subse-
quent fertility. Fertil Steril 2007;87:4302. (Level III)
56. Merhi ZO. Challenging oral contraception after weight
loss by bariatric surgery. Gynecol Obstet Invest 2007;
64:1002. (Level III)
57. Hanker JP. Gastrointestinal disease and oral contracep-
tion. Am J Obstet Gynecol 1990;163:22047. (Level III)
58. Gerrits EG, Ceulemans R, van Hee R, Hendrickx L, Totte
E. Contraceptive treatment after biliopancreatic diversion
needs consensus. Obes Surg 2003;13:37882. (Level III)
59. Victor A, Odlind V, Kral JG. Oral contraceptive absorp-
tion and sex hormone binding globulins in obese women:
effects of jejunoileal bypass. Gastroenterol Clin North Am
1987;16:48391. (Level III)
60. Marceau P, Kaufman D, Biron S, Hould FS, Lebel S,
Marceau S, et al. Outcome of pregnancies after biliopan-
creatic diversion. Obes Surg 2004;14:31824. (Level III)
61. Wax JR, Cartin A, Wolff R, Lepich S, Pinette MG,
Blackstone J. Pregnancy following gastric bypass surgery
for morbid obesity: maternal and neonatal outcomes.
Obes Surg 2008;18:5404. (Level II-3)
62. Dixon JB, Dixon ME, OBrien PE. Pregnancy after Lap-
Band surgery: management of the band to achieve healthy
weight outcomes. Obes Surg 2001;11:5965. (Level III)
63. Weiss HG, Nehoda H, Labeck B, Hourmont K, Marth C,
Aigner F. Pregnancies after adjustable gastric banding.
Obes Surg 2001;11:3036. (Level III)
64. Sheiner E, Levy A, Silverberg D, Menes TS, Levy I, Katz
M, et al. Pregnancy after bariatric surgery is not associat-
ed with adverse perinatal outcome. Am J Obstet Gynecol
2004;190:133540. (Level II-2)
65. Richards DS, Miller DK, Goodman GN. Pregnancy after
gastric bypass for morbid obesity. J Reprod Med 1987;
32:1726. (Level II-3)
66. Winetraub AY, Levy A, Levi I, Mazor M, Wiznitzer A,
Sheiner E. Effect of bariatric surgery on pregnancy out-
come. Int J Gynecol Obstet 2008;103:24651. (Level
II-2)
67. Maggard MA, Yermilov I, Li Z, Maglione M, Newberry S,
Suttrop M, et al. Pregnancy and fertility following bariatric
surgery: a systemic review. JAMA 2008;300: 228696.
(Systematic review)
1109 PRACTICE BULLETINS
68. Dixon JB, Dixon ME, OBrien PE. Birth outcomes in
obese women after laparoscopic adjustable gastric band-
ing. Obstet Gynecol 2005;106:96572. (Level II-2)
69. Skull AJ, Slater GH, Duncombe JE, Fielding GA.
Laparoscopic adjustable banding in pregnancy: safety,
patient tolerance and effect on obesity-related pregnancy
outcomes. Obes Surg 2004;14:2305. (Level II-3)
70. Ducarme G, Revaux A, Rodrigues A, Aissaoui F,
Pharisien I, Uzan M. Obstetric outcome following laparo-
scopic adjustable gastric banding. Int J Gynaecol Obstet
2007;98:2447. (Level II-3)
71. Patel JA, Patel NA, Thomas RL, Nelms JK, Colella JJ.
Pregnancy outcomes after laparoscopic Roux-en-Y gastric
bypass. Surg Obes Relat Dis 2008;4:3945. (Level II-3)
72. Ramirez MM, Turrentine MA. Gastrointestinal hemor-
rhage during pregnancy in a patient with a history of ver-
tical-banded gastroplasty. Am J Obstet Gynecol 1995;
173:16301. (Level III)
73. Wax JR, Wolff R, Cobean R, Pinette MG, Blackstone J,
Cartin A. Intussusception complicating pregnancy follow-
ing laparoscopic Roux-en-Y gastric bypass. Obes Surg
2007;17:9779. (Level III)
74. Erez O, Maymon E, Mazor M. Acute gastric ulcer perfora-
tion in a 35 weeks nulliparous patient with gastric band-
ing. Am J Obstet Gynecol 2004;191:17212. (Level III)
75. Moore KA, Ouyang DW, Whang EE. Maternal and fetal
deaths after gastric bypass surgery for morbid obesity.
N Engl J Med 2004;351:7212. (Level III)
76. Loar PV 3rd, Sanchez-Ramos L, Kaunitz AM, Kerwin AJ,
Diaz J. Maternal death caused by midgut volvulus after
bariatric surgery. Am J Obstet Gynecol 2005;193:17489.
(Level III)
77. Knudsen LB, Kallen B. Gastric bypass, pregnancy, and
neural tube defects. Lancet 1986;2:227. (Level III)
78. Abrams BF, Laros RK Jr. Prepregnancy weight, weight
gain, and birth weight [published erratum appears in Am
J Obstet Gynecol 1986;155:918]. Am J Obstet Gynecol
1986;154:5039. (Level II-3)
79. Wittgrove AC, Jester L, Wittgrove P, Clark GW.
Pregnancy following gastric bypass for morbid obesity.
Obes Surg 1998;8:4614; discussion 4656. (Level III)
80. Roehrig HR, Xanthakos SA, Sweeney J, Zeller MH, Inge
TH. Pregnancy after gastric bypass surgery in adolescents.
Obes Surg 2007;17:8737. (Level III)
81. Apovian CM, Baker C, Ludwig DS, Hoppin AG, Hsu G,
Lenders C, et al. Best practice guidelines in pediatric/ado-
lescent weight loss surgery. Obes Res 2005;13:274.
(Level III)
82. Poitou Bernert C, Ciangura C, Coupaye M, Czernichow
S, Bouillot JL, Basdevant A. Nutritional deficiency after
gastric bypass: diagnosis, prevention and treatment.
Diabetes Metab 2007;33:1324. (Level III)
83. Woodard CB. Pregnancy following bariatric surgery. J
Perinat Neonatal Nurs 2004;18:32940. (Level III)
84. Magee SR, Shih G, Hume A. Malabsorption of oral antibi-
otics in pregnancy after gastric bypass surgery. J Am
Board Fam Med 2007;20:3103. (Level III)
85. Dixon JB, Dixon ME, OBrien PE. Elevated homocys-
teine levels with weight loss after Lap-Band surgery:
higher folate and vitamin B12 levels required to maintain
homocysteine level. Int J Obes Relat Metab Disord
2001;25:21927. (Level II-2)
86. Rand CS, Macgregor AM. Adolescents having obesity
surgery: a 6-year follow-up. South Med J 1994;87:1208
13. (Level III)
87. Kramer MS, Kakuma R. Energy and protein intake in
pregnancy. Cochrane Database of Systematic Reviews
2003, Issue 4. Art. No.: CD000032. DOI: 10.1002/
14651858.CD000032. (Meta-analysis)
88. Dao T, Kuhn J, Ehmer D, Fisher T, McCarty T. Pregnancy
outcomes after gastric-bypass surgery. Am J Surg 2006;
192:7626. (Level III)
89. Grange DK, Finlay JL. Nutritional vitamin B12 deficien-
cy in a breastfed infant following maternal gastric bypass.
Pediatr Hematol Oncol 1994;11:3118. (Level III)
90. Campbell CD, Ganesh J, Ficicioglu C. Two newborns with
nutritional vitamin B12 deficiency: challenges in newborn
screening for vitamin B12 deficiency. Haematologica 2005;
90:ECR45. (Level III)
91. Martin LF, Finigan KM, Nolan TE. Pregnancy after
adjustable gastric banding. Obstet Gynecol 2000;95:
92730. (Level III)
92. American Diabetes Association. Gestational diabetes mel-
litus. Practice Guideline. Diabetes Care. 27 Suppl
1:S8890, 2004 Jan. (Level III)
93. Edmiston CE, Krepel C, Kelly H, Larson J, Andris D,
Hennen C, et al. Perioperative antibiotic prophylaxis in
the gastric bypass patient: do we achieve therapeutic lev-
els? Surgery 2004;136:73847. (Level II-3)
94. Prince RA, Pincheira JC, Mason EE, Printen KJ.
Influence of bariatric surgery on erythromycin absorption.
J Clin Pharmacol 1984;24:5237. (Level III)
95. Miller AD, Smith KM. Medication and nutrient adminis-
tration considerations after bariatric surgery. Am J Health
Syst Pharm 2006;63:18527. (Level III)
COMPENDIUM OF SELECTED PUBLICATIONS 1110
The MEDLINE database, the Cochrane Library, and
ACOGs own internal resources and documents were used
to conduct a literature search to locate relevant articles pub-
lished between January 1975 and November 2008. The
search was restricted to articles published in the English lan-
guage. Priority was given to articles reporting results of
original research, although review articles and commentar-
ies also were consulted. Abstracts of research presented at
symposia and scientific conferences were not considered
adequate for inclusion in this document. Guidelines pub-
lished by organizations or institutions such as the National
Institutes of Health and the American College of Obstetri-
cians and Gynecologists were reviewed, and additional
studies were located by reviewing bibliographies of identi-
fied articles. When reliable research was not available,
expert opinions from obstetriciangynecologists were used.
Studies were reviewed and evaluated for quality according
to the method outlined by the U.S. Preventive Services
Task Force:
I Evidence obtained from at least one properly
designed randomized controlled trial.
II-1 Evidence obtained from well-designed controlled
trials without randomization.
II-2 Evidence obtained from well-designed cohort or
casecontrol analytic studies, preferably from more
than one center or research group.
II-3 Evidence obtained from multiple time series with or
without the intervention. Dramatic results in uncon-
trolled experiments also could be regarded as this
type of evidence.
III Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees.
Based on the highest level of evidence found in the data,
recommendations are provided and graded according to the
following categories:
Level ARecommendations are based on good and con-
sistent scientific evidence.
Level BRecommendations are based on limited or incon-
sistent scientific evidence.
Level CRecommendations are based primarily on con-
sensus and expert opinion.
Copyright June 2009 by the American College of Obstetri-
cians and Gynecologists. All rights reserved. No part of this
publication may be reproduced, stored in a retrieval system,
posted on the Internet, or transmitted, in any form or by any
means, electronic, mechanical, photocopying, recording, or
otherwise, without prior written permission from the publisher.
Requests for authorization to make photocopies should be
directed to Copyright Clearance Center, 222 Rosewood Drive,
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
The American College of Obstetricians and Gynecologists
409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920
Bariatric surgery and pregnancy. ACOG Practice Bulletin No. 105.
American College of Obstetricians and Gynecologists. Obstet Gynecol
2009;113:140513.
1111 PRACTICE BULLETINS
CLINICAL MANAGEMENT GUIDELINES FOR OBSTETRICIANGYNECOLOGISTS
NUMBER 106, JULY 2009
Replaces Practice Bulletin Number 70, December 2005
ACOG
PRACTICE
BULLETIN
This Practice Bulletin was devel-
oped by the ACOG Committee on
Practice BulletinsObstetrics with
the assistance of George A. Macones,
MD. The information is designed to
aid practitioners in making deci-
sions about appropriate obstetric
and gynecologic care. These guide-
lines should not be construed as
dictating an exclusive course of
treatment or procedure. Variations
in practice may be warranted based
on the needs of the individual
patient, resources, and limitations
unique to the institution or type of
practice.
THE AMERICAN COLLEGE OF
OBSTETRICIANS AND
GYNECOLOGISTS
WOMENS HEALTH CARE PHYSICIANS
Intrapartum Fetal Heart Rate
Monitoring: Nomenclature,
Interpretation, and General
Management Principles
In the most recent year for which data are available, approximately 3.4 million
fetuses (85% of approximately 4 million live births) in the United States were
assessed with electronic fetal monitoring (EFM), making it the most common
obstetric procedure (1). Despite its widespread use, there is controversy about
the efficacy of EFM, interobserver and intraobserver variability, nomenclature,
systems for interpretation, and management algorithms. Moreover, there is evi-
dence that the use of EFM increases the rate of cesarean deliveries and opera-
tive vaginal deliveries. The purpose of this document is to review nomenclature
for fetal heart rate assessment, review the data on the efficacy of EFM, delin-
eate the strengths and shortcomings of EFM, and describe a system for EFM
classification.
Background
A complex interplay of antepartum complications, suboptimal uterine perfu-
sion, placental dysfunction, and intrapartum events can result in adverse neona-
tal outcome. Known obstetric conditions, such as hypertensive disease, fetal
growth restriction, and preterm birth, predispose fetuses to poor outcomes, but
they account for a small proportion of asphyxial injury. In a study of term preg-
nancies with fetal asphyxia, 63% had no known risk factors (2).
The fetal brain modulates the fetal heart rate through an interplay of sym-
pathetic and parasympathetic forces. Thus, fetal heart rate (FHR) monitoring
can be used to determine if a fetus is well oxygenated. It was used among 45%
of laboring women in 1980, 62% in 1988, 74% in 1992, and 85% in 2002 (1).
COMPENDIUM OF SELECTED PUBLICATIONS 1112
Despite the frequency of its use, limitations of EFM
include poor interobserver and intraobserver reliability,
uncertain efficacy, and a high false-positive rate.
Fetal heart rate monitoring may be performed exter-
nally or internally. Most external monitors use a Doppler
device with computerized logic to interpret and count the
Doppler signals. Internal FHR monitoring is accom-
plished with a fetal electrode, which is a spiral wire
placed directly on the fetal scalp or other presenting part.
Guidelines for Nomenclature and
Interpretation of Electronic Fetal
Heart Rate Monitoring
In 2008, the Eunice Kennedy Shriver National Institute
of Child Health and Human Development partnered with
the American College of Obstetricians and Gynecolo-
gists and the Society for MaternalFetal Medicine to
sponsor a workshop focused on electronic FHR monitor-
ing (3). This 2008 workshop gathered a diverse group of
investigators with expertise and interest in the field to
accomplish three goals: 1) to review and update the def-
initions for FHR pattern categorization from the prior
workshop; 2) to assess existing classification systems for
interpreting specific FHR patterns and make recommen-
dations about a system for use in the United States; and
3) to make recommendations for research priorities for
EFM. A complete clinical understanding of EFM neces-
sitates discussion of uterine contractions, baseline FHR
rate and variability, presence of accelerations, periodic
or episodic decelerations, and the changes in these char-
acteristics over time. A number of assumptions and fac-
tors common to FHR interpretation in the United States
are central to the proposed system of nomenclature
and interpretation (3). Two such assumptions are of par-
ticular importance. First, the definitions are primarily
developed for visual interpretation of FHR patterns, but
should be adaptable to computerized systems of inter-
pretation. Second, the definitions should be applied to
intrapartum patterns, but also are applicable to antepar-
tum observations.
Uterine contractions are quantified as the number of
contractions present in a 10-minute window, averaged
over a 30-minute period. Contraction frequency alone is
a partial assessment of uterine activity. Other factors
such as duration, intensity, and relaxation time between
contractions are equally important in clinical practice.
Listed as follows is terminology used to describe
uterine activity:
Normal: five contractions or less in 10 minutes,
averaged over a 30-minute window
Tachysystole: more than five contractions in 10 min-
utes, averaged over a 30-minute window
Characteristics of uterine contractions
The terms hyperstimulation and hypercontractility
are not defined and should be abandoned.
Tachysystole should always be qualified as to the
presence or absence of associated FHR decelera-
tions.
The term tachysystole applies to both spontaneous
and stimulated labor. The clinical response to tachy-
systole may differ depending on whether contrac-
tions are spontaneous or stimulated.
Table 1 provides EFM definitions and descriptions
based on the 2008 National Institute of Child Health and
Human Development Working Group findings. Deceler-
ations are defined as recurrent if they occur with at least
one half of the contractions.
Classification of Fetal Heart
Rate Tracings
A variety of systems for EFM interpretation have been
used in the United States and worldwide (46). Based on
careful review of the available options, a three-tiered
system for the categorization of FHR patterns is recom-
mended (see box). It is important to recognize that FHR
tracing patterns provide information only on the current
acidbase status of the fetus. Categorization of the FHR
tracing evaluates the fetus at that point in time; tracing
patterns can and will change. An FHR tracing may move
back and forth between the categories depending on the
clinical situation and management strategies used.
Category I FHR tracings are normal. Category I FHR
tracings are strongly predictive of normal fetal acidbase
status at the time of observation. Category I FHR trac-
ings may be monitored in a routine manner, and no spe-
cific action is required.
Category II FHR tracings are indeterminate. Category
II FHR tracings are not predictive of abnormal fetal
acidbase status, yet presently there is not adequate evi-
dence to classify these as Category I or Category III.
Category II FHR tracings require evaluation and contin-
ued surveillance and reevaluation, taking into account
the entire associated clinical circumstances. In some cir-
cumstances, either ancillary tests to ensure fetal well-
being or intrauterine resuscitative measures may be used
with Category II tracings.
Category III FHR tracings are abnormal. Category III
tracings are associated with abnormal fetal acidbase
status at the time of observation. Category III FHR trac-
ings require prompt evaluation. Depending on the clini-
cal situation, efforts to expeditiously resolve the abnor-
1113 PRACTICE BULLETINS
Table 1. Electronic Fetal Monitoring Definitions
Pattern Definition
Baseline The mean FHR rounded to increments of 5 beats per minute during a 10-minute segment, excluding:
Periodic or episodic changes
Periods of marked FHR variability
Segments of baseline that differ by more than 25 beats per minute
The baseline must be for a minimum of 2 minutes in any 10-minute segment, or the baseline for that time period
is indeterminate. In this case, one may refer to the prior 10-minute window for determination of baseline.
Normal FHR baseline: 110160 beats per minute
Tachycardia: FHR baseline is greater than 160 beats per minute
Bradycardia: FHR baseline is less than 110 beats per minute
Baseline variability Fluctuations in the baseline FHR that are irregular in amplitude and frequency
Variability is visually quantitated as the amplitude of peak-to-trough in beats per minute.
Absentamplitude range undetectable
Minimalamplitude range detectable but 5 beats per minute or fewer
Moderate (normal)amplitude range 625 beats per minute
Markedamplitude range greater than 25 beats per minute
Acceleration A visually apparent abrupt increase (onset to peak in less than 30 seconds) in the FHR
At 32 weeks of gestation and beyond, an acceleration has a peak of 15 beats per minute or more above baseline,
with a duration of 15 seconds or more but less than 2 minutes from onset to return.
Before 32 weeks of gestation, an acceleration has a peak of 10 beats per minute or more above baseline, with a
duration of 10 seconds or more but less than 2 minutes from onset to return.
Prolonged acceleration lasts 2 minutes or more but less than 10 minutes in duration.
If an acceleration lasts 10 minutes or longer, it is a baseline change.
Early deceleration Visually apparent usually symmetrical gradual decrease and return of the FHR associated with a uterine contraction
A gradual FHR decrease is defined as from the onset to the FHR nadir of 30 seconds or more.
The decrease in FHR is calculated from the onset to the nadir of the deceleration.
The nadir of the deceleration occurs at the same time as the peak of the contraction.
In most cases the onset, nadir, and recovery of the deceleration are coincident with the beginning, peak, and
ending of the contraction, respectively.
Late deceleration Visually apparent usually symmetrical gradual decrease and return of the FHR associated with a uterine contraction
A gradual FHR decrease is defined as from the onset to the FHR nadir of 30 seconds or more.
The decrease in FHR is calculated from the onset to the nadir of the deceleration.
The deceleration is delayed in timing, with the nadir of the deceleration occurring after the peak of the contraction.
In most cases, the onset, nadir, and recovery of the deceleration occur after the beginning, peak, and ending of
the contraction, respectively.
