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Volume 65, Number 2


Copyright © 2010
by Lippincott Williams & Wilkins CME REVIEWARTICLE
CHIEF EDITOR’S NOTE: This article is part of a series of continuing education activities in this Journal through which a total
of 36 AMA/PRA Category 1 CreditsTM can be earned in 2010. Instructions for how CME credits can be earned appear on the
last page of the Table of Contents.

Preconception Care
Vincenzo Berghella, MD,* Edward Buchanan, MD,†
Leonardo Pereira, MD,‡ and Jason K. Baxter, MD, MSCP§
*Director, Division of Maternal-Fetal Medicine; Director, MFM Fellowship Program, Professor, Department
of Obstetrics and Gynecology, Thomas Jefferson University, Philadelphia, PA; †Assistant Professor,
Department of Family and Community Medicine, Thomas Jefferson University, Philadelphia, PA; ‡Director,
Division of Maternal-Fetal Medicine; Associate Professor, Obstetrics and Gynecology, Oregon Health &
Sciences University, Portland, OR; §Director, Division of Research; Associate Professor, Department of
Obstetrics and Gynecology, Thomas Jefferson University, Philadelphia, PA

Our objective was to provide the clinician with easy-to-use evidence-based guidelines, based on the best
available literature, for offering effective preconception care, aimed at decreasing maternal and fetal/
neonatal morbidity and mortality. We searched the Cochrane Library, MEDLINE, and PUBMED from 1966
until January 2009. We used the search terms “preconception,” “preconception care,” “prepregnancy,” and
“inter-pregnancy.” We focused on level I publications