Variable deceleration Visually apparent abrupt decrease in FHR
An abrupt FHR decrease is defined as from the onset of the deceleration to the beginning of the FHR nadir of less
than 30 seconds.
The decrease in FHR is calculated from the onset to the nadir of the deceleration.
The decrease in FHR is 15 beats per minute or greater, lasting 15 seconds or greater, and less than 2 minutes in
duration.
When variable decelerations are associated with uterine contractions, their onset, depth, and duration commonly
vary with successive uterine contractions.
Prolonged deceleration Visually apparent decrease in the FHR below the baseline
Decrease in FHR from the baseline that is 15 beats per minute or more, lasting 2 minutes or more but less than 10
minutes in duration.
If a deceleration lasts 10 minutes or longer, it is a baseline change.
Sinusoidal pattern Visually apparent, smooth, sine wave-like undulating pattern in FHR baseline with a cycle frequency of 35 per
minute which persists for 20 minutes or more.
Abbreviation: FHR, fetal heart rate.
Macones GA, Hankins GD, Spong CY, Hauth J, Moore T. The 2008 National Institute of Child Health and Human Development workshop report on electronic fetal mon-
itoring: update on definitions, interpretation, and research guidelines. Obstet Gynecol 2008;112:6616.
COMPENDIUM OF SELECTED PUBLICATIONS 1114
Three-Tiered Fetal Heart Rate Interpretation System
Category I
Category I FHR tracings include all of the following:
Baseline rate: 110160 beats per minute
Baseline FHR variability: moderate
Late or variable decelerations: absent
Early decelerations: present or absent
Accelerations: present or absent
Category II
Category II FHR tracings includes all FHR tracings not
categorized as Category I or Category III. Category II
tracings may represent an appreciable fraction of those
encountered in clinical care. Examples of Category II
FHR tracings include any of the following:
Baseline rate
Bradycardia not accompanied by absent baseline
variability
Tachycardia
Baseline FHR variability
Minimal baseline variability
Absent baseline variability with no recurrent
decelerations
Marked baseline variability
Accelerations
Absence of induced accelerations after fetal stimulation
Periodic or episodic decelerations
Recurrent variable decelerations accompanied by
minimal or moderate baseline variability
Prolonged deceleration more than 2 minutes but
less than10 minutes
Recurrent late decelerations with moderate baseline
variability
Variable decelerations with other characteristics such
as slow return to baseline, overshoots, or shoulders
Category III
Category III FHR tracings include either
Absent baseline FHR variability and any of the
following:
Recurrent late decelerations
Recurrent variable decelerations
Bradycardia
Sinusoidal pattern
Abbreviation: FHR, fetal heart rate
Macones GA, Hankins GD, Spong CY, Hauth J, Moore T. The 2008
National Institute of Child Health and Human Development workshop
report on electronic fetal monitoring: update on definitions, interpreta-
tion, and research guidelines. Obstet Gynecol 2008;112:6616.
mal FHR pattern may include but are not limited to pro-
vision of maternal oxygen, change in maternal position,
discontinuation of labor stimulation, treatment of mater-
nal hypotension, and treatment of tachysystole with FHR
changes. If a Category III tracing does not resolve with
these measures, delivery should be undertaken.
Guidelines for Review of Electronic
Fetal Heart Rate Monitoring
When EFM is used during labor, the nurses or physicians
should review it frequently. In a patient without compli-
cations, the FHR tracing should be reviewed approxi-
mately every 30 minutes in the first stage of labor and
every 15 minutes during the second stage. The corre-
sponding frequency for patients with complications (eg,
fetal growth restriction, preeclampsia) is approximately
every 15 minutes in the first stage of labor and every 5
minutes during the second stage. Health care providers
should periodically document that they have reviewed
the tracing. The FHR tracing, as part of the medical
record, should be labeled and available for review if the
need arises. Computer storage of the FHR tracing that
does not permit overwriting or revisions is reasonable, as
is microfilm recording.
Clinical Considerations and
Recommendations
How efficacious is intrapartum electronic
fetal heart rate monitoring?
The efficacy of EFM during labor is judged by its abili-
ty to decrease complications, such as neonatal seizures,
cerebral palsy, or intrapartum fetal death, while mini-
mizing the need for unnecessary obstetric interventions,
such as operative vaginal delivery or cesarean delivery.
There are no randomized clinical trials to compare the
benefits of EFM with any form of monitoring during
labor (7). Thus, the benefits of EFM are gauged from
reports comparing it with intermittent auscultation.
A meta-analysis synthesizing the results of the ran-
domized clinical trials comparing the modalities had the
following conclusions (8):
The use of EFM compared with intermittent auscul-
tation increased the overall cesarean delivery rate
(relative risk [RR], 1.66; 95% confidence interval
[CI], 1.302.13) and the cesarean delivery rate for
abnormal FHR or acidosis or both (RR, 2.37; 95%
CI, 1.883.00).
1115 PRACTICE BULLETINS
The use of EFM increased the risk of both vacuum
and forceps operative vaginal delivery (RR, 1.16;
95% CI, 1.011.32).
The use of EFM did not reduce perinatal mortality
(RR, 0.85; 95% CI, 0.591.23).
The use of EFM reduced the risk of neonatal seizures
(RR, 0.50; 95% CI, 0.310.80).
The use of EFM did not reduce the risk of cerebral
palsy (RR, 1.74; 95% CI, 0.973.11).
There is an unrealistic expectation that a nonreas-
suring FHR tracing is predictive of cerebral palsy. The
positive predictive value of a nonreassuring pattern to
predict cerebral palsy among singleton newborns with
birth weights of 2,500 g or more is 0.14%, meaning that
out of 1,000 fetuses with a nonreassuring FHR pattern,
only one or two will develop cerebral palsy (9). The false-
positive rate of EFM for predicting cerebral palsy is
extremely high, at greater than 99%.
Available data, although limited in quantity, suggest
that the use of EFM does not result in a reduction in cere-
bral palsy (8). This is consistent with data that suggest
that the occurrence of cerebral palsy has been stable over
time, despite the widespread introduction of EFM (10).
The principal explanation for why the prevalence of
cerebral palsy has not diminished despite the use of EFM
is that 70% of cases occur before the onset of labor; only
4% of cases of encephalopathy can be attributed solely
to intrapartum events (11, 12).
Given that the available data do not show a clear
benefit for the use of EFM over intermittent auscultation,
either option is acceptable in a patient without complica-
tions. Logistically, it may not be feasible to adhere to
guidelines for how frequently the heart rate should be
auscultated. One prospective study noted that the proto-
col for intermittent auscultation was successfully com-
pleted in only 3% of the cases (13). The most common
reasons for unsuccessful intermittent auscultation
included the frequency of recording and the require-
ments for recording.
Intermittent auscultation may not be appropriate for
all pregnancies. Most of the clinical trials that compare
EFM with intermittent auscultation have excluded par-
ticipants at high risk of adverse outcomes, and the rela-
tive safety of intermittent auscultation in such cases is
uncertain. The labor of women with high-risk conditions
(eg, suspected fetal growth restriction, preeclampsia, and
type 1 diabetes) should be monitored with continuous
FHR monitoring.
There are no comparative data indicating the opti-
mal frequency at which intermittent auscultation should
be performed in the absence of risk factors. One method
is to evaluate and record the FHR at least every 15 min-
utes in the active phase of the first stage of labor and at
least every 5 minutes in the second stage (14).
What is the interobserver and intraobserver
variability of intrapartum electronic fetal
heart rate monitoring assessment?
There is high interobserver and intraobserver variability
in the interpretation of FHR tracings. For example, when
four obstetricians examined 50 cardiotocograms, they
agreed in only 22% of the cases (15). Two months later,
during the second review of the same 50 tracings, the
clinicians interpreted 21% of the tracings differently
than they did during the first evaluation. In another study,
five obstetricians independently interpreted 150 car-
diotoco-grams (16). The obstetricians interpreted the
tracings similarly in 29% of the cases, suggesting poor
interobserver reliability.
The interpretation of cardiotocograms is more con-
sistent when the tracing is normal (17). With retrospec-
tive reviews, the foreknowledge of neonatal outcome may
alter the reviewers impressions of the tracing. Given the
same intrapartum tracing, a reviewer is more likely to
find evidence of fetal hypoxia and criticize the obstetri-
cians management if the outcome was poor versus good
(18). Therefore, reinterpretation of the FHR tracing,
especially if neonatal outcome is known, may not be
reliable.
When should the very preterm fetus be
monitored?
The decision to monitor the very preterm fetus requires
a discussion between the obstetrician, pediatrician, and
patient concerning the likelihood of survival or severe
morbidity of the preterm child (based on gestational age,
estimated fetal weight, and other factors) and issues
related to mode of delivery. If a patient undergoes a
cesarean delivery for indications related to a preterm
fetus, continuous monitoring should be used rather than
intermittent auscultation. The earliest gestational age
that this will occur may vary.
Nonreassuring FHR patterns may occur with up to
60% of women with preterm labor, with the most com-
mon abnormality being deceleration and bradycardia,
followed by tachycardia and minimal or absent baseline
variability (19). Variable decelerations are more com-
mon among preterm (5570%) deliveries than term
(2030%) deliveries (20). If FHR abnormalities are per-
sistent, intrauterine resuscitation, ancillary tests to
ensure fetal well-being, and possibly delivery should be
undertaken (21).
COMPENDIUM OF SELECTED PUBLICATIONS 1116
What medications can affect the fetal heart
rate?
Fetal heart rate patterns can be influenced by the med-
ications administered in the intrapartum period. Most
often, these changes are transient, although they some-
times lead to obstetric interventions.
Epidural analgesia with local anesthetic agents (ie,
lidocaine, bupivacaine) can lead to sympathetic block-
ade, maternal hypotension, transient uteroplacental insuf-
ficiency, and alterations in the FHR. Parenteral narcotics
also may affect the FHR. A randomized trial comparing
epidural anesthesia with 0.25% of bupivacaine and intra-
venous meperidine reported that the variability was
decreased, and FHR accelerations were significantly less
common with parenteral analgesia compared with
regional analgesia (22). The rates of decelerations and
cesarean delivery for nonreassuring FHR tracings
were similar for the two groups. A systematic review of
five randomized trials and seven observational studies
also noted that the rate of cesarean delivery for nonreas-
suring FHR was similar between those who did and
those who did not receive epidural analgesia during labor
(23).
Concern has been raised about combined spinal
epidural anesthesia during labor. An intent-to-treat
analysis of 1,223 laboring women randomized to com-
bined spinalepidural anesthesia (10 mcg of intrathecal
sufentanil, followed by epidural bupivacaine and fen-
tanyl at the next request for analgesia) or intravenous
meperidine (50 mg on demand, maximum 200 mg in
4 hours) noted a significantly higher rate of bradycar-
dia and emergent cesarean delivery for abnormal FHR
in the group randomized to combined spinalepidural
anesthesia (24). Neonatal outcome, however, was not
significantly different between the two groups. There
are some methodological concerns with this study.
Another randomized controlled trial compared the
occurrence of FHR tracing abnormalities in laboring
women who received combined spinalepidural anes-
thesia (n=41) to epidural anesthesia (n=46). In this
study, FHR abnormalities were more common in
women receiving combined spinalepidural anesthesia
(25). Additional trials are necessary to determine the
potential safety and efficacy of the combined spinal
epidural technique.
Other medications that influence FHR tracing have
been studied (see Table 2). Of note, multiple regression
analysis indicated that decreased variability attributed to
the use of magnesium sulfate was related to early gesta-
tional age but not the serum magnesium level (26).
Studies report different findings with regard to the effect
of magnesium on FHR patterns. Some show no indepen-
dent effect; others show small changes in baseline or
variability. In general, however, caution should be used
in ascribing unfavorable findings on EFM to the use of
magnesium alone.
Transient sinusoidal FHR patterns occurred in 75%
of patients who received butorphanol during labor, but
this was not associated with adverse outcomes (27).
Fetuses exposed to cocaine did not exhibit any charac-
teristic changes in the heart rate pattern, although they
did have frequent contractions even when labor was
unstimulated (28). As determined by computer analysis
of cardiotocograms, a randomized trial reported that
compared with meperidine, nalbuphine used for intra-
partum analgesia decreased the likelihood of two 15-sec-
ond accelerations over 20 minutes (29). In antepartum
patients, administration of morphine decreased not only
the fetal breathing movement but also the number of
accelerations (30).
The effect of corticosteroids, which are used to
enhance pulmonary maturity of fetuses during preterm
labor, on FHR has been studied (Table 2). Among twins
(31) and singletons (32, 33), the use of betamethasone
transiently decreased the FHR variability, which returned
to pretreatment status by the fourth to seventh day. There
also may be a decrease in the rate of accelerations with
the use of betamethasone. These changes, however, were
not associated with increased obstetric interventions or
with adverse outcomes (31). The biologic mechanism of
this is unknown. Computerized analysis of the cardioto-
cograms indicates that use of dexamethasone is not asso-
ciated with a decrease in the FHR variability (33).
What findings on EFM are consistent with
normal fetal acidbase status?
The presence of FHR accelerations generally ensures that
the fetus is not acidemic. The data relating FHR variabil-
ity to clinical outcomes, however, are sparse. Results of
an observational study suggest that moderate FHR vari-
ability is strongly associated with an arterial umbilical
cord pH higher than 7.15 (34). One study reported that in
the presence of late or variable decelerations, the umbili-
cal arterial pH was higher than 7.00 in 97% of the cases
if the FHR tracing had normal variability (35). In anoth-
er retrospective study, most cases of adverse neonatal out-
come demonstrated normal FHR variability (36). This
study is limited because it did not consider other charac-
teristics of the FHR tracing, such as the presence of accel-
erations or decelerations. However, in most cases, normal
FHR variability provides reassurance about fetal status
and the absence of metabolic acidemia.
1117 PRACTICE BULLETINS
Table 2. Effects of Commonly Used Medications on Fetal Heart Rate Patterns
Medications Comments References
Narcotics At equivalent doses, all narcotics (with or without added antiemetics) have similar 17
effects: a decrease in variability and a decrease in the frequency of accelerations
75 mg meperidine = 10 mg morphine = 0.1 mg fentanyl = 10 mg nalbuphine
Butorphanol Transient sinusoidal FHR pattern, slight increased mean heart rate compared with meperidine 8, 9
Cocaine Decreased long-term variability 10, 11
Corticosteroids Decrease in FHR variability with beta-methasone but not dexamethasone, abolishment 1215
of diurnal fetal rhythms, increased effect at greater than 29 weeks of gestation
Magnesium sulfate A significant decrease in short-term variability, clinically insignificant decrease in FHR, 16, 17
inhibits the increase in accelerations with advancing gestational age
Terbutaline Increase in baseline FHR and incidence of fetal tachycardia 18, 19
Zidovudine No difference in the FHR baseline, variability, number of accelerations, or decelerations 20
Abbreviation: FHR, fetal heart rate.
References
1. Hill JB, Alexander JM, Sharma SK, McIntire DD, Leveno KJ. A comparison of the effects of epidural and meperidine analgesia during labor on fetal heart rate. Obstet
Gynecol 2003;102:3337.
2. Panayotopoulos N, Salamalekis E, Kassanos D, Vitoratos N, Loghis C, Batalias L. Intrapartum vibratory acoustic stimulation after maternal meperidine administra-
tion. Clin Exp Obstet Gynecol 1998;25:13940.
3. Zimmer EZ, Divon MY, Vadasz A. Influence of meperidine on fetal movements and heart rate beat-to-beat variability in the active phase of labor. Am J Perinatol
1988;5:197200.
4. Kopecky EA, Ryan ML, Barrett JF, Seaward PG, Ryan G, Koren G, et al. Fetal response to maternally administered morphine. Am J Obstet Gynecol 2000;183:42430.
5. Rayburn W, Rathke A, Leuschen MP, Chleborad J, Weidner W. Fentanyl citrate analgesia during labor. Am J Obstet Gynecol 1989;161:2026.
6. Nicolle E, Devillier P, Delanoy B, Durand C, Bessard G. Therapeutic monitoring of nalbuphine: transplacental transfer and estimated pharmacokinetics in the
neonate. Eur J Clin Pharmacol 1996;49:4859.
7. Poehlmann S, Pinette M, Stubblefield P. Effect of labor analgesia with nalbuphine hydrochloride on fetal response to vibroacoustic stimulation. J Reprod Med
1995;40:70710.
8. Hatjis CG, Meis PJ. Sinusoidal fetal heart rate pattern associated with butorphanol administration. Obstet Gynecol 1986;67:37780.
9. Quilligan EJ, Keegan KA, Donahue MJ. Double-blind comparison of intravenously injected butorphanol and meperidine in parturients. Int J Gynaecol Obstet
1980;18:3637.
10. Chazotte C, Forman L, Gandhi J. Heart rate patterns in fetuses exposed to cocaine. Obstet Gynecol 1991;78:3235.
11. Tabor BL, Soffici AR, Smith-Wallace T, Yonekura ML. The effect of maternal cocaine use on the fetus: changes in antepartum fetal heart rate tracings. Am J Obstet
Gynecol 1991;165:127881.
12. Senat MV, Minoui S, Multon O, Fernandez H, Frydman R, Ville Y. Effect of dexamethasone and betamethasone on fetal heart rate variability in preterm labour: a
randomised study. Br J Obstet Gynaecol 1998;105:74955.
13. Rotmensch S, Liberati M, Vishne TH, Celentano C, Ben-Rafael Z, Bellati U. The effect of betamethasone and dexamethasone on fetal heart rate patterns and bio-
physical activities. A prospective randomized trial. Acta Obstet Gynecol Scand 1999;78:493500.
14. Koenen SV, Mulder EJ, Wijnberger LD, Visser GH. Transient loss of the diurnal rhythms of fetal movements, heart rate, and its variation after maternal betametha-
sone administration. Pediatr Res 2005;57:6626.
15. Mulder EJ, Koenen SV, Blom I, Visser GH. The effects of antenatal betamethasone administration on fetal heart rate and behaviour depend on gestational age. Early
Hum Dev 2004;76:6577.
16. Hallak M, Martinez-Poyer J, Kruger ML, Hassan S, Blackwell SC, Sorokin Y. The effect of magnesium sulfate on fetal heart rate parameters: a randomized, placebo-
controlled trial. Am J Obstet Gynecol 1999;181:11227.
17. Wright JW, Ridgway LE, Wright BD, Covington DL, Bobitt JR. Effect of MgSO4 on heart rate monitoring in the preterm fetus. J Reprod Med 1996;41:6058.
18. Mawaldi L, Duminy P, Tamim H. Terbutaline versus nifedipine for prolongation of pregnancy in patients with preterm labor. Int J Gynaecol Obstet 2008;100:658.
19. Roth AC, Milsom I, Forssman L, Ekman LG, Hedner T. Effects of intravenous terbutaline on maternal circulation and fetal heart activity. Acta Obstet Gynecol Scand
1990;69:2238.
20. Blackwell SC, Sahai A, Hassan SS, Treadwell MC, Tomlinson MW, Jones TB, et al. Effects of intrapartum zidovudine therapy on fetal heart rate parameters in women
with human immunodeficiency virus infection. Fetal Diagn Ther 2001;16:4136.
COMPENDIUM OF SELECTED PUBLICATIONS 1118
Are there ancillary tests that can aid in the
management of Category II or Category III
fetal heart rate tracings?
There are some ancillary tests available that help to
ensure fetal well-being in the face of a Category II or
Category III FHR tracing, thereby reducing the high
false-positive rate of EFM.
In the case of an EFM tracing with minimal or
absent variability and without spontaneous acceleration,
an effort should be made to elicit one. A meta-analysis of
11 studies of intrapartum fetal stimulation noted that
four techniques are available to stimulate the fetus: 1)
fetal scalp sampling, 2) Allis clamp scalp stimulation,
3) vibroacoustic stimulation, and 4) digital scalp stimu-
lation (37). Because vibroacoustic stimulation and digi-
tal scalp stimulation are less invasive than the other two
methods, they are the preferred methods. When there is
an acceleration following stimulation, acidemia is
unlikely and labor can continue.
When a Category III FHR tracing is persistent, a
scalp blood sample for the determination of pH or lactate
may be considered. However, the use of scalp pH assess-
ment has decreased (38), and this test may not even be
available at some tertiary hospitals (39). There are likely
many reasons for this decrease, including physician
experience, difficulty in obtaining and processing an
adequate sample in a short amount of time, and the need
for routine maintenance and calibration of laboratory
equipment that may be used infrequently. More impor-
tantly, scalp stimulation, which is less invasive, provides
similar information about the likelihood of fetal
acidemia as does scalp pH.
In one study, the sensitivity and positive predictive
value of a low scalp pH (defined in the study as less than
7.21 because it is the 75th percentile) to predict umbili-
cal arterial pH less than 7.00 was 36% and 9%, respec-
tively (40). More importantly, the sensitivity and positive
predictive value of a low scalp pH to identify a newborn
with hypoxicischemic encephalopathy was 50% and
3%, respectively. However, the greater utility of scalp pH
is in its high negative predictive value (9799%). There
are some data to suggest that fetal scalp lactate levels
have higher sensitivity and specificity than scalp pH
(40). However, a recent large randomized clinical trial
that compared the use of scalp pH assessment to scalp
lactate level assessment in cases of intrapartum fetal
distress did not demonstrate a difference in the rate of
acidemia at birth, Apgar scores, or neonatal intensive
care unit admissions (41). Although scalp stimulation
has largely replaced scalp pH and scalp lactate assess-
ment in the United States, if available, these tests may
provide additional information in the setting of a
Category III tracing.
Pulse oximetry has not been demonstrated to be a
clinically useful test in evaluating fetal status (4244).
Are there methods of intrauterine resuscita-
tion that can be used for Category II or
Category III tracings?
A Category II or Category III FHR tracing requires eval-
uation of the possible causes. Initial evaluation and treat-
ment may include the following:
Discontinuation of any labor stimulating agent
Cervical examination to determine umbilical cord
prolapse, rapid cervical dilation, or descent of the
fetal head
Changing maternal position to left or right lateral
recumbent position, reducing compression of the
vena cava and improving uteroplacental blood flow
Monitoring maternal blood pressure level for evi-
dence of hypotension, especially in those with
regional anesthesia (if present, treatment with vol-
ume expansion or with ephedrine or both, or
phenylephrine may be warranted)
Assessment of patient for uterine tachysystole by
evaluating uterine contraction frequency and duration
Supplemental maternal oxygen commonly is used in
cases of an indeterminate or abnormal pattern. There are
no data on the efficacy or safety of this therapy. Often,
the FHR patterns persist and do not respond to change in
position or oxygenation. In such cases, the use of
tocolytic agents has been suggested to stop uterine con-
tractions and perhaps avoid umbilical cord compression.
A meta-analysis reported the pooled results of three ran-
domized clinical trials that compared tocolytic therapy
(terbutaline, hexoprenaline, or magnesium sulfate) with
untreated controls in the management of a suspected
nonreassuring FHR tracing (45). Compared with no
treatment, tocolytic therapy more commonly improved
the FHR tracing. However, there were no differences in
rates of perinatal mortality, low 5-minute Apgar score, or
admission to the neonatal intensive care unit between the
groups (possibly because of the small sample size).
Thus, although tocolytic therapy appears to reduce the
number of FHR abnormalities, there is insufficient evi-
dence to recommend it.
Tachysystole with associated FHR changes can be
successfully treated with
2
-adrenergic drugs (hexopre-
naline or terbutaline). A retrospective study suggested that
98% of such cases respond to treatment with a -agonist
(46).
1119 PRACTICE BULLETINS
When the FHR tracing includes recurrent variable
decelerations, amnioinfusion to relieve umbilical cord
compression may be considered (47). A meta-analysis of
12 randomized trials that allocated patients to no treat-
ment or transcervical amnioinfusion noted that place-
ment of fluid in the uterine cavity significantly reduced
the rate of decelerations (RR, 0.54; 95% CI, 0.430.68)
and cesarean delivery for suspected fetal distress (RR,
0.35; 95% CI, 0.240.52) (48). Because of the lower rate
of cesarean delivery, amnioinfusion also decreased the
likelihood that either the patient or the newborn will stay
in the hospital more than 3 days (48). Amnioinfusion can
be done by bolus or continuous infusion technique. A
randomized trial compared the two techniques of amnio-
infusion and concluded that both have a similar ability to
relieve recurrent variable decelerations (49).
Another common cause of a Category II or Category
III FHR pattern is maternal hypotension secondary to
regional anesthesia. If maternal hypotension is identified
and suspected to be secondary to regional anesthesia,
treatment with volume expansion or intravenous ephe-
drine or both is warranted.
Summary of
Recommendations and
Conclusions
The following recommendations and conclusions
are based on good and consistent scientific evi-
dence (Level A):
The false-positive rate of EFM for predicting cere-
bral palsy is high, at greater than 99%.
The use of EFM is associated with an increased
rate of both vacuum and forceps operative vaginal
delivery, and cesarean delivery for abnormal FHR
patterns or acidosis or both.
When the FHR tracing includes recurrent variable
decelerations, amnioinfusion to relieve umbilical cord
compression should be considered.
Pulse oximetry has not been demonstrated to be a
clinically useful test in evaluating fetal status.
The following conclusions are based on limited or
inconsistent scientific evidence (Level B):
There is high interobserver and intraobserver vari-
ability in interpretation of FHR tracing.
Reinterpretation of the FHR tracing, especially if
the neonatal outcome is known, may not be reliable.
The use of EFM does not result in a reduction of
cerebral palsy.
The following recommendations are based on
expert opinion (Level C):
A three-tiered system for the categorization of FHR
patterns is recommended.
The labor of women with high-risk conditions should
be monitored with continuous FHR monitoring.
The terms hyperstimulation and hypercontractility
should be abandoned.
References
1. Martin JA, Hamilton BE, Sutton PD, Ventura SJ,
Menacker F, Munson ML. Births: final data for 2002. Natl
Vital Stat Rep 2003;52:1113. (Level II-3)
2. Low JA, Pickersgill H, Killen H, Derrick EJ. The predic-
tion and prevention of intrapartum fetal asphyxia in term
pregnancies. Am J Obstet Gynecol 2001;184:72430.
(Level II-2)
3. Macones GA, Hankins GD, Spong CY, Hauth J, Moore T.
The 2008 National Institute of Child Health and Human
Development workshop report on electronic fetal moni-
toring: update on definitions, interpretation, and research
guidelines. Obstet Gynecol 2008;112:6616. (Level III)
4. Royal College of Obstetricians and Gynaecologists. The
use of electronic fetal monitoring: the use and interpreta-
tion of cardiotocography in intrapartum fetal surveillance.
Evidence-based Clinical Guideline No. 8. London (UK):
RCOG; 2001. http://www.rcog.org.uk/files/rcog-corp/
uploaded-files/NEBEFMGuidelineFinal2may2001.pdf
(Level III)
5. Liston R, Sawchuck D, Young D. Fetal health surveil-
lance: antepartum and intrapartum consensus guideline.
Society of Obstetrics and Gynaecologists of Canada;
British Columbia Perinatal Health Program [published
erratum appears in J Obstet Gynaecol Can 2007;29:909].
J Obstet Gynaecol Can 2007;29(suppl 4):S356. (Level III)
6. Parer JT, Ikeda T. A framework for standardized manage-
ment of intrapartum fetal heart rate patterns. Am J Obstet
Gynecol 2007;197:26.e126.e6. (Level III)
7. Freeman RK. Problems with intrapartum fetal heart rate
monitoring interpretation and patient management. Obstet
Gynecol 2002;100:81326. (Level III)
8. Alfirevic Z, Devane D, Gyte GML. Continuous car-
diotocography (CTG) as a form of electronic fetal monitor-
ing (EFM) for fetal assessment during labour. Cochrane
Database of Systematic Reviews 2006, Issue 3. Art. No.:
CD006066. DOI: 10.1002/14651858.CD006066. (Meta-
analysis)
9. Nelson KB, Dambrosia JM, Ting TY, Grether JK.
Uncertain value of electronic fetal monitoring in predict-
ing cerebral palsy. N Engl J Med 1996;334:6138. (Level
II-2)
COMPENDIUM OF SELECTED PUBLICATIONS 1120
10. Clark SL, Hankins GD. Temporal and demographic trends
in cerebral palsyfact and fiction. Am J Obstet Gynecol
2003;188:62833. (Level III)
11. Hankins GD, Speer M. Defining the pathogenesis and
pathophysiology of neonatal encephalopathy and cerebral
palsy. Obstet Gynecol 2003;102:62836. (Level III)
12. Badawi N, Kurinczuk JJ, Keogh JM, Alessandri LM,
OSullivan F, Burton PR, et al. Antepartum risk factors for
newborn encephalopathy: the Western Australian case-
control study. BMJ 1998;317:154953. (Level II-2)
13. Morrison JC, Chez BF, Davis ID, Martin RW, Roberts
WE, Martin JN Jr, et al. Intrapartum fetal heart rate
assessment: monitoring by auscultation or electronic
means. Am J Obstet Gynecol 1993;168:636. (Level III)
14. Vintzileos AM, Nochimson DJ, Antsaklis A, Varvarigos I,
Guzman ER, Knuppel RA. Comparison of intrapartum
electronic fetal heart rate monitoring versus intermittent
auscultation in detecting fetal acidemia at birth. Am J
Obstet Gynecol 1995;173:10214. (Level II-1)
15. Nielsen PV, Stigsby B, Nickelsen C, Nim J. Intra- and
inter-observer variability in the assessment of intrapartum
cardiotocograms. Acta Obstet Gynecol Scand 1987;66:
4214. (Level III)
16. Beaulieu MD, Fabia J, Leduc B, Brisson J, Bastide A,
Blouin D, et al. The reproducibility of intrapartum car-
diotocogram assessments. Can Med Assoc J 1982;127:
2146. (Level III)
17. Blix E, Sviggum O, Koss KS, Oian P. Inter-observer vari-
ation in assessment of 845 labour admission tests: com-
parison between midwives and obstetricians in the clinical
setting and two experts. BJOG 2003;110:15. (Level III)
18. Zain HA, Wright JW, Parrish GE, Diehl SJ. Interpreting
the fetal heart rate tracing. Effect of knowledge of neona-
tal outcome. J Reprod Med 1998;43:36770. (Level III)
19. Ayoubi JM, Audibert F, Vial M, Pons JC, Taylor S,
Frydman R. Fetal heart rate and survival of the very pre-
mature newborn. Am J Obstet Gynecol 2002;187:1026
30. (Level II-2)
20. Westgren M, Holmquist P, Svenningsen NW, Ingemarsson
I. Intrapartum fetal monitoring in preterm deliveries:
prospective study. Obstet Gynecol 1982;60:99106.
(Level II-2)
21. Westgren M, Hormquist P, Ingemarsson I, Svenningsen N.
Intrapartum fetal acidosis in preterm infants: fetal moni-
toring and long-term morbidity. Obstet Gynecol 1984;63:
3559. (Level II-2)
22. Hill JB, Alexander JM, Sharma SK, McIntire DD, Leveno
KJ. A comparison of the effects of epidural and meperi-
dine analgesia during labor on fetal heart rate. Obstet
Gynecol 2003;102:3337. (Level I)
23. Lieberman E, ODonoghue C. Unintended effects of
epidural analgesia during labor: a systematic review. Am
J Obstet Gynecol 2002;186(suppl 1):S3168. (Level III)
24. Gambling DR, Sharma SK, Ramin SM, Lucas MJ,
Leveno KJ, Wiley J, et al. A randomized study of com-
bined spinal-epidural analgesia versus intravenous
meperidine during labor: impact on cesarean delivery rate.
Anesthesiology 1998;89:133644. (Level I)
25. Abrao KC, Francisco RP, Miyadahira S, Cicarelli DD,
Zugaib M. Elevation of uterine basal tone and fetal heart
rate abnormalities after labor analgesia: a randomized
controlled trial. Obstet Gynecol 2009;113:417. (Level I)
26. Wright JW, Ridgway LE, Wright BD, Covington DL,
Bobitt JR. Effect of MgSO4 on heart rate monitoring in
the preterm fetus. J Reprod Med 1996;41:6058. (Level
II-2)
27. Hatjis CG, Meis PJ. Sinusoidal fetal heart rate pattern
associated with butorphanol administration. Obstet
Gynecol 1986;67:37780. (Level II-2)
28. Chazotte C, Forman L, Gandhi J. Heart rate patterns in
fetuses exposed to cocaine. Obstet Gynecol 1991;78:
3235. (Level II-3)
29. Giannina G, Guzman ER, Lai YL, Lake MF, Cernadas M,
Vintzileos AM. Comparison of the effects of meperidine
and nalbuphine on intrapartum fetal heart rate tracings.
Obstet Gynecol 1995;86:4415. (Level I)
30. Kopecky EA, Ryan ML, Barrett JF, Seaward PG, Ryan G,
Koren G, et al. Fetal response to maternally administered
morphine. Am J Obstet Gynecol 2000;183:42430.
(Level II-2)
31. Ville Y, Vincent Y, Tordjman N, Hue MV, Fernandez H,
Frydman R. Effect of betamethasone on the fetal heart
rate pattern assessed by computerized cardiotocography
in normal twin pregnancies. Fetal Diagn Ther 1995;10:
3016. (Level II-3)
32. Subtil D, Tiberghien P, Devos P, Therby D, Leclerc G,
Vaast P, et al. Immediate and delayed effects of antenatal
corticosteroids on fetal heart rate: a randomized trial that
compares betamethasone acetate and phosphate,
betamethasone phosphate, and dexamethasone. Am J
Obstet Gynecol 2003;188:52431. (Level I)
33. Senat MV, Minoui S, Multon O, Fernandez H, Frydman
R, Ville Y. Effect of dexamethasone and betamethasone on
fetal heart rate variability in preterm labour: a randomised
study. Br J Obstet Gynaecol 1998;105:74955. (Level I)
34. Parer JT, King T, Flanders S, Fox M, Kilpatrick SJ. Fetal
acidemia and electronic fetal heart rate patterns: is there
evidence of an association? J Matern Fetal Neonatal Med
2006;19:28994. (Level III)
35. Williams KP, Galerneau F. Intrapartum fetal heart rate
patterns in the prediction of neonatal acidemia. Am J
Obstet Gynecol 2003;188:8203. (Level II-3)
36. Samueloff A, Langer O, Berkus M, Field N, Xenakis E,
Ridgway L. Is fetal heart rate variability a good predictor
of fetal outcome? Acta Obstet Gynecol Scand 1994;73:
3944. (Level II-2)
37. Skupski DW, Rosenberg CR, Eglinton GS. Intrapartum
fetal stimulation tests: a meta-analysis. Obstet Gynecol
2002;99:12934. (Meta-analysis)
38. Goodwin TM, Milner-Masterson L, Paul RH. Elimination
of fetal scalp blood sampling on a large clinical service.
Obstet Gynecol 1994;83:9714. (Level II-3)
39. Hendrix NW, Chauhan SP, Scardo JA, Ellings JM, Devoe
LD. Managing nonreassuring fetal heart rate patterns
before cesarean delivery. Compliance with ACOG recom-
mendations. J Reprod Med 2000;45:9959. (Level III)
1121 PRACTICE BULLETINS
40. Kruger K, Hallberg B, Blennow M, Kublickas M,
Westgren M. Predictive value of fetal scalp blood lactate
concentration and pH as markers of neurologic disability.
Am J Obstet Gynecol 1999;181:10728. (Level II-3)
41. Wiberg-Itzel E, Lipponer C, Norman M, Herbst A,
Prebensen D, Hansson A, et al. Determination of pH or
lactate in fetal scalp blood in management of intrapartum
fetal distress: randomised controlled multicentre trial.
BMJ 2008;336:12847. (Level I)
42. Garite TJ, Dildy GA, McNamara H, Nageotte MP, Boehm
FH, Dellinger EH, et al. A multicenter controlled trial of
fetal pulse oximetry in the intrapartum management of
nonreassuring fetal heart rate patterns. Am J Obstet
Gynecol 2000;183:104958. (Level I)
43. Bloom SL, Spong CY, Thom E, Varner MW, Rouse DJ,
Weininger S, et al. Fetal pulse oximetry and cesarean
delivery. National Institute of Child Health and Human
Development Maternal-Fetal Medicine Units Network. N
Engl J Med 2006;355:2195202. (Level I)
44. East CE, Chan FY, Colditz PB, Begg L. Fetal pulse
oximetry for fetal assessment in labour. Cochrane
Database of Systematic Reviews 2007, Issue 2. Art.
No.: CD004075. DOI: 10.1002/14651858.CD004075.
pub3. (Meta-analysis)
45. Kulier R, Hofmeyr GJ. Tocolytics for suspected intra-
partum fetal distress. Cochrane Database of Systematic
Reviews 1998, Issue 2. Art. No.: CD000035. DOI: 10.
1002/14651858.CD000035. (Meta-analysis)
46. Egarter CH, Husslein PW, Rayburn WF. Uterine hyper-
stimulation after low-dose prostaglandin E2 therapy:
tocolytic treatment in 181 cases. Am J Obstet Gynecol
1990;163:7946. (Level II-2)
47. Miyazaki FS, Taylor NA. Saline amnioinfusion for relief
of variable or prolonged decelerations. A preliminary
report. Am J Obstet Gynecol 1983;146:6708. (Level III)
48. Hofmeyr GJ. Amnioinfusion for potential or suspected
umbilical cord compression in labour. Cochrane Database
of Systematic Reviews 1998, Issue 1. Art. No.: CD000013.
DOI: 10.1002/14651858.CD000013. (Meta-analysis)
49. Rinehart BK, Terrone DA, Barrow JH, Isler CM,
Barrilleaux PS, Roberts WE. Randomized trial of inter-
mittent or continuous amnioinfusion for variable deceler-
ations. Obstet Gynecol 2000;96:5714. (Level I)
The MEDLINE database, the Cochrane Library, and
ACOGs own internal resources and documents were used
to conduct a literature search to locate relevant articles pub-
lished between January 1985 and January 2009. The search
was restricted to articles published in the English language.
Priority was given to articles reporting results of original re-
search, although review articles and commentaries also
were consulted. Abstracts of research presented at symposia
and scientific conferences were not considered adequate for
inclusion in this document. Guidelines published by organi-
zations or institutions such as the National Institutes of
Health and the American College of Obstetricians and
Gynecologists were reviewed, and additional studies were
located by reviewing bibliographies of identified articles.
When reliable research was not available, expert opinions
from obstetriciangynecologists were used.
Studies were reviewed and evaluated for quality according
to the method outlined by the U.S. Preventive Services
Task Force:
I Evidence obtained from at least one properly
designed randomized controlled trial.
II-1 Evidence obtained from well-designed controlled
trials without randomization.
II-2 Evidence obtained from well-designed cohort or
casecontrol analytic studies, preferably from more
than one center or research group.
II-3 Evidence obtained from multiple time series with or
without the intervention. Dramatic results in uncon-
trolled experiments also could be regarded as this
type of evidence.
III Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees.
Based on the highest level of evidence found in the data,
recommendations are provided and graded according to the
following categories:
Level ARecommendations are based on good and con-
sistent scientific evidence.
Level BRecommendations are based on limited or incon-
sistent scientific evidence.
Level CRecommendations are based primarily on con-
sensus and expert opinion.
Copyright July 2009 by the American College of Obstetri-
cians and Gynecologists. All rights reserved. No part of this
publication may be reproduced, stored in a retrieval system,
posted on the Internet, or transmitted, in any form or by any
means, electronic, mechanical, photocopying, recording, or
otherwise, without prior written permission from the publisher.
Requests for authorization to make photocopies should be
directed to Copyright Clearance Center, 222 Rosewood Drive,
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
The American College of Obstetricians and Gynecologists
409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920
Intrapartum fetal heart rate monitoring: nomenclature, interpretation,
and general management principles. ACOG Practice Bulletin No. 106.
American College of Obstetricians and Gynecologists. Obstet Gynecol
2009;114:192202.
COMPENDIUM OF SELECTED PUBLICATIONS 1122
CLINICAL MANAGEMENT GUIDELINES FOR OBSTETRICIANGYNECOLOGISTS
NUMBER 107, AUGUST 2009
Replaces Practice Bulletin Number 10, November 1999; Committee Opinion Number 228, November
1999; Committee Opinion Number 248, December 2000; Committee Opinion Number 283, May 2003
ACOG
PRACTICE
BULLETIN
This Practice Bulletin was devel-
oped by the ACOG Committee on
Practice BulletinsObstetrics with
the assistance of Mildred Ramirez,
MD, and Susan Ramin, MD. The
information is designed to aid prac-
titioners in making decisions about
appropriate obstetric and gyneco-
logic care. These guidelines should
not be construed as dictating an
exclusive course of treatment or
procedure. Variations in practice
may be warranted based on the
needs of the individual patient,
resources, and limitations unique to
the institution or type of practice.
THE AMERICAN COLLEGE OF
OBSTETRICIANS AND
GYNECOLOGISTS
WOMENS HEALTH CARE PHYSICIANS
Induction of Labor
More than 22% of all gravid women undergo induction of labor in the United
States, and the overall rate of induction of labor in the United States has more
than doubled since 1990 to 225 per 1,000 live births in 2006 (1). The goal of
induction of labor is to achieve vaginal delivery by stimulating uterine con-
tractions before the spontaneous onset of labor. Generally, induction of labor
has merit as a therapeutic option when the benefits of expeditious delivery out-
weigh the risks of continuing the pregnancy. The benefits of labor induction
must be weighed against the potential maternal and fetal risks associated with
this procedure (2). The purpose of this document is to review current methods
for cervical ripening and induction of labor and to summarize the effectiveness
of these approaches based on appropriately conducted outcomes-based
research. These practice guidelines classify the indications for and contraindi-
cations to induction of labor, describe the various agents used for cervical
ripening, cite methods used to induce labor, and outline the requirements for the
safe clinical use of the various methods of inducing labor.
Background
In 1948, Theobald and associates described their use of the posterior pituitary
extract, oxytocin, by intravenous drip for labor induction (3). Five years later,
oxytocin was the first polypeptide hormone synthesized by du Vigneaud and
associates (4). This synthetic polypeptide hormone has since been used to stim-
ulate uterine contractions. Other methods used for induction of labor include
membrane stripping, amniotomy, nipple stimulation, and administration of
prostaglandin E analogues.
Cervical Ripening
The goal of cervical ripening is to facilitate the process of cervical softening,
thinning, and dilating with resultant reduction in the rate of failed induction and
1123 PRACTICE BULLETINS
induction to delivery time. Cervical remodeling is a crit-
ical component of normal parturition. Observed changes
not only include collagen breakdown and rearrangement
but also changes in the glycosaminoglycans, increased
production of cytokines, and white blood cell infiltration
(5). If induction is indicated and the status of the cervix
is unfavorable, agents for cervical ripening may be used.
The status of the cervix can be determined by the Bishop
pelvic scoring system (Table 1) (6). An unfavorable cer-
vix generally has been defined as a Bishop score of 6 or
less in most randomized trials. If the total score is more
than 8, the probability of vaginal delivery after labor
induction is similar to that after spontaneous labor.
Effective methods for cervical ripening include the
use of mechanical cervical dilators and administration of
synthetic prostaglandin E
1
(PGE
1
) and prostaglandin E
2
(PGE
2
) (710). Mechanical dilation methods are effec-
tive in ripening the cervix and include hygroscopic dila-
tors, osmotic dilators (Laminaria japonicum), Foley
catheters (1426 F) with inflation volume of 3080 mL,
double balloon devices (Atad Ripener Device), and
extraamniotic saline infusion using infusion rates of
3040 mL/h (1119). Laminaria japonicum ripens the
cervix but may be associated with increased peripartum
infections (7, 20). In women undergoing induction with
an unfavorable cervix, mechanical methods, except
extraamniotic saline infusion, are associated with a
decreased cesarean delivery rate when compared with
oxytocin alone (18). Multiple studies have demonstrated
the efficacy of mechanical cervical dilators. There is
insufficient evidence to assess how effective (vaginal
delivery within 24 hours) mechanical methods are com-
pared with prostaglandins (18). Advantages of the Foley
catheter include low cost when compared with
prostaglandins, stability at room temperature, and
reduced risk of uterine tachysystole with or without fetal
heart rate (FHR) changes (18, 21).
Misoprostol, a synthetic PGE
1
analogue, can be
administered intravaginally, orally, or sublingually and is
used for both cervical ripening and induction of labor. It
currently is available in a 100-mcg (unscored) or a 200-
mcg tablet, and can be broken to provide 25-mcg or 50-
mcg doses. There is extensive clinical experience with
this agent and a large body of published reports support-
ing its safety and efficacy when used appropriately. No
studies indicate that intrapartum exposure to misoprostol
(or other prostaglandin cervical ripening agents) has any
long-term adverse health consequences to the fetus in the
absence of fetal distress, nor is there a plausible biologic
basis for such a concern. Although misoprostol currently
is approved by the U.S. Food and Drug Administration
(FDA) for the prevention of peptic ulcers, the FDA in
2002 approved a new label on the use of misoprostol
during pregnancy for cervical ripening and for the induc-
tion of labor. This labeling does not contain claims
regarding the efficacy or safety of misoprostol, nor does
it stipulate doses or dose intervals. The majority of ad-
verse maternal and fetal outcomes associated with miso-
prostol therapy resulted from the use of doses greater than
25 mcg.
Two PGE
2
preparations are commercially available:
a gel available in a 2.5-mL syringe containing 0.5 mg of
dinoprostone and a vaginal insert containing 10 mg of
dinoprostone. Both are approved by the FDA for cervi-
cal ripening in women at or near term. The vaginal insert
releases prostaglandins at a slower rate (0.3 mg/h) than
the gel. Compared with placebo or oxytocin alone, vagi-
nal prostaglandins used for cervical ripening increase the
likelihood of delivery within 24 hours, do not reduce the
rate of cesarean delivery, and increase the risk of uterine
tachysystole with associated FHR changes (22).
Methods of Labor Induction
Oxytocin
Oxytocin is one of the most commonly used drugs in the
United States. The physiology of oxytocin-stimulated
labor is similar to that of spontaneous labor, although
individual patients vary in sensitivity and response to
oxytocin. Based on pharmacokinetic studies of synthetic
Table 1. Bishop Scoring System
Factor
Score Dilation (cm) Position of Cervix Effacement (%) Station* Cervical Consistency
0 Closed Posterior 030 3 Firm
1 12 Midposition 4050 2 Medium
2 34 Anterior 6070 1, 0 Soft
3 56 80 +1, +2
*Station reflects a 3 to +3 scale.
Modified from Bishop EH. Pelvic scoring for elective induction. Obstet Gynecol 1964;24:267.
COMPENDIUM OF SELECTED PUBLICATIONS 1124
oxytocin, uterine response ensues after 35 minutes of
infusion, and a steady level of oxytocin in plasma is
achieved by 40 minutes (23). The uterine response to
oxytocin depends on the duration of the pregnancy; there
is a gradual increase in response from 20 to 30 weeks of
gestation, followed by a plateau from 34 weeks of gesta-
tion until term, when sensitivity increases (24). Lower
body mass index and greater cervical dilation, parity, or
gestational age are predictors of successful response to
oxytocin for induction (25).
Membrane Stripping
Stripping or sweeping the amniotic membranes is com-
monly practiced to induce labor. Significant increases in
phospholipase A
2
activity and prostaglandin F
2
(PGF
2
)
levels occur from membrane stripping (26). Stripping
membranes increases the likelihood of spontaneous
labor within 48 hours and reduces the incidence of induc-
tion with other methods (27). Although membrane sweep-
ing has been associated with increased risk of prelabor
rupture of membranes (28), other published systematic
reviews, including one with 1,525 women, have not
corroborated this finding (27). Women who undergo
membrane stripping may experience discomfort from the
procedure as well as vaginal bleeding and irregular uter-
ine contractions within the ensuing 24 hours (27). There
are insufficient data to guide clinical practice for mem-
brane stripping in women whose group B streptococcus
culture is positive.
Amniotomy
Artificial rupture of the membranes may be used as a
method of labor induction, especially if the condition of
the cervix is favorable. Used alone for inducing labor,
amniotomy can be associated with unpredictable and
sometimes long intervals before the onset of contrac-
tions. There is insufficient evidence on the efficacy and
safety of amniotomy alone for labor induction (29). In a
trial of amniotomy combined with early oxytocin infusion
compared with amniotomy alone, the induction-to-deliv-
ery interval was shorter with the amniotomy-plus-oxy-
tocin method (30). There are insufficient data to guide the
timing of amniotomy in patients who are receiving intra-
partum prophylaxis for group B streptococcal infection.
Nipple Stimulation
Nipple stimulation or unilateral breast stimulation has
been used as a natural and inexpensive nonmedical
method for inducing labor. In a systematic review of 6
trials including 719 women that compared breast stimu-
lation with no intervention, a significant decrease in the
number of women not in labor at 72 hours was noted, but
only in women with favorable cervices (31). None of the
women had uterine tachysystole with or without FHR
changes, and there were no differences in meconium-
stained amniotic fluid or cesarean delivery rates (31).
Breast stimulation was associated with a decrease in
postpartum hemorrhage (31). This method has only been
studied in low-risk pregnancies.
Labor Induction Terminology
At a 2008 workshop sponsored by the American College
of Obstetricians and Gynecologists, the Eunice Kennedy
Shriver National Institute of Child Health and Human
Development, and the Society for MaternalFetal Med-
icine on intrapartum electronic FHR monitoring, the defi-
nitions for FHR pattern categorization were reviewed and
updated. The existing classification systems for FHR pat-
terns were assessed and new recommendations for use in
the United States were made (32). In particular, it was
determined that the terms hyperstimulation and hypercon-
tractility should be abandoned. It was recommended that
the term tachysystole, with or without corresponding FHR
decelerations, be used instead.
Uterine Contractions
Uterine contractions are quantified as the number of con-
tractions present in a 10-minute window, averaged over
30 minutes. Contraction frequency alone is a partial assess-
ment of uterine activity. Other factors such as duration,
intensity, and relaxation time between contractions are
equally important in clinical practice. The following rep-
resents terminology to describe uterine activity:
Normal: Five contractions or less in 10 minutes,
averaged over a 30-minute window
Tachysystole: More than five contractions in 10 min-
utes, averaged over a 30-minute window
Listed are characteristics of uterine contractions:
Tachysystole should always be qualified as to the
presence or absence of associated FHR decelera-
tions.
The term tachysystole applies to both spontaneous
and stimulated labor. The clinical response to tachy-
systole may differ depending on whether contrac-
tions are spontaneous or stimulated.
The majority of literature cited in this Practice
Bulletin was published prior to the 2008 NICHD defini-
tions and interpretations of FHR tracings. Consequently,
it is difficult to generalize the results of the cited litera-
ture, which used nonstandardized and ambiguous defin-
itions for FHR patterns.
1125 PRACTICE BULLETINS
Clinical Considerations and
Recommendations
What are the indications and contraindica-
tions to induction of labor?
Indications for induction of labor are not absolute but
should take into account maternal and fetal conditions,
gestational age, cervical status, and other factors.
Following are examples of maternal or fetal conditions
that may be indications for induction of labor:
Abruptio placentae
Chorioamnionitis
Fetal demise
Gestational hypertension
Preeclampsia, eclampsia
Premature rupture of membranes
Postterm pregnancy
Maternal medical conditions (eg, diabetes mellitus,
renal disease, chronic pulmonary disease, chronic
hypertension, antiphospholipid syndrome)
Fetal compromise (eg, severe fetal growth restric-
tion, isoimmunization, oligohydramnios)
Labor also may be induced for logistic reasons, for
example, risk of rapid labor, distance from hospital, or
psychosocial indications. In such circumstances, at least
one of the gestational age criteria in the box should be
met, or fetal lung maturity should be established. A
mature fetal lung test result before 39 weeks of gestation,
in the absence of appropriate clinical circumstances, is
not an indication for delivery.
The individual patient and clinical situation should
be considered in determining when induction of labor is
contraindicated. Generally, the contraindications to labor
induction are the same as those for spontaneous labor
and vaginal delivery. They include, but are not limited to,
the following situations:
Vasa previa or complete placenta previa
Transverse fetal lie
Umbilical cord prolapse
Previous classical cesarean delivery
Active genital herpes infection
Previous myomectomy entering the endometrial cavity
What criteria should be met before the cervix
is ripened or labor is induced?
Assessment of gestational age and consideration of any
potential risks to the mother or fetus are of paramount
importance for appropriate evaluation and counseling
before initiating cervical ripening or labor induction. The
patient should be counseled regarding the indications for
induction, the agents and methods of labor stimulation,
and the possible need for repeat induction or cesarean
delivery. Although prospective studies are limited in
evaluating the benefits of elective induction of labor, nul-
liparous women undergoing induction of labor with
unfavorable cervices should be counseled about a two-
fold increased risk of cesarean delivery (33, 34, 35). In
addition, labor progression differs significantly for
women with an elective induction of labor compared
with women who have spontaneous onset of labor (36).
Allowing at least 1218 hours of latent labor before
diagnosing a failed induction may reduce the risk of
cesarean delivery (37, 38).
Additional requirements for cervical ripening and
induction of labor include assessment of the cervix,
pelvis, fetal size, and presentation. Monitoring FHR and
uterine contractions is recommended as for any high-risk
patient in active labor. Although trained nursing person-
nel can monitor labor induction, a physician capable
of performing a cesarean delivery should be readily
available.
What is the relative effectiveness of available
methods for cervical ripening in reducing the
duration of labor?
A systematic review found that in patients with an unfa-
vorable cervix, Foley catheter placement before oxytocin
induction significantly reduced the duration of labor
(21). This review also concluded that catheter placement
resulted in a reduced risk of cesarean delivery. When the
Foley catheter was compared with PGE
2
gel, the majority
of the studies have found no difference in duration of
induction to delivery or cesarean delivery rate. The use
of prostaglandins is associated with an increased risk of
tachysystole with or without FHR changes when com-
pared with the Foley catheter (21). The use of different
size Foley catheters, insufflation volumes, as well as dif-
Confirmation of Term Gestation
Ultrasound measurement at less than 20 weeks of
gestation supports gestational age of 39 weeks or
greater.
Fetal heart tones have been documented as present
for 30 weeks by Doppler ultrasonography.
It has been 36 weeks since a positive serum or urine
human chorionic gonadotropin pregnancy test result.
COMPENDIUM OF SELECTED PUBLICATIONS 1126
ferent misoprostol protocols, yields inconsistent results
to determine induction to delivery times, cesarean deliv-
ery rate, and risk of meconium passage (18, 21). The
addition of oxytocin along with the use of the Foley
catheter does not appear to shorten the time of delivery
in a randomized controlled trial (39).
Studies examining extraamniotic saline infused
through the Foley catheter compared with use of the
Foley catheter with concurrent oxytocin administration
report conflicting results on the time from induction to
delivery (19, 40, 41). Differences in methodology could
explain the opposing findings. The Foley catheter is a
reasonable and effective alternative for cervical ripening
and inducing labor.
Intracervical or intravaginal PGE
2
(dinoprostone)
commonly is used and is superior to placebo or no therapy
in promoting cervical ripening (42). Several prospective
randomized clinical trials and two meta-analyses have
demonstrated that PGE
1
(misoprostol) is an effective
method for cervical ripening (4348). Misoprostol admin-
istered intravaginally has been reported to be either supe-
rior to or as efficacious as dinoprostone gel (4851).
Vaginal misoprostol has been associated with less use of
epidural analgesia, more vaginal deliveries within 24
hours, and more uterine tachysystole with or without FHR
changes compared with dinoprostone and oxytocin (48).
In contrast, misoprostol compared with oxytocin for cer-
vical ripening resulted in longer intervals to active labor
and delivery in a randomized controlled trial (52). It is dif-
ficult, however, to compare the results of studies on miso-
prostol because of differences in endpoints, including
Bishop score, duration of labor, total oxytocin use, suc-
cessful induction, and cesarean delivery rate. Pharma-
cologic methods for cervical ripening do not decrease the
likelihood of cesarean delivery.
How should prostaglandins be administered?
One quarter of an unscored 100-mcg tablet (ie, approxi-
mately 25 mcg) of misoprostol should be considered as
the initial dose for cervical ripening and labor induction.
The frequency of administration should not be more than
every 36 hours. In addition, oxytocin should not be
administered less than 4 hours after the last misoprostol
dose. Misoprostol in higher doses (50 mcg every 6
hours) may be appropriate in some situations, although
higher doses are associated with an increased risk of
complications, including uterine tachysystole with FHR
decelerations.
If there is inadequate cervical change with minimal
uterine activity after one dose of intracervical dinopros-
tone, a second dose may be given 612 hours later. The
manufacturers recommend a maximum cumulative dose
of 1.5 mg of dinoprostone (three doses or 7.5 mL of gel)
within a 24-hour period. A minimum safe time interval
between prostaglandin administration and initiation of
oxytocin has not been determined. According to the
manufacturers guidelines, after use of 1.5 mg of dino-
prostone in the cervix or 2.5 mg in the vagina, oxytocin
induction should be delayed for 612 hours because the
effect of prostaglandins may be heightened with oxy-
tocin. After use of dinoprostone in sustained-release
form, delaying oxytocin induction for 3060 minutes
after removal is sufficient. Limited data are available on
the use of buccal or sublingual misoprostol for cervical
ripening or induction of labor, and these methods are not
recommended for clinical use until further studies sup-
port their safety (53).
What are the potential complications with
each method of cervical ripening, and how
are they managed?
Tachysystole with or without FHR changes is more
common with vaginal misoprostol compared with vaginal
prostaglandin E
2
, intracervical prostaglandin E
2
, and oxy-
tocin (48). Tachysystole (defined in some studies as greater
than 5 uterine contractions in 10 minutes in consecutive
10-minute intervals) and tachysystole with associated
FHR decelerations are increased with a 50-mcg or greater
dose of misoprostol (43, 47, 48, 54). There seems to be
a trend toward lower rates of uterine tachysystole with
FHR changes with lower dosages of misoprostol (25
mcg every 6 hours versus every 3 hours) (48).
The use of misoprostol in women with prior cesare-
an delivery or major uterine surgery has been associated
with an increase in uterine rupture and, therefore, should
be avoided in the third trimester (55, 56). An increase in
meconium-stained amniotic fluid also has been reported
with misoprostol use (47, 48). Although misoprostol appears
to be safe and effective in inducing labor in women with
unfavorable cervices, further studies are needed to deter-
mine the optimal route, dosage, timing interval, and phar-
macokinetics of misoprostol. Moreover, data are needed on
the management of complications related to misoprostol
use and when it should be discontinued. If uterine tachy-
systole and a Category III FHR tracing (defined as either
a sinusoidal pattern or an absent baseline FHR variability
and any of the following: recurrent late decelerations, recur-
rent variable decelerations, or bradycardia) occurs with
misoprostol use and there is no response to routine cor-
rective measures (maternal repositioning and supplemen-
tal oxygen administration), cesarean delivery should be
considered (32). Subcutaneous terbutaline also can be used
in an attempt to correct the Category III FHR tracing or
uterine tachysystole.
1127 PRACTICE BULLETINS
The intracervical PGE
2
gel (0.5 mg) has a 1% rate of
uterine tachysystole with associated FHR changes while
the intravaginal PGE
2
gel (25 mg) or vaginal insert is
associated with a 5% rate (42, 57, 58). Uterine tachysys-
tole typically begins within 1 hour after the gel or insert
is placed but may occur up to 9 1/2 hours after the vagi-
nal insert has been placed (5759).
Removing the PGE
2
vaginal insert usually will help
reverse the effect of uterine tachysystole. Irrigation of the
cervix and vagina is not beneficial. Maternal side effects
from the use of low-dose PGE
2
(fever, vomiting, and diar-
rhea) are quite uncommon (60). Prophylactic antiemetics,
antipyretics, and antidiarrheal agents usually are not
needed. The manufacturers recommend that caution be
exercised when using PGE
2
in patients with glaucoma,
severe hepatic or renal dysfunction, or asthma. However,
PGE
2
is a bronchodilator, and there are no reports of bron-
choconstriction or significant blood pressure changes after
the administration of the low-dose gel.
Increased maternal and neonatal infections have been
reported in connection with the use of Laminaria japon-
icum and hygroscopic dilators when compared with the
PGE
2
analogues (7, 13, 20). The Foley catheter can cause
significant vaginal bleeding in women with a low-lying
placenta (21). Other reported complications include rup-
ture of membranes, febrile morbidity, and displacement of
the presenting part (61).
What are the recommended guidelines for
fetal surveillance after prostaglandin use?
The prostaglandin preparations should be administered
where uterine activity and the FHR can be monitored
continuously for an initial observation period. Further
monitoring can be governed by individual indications for
induction and fetal status.
The patient should remain recumbent for at least 30
minutes. The FHR and uterine activity should be moni-
tored continuously for a period of 30 minutes to 2 hours
after administration of the PGE
2
gel (62). Uterine con-
tractions usually are evident in the first hour and exhibit
peak activity in the first 4 hours (62, 63). The FHR
monitoring should be continued if regular uterine con-
tractions persist; maternal vital signs also should be
recorded.
Are cervical ripening methods appropriate in
an outpatient setting?
Limited information is available on the safety of outpa-
tient management of induction of labor. In a randomized,
double-blind, controlled trial comparing 2 mg of intrav-
aginal PGE
2
gel with placebo for 5 consecutive days as
an outpatient procedure, it was noted that PGE
2
gel was
effective and safe for initiation of labor in women at term
with a Bishop score of 6 or less (64). No significant dif-
ferences in adverse outcomes were noted in another ran-
domized trial of 300 women at term comparing the use
of controlled-release PGE
2
in an outpatient versus inpa-
tient setting (65). Larger controlled studies are needed to
establish an effective and safe dose and vehicle for PGE
2
before use on an outpatient basis can be recommended.
However, outpatient use may be appropriate in carefully
selected patients. Mechanical methods may be particu-
larly appropriate in the outpatient setting. A randomized
trial comparing the Foley catheter in an outpatient versus
inpatient setting for preinduction cervical ripening
demonstrated similar efficacy and safety with a reduc-
tion of hospital stay of 9.6 hours (66).
What are the potential complications of
various methods of induction?
The side effects of oxytocin use are principally dose
related; uterine tachysystole and Category II or III FHR
tracings are the most common side effects. Uterine tachy-
systole may result in abruptio placentae or uterine rupture.
Uterine rupture secondary to oxytocin use is rare even in
parous women (67). Water intoxication can occur with
high concentrations of oxytocin infused with large quanti-
ties of hypotonic solutions, but is rare in doses used for
labor induction.
Misoprostol appears to be safe and beneficial for
inducing labor in a woman with an unfavorable cervix.
Although the exact incidence of uterine tachysystole
with or without FHR changes is unknown and the crite-
ria used to define this complication are not always clear
in the various reports, there are reports of uterine
tachysystole with or without FHR changes occurring
more frequently in women given misoprostol compared
with women given PGE
2
(43, 45, 48, 68). There does not
appear to be a significant increase in adverse fetal out-
comes from tachysystole without associated FHR decel-
erations (68, 69). The occurrence of complications does
appear to be dose-dependent (10, 48). Clinical trials have
shown that at an equivalent dosage, the vaginal route
produces greater clinical efficacy than the oral route
(53). Oral misoprostol administration is associated with
fewer abnormal FHR patterns and episodes of uterine
tachy-systole with associated FHR changes when com-
pared with vaginal administration (70, 71).
The potential risks associated with amniotomy
include prolapse of the umbilical cord, chorioamnionitis,
significant umbilical cord compression, and rupture of
vasa previa. The physician should palpate for an umbili-
cal cord and avoid dislodging the fetal head. The FHR
COMPENDIUM OF SELECTED PUBLICATIONS 1128
should be assessed before and immediately after amni-
otomy. Amniotomy for induction of labor may be con-
traindicated in women known to have HIV infection
because duration of ruptured membranes has been iden-
tified as an independent risk factor for vertical transmis-
sion of HIV infection (29).
Stripping the amniotic membranes is associated with
bleeding from undiagnosed placenta previa or low-lying
placenta, and accidental amniotomy. Bilateral breast stim-
ulation has been associated with uterine tachysystole with
associated FHR decelerations. In a systematic review,
breast stimulation was associated with an increased trend
in perinatal death (31). Until safety issues are studied fur-
ther, this practice is not recommended in an unmonitored
setting.
When oxytocin is used for induction of labor,
what dosage should be used and what pre-
cautions should be taken?
Any of the low- or high-dose oxytocin regimens outlined
in Table 2 are appropriate for labor induction (7278).
Low-dose regimens and less frequent increases in dose
are associated with decreased uterine tachysystole with
associated FHR changes (70). High-dose regimens and
more frequent dose increases are associated with shorter
labor and less frequent cases of chorioamnionitis and
cesarean delivery for dystocia, but increased rates of uter-
ine tachysystole with associated FHR changes (74, 79).
Each hospitals obstetrics and gynecology depart-
ment should develop guidelines for the preparation and
administration of oxytocin. Synthetic oxytocin generally
is diluted 10 units in 1,000 mL of an isotonic solution for
an oxytocin concentration of 10 mU/mL. Oxytocin should
be administered by infusion using a pump that allows
precise control of the flow rate and permits accurate
minute-to-minute control. Bolus administration of oxy-
tocin can be avoided by piggybacking the infusion into
the main intravenous line near the venipuncture site.
A numeric value for the maximum dose of oxytocin
has not been established. The FHR and uterine contrac-
tions should be monitored closely. Oxytocin should be
administered by trained personnel who are familiar with
its effects.
How should complications associated with
oxytocin use be managed?
If uterine tachysystole with Category III FHR tracings
occur, prompt evaluation is required and intravenous
infusion of oxytocin should be decreased or discontin-
ued to correct the pattern (32). Additional measures may
include turning the woman on her side and administer-
ing oxygen or more intravenous fluid. If uterine
tachysystole persists, use of terbutaline or other tocolyt-
ics may be considered. Hypotension may occur follow-
ing a rapid intravenous injection of oxytocin; therefore,
it is imperative that a dilute oxytocin infusion be used
even in the immediate puerperium.
Are there special considerations that apply
for induction in a woman with ruptured
membranes?
The largest randomized study to date found that oxy-
tocin induction reduced the time interval between pre-
mature rupture of membranes and delivery as well as the
frequencies of chorioamnionitis, postpartum febrile mor-
bidity, and neonatal antibiotic treatments, without increas-
ing cesarean deliveries or neonatal infections (80). These
data suggest that for women with premature rupture of
membranes at term, labor should be induced at the time of
presentation, generally with oxytocin infusion, to reduce
the risk of chorioamnionitis. An adequate time for the
latent phase of labor to progress should be allowed.
The same precautions should be exercised when
prostaglandins are used for induction of labor with rup-
tured membranes as for intact membranes. Intravaginal
PGE
2
for induction of labor in women with premature
rupture of membranes appears to be safe and effective
(81). In a randomized study of labor induction in women
with premature rupture of membranes at term, only one
dose of intravaginal misoprostol was necessary for suc-
cessful labor induction in 86% of the patients (67).
There is no evidence that use of either of these prostag-
Table 2. Labor Stimulation with Oxytocin: Examples of Low-
and High-Dose Oxytocin
Starting Incremental Dosage
Regimen Dose Increase (mU/min) Interval (min)
Low-Dose 0.52 12 1540
High-Dose 6 36* 1540
*The incremental increase is reduced to 3 mU/min in presence of hyperstimula-
tion and reduced to 1 mU/min with recurrent hyperstimulation.
Data from Hauth JC, Hankins GD, Gilstrap LC 3rd, Strickland DM, Vance P.
Uterine contraction pressures with oxytocin induction/augmentation. Obstet
Gynecol 1986;68:3059; Satin AJ, Leveno KJ, Sherman ML, Brewster DS,
Cunningham FG. High- versus low-dose oxytocin for labor stimulation. Obstet
Gynecol 1992;80:1116; Crane JM, Young DC. Meta-analysis of low-dose versus
high-dose oxytocin for labour induction. J SOGC 1998;20:121523; Cummiskey
KC, Dawood MY. Induction of labor with pulsatile oxytocin. Am J Obstet Gynecol
1990;163:186874; Blakemore KJ, Qin NG, Petrie RH, Paine LL. A prospective
comparison of hourly and quarter-hourly oxytocin dose increase intervals for the
induction of labor at term. Obstet Gynecol 1990;75:75761; Mercer B, Pilgrim
P, Sibai B. Labor induction with continuous low-dose oxytocin infusion: a ran-
domized trial. Obstet Gynecol 1991;77:65963; and Muller PR, Stubbs TM,
Laurent SL. A prospective randomized clinical trial comparing two oxytocin
induction protocols. Am J Obstet Gynecol 1992;167:37380; discussion 3801.
1129 PRACTICE BULLETINS
landins increases the risk of infection in women with
ruptured membranes (67, 81). There is insufficient evi-
dence to guide the physician on use of mechanical dila-
tors in women with ruptured membranes.
A meta-analysis that included 6,814 women with pre-
mature rupture of membranes at term compared induction
of labor with prostaglandins or oxytocin to expectant
management (82). A significant reduction in the risk of
women developing chorioamnionitis or endometritis and a
reduced number of neonates requiring admission to the
neonatal intensive care unit was noted in the women who
underwent induction of labor compared with expectant
management (82).
What methods can be used for induction of
labor with intrauterine fetal demise in the
late second or third trimester?
The method and timing of delivery after a fetal death
depends on the gestational age at which the death occur-
red, on the maternal history of a previous uterine scar, and
maternal preference. Although most patients will desire
prompt delivery, the timing of delivery is not critical;
coagulopathies are associated with prolonged fetal reten-
tion and are uncommon. In the second trimester, dilation
and evacuation can be offered if an experienced health
care provider is available, although patients should be
counseled that dilation and evacuation may limit efficacy
of autopsy for the detection of macroscopic fetal abnor-
malities.
Labor induction is appropriate at later gestational
ages, if second-trimester dilation and evacuation is un-
available, or based on patient preference. Much of the
data for management of fetal demise has been extrapo-
lated from randomized trials of management of second
trimester pregnancy termination. Available evidence from
randomized trials supports the use of vaginal misopros-
tol as a medical treatment to terminate nonviable preg-
nancies before 24 weeks of gestation (83). Based on
limited data, the use of misoprostol between 24 to 28
weeks of gestation also appears to be safe and effective
(84, 85). Before 28 weeks of gestation, vaginal miso-
prostol appears to be the most efficient method of labor
induction, regardless of cervical Bishop score (84, 86),
although high-dose oxytocin infusion also is an accept-
able choice (87, 88). Typical dosages for misoprostol use
are 200400 mcg vaginally every 412 hours. After 28
weeks of gestation, induction of labor should be managed
according to usual obstetric protocols. Cesarean delivery
for fetal demise should be reserved for unusual circum-
stances because it is associated with potential maternal
morbidity without any fetal benefit.
Several studies have evaluated the use of misopros-
tol at a dosage of 400 mcg every 6 hours in women with
a stillbirth up to 28 weeks of gestation and a prior uter-
ine scar (85, 89). There does not appear to be an increase
in complications in those women. Further research is
required to assess effectiveness and safety, optimal route
of administration, and dose.
In patients after 28 weeks of gestation, cervical ripen-
ing with a transcervical Foley catheter has been associated
with uterine rupture rates comparable to spontaneous
labor (90) and this may be a helpful adjunct in patients
with an unfavorable cervical assessment. Therefore, in
patients with a prior low transverse cesarean delivery, trial
of labor remains a favorable option. There are limited data
to guide clinical practice in a patient with a prior classical
cesarean delivery, and the delivery plan should be individ-
ualized.
Summary of
Recommendations and
Conclusions
The following recommendations and conclusions
are based on good and consistent scientific evi-
dence (Level A):
Prostaglandin E analogues are effective for cervical
ripening and inducing labor.
Low- or high-dose oxytocin regimens are appropri-
ate for women in whom induction of labor is indi-
cated (Table 2).
Before 28 weeks of gestation, vaginal misoprostol
appears to be the most efficient method of labor
induction regardless of Bishop score, although high-
dose oxytocin infusion also is an acceptable choice.
Approximately 25 mcg of misoprostol should be
considered as the initial dose for cervical ripening
and labor induction. The frequency of administra-
tion should not be more than every 36 hours.
Intravaginal PGE
2
for induction of labor in women
with premature rupture of membranes appears to be
safe and effective.
The use of misoprostol in women with prior cesarean
delivery or major uterine surgery has been associated
with an increase in uterine rupture and, therefore,
should be avoided in the third trimester.
The Foley catheter is a reasonable and effective
alternative for cervical ripening and inducing labor.
COMPENDIUM OF SELECTED PUBLICATIONS 1130
The following recommendation is based on evi-
dence that may be limited or inconsistent (Level B)
Misoprostol (50 mcg every 6 hours) to induce labor
may be appropriate in some situations, although
higher doses are associated with an increased risk of
complications, including uterine tachysystole with
FHR decelerations.
Proposed Performance
Measure
Percentage of patients in whom gestational age is estab-
lished by clinical criteria when labor is being induced for
logistic or psychosocial indications
References
1. Martin JA, Hamilton BE, Sutton PD, Ventura SJ,
Menacker F, Kirmeyer S, et al. Births: final data for 2006.
Natl Vital Stat Rep 2009;57:1102. (Level II-3)
2. Agency for Healthcare Research and Quality. Maternal
and neonatal outcomes of elective induction of labor.
AHRQ Evidence Report/Technology Assessment No.
176. Rockville (MD): AHRQ; 2009. (Systematic review)
3. Theobald GW, Graham A, Campbell J, Gange PD,
Driscoll WJ. Use of post-pituitary extract in obstetrics.
Br Med J 1948;2:1237. (Level III)
4. du Vigneaud V, Ressler C, Swan JM, Roberts CW,
Katsoyannis PG, Gordon S. The synthesis of an octapep-
tide amide with the hormonal activity of oxytocin.
J Am Chem Soc 1953;75:487980. (Level III)
5. Smith R. Parturition. N Engl J Med 2007;356:27183.
(Level III)
6. Bishop EH. Pelvic scoring for elective induction. Obstet
Gynecol 1964;24:2668. (Level III)
7. Krammer J, Williams MC, Sawai SK, OBrien WF. Pre-
induction cervical ripening: a randomized comparison of
two methods. Obstet Gynecol 1995;85:6148. (Level I)
8. Fletcher HM, Mitchell S, Simeon D, Frederick J, Brown D.
Intravaginal misoprostol as a cervical ripening agent. Br J
Obstet Gynaecol 1993;100:6414. (Level I)
9. Porto M. The unfavorable cervix: methods of cervical
priming. Clin Obstet Gynecol 1989;32:2628. (Level III)
10. Wing DA, Jones MM, Rahall A, Goodwin TM, Paul RH.
A comparison of misoprostol and prostaglandin E2 gel for
preinduction cervical ripening and labor induction. Am J
Obstet Gynecol 1995;172:180410. (Level I)
11. Atad J, Hallak M, Ben-David Y, Auslender R, Abramovici H.
Ripening and dilatation of the unfavourable cervix for
induction of labour by a double balloon device: experi-
ence with 250 cases. Br J Obstet Gynaecol 1997;104:
2932. (Level III)
12. Blumenthal PD, Ramanauskas R. Randomized trial of
Dilapan and Laminaria as cervical ripening agents before
induction of labor. Obstet Gynecol 1990;75:3658. (Level I)
13. Chua S, Arulkumaran S, Vanaja K, Ratnam SS. Preinduc-
tion cervical ripening: prostaglandin E2 gel vs hygroscopic
mechanical dilator. J Obstet Gynaecol Res 1997;23:
1717. (Level I)
14. Gilson GJ, Russell DJ, Izquierdo LA, Qualls CR, Curet
LB. A prospective randomized evaluation of a hygroscopic
cervical dilator, Dilapan, in the preinduction ripening of
patients undergoing induction of labor. Am J Obstet
Gynecol 1996;175:1459. (Level I)
15. Lin A, Kupferminc M, Dooley SL. A randomized trial of
extra-amniotic saline infusion versus laminaria for cervi-
cal ripening. Obstet Gynecol 1995;86:5459. (Level I)
16. Lyndrup J, Nickelsen C, Weber T, Molnitz E, Guldbaek E.
Induction of labour by balloon catheter with extra-amni-
otic saline infusion (BCEAS): a randomised comparison
with PGE2 vaginal pessaries. Eur J Obstet Gynecol
Reprod Biol 1994;53:18997. (Level I)
17. Mullin PM, House M, Paul RH, Wing DA. A comparison
of vaginally administered misoprostol with extra-amniotic
saline solution infusion for cervical ripening and labor
induction. Am J Obstet Gynecol 2002;187:84752. (Level I)
18. Boulvain M, Kelly A, Lohse C, Stan C, Irion O.
Mechanical methods for induction of labour. Cochrane
Database of Systematic Reviews 2001, Issue 4. Art.
No.: CD001233. DOI: 10.1002/14651858.CD001233.
(Level III)
19. Guinn DA, Davies JK, Jones RO, Sullivan L, Wolf D.
Labor induction in women with an unfavorable Bishop
score: randomize controlled trial of intrauterine Foley
catheter with concurrent oxytocin infusion versus Foley
catheter with extra-amniotic saline infusion with concur-
rent oxytocin infusion. Am J Obstet Gynecol 2004;191:
2259. (Level I)
20. Kazzi GM, Bottoms SF, Rosen MG. Efficacy and safety
of Laminaria digitata for preinduction ripening of the
cervix. Obstet Gynecol 1982;60:4403. (Level II-2)
21. Gelber S, Sciscione A. Mechanical methods of cervical
ripening and labor induction. Clin Obstet Gynecol 2006;
49:64257. (Level III)
22. Kelly AJ, Kavanagh J, Thomas J. Vaginal prostaglandin
(PGE2 and PGF2a) for induction of labour at term.
Cochrane Database of Systematic Reviews 2003, Issue 4.
Art. No.: CD003101. DOI: 10.1002/14651858.CD003101.
(Level III)
23. Seitchik J, Amico J, Robinson AG, Castillo M. Oxytocin
augmentation of dysfunctional labor. IV. Oxytocin phar-
macokinetics. Am J Obstet Gynecol 1984;150:2258.
(Level III)
24. Caldeyro-Barcia R, Poseiro JJ. Physiology of the uterine
contraction. Clin Obstet Gynecol 1960;3:386408. (Level
III)
25. Satin AJ, Leveno KJ, Sherman ML, McIntire DD. Factors
affecting the dose response to oxytocin for labor stimula-
tion. Am J Obstet Gynecol 1992;166:12601. (Level II-3)
1131 PRACTICE BULLETINS
26. McColgin SW, Bennett WA, Roach H, Cowan BD,
Martin JN Jr, Morrison JC. Parturitional factors associated
with membrane stripping. Am J Obstet Gynecol 1993;169:
717. (Level I)
27. Boulvain M, Stan C, Irion O. Membrane sweeping for
induction of labour. Cochrane Database of Systematic
Reviews 2005, Issue 1. Art. No.: CD000451. DOI: 10.1002/
14651858.CD000451.pub2. (Level III)
28. Hill MJ, McWilliams GD, Garcia-Sur D, Chen B, Munroe M,
Hoeldtke NJ. The effect of membrane sweeping on prela-
bor rupture of membranes: a randomized controlled trial.
Obstet Gynecol 2008;111:13139. (Level I)
29. Bricker L, Luckas M. Amniotomy alone for induction of
labour. Cochrane Database of Systematic Reviews 2000,
Issue 4. Art. No.: CD002862. DOI: 10.1002/14651858.
CD002862. (Level III)
30. Moldin PG, Sundell G. Induction of labour: a randomised
clinical trial of amniotomy versus amniotomy with oxy-
tocin infusion. Br J Obstet Gynaecol 1996;103:30612.
(Level I)
31. Kavanagh J, Kelly AJ, Thomas J. Breast stimulation for
cervical ripening and induction of labour. Cochrane
Database of Systematic Reviews 2005, Issue 3. Art. No.:
CD003392. DOI: 10.1002/14651858.CD003392.pub2.
(Level III)
32. Macones GA, Hankins GDV, Spong CY, Hauth J, Moore T.
The 2008 National Institute of Child Health and Human
Development Workshop Report on Electronic Fetal
Monitoring. Obstet Gynecol 2008;11:6616. (Level III)
33. Moore LE, Rayburn WF. Elective induction of labor. Clin
Obstet Gynecol 2006;49:698704. (Level III)
34. Luthy DA, Malmgren JA, Zingheim RW. Cesarean deliv-
ery after elective induction in nulliparous women: the
physician effect. Am J Obstet Gynecol 2004;191:15115.
(Level II-2)
35. Vrouenraets FP, Roumen FJ, Dehing CJ, van den Akker ES,
Aarts MJ, Scheve EJ. Bishop score and risk of cesarean
delivery after induction of labor in nulliparous women.
Obstet Gynecol 2005;105:6907. (Level II-2)
36. Vahratian A, Zhang J, Troendle JF, Sciscione AC,
Hoffman MK. Labor progression and risk of cesarean
delivery in electively induced nulliparas. Obstet Gynecol
2005;105:698704. (Level II-2)
37. Rouse DJ, Owen J, Hauth JC. Criteria for failed labor
induction: prospective evaluation of a standardized proto-
col. Obstet Gynecol 2000;96:6717. (Level II-3)
38. Simon CE, Grobman WA. When has an induction failed?
Obstet Gynecol 2005;105:7059. (Level II-2)
39. Pettker CM, Pocock SB, Smok DP, Lee SM, Devine PC.
Transcervical Foley catheter with and without oxytocin
for cervical ripening: a randomized controlled trial.
Obstet Gynecol 2008;111:13206. (Level I)
40. Karjane NW, Brock EL, Walsh SW. Induction of labor
using a Foley balloon, with and without extra-amniotic saline
infusion. Obstet Gynecol 2006;107:2349. (Level II-1)
41. Lin MG, Reid KJ, Treaster MR, Nuthalapaty FS, Ramsey PS,
Lu GC. Transcervical Foley catheter with and without
extraamniotic saline infusion for labor induction: a ran-
domized controlled trial. Obstet Gynecol 2007;110:
55865. (Level I)
42. Rayburn WF. Prostaglandin E2 gel for cervical ripening
and induction of labor: a critical analysis. Am J Obstet
Gynecol 1989;160:52934. (Level III)
43. Buser D, Mora G, Arias F. A randomized comparison
between misoprostol and dinoprostone for cervical ripen-
ing and labor induction in patients with unfavorable cer-
vices. Obstet Gynecol 1997;89:5815. (Level I)
44. Sanchez-Ramos L, Kaunitz AM, Wears RL, Delke I,
Gaudier FL. Misoprostol for cervical ripening and labor
induction: a meta-analysis. Obstet Gynecol 1997;89:633
42. (Level III)
45. Sanchez-Ramos L, Peterson DE, Delke I, Gaudier FL,
Kaunitz AM. Labor induction with prostaglandin E1
misoprostol compared with dinoprostone vaginal insert: a
randomized trial. Obstet Gynecol 1998;91:4015. (Level I)
46. Srisomboon J, Piyamongkol W, Aiewsakul P. Comparison
of intracervical and intravaginal misoprostol for cervical
ripening and labour induction in patients with an
unfavourable cervix. J Med Assoc Thai 1997;80:18994.
(Level I)
47. Wing DA, Rahall A, Jones MM, Goodwin TM, Paul RH.
Misoprostol: an effective agent for cervical ripening and
labor induction. Am J Obstet Gynecol 1995;172:18116.
(Level I)
48. Hofmeyr GJ, Gulmezoglu AM. Vaginal misoprostol for
cervical ripening and induction of labour. Cochrane
Database of Systematic Reviews 2003, Issue 1. Art. No.:
CD000941. DOI: 10.1002/14651858.CD000941. (Level III)
49. Gregson S, Waterstone M, Norman I, Murrells T. A ran-
domised controlled trial comparing low dose vaginal
misoprostol and dinoprostone vaginal gel for inducing
labour at term. BJOG 2005;112:43844. (Level I)
50. Garry D, Figueroa R, Kalish RB, Catalano CJ, Maulik D.
Randomized controlled trial of vaginal misoprostol versus
dinoprostone vaginal insert for labor induction. J Matern
Fetal Neonatal Med 2003;13:2549. (Level I)
51. Pandis GK, Papageorghiou AT, Ramanathan VG,
Thompson MO, Nicolaides KH. Preinduction sonographic
measurement of cervical length in the prediction of suc-
cessful induction of labor. Ultrasound Obstet Gynecol
2001;18:6238. (Level II-3)
52. Fonseca L, Wood HC, Lucas MJ, Ramin SM, Phatak D,
Gilstrap LC 3rd, et al. Randomized trial of preinduction
cervical ripening: misoprostol vs oxytocin. Am J Obstet
Gynecol 2008;199(3):305.e15. (Level I)
53. Muzonzini G, Hofmeyr GJ. Buccal or sublingual miso-
prostol for cervical ripening and induction of labour.
Cochrane Database of Systematic Reviews 2004, Issue 4.
Art. No.: CD004221. DOI: 10.1002/14651858.CD004221.
pub2. (Level III)
54. Magtibay PM, Ramin KD, Harris DY, Ramsey PS,
Ogburn PL Jr. Misoprostol as a labor induction agent. J
Matern Fetal Med 1998;7:158. (Level I)
55. Wing DA, Lovett K, Paul RH. Disruption of prior uterine
incision following misoprostol for labor induction in
COMPENDIUM OF SELECTED PUBLICATIONS 1132
women with previous cesarean delivery. Obstet Gynecol
1998;91:82830. (Level III)
56. Induction of labor for VBAC. ACOG Committee Opinion
No. 342. American College of Obstetricians and Gynecol-
ogists. Obstet Gynecol 2006;108:4657. (Level III)
57. Rayburn WF, Wapner RJ, Barss VA, Spitzberg E, Molina RD,
Mandsager N, et al. An intravaginal controlled-release
prostaglandin E2 pessary for cervical ripening and initia-
tion of labor at term. Obstet Gynecol 1992;79:3749.
(Level I)
58. Witter FR, Rocco LE, Johnson TR. A randomized trial of
prostaglandin E2 in a controlled-release vaginal pessary
for cervical ripening at term. Am J Obstet Gynecol 1992;
166:8304. (Level I)
59. Witter FR, Mercer BM. Improved intravaginal controlled-
release prostaglandin E2 insert for cervical ripening at
term. The Prostaglandin E2 insert Study Group. J Matern
Fetal Med 1996;5:649. (Level I)
60. Brindley BA, Sokol RJ. Induction and augmentation of
labor: basis and methods for current practice. Obstet
Gynecol Surv 1988;43:73043. (Level III)
61. Sherman DJ, Frenkel E, Tovbin J, Arieli S, Caspi E,
Bukovsky I. Ripening of the unfavorable cervix with
extraamniotic catheter balloon: clinical experience and
review. Obstet Gynecol Surv 1996;51:6217. (Level III)
62. Bernstein P. Prostaglandin E2 gel for cervical ripening
and labour induction: a multicentre placebo-controlled
trial. CMAJ 1991;145:124954. (Level I)
63. Miller AM, Rayburn WF, Smith CV. Patterns of uterine
activity after intravaginal prostaglandin E2 during prein-
duction cervical ripening. Am J Obstet Gynecol 1991;
165:10069. (Level II-1)
64. OBrien JM, Mercer BM, Cleary NT, Sibai BM. Efficacy
of outpatient induction with low-dose intravaginal
prostaglandin E2: a randomized, double-blind, placebo-
controlled trial. Am J Obstet Gynecol 1995;173:18559.
(Level I)
65. Biem SR, Turnell RW, Olatunbosun O, Tauh M, Biem HJ.
A randomized controlled trial of outpatient versus inpa-
tient labour induction with vaginal controlled-release
prostaglandin-E2: effectiveness and satisfaction. J Obstet
Gynaecol Can 2003;25:2331. (Level I)
66. Sciscione AC, Muench M, Pollock M, Jenkins TM,
Tildon-Burton J, Colmorgen GH. Transcervical Foley
catheter for preinduction cervical ripening in an outpatient
versus inpatient setting. Obstet Gynecol 2001;98:7516.
(Level I)
67. Flannelly GM, Turner MJ, Rassmussen MJ, Stronge JM.
Rupture of the uterus in Dublin; an update. J Obstet
Gynaecol 1993;13:4403. (Level II-3)
68. Sanchez-Ramos L, Chen AH, Kaunitz AM, Gaudier FL,
Delke I. Labor induction with intravaginal misoprostol in
term premature rupture of membranes: a randomized
study. Obstet Gynecol 1997;89:90912. (Level I)
69. Wing DA, Ortiz-Omphroy G, Paul RH. A comparison of
intermittent vaginal administration of misoprostol with
continuous dinoprostone for cervical ripening and labor
induction. Am J Obstet Gynecol 1997;177:6128. (Level I)
70. Toppozada MK, Anwar MY, Hassan HA, el-Gazaerly WS.
Oral or vaginal misoprostol for induction of labor.
Int J Gynaecol Obstet 1997;56:1359. (Level I)
71. Weeks A, Alfirevic Z. Oral misoprostol administration for
labor induction. Clin Obstet Gynecol 2006;49:65871.
(Level III)
72. Hauth JC, Hankins GD, Gilstrap LC 3rd, Strickland DM,
Vance P. Uterine contraction pressures with oxytocin
induction/augmentation. Obstet Gynecol 1986;68:3059.
(Level II-2)
73. Satin AJ, Leveno KJ, Sherman ML, Brewster DS,
Cunningham FG. High- versus low-dose oxytocin for
labor stimulation. Obstet Gynecol 1992;80:1116.
(Level II-1)
74. Crane JM, Young DC. Meta-analysis of low-dose versus
high-dose oxytocin for labour induction. J SOGC 1998;
20:121523. (Level III)
75. Cummiskey KC, Dawood MY. Induction of labor with
pulsatile oxytocin. Am J Obstet Gynecol 1990;163:1868
74. (Level I)
76. Blakemore KJ, Qin NG, Petrie RH, Paine LL. A prospec-
tive comparison of hourly and quarter-hourly oxytocin
dose increase intervals for the induction of labor at term.
Obstet Gynecol 1990;75:75761. (Level I)
77. Mercer B, Pilgrim P, Sibai B. Labor induction with con-
tinuous low-dose oxytocin infusion: a randomized trial.
Obstet Gynecol 1991;77:65963. (Level I)
78. Muller PR, Stubbs TM, Laurent SL. A prospective ran-
domized clinical trial comparing two oxytocin induction
protocols. Am J Obstet Gynecol 1992;167:37380; dis-
cussion 3801. (Level I)
79. Hannah ME, Ohlsson A, Farine D, Hewson SA, Hodnett ED,
Myhr TL, et al. Induction of labor compared with expec-
tant management for prelabor rupture of the membranes at
term. TERMPROM Study Group. N Engl J Med 1996;
334:100510. (Level I)
80. Merrill DC, Zlatnik FJ. Randomized, double-masked
comparison of oxytocin dosage in induction and augmen-
tation of labor. Obstet Gynecol 1999;94:45563. (Level I)
81. Ray DA, Garite TJ. Prostaglandin E2 for induction of
labor in patients with premature rupture of membranes at
term. Am J Obstet Gynecol 1992;166:83643. (Level I)
82. Dare MR, Middleton P, Crowther CA, Flenady VJ,
Varatharaju B. Planned early birth versus expectant man-
agement (waiting) for prelabour rupture of membranes
at term (37 weeks or more). Cochrane Database of
Systematic Reviews 2006, Issue 1. Art. No.: CD005302.
DOI: 10.1002/14651858.CD005302.pub2. (Level III)
83. Neilson JP, Hickey M, Vazquez J. Medical treatment for
early fetal death (less than 24 weeks). Cochrane Database
of Systematic Reviews 2006, Issue 3. Art. No.: CD002253.
DOI: 10.1002/14651858.CD002253.pub3. (Level I)
84. Dickinson JE, Evans SF. The optimization of intravaginal
misoprostol dosing schedules in second-trimester preg-
nancy termination [published erratum appears in Am J
Obstet Gynecol 2005;193:597]. Am J Obstet Gynecol
2002;186:4704. (Level I)
1133 PRACTICE BULLETINS
85. Dickinson JE. Misoprostol for second-trimester pregnancy
termination in women with a prior cesarean delivery.
Obstet Gynecol 2005;105:3526. (Level II-2)
86. Tang OS, Lau WN, Chan CC, Ho PC. A prospective ran-
domised comparison of sublingual and vaginal misopros-
tol in second trimester termination of pregnancy. BJOG
2004;111:10015. (Level I)
87. Toaff R, Ayalon D, Gogol G. Clinical use of high concen-
tration oxytocin drip. Obstet Gynecol 1971;37:11220.
(Level II-3)
88. Winkler CL, Gray SE, Hauth JC, Owen J, Tucker JM.
Mid-second-trimester labor induction: concentrated oxy-
tocin compared with prostaglandin E2 vaginal supposito-
ries. Obstet Gynecol 1991;77:297300. (Level II-3)
89. Daskalakis GJ, Mesogitis SA, Papantoniou NE,
Moulopoulos GG, Papapanagiotou AA, Antsaklis AJ.
Misoprostol for second trimester pregnancy termination
in women with prior caesarean section. BJOG 2005;112:
979. (Level II-2)
90. Bujold E, Blackwell SC, Gauthier RJ. Cervical ripening
with transcervical Foley catheter and the risk of uterine
rupture. Obstet Gynecol 2004;103:1823. (Level II-2)
The MEDLINE database, the Cochrane Library, and
ACOGs own internal resources and documents were used
to conduct a literature search to locate relevant articles pub-
lished between January 1985 and January 2009. The search
was restricted to articles published in the English language.
Priority was given to articles reporting results of original re-
search, although review articles and commentaries also
were consulted. Abstracts of research presented at symposia
and scientific conferences were not considered adequate for
inclusion in this document. Guidelines published by organi-
zations or institutions such as the National Institutes of
Health and the American College of Obstetricians and
Gynecologists were reviewed, and additional studies were
located by reviewing bibliographies of identified articles.
When reliable research was not available, expert opinions
from obstetriciangynecologists were used.
Studies were reviewed and evaluated for quality according
to the method outlined by the U.S. Preventive Services
Task Force:
I Evidence obtained from at least one properly
designed randomized controlled trial.
II-1 Evidence obtained from well-designed controlled
trials without randomization.
II-2 Evidence obtained from well-designed cohort or
casecontrol analytic studies, preferably from more
than one center or research group.
II-3 Evidence obtained from multiple time series with or
without the intervention. Dramatic results in uncon-
trolled experiments also could be regarded as this
type of evidence.
III Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees.
Based on the highest level of evidence found in the data,
recommendations are provided and graded according to the
following categories:
Level ARecommendations are based on good and con-
sistent scientific evidence.
Level BRecommendations are based on limited or incon-
sistent scientific evidence.
Level CRecommendations are based primarily on con-
sensus and expert opinion.
Copyright August 2009 by the American College of Obstetri-
cians and Gynecologists. All rights reserved. No part of this
publication may be reproduced, stored in a retrieval system,
posted on the Internet, or transmitted, in any form or by any
means, electronic, mechanical, photocopying, recording, or
otherwise, without prior written permission from the publisher.
Requests for authorization to make photocopies should be
directed to Copyright Clearance Center, 222 Rosewood Drive,
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
The American College of Obstetricians and Gynecologists
409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920
Induction of labor. ACOG Practice Bulletin No. 107. American College
of Obstetricians and Gynecologists. Obstet Gynecol 2009;114:
38697.
COMPENDIUM OF SELECTED PUBLICATIONS 1134
Replaces Number 151, January 1991, and Number 161, November 1991
This Educational Bulletin was developed
under the direction of the Committee on
Educational Bulletins of the American Col-
lege of Obstetricians and Gynecologists as
an aid to obstetricians and gynecologists.
The College wishes to thank Mark
Pearlman, MD, and Cosmas van de Ven,
MD, for their assistance in the development
of this bulletin. This document is not to be
construed as establishing a standard of
practice or dictating an exclusive course of
treatment. Rather, it is intended as an edu-
cational tool that presents current informa-
tion on obstetricgynecologic issues.
Reaffirmed 2006
Number 251, September 1998
BULLETIN
EDUCATIONAL
Obstetric Aspects of Trauma
Management
Trauma has become one of the leading causes of morbidity and mortality of
women in the world, resulting in nearly one million deaths each year. It also has
become one of the leading causes of morbidity and mortality during pregnancy
(1, 2). It is estimated that physical trauma complicates approximately 1 in every
12 pregnancies, with motor vehicle crashes being the most significant contribu-
tor to fetal death due to trauma (3). Nearly 50,000 of the estimated 250 million
people in the United States die each year from motor vehicle crashes. This rate is
equivalent to approximately 20 deaths due to motor vehicle crashes for every
100,000 persons in the United States.
The incidence and severity of injuries can be lessened by the appropriate use
of automobile safety restraints. Physicians should counsel patients about such use
and reassure them of the safety of these devices during pregnancy. Despite these
precautions, injuries will occur during pregnancy and obstetriciangynecologists
should be equipped to handle them.
Optimum management of the seriously injured pregnant woman requires an
integrated effort of multiple specialties, starting with emergency medical techni-
cians, emergency medicine physicians, trauma surgeons, and other specialists,
depending on the type of injury. Obstetricians play a central role in the manage-
ment of injured pregnant women. Their knowledge and expertise are vital to
management decisions regarding both the woman and the fetus. The effects of
various drugs on uterine blood flow, potential teratogenic and mutagenic effects
of diagnostic radiation and medications, the effect of surgery on pregnancy, and
the assessment of gestational age are critical management issues. In addition,
complications of pregnancy unrelated to the trauma may be superimposed in the
injured gravida (eg, pregnancy-induced hypertension, placenta previa) and are
best managed by the obstetrician. The obstetrician may be consulted regarding
the condition of a pregnant trauma patient or, more commonly, may be the pri-
mary physician caring for the patient following trauma. In either case, the ap-
proach must be systematic, ensuring that the woman is medically stable prior to
evaluation of the fetus.
Obstetricians who are involved with the care of pregnant trauma patients
should seek consultation with experienced trauma surgeons. It also is helpful
for all physicians to be knowledgeable about advanced trauma life-support
measures.
ACOG
1135 PRACTICE BULLETINS
Incidence
In industrialized nations, approximately two thirds of all
trauma during pregnancy results from motor vehicle
crashes. Other frequent causes of trauma during pregnan-
cy are falls and direct assaults to the abdomen (3, 4).
According to the National Safety Council, female drivers
are more likely to be involved in automobile accidents
than male drivers (84 female drivers versus 73 male dri-
vers per 10 million miles driven) (5).
Domestic violence has reached epidemic proportion
in the United States. It is estimated that approximately 2
million women per year are reported to have been assault-
ed by their male partners (6). Researchers have found a
prevalence of violence against pregnant women ranging
from 1% to 20% (7). Domestic violence and battery were
found to occur in 1 of every 12 pregnant women in an
inner-city setting (8). Among victims of physical abuse,
moderate or severe violence during pregnancy was
reported by 20% of women in the Baltimore area, 17% in
Houston, 7% in Galveston, and 7% in Toronto (9, 10).
Sixty percent of victims report two or more episodes of
physical assault during pregnancy (11). This latter statis-
tic emphasizes the importance of early identification of
physical abuse during pregnancy and implementation of
effective intervention methods, which are discussed else-
where (6).
Maternal Mortality
Trauma, either accidental (as in traffic accidents) or inten-
tional (as in homicide or domestic violence), is a leading
cause of death in women of reproductive age (1). Trauma
also is the leading cause of nonobstetric maternal death
(12); for example, it accounted for an average of 22% of
all maternal deaths in Iowa and caused nearly one half of
95 maternal deaths from 1986 to 1989 in Cook County,
Illinois (2).
Fetal Mortality
Accurate statistics on the number of fetal losses due to
trauma each year are not available. Estimates extrapolat-
ed from published case series suggest that between 1,300
and 3,900 pregnancies are lost each year in the United
States as a result of trauma (13).
Life-threatening maternal trauma (eg, maternal
shock, head injury resulting in coma, emergency
laparotomy for maternal indications) is associated with a
4050% fetal loss rate, whereas minor or nonlife-threat-
ening injuries resulted in a 15% pregnancy loss (14).
Because minor injuries are more common, most fetal
losses result from minor maternal injuries (4, 15, 16). It is
estimated that abruptio placentae is a complication in
4050% of pregnant women who sustain severe trauma,
compared with the 15% incidence in pregnant women
who experience nonlife-threatening trauma (4, 1619).
Several series of fetal losses resulting from trauma indi-
cate that more than 50% of fetal losses occur in associa-
tion with seemingly minor or insignificant maternal trauma
(4, 15, 16, 18, 20).
Numerous retrospective studies have attempted to
predict fetal or neonatal outcome based on an injury
severity score. However, one study suggests that injury
severity scoring is not a good predictor of adverse fetal
outcome (21).
Types of Trauma
Blunt Abdominal Trauma
The evaluation and management of blunt abdominal
trauma during pregnancy involves several key issues.
Gestational age at the time of injury, extent and severity
of maternal injury, and mechanism of injury should be
considered.
The gestational age at the time of injury is valuable
in determining the need for fetal assessment as well as in
managing the mothers condition. The possibility of fetal
viability in an extrauterine environment (ie, beyond
2426 weeks of gestation) can significantly change man-
agement decisions if there is evidence of fetal compro-
mise. Furthermore, enlargement of the uterus beyond
1820 weeks of gestation compresses both the inferior
vena cava and aorta in the supine position, increasing the
likelihood of hypotension and decreased uterine perfu-
sion. Finally, the type of maternal and fetal injury patterns
may depend to a great extent on gestational age at the
time of injury. For example, direct injury to the uterus and
fetus prior to 13 weeks of gestation is extremely unlikely
because they are protected by the bony pelvis. Generally,
trauma in the first trimester does not cause pregnancy
loss, with the exception of profound hypotension and
associated hypoperfusion of the uterus and its contents.
Although it is not the highest priority in managing the
injured gravida, gestational age should be assessed as
soon as feasible.
Fetal loss resulting from blunt abdominal trauma
may result from abruptio placentae or other placental
injury, direct fetal injury, uterine rupture, maternal shock,
or death or some combination thereof. Several studies of
trauma and fetal loss show that at least 50% of fetal loss-
es with known etiology were the result of abruptio pla-
centa (4, 15, 16, 18). In one report of severe car crashes
involving pregnant women, maternal loss of life was the
most frequent cause of fetal death (17).
There are several potential mechanisms of abruptio
placentae due to trauma. Differences in tissue properties
between the elastic myometrium and the relatively inelas-
COMPENDIUM OF SELECTED PUBLICATIONS 1136
penetrating trauma usually occurs through direct injury or
by injury to the cord or placenta. Maternal outcome gen-
erally is more favorable because the maternal viscera are
shielded by the uterus and its contents, which absorbs
much of the projectile energy.
The extent and severity of maternal and fetal injury
due to gunshot wounds depends on a number of factors
including the size and velocity of the bullet; the anatom-
ic region penetrated; the angle of entry; deflection of the
bullets trajectory by muscle, bone, or viscera; the gesta-
tional age of the fetus; and the distance from which the
bullet was fired. Frequently, more internal damage occurs
than that suggested by the appearance of the entrance
wound.
The enlarged uterus tends to protect the bowel from
injury when stab wounds penetrate the lower abdomen
because the bowel is displaced into the upper abdomen.
However, as a result of cephalad displacement of the
bowel by the enlarging uterus, stab wounds to the upper
abdomen can frequently result in more complex bowel
injury than in the nonpregnant woman.
Management
The primary goal and initial efforts in managing the
injured pregnant woman should be evaluation and stabi-
lization of maternal vital signs. If attention is drawn to the
fetus before the woman is stabilized, serious or life-
threatening maternal injuries may be overlooked, or cir-
cumstances that can compromise fetal oxygenation (eg,
maternal hypoxemia, hypovolemia, or supine hypoten-
sion) may be ignored, lessening the likelihood of both
maternal and fetal survival.
A systematic approach begins with a primary survey
of the woman by securing and maintaining an airway, en-
suring adequate breathing, and maintaining adequate cir-
culatory volume. The placement of two large-bore (1416
gauge) intravenous lines is necessary in most seriously
injured trauma patients. Supplemental oxygen should be
administered by nasal cannula, mask, or endotracheal
intubation as required to maintain a hemoglobin satura-
tion of 90% or greater. Crystalloid in the form of lactated
Ringers solution or normal saline should be given over
the first 3060 minutes of acute resuscitation as a 3:1 re-
placement based on blood loss. The use of vasopressors
to restore maternal blood pressure should be avoided until
appropriate volume replacement has been administered.
Although these agents may reduce uterine blood flow in
normovolemic patients, they should not be withheld if
needed in the resuscitation of the mother. Displacement
of the uterus off the inferior vena cava and abdominal
aorta with the patient in a supine position is helpful in
trauma patients beyond midpregnancy. This can be effect-
ed by having the patient lie in the lateral decubitus posi-
tic placenta can result in a shearing at the tissue interface.
Because fluid is noncompressible, intrusion of the elastic
uterine wall will result in displacement of amniotic fluid
and distention of the other parts of the uterus. Therefore,
a shear force can occur regardless of placental location.
The risk of abruptio placentae appears to be independent
of the placental location (3).
Direct fetal injury (eg, skull fracture) complicates
less than 1% of all pregnancies in which trauma occurs.
Although case reports of fetal skull fractures have been
described following relatively minor trauma, most cases
result from significant maternal injury later in gestation
(22, 23).
Uterine rupture is an infrequent but life-threatening
complication of trauma. It occurs in only 0.6% of all
injuries during pregnancy and tends to complicate trauma
resulting from direct abdominal impact associated with
substantial force (24, 25). The extent of uterine injury can
be variable, and it may result in serosal hemorrhage or
abrasions; avulsion of the uterine vasculature with hem-
orrhage; complete disruption of the myometrial wall with
extrusion of the fetus, placenta, or umbilical cord into the
abdominal cavity; or complete uterine avulsion. Approxi-
mately 75% of reported cases of uterine rupture involve
the fundus. The presentation of uterine rupture can range
from subtle findings (eg, uterine tenderness, nonreassur-
ing fetal heart rate patterns) without changes in maternal
vital signs, to rapid onset of maternal hypovolemic shock.
Signs of peritoneal irritation, such as distention, rebound
tenderness, guarding, and rigidity are frequently detected
upon examination but may be less pronounced during
pregnancy.
Pelvic Fractures
Pelvic fractures may result in significant retroperitoneal
bleeding, which is associated with substantial morbidity
and mortality. When combined with the possibility of in-
traperitoneal bleeding, pelvic fractures are frequently
associated with hypovolemic shock. Associated injuries
of the bladder or urethral disruption can result in hema-
turia and also may pose difficulty in placing a urinary
catheter.
Pelvic fracture is not a definite contraindication for
vaginal delivery. Even in the presence of a slightly dis-
placed pelvic fracture, safe vaginal delivery can be ac-
complished. However, a severe, dislocated, or unstable
fracture or a large healing callus may preclude an attempt
at vaginal delivery.
Penetrating Trauma
Most penetrating abdominal trauma results from gunshot
wounds or stab wounds. Penetrating abdominal trauma
during pregnancy has a remarkably disparate prognosis
for the fetus and the woman (26, 27). Fetal loss due to
1137 PRACTICE BULLETINS
abdominal gunshot wounds involves exploratory laparot-
omy, although laparotomy can be used selectively (26).
Although stab wounds that do not appear to penetrate
beyond the abdominal wall have been managed non-
operatively, evidence of peritoneal penetration usually
requires exploratory laparotomy, particularly if there are
signs of intraperitoneal hemorrhage or bowel perforation
(30). The indications for tetanus prophylaxis do not
change in pregnancy, and appropriate candidates should
be vaccinated.
If adequate oxygenation and uterine perfusion are
maintained, the fetus usually tolerates surgery and anes-
thesia well. Intraoperative fetal heart rate monitoring
should be considered if the fetus is viable. A Doppler
device or ultrasound transducer wrapped in a sterile plas-
tic bag may be used for this purpose. When the uterus has
been penetrated by an object or projectile, the fetus prob-
ably has been injured. If the fetus is alive, the decision to
perform cesarean delivery should be weighed against the
likelihood of fetal survival. Factors involved in this deci-
sion include gestational age, the condition of the fetus
based on any antenatal testing that may have been per-
formed, the extent of injury to the uterus (ie, a cesarean
hysterectomy may be necessary with extensive injuries),
and whether the gravid uterus allows adequate explo-
ration of the peritoneal cavity. These decisions often are
made jointly with the trauma surgeon. The need to
perform a laparotomy, by itself, is not an indication to
proceed with cesarean delivery. If the uterus has been
penetrated and delivery must proceed, a pediatric surgeon
and a neonatologist should be available if possible.
Fetal Assessment
The use of electronic fetal cardiac and uterine activity
monitoring in pregnant trauma victims beyond 20 weeks
of gestation may be predictive of abruptio placentae.
Placental abruption did not occur in trauma patients in
whom uterine contractions occurred at a frequency of less
than one every 10 minutes during 4 hours of monitoring
(16, 18). Of those women who had uterine contractions of
greater frequency, however, almost 20% had placental
abruption (16). Abnormal fetal heart tracings, including
tachycardia and late deceleration, were seen frequently in
cases of abruptio placentae.
Because abruption usually becomes apparent shortly
after injury, monitoring should be initiated as soon as the
woman is stabilized. Recommended minimum time of
posttrauma monitoring includes 4 hours (3, 18) and 26
hours (31). However, none of these times have been vali-
dated by large, prospective studies. Monitoring should be
continued and further evaluation carried out if uterine
contractions, a nonreassuring fetal heart rate pattern, vag-
inal bleeding, significant uterine tenderness or irritability,
serious maternal injury, or rupture of the amniotic mem-
tion. If the patient must remain supine (eg, if a spinal
injury is suspected or if cardiopulmonary resuscitation is
being administered), manual displacement of the uterus
laterally with a hand or placement of a wedge under a
backboard will accomplish this goal.
Following stabilization, a more detailed secondary
survey of the patient, including fetal evaluation, should
be performed. All body regions must be thoroughly ex-
amined. Pregnancy should not alter necessary treatment
and evaluation of the trauma patient. The abdomen is of
particular importance, because a substantial percentage of
serious injuries involve the uterus, intraperitoneal struc-
tures, and retroperitoneum. The uterus should be
examined for evidence of gross deformity, tenderness, or
contractions.
Computed tomography can be used to evaluate pa-
tients who have suffered significant trauma. Computed
tomographic scanning of the abdomen exposes the fetus
to approximately 3.5 rad, depending on the number and
thickness of the images and the equipment used. As with
any procedure involving ionizing radiation, scanning
closer to the uterus increases fetal exposure. Fetal expo-
sure exceeding 20 rad may be sufficient to induce adverse
effects in early pregnancy (28).
Open peritoneal lavage can be effective in the diag-
nosis of intraperitoneal hemorrhage during pregnancy
(29). Open lavage with sharp dissection and opening of
the anterior abdominal peritoneum under direct vision,
usually periumbilically, is advocated over a blind needle
insertion to lessen the likelihood of injury to the uterus or
to other displaced intraabdominal organs. Peritoneal
lavage is unnecessary if clinically obvious intraperitoneal
bleeding is present. Following are some indications for
peritoneal lavage after trauma during pregnancy:
Abdominal signs or symptoms suggestive of intra-
peritoneal bleeding
Altered sensorium
Unexplained shock
Major thoracic injuries
Multiple major orthopedic injuries
Penetrating trauma requires the complete undressing
of the patient for careful inspection of all entrance and
exit wounds because occasionally victims are shot or
stabbed multiple times, and entrance and exit wounds of
high-velocity projectiles are unpredictable. Radiographs
of the area in multiple projections often are helpful to
localize a bullet if an exit wound is not seen. The uterus
and its contents can often stop the progression of a pro-
jectile, limiting the extent of maternal injury to the
abdominal wall and the uterus. Signs of peritoneal irrita-
tion are less reliable during pregnancy, however, and
changes in vital signs due to blood loss may occur rela-
tively late because of the increase in blood volume relat-
ed to pregnancy. The general approach to management of
COMPENDIUM OF SELECTED PUBLICATIONS 1138
abdominal delivery when efforts at resuscitation have
failed. Based on isolated case reports, cesarean delivery
should be considered for both maternal and fetal benefit 4
minutes after a woman has experienced cardiopulmonary
arrest in the third trimester (33).
Safety Restraint Use During Pregnancy
There is substantial evidence that seat belt use during
pregnancy protects both the mother and the fetus (17, 34,
35). Nonetheless, many pregnant women do not wear seat
belts properly (13). Prenatal education on the use of seat
belts improves compliance of seat belt use as well as
improves knowledge of proper use (13). Current recom-
mendations indicate that throughout pregnancy, safety
belts should be used with both the lap belt and shoulder
harness in place. The lap belt portion should be placed
under the pregnant womans abdomen, over both anterior
superior iliac spines and the pubic symphysis. The shoul-
der harness should be positioned between the breasts.
There should not be excessive slack in either belt, and
both the lap and shoulder restraints should be applied as
snugly as comfort will allow. Placement of the lap belt
over the dome of the uterus significantly increases pres-
sure transmission to the uterus and has been associated
with significant uterine and fetal injury (36, 37). Based on
preliminary data using a crash dummy that simulates a
pregnant woman, there does not appear to be extraordi-
nary force transmission to the pregnant uterus when seat
belts are properly placed (37).
Airbag deployment during pregnancy does not
appear to be associated with an increased risk for either
maternal or fetal injury. Based on limited existing infor-
mation, it does not appear reasonable to recommend dis-
abling airbags during pregnancy.
Summary
Trauma is one of the leading causes of death of young
people in this country; in many cases, it is preventable.
The appropriate use of safety restraint systems in auto-
mobiles, compliance with traffic laws, and early identifi-
cation and intervention in suspected cases of domestic
violence are all preventive measures that may reduce the
likelihood of both maternal and fetal morbidity and mor-
tality. The obstetriciangynecologist plays a central role
both in the education of pregnant women and in the early
identification of suspected abuse.
When trauma has occurred, an organized approach to
management is critically important to optimize outcome.
The first priority is treatment and stabilization of the
woman; only then should attention be directed to the
fetus. Electronic fetal and uterine monitoring is an impor-
tant component of management beyond midtrimester
trauma.
branes is present. If these findings are not present, the
patient may be discharged or transferred (20). Upon dis-
charge, the patient should be instructed to return if she
develops vaginal bleeding, leakage of fluid, decreased
fetal movement, or severe abdominal pain.
The use of ultrasonography following trauma during
pregnancy does not appear to be as sensitive as cardio-
tocographic monitoring for diagnosing abruptio placentae
(4, 16, 18, 20). However, ultrasonography is useful in the
setting of trauma during pregnancy for establishing gesta-
tional age, locating the placenta, determining fetal well-
being and extent of fetal injury or demise, and estimating
amniotic fluid volume. In the woman, ultrasonography
also may reveal the presence of intraabdominal fluid and
increase the index of suspicion for intraperitoneal hemor-
rhage.
FetalMaternal Hemorrhage
Complications of fetalmaternal hemorrhage in trauma
patients include fetal and neonatal anemia, fetal cardiac
arrhythmias, and fetal death. There is no evidence that
laboratory testing for fetalmaternal hemorrhage (eg,
KleihauerBetke test) can predict adverse immediate se-
quelae due to hemorrhage (32). Among women who
exhibit signs of fetalmaternal hemorrhage due to trauma,
the mean estimated blood volume of injected fetal blood
usually is less than 15 mL, and more than 90% of the
hemorrhages are less than 30 mL (4, 16). Therefore, ad-
ministration of 300 g (one ampule) of D immune glob-
ulin would protect nearly all D-negative trauma victims
from D alloimmunization. The routine use of the
KleihauerBetke assay or other similar quantitative
assays of fetalmaternal hemorrhage may be useful in
identifying those few unsensitized, D-negative trauma
patients who are found to have more than 30 mL transfu-
sion. Additional D immune globulin (300 g for every 30
mL of whole blood transfused) may be administered to
these patients. Administration of D immune globulin at
any time within the first 72 hours following fetal
maternal hemorrhage appears to provide protection from
alloimmunization. Consideration should be given to
administering D immune globulin to all unsensitized
D-negative pregnant patients who have experienced
abdominal trauma.
Special Considerations
Perimortem Cesarean Delivery
Although there are no clear guidelines regarding peri-
mortem cesarean delivery, fetal survival is unlikely if
more than 1520 minutes have transpired since the loss of
maternal vital signs. There are insufficient data on which
to base conclusions regarding the appropriateness of
1139 PRACTICE BULLETINS
19. Rothenberger D, Quattlebaum FW, Perry JF Jr, Zabel J,
Fischer RP. Blunt maternal trauma: a review of 103 cases.
J Trauma 1978;18:173179
20. Williams JK, McClain L, Rosemurgy AS, Colorado NM.
Evaluation of blunt abdominal trauma in the third trimester
of pregnancy: maternal and fetal considerations. Obstet
Gynecol 1990;75:3337
21. Biester EM, Tomich PG, Esposito TJ, Weber L. Trauma in
pregnancy: normal revised trauma score in relation to other
markers of maternofetal statusa preliminary study. Am J
Obstet Gynecol 1997;176:12061212
22. Evrard JR, Sturner WQ, Murray EJ. Fetal skull fracture
from an automobile accident. Am J Forensic Med Pathol
1989;10:232234
23. Hartl R, Ko K. In utero skull fracture: case report. J Trauma
1996;41:549552
24. Astarita DC, Feldman B. Seat belt placement resulting in
uterine rupture. J Trauma 1997;42:738740
25. Buchsbaum HJ. Accidental injury complicating pregnancy.
Am J Obstet Gynecol 1968;102:752769
26. Awwad JT, Azar GB, Seoud MA, Mroueh AM, Karam KS.
High-velocity penetrating wounds of the gravid uterus: re-
view of 16 years of civil war. Obstet Gynecol 1994;83:
259264
27. Kissinger DP, Rozycki GS, Morris JA Jr, Knudson M,
Copes WS, Bass SM, et al. Trauma in pregnancy: predict-
ing pregnancy outcome. Arch Surg 1991;126:10791086
28. American College of Obstetricians and Gynecologists.
Guidelines for diagnostic imaging during pregnancy.
ACOG Committee Opinion 158. Washington, DC: ACOG,
1995
29. Esposito TJ, Gens DR, Smith LG, Scorpio R. Evaluation
of blunt abdominal trauma occurring during pregnancy. J
Trauma 1989;29:16281632
30. Grubb DK. Nonsurgical management of penetrating uter-
ine trauma in pregnancy: a case report. Am J Obstet
Gynecol 1992;166:583584
31. American Academy of Pediatrics, American College of
Obstetricians and Gynecologists. Guidelines for perinatal
care. 4th ed. Elk Grove Village, Illinois: AAP; Washington,
DC: ACOG, 1997
32. Boyle J, Kim J, Walerius H, Samuels P. The clinical use of
the KleihauerBetke test in Rh positive patients. Am J
Obstet Gynecol 1996;174:343
33. Katz VL, Dotters DJ, Droegemueller W. Perimortem cesar-
ean delivery. Obstet Gynecol 1986;68:571576
34. Crosby WM, King AI, Stout LC. Fetal survival following
impact: improvement with shoulder harness restraint. Am J
Obstet Gynecol 1972;112:11011106
35. Wolf ME, Alexander BH, Rivara FP, Hickok DE, Maier
RV, Starzyk PM. A retrospective cohort study of seatbelt
use and pregnancy outcome after a motor vehicle crash. J
Trauma 1993;34:116119
References
1. Dannenberg AL, Carter DM, Lawson HW, Ashton DM,
Dorfman SF, Graham EH. Homicide and other injuries as
causes of maternal death in New York City, 1987 through
1991. Am J Obstet Gynecol 1995;172:15571564
2. Fildes J, Reed L, Jones N, Martin M, Barrett J. Trauma: the
leading cause of maternal death. J Trauma 1992;32:643
645
3. Pearlman MD, Tintinalli JE, Lorenz RP. A prospective con-
trolled study of outcome after trauma during pregnancy.
Am J Obstet Gynecol 1990;162:15021510
4. Goodwin TM, Breen MT. Pregnancy outcome and feto-
maternal hemorrhage after noncatastrophic trauma. Am J
Obstet Gynecol 1990;162:665671
5. National Safety Council. Accident facts. Chicago: Nation-
al Safety Council, 1997
6. American College of Obstetricians and Gynecologists. Do-
mestic violence. ACOG Technical Bulletin 209. Washing-
ton, DC: ACOG, 1995
7. Gazamararian JA, Lazorick S, Spitz AM, Ballard TJ,
Saltzman LE, Marks JS. Prevalence of violence against
pregnant women. JAMA 1996;275:19151920
8. Helton AS, McFarlane J, Anderson ET. Battered and preg-
nant: a prevalence study. Am J Public Health 1987;77:
13371339
9. Berenson AB, Stiglich NJ, Wilkinson GS, Anderson GD.
Drug abuse and other risk factors for physical abuse in
pregnancy among white non-Hispanic, black, and Hispan-
ic women. Am J Obstet Gynecol 1991;164:14911499
10. McFarlane J, Parker B, Soeken K, Bullock L. Assessing for
abuse during pregnancy. Severity and frequency of injuries
and associated entry into prenatal care. JAMA 1992;267:
31763178
11. Stewart DE, Cecutti A. Physical abuse in pregnancy. Can
Med Assoc J 1993;149:12571263
12. Varner MW. Maternal mortality in Iowa from 1952 to
1986. Surg Gynecol Obstet 1989;168:555562
13. Pearlman MD, Phillips ME. Safety belt use during preg-
nancy. Obstet Gynecol 1996;88:10261029
14. Pearlman MD, Tintinalli JE. Evaluation and treatment of
the gravida and fetus following trauma during pregnancy.
Obstet Gynecol Clin North Am 1991;18:371381
15. Fries MH, Hankins GDV. Motor vehicle accident associat-
ed with minimal maternal trauma but subsequent fetal
demise. Ann Emerg Med 1989;18:301304
16. Pearlman MD, Tintinalli JE, Lorenz RP. Blunt trauma dur-
ing pregnancy. N Engl J Med 1990;323:16091613
17. Crosby WM, Costiloe JP. Safety of lap-belt restraint for
pregnant victims of automobile collisions. N Engl J Med
1971;284:632636
18. Dahmus MA, Sibai BM. Blunt abdominal trauma: are there
predictive factors for abruptio placentae or maternalfetal
distress? Am J Obstet Gynecol 1993;169:10541059
COMPENDIUM OF SELECTED PUBLICATIONS 1140
36. McCormick RD. Seat belt injury: case of complete transec-
tion of pregnant uterus. J Am Osteopath Assoc 1968;67:
11391141
37. Pearlman MD, Viano D. Automobile crash simulation with
the first pregnant crash test dummy. Am J Obstet Gynecol
1996;175:977981
Requests for authorization to make photocopies should be
directed to the Copyright Clearance Center, 222
Rosewood Drive, Danvers, MA 01923; telephone (978)
750-8400.
Copyright September 1998
ISSN 1074-8628
The American College of
Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
PRACTICE BULLETINS
COMMITTEE ON PRACTICE BULLETINSGYNECOLOGY
PRACTICE BULLETINS
COMMITTEE ON PRACTICE BULLETINSGYNECOLOGY
1143
CLINICAL MANAGEMENT GUIDELINES FOR
OBSTETRICIANGYNECOLOGISTS
NUMBER 11, DECEMBER 1999
(Replaces Technical Bulletin Number 184, September 1993)
This Practice Bulletin was
developed by the ACOG Com-
mittee on Practice Bulletins
Gynecology with the assistance
of Kamran S. Moghissi, MD
and Craig A. Winkel, MD. The
information is designed to aid
practitioners in making deci-
sions about appropriate obstet-
ric and gynecologic care. These
guidelines should not be con-
strued as dictating an exclusive
course of treatment or proce-
dure. Variations in practice may
be warranted based on the
needs of the individual patient,
resources, and limitations
unique to the institution or type
of practice.
Reaffirmed 2007
Medical Management of
Endometriosis
Endometriosis represents a significant health problem for women of reproduc-
tive age. Defined as the presence of endometrial-like glands and stroma in any
extrauterine site, endometriosis continues to defy our complete understanding
regarding etiology, the relationship between extent of disease and the degree of
symptoms, its relationship to fertility, and the most appropriate means of ther-
apy. The purpose of this document is to present the evidence, including risks
and benefits, for the effectiveness of medical therapy for women who experi-
ence symptoms and problems believed to be secondary to endometriosis.
Background
Incidence
Endometriosis is a gynecologic condition that occurs in 710% of women in the
general population and up to 50% of premenopausal women (1), with a prevalence
of 38% (range, 2050%) (24) in infertile women, and in 7187% of women with
chronic pelvic pain (57). Contrary to much speculation, there are no data to sup-
port the view that the incidence of endometriosis is increasing, although improved
recognition of endometriosis lesions (8) may have led to an increase in the rate of
detection. There also appears to be no particular racial predisposition to endo-
metriosis.
A familial association of endometriosis has been documented (9), and patients
with an affected first-degree relative have nearly a 10-fold increased risk of devel-
oping endometriosis. The proposed inheritance is characteristic of a polygenic-
multifactorial mechanism.
Etiology
Although the pathogenesis of endometriosis remains unclear, leading theories
include retrograde menstruation, hematogenous or lymphatogenous transport,
ACOG
PRACTICE
BULLETIN
COMPENDIUM OF SELECTED PUBLICATIONS 1144
and coelomic metaplasia. It has been suggested that virtual-
ly all women are potentially vulnerable to the development
of the lesions of endometriosis, but appropriate immuno-
competency in most eradicates such lesions in a timely
fashion, preventing clinical sequelae (10). Menstrual flow
that produces a greater volume of retrograde menstruation
may increase the risk of developing endometriosis. Cervical
or vaginal atresia with outflow obstruction also is linked
with the development of endometriosis (11). Early menar-
che, regular cycles (especially without intervening pregnan-
cy-induced amenorrhea), and a longer and heavier than
normal flow are associated with this disease (12). Because
endometriosis is an estrogen-dependent disease, factors that
reduce estrogen levels, such as exercise-induced menstrual
disorders, decreased body-fat content, and tobacco smok-
ing, are associated with reduced risk of developing
endometriosis (12).
Clinical Manifestations
The clinical manifestations of endometriosis are variable
and unpredictable in both presentation and course. Dys-
menorrhea, chronic pelvic pain, dyspareunia, uterosacral lig-
ament nodularity, and adnexal mass (either symptomatic or
asymptomatic) are among the most well-recognized mani-
festations (1316). A significant number of women with
endometriosis remain asymptomatic.
The association between endometriosis and infertility
remains the subject of considerable debate. It is clear that
endometriosis may induce infertility as a result of anatomic
distortion secondary to invasive endometriosis and related
adhesions. Although it was previously believed that patients
with minimal and mild endometriosis displayed reduced
monthly fecundity rates (17), a cause-and-effect relationship
has not been proven, and more recent prospective controlled
trials suggest that minimal to mild endometriosis is not asso-
ciated with reduced fecundity (18) and may not be a direct
cause of infertility (19).
Pelvic pain that is typical of endometriosis is character-
istically described as secondary dysmenorrhea (with pain
frequently commencing prior to the onset of menses), deep
dyspareunia (exaggerated during menses), or sacral back-
ache with menses. Endometriosis that involves specific
organs may result in pain or physiologic dysfunction of
those organs, such as perimenstrual tenesmus or diarrhea in
cases of bowel involvement or dysuria and hematuria in
cases of bladder involvement.
The pain associated with endometriosis has little rela-
tionship to the type or location of the lesions that are visible
at laparoscopy (20). Surgical assessment is complicated by
the varying, and subtle appearances of endometriosis (21,
22), and may be demonstrated histologically in a normal-
appearing peritoneum (23, 24). It has been shown that the
depth of infiltration of endometriosis lesions correlates
best with pain severity (6, 25, 26). Systematic analysis of
the source of pain in awake patients undergoing
laparoscopy (sometimes referred to as pain mapping)
demonstrates that pain arises from stimulation of adjacent
normal peritoneal surfaces that extend well beyond the
visible lesions of endometriosis. This suggests that painful
lesions are those involving peritoneal surfaces innervated
by peripheral spinal nerves, rather than those innervated
by the autonomic nervous system (20).
Diagnosis
Direct visualization confirmed by histologic examination,
especially of lesions with nonclassical appearance (21, 22,
27), remains the standard for diagnosing endometriosis.
The presence of two or more of the following histologic
features is used as the threshold criteria for the diagnosis
by a pathologist (28):
Endometrial epithelium
Endometrial glands
Endometrial stroma
Hemosiderin-laden macrophages
Visual inspection as the sole means for making the
diagnosis of endometriosis requires an experienced sur-
geon who is familiar with the protean appearances of
endometriosis. Experience is associated with increased
diagnostic accuracy (8, 21, 22), but the correlation
between visual inspection and histologic confirmation of
the presence of endometriosis in biopsy specimens is
imperfect (22). The finding of microscopic endometriosis
in normal-appearing peritoneum (23, 24) exemplifies the
inaccuracy of diagnosis by visualization alone. Peritoneal
biopsy may be used for diagnosing questionable peri-
toneal lesions (22).
Because tissue confirmation of the diagnosis of en-
dometriosis requires a surgical procedure, investigators
have searched for a noninvasive alternative. The correla-
tion between the presence of moderate and severe
endometriosis and an increased concentration of CA 125
in serum has been known for more than 10 years (29).
Although the specificity of CA 125 measurements had
been reported to be greater than 85%, with sensitivities
between 20% and 50% (3033), the clinical utility of
measuring CA 125 as a diagnostic marker for endometrio-
sis appears to be limited. Determining the level of CA 125
in serum appears to be useful in detecting women with
severe endometriosis but is of questionable value in
detecting women with minimal or mild disease (34, 35).
1145 PRACTICE BULLETINS
Measurement of peritoneal fluid levels, however, appears
to be better for detecting minimal and moderate disease
(34).
Concentrations of CA 125 in serum also have been
studied as a marker to determine the response to medical
therapy for endometriosis. Although CA 125 levels may
decrease during treatment when compared with pretreat-
ment values (3638), posttreatment values that are normal
do not confirm the absence of endometriosis (36, 38), nor
are they useful for predicting disease recurrence (37).
Imaging studies, such as ultrasonography, magnetic
resonance imaging, and computed tomography, appear to
be useful only in the presence of a pelvic or adnexal mass.
Ovarian endometriomas, visualized ultrasonographically,
typically appear as cysts that contain low-level, homoge-
neous internal echoes consistent with old blood. Imaging
studies alone appear to have greater predictive accuracy in
differentiating ovarian endometriomas from other adnexal
masses than when used in combination with measurement
of CA 125 levels in plasma (39). Magnetic resonance imag-
ing may detect deeply infiltrating endometriosis that in-
volves the uterosacral ligaments and the cul-de-sac, but
lacks sensitivity in detecting rectal involvement (40).
Figure 1. Modified from
the revised American
Fertility Society classifica-
tion of endometriosis.
(Reprinted with permis-
sion from the American
Society for Reproductive
Medicine. Fertility and
Sterility 1996;67(5):819
820)
American Society for Reproductive Medicine
Revised Classification of Endometriosis
Patients name Date
Stage I (minimal) 15
Stage II (mild) 615
Stage III (moderate) 1640
Stage IV (severe) >40
Total
Laparoscopy Laparotomy Photography
Recommended treatment
Prognosis
*If the fimbriated end of the fallopian tube is completely enclosed, change the point assignment to 16.
Denote appearance of superficial implant types as red [(R), red, red-pink, flamelike, vesicular blobs,
clear vesicles], white [(W), opacifications, peritoneal defects, yellow-brown], or black [(B), black,
hemosiderin deposits, blue]. Denote percent of total described as R %, W %, and B %. Total
should equal 100%.
Endometriosis <1 cm 13 cm >3 cm
Superficial 1 2 4
Deep 2 4 6
R Superficial 1 2 4
Deep 4 16 20
L Superficial 1 2 4
Deep 4 16 20
O
v
a
r
y
P
e
r
i
t
o
n
e
u
m
Posterior
cul-de-sac
obliteration
Partial Complete
4 40
O
v
a
r
y
T
u
b
e
Adhesions <
1
/3 Enclosure
1
/3
2
/3 Enclosure >
2
/3 Enclosure
R Filmy 1 2 4
Dense 4 8 16
L Filmy 1 2 4
Dense 4 8 16
R Filmy 1 2 4
Dense 4* 8* 16
L Filmy 1 2 4
Dense 4* 8* 16
COMPENDIUM OF SELECTED PUBLICATIONS 1146
Classification
Numerous classification schemas have been proposed to
describe endometriosis by anatomic location and severity of
disease. The American Society for Reproductive Medicine
(ASRM [formerly the American Fertility Society]) classifi-
cation, which is the most commonly used system, was
revised for the third time in 1996 (41) (see Figure 1) but still
has limitations and inherent defects. The system is not a
good predictor of pregnancy following treatment despite
adjustments to the point scores and cut-points for disease
stage. The ASRM system does not correlate well with the
symptoms of pain and dyspareunia (6). The true value of
the ASRM 1996 revised system is in uniform recording
of operative findings and perhaps for comparing the results
of various therapies.
Clinical Considerations and
Recommendations
In women with endometriosis-related pain
who desire future fertility, how does medical
therapy compare with no therapy for the treat-
ment of pain and long-term preservation of
fertility potential?
Deeply infiltrating endometriosis, rather than surface nonin-
filtrating endometriosis, is commonly associated with pelvic
pain (6). At present, evidence suggests that pain associated
with endometriosis can be reduced with the use of a variety
of medications (progestins, danazol, oral contraceptives,
nonsteroidal antiinflammatory drugs, and gonadotropin-
releasing hormone [GnRH] agonists) (4247). There is also
evidence that such medical therapies are likely to reduce the
size of endometriosis lesions and, thus, the stage of disease
(42, 48, 49). There are no data, however, showing that med-
ical therapy eradicates the lesions. Although medical treat-
ment may eliminate the symptoms associated with
endometriosis, there is no evidence that such treatment has
an impact on the future fertility of women with endometrio-
sis. Because early-stage endometriosis is more likely to be
associated with pain symptoms without associated alter-
ations in fecundity, it is unlikely that such data will be forth-
coming. Furthermore, whereas infiltrating lesions of
endometriosis are associated with pain, studies are lacking
that suggest the absence of treatment is associated with a
progressive or future decline in fertility.
In a woman with normal or minor gynecologic find-
ings suggesting mild disease (pelvic tenderness, uterosacral
nodularity), ovarian suppression with a combination oral
contraceptive may be effective in reducing pain (50). The
efficacy of continuous administration of oral contracep-
tives compared with cyclic administration has not been
tested in a prospective fashion. Oral contraceptives proba-
bly should not be used for more than 3 months if the patient
experiences no relief of symptoms. Furthermore, there is
no reason to suspect that one oral contraceptive is better
than another for suppression of pain symptoms. If recurrent
symptoms do not respond to oral contraceptives, then ther-
apy with medroxyprogesterone acetate (MPA), danazol, or
a GnRH agonist may be appropriate.
Danazol, when used in doses of 600800 mg per day
appears to as effective as GnRH agonists for pain relief in
most patients, but is associated with a significantly greater
incidence of side effects (51). The cost of treatment with
danazol is about one third less than treatment with a GnRH
agonist but nearly twice as costly as treatment with oral
contraceptives and oral or depot MPA.
In women with endometriosis-related pain
who desire future fertility, how does medical
therapy compare with surgical therapy alone
for the management of pain and long-term
preservation of fertility potential?
The debate regarding medical treatment versus surgical
treatment for the management of pain related to en-
dometriosis continues despite of the lack of substantive
data on either side of the argument. Surgical therapy for
women with endometriosis is associated with a significant
reduction in pain symptoms during the first 6 months fol-
lowing surgery (52). With continued follow-up, however, a
substantial portion (44%) of women experience recurrence
of symptoms within 1 year postoperatively (53). The
cumulative recurrence rate of pain symptoms during the
initial 5 years following discontinuation of therapy with a
GnRH agonist is 53% (54). No evidence exists regarding
the effectiveness of adjunctive treatment with danazol, oral
contraceptives, or progestins in comparison with surgical
treatment alone in the management of endometriosis-relat-
ed pelvic pain. A major issue in considering comparisons
of surgical treatment with medical treatment is the experi-
ence and expertise of the surgeon.
Likewise, debate continues over the best means of sur-
gical therapy. One opinion considers vaporization or
cautery of peritoneal implants adequate, whereas the other
recommends surgical excision as necessary for adequate
treatment (55). Currently, there are limited data to show
that one method is better than the other. Moreover, there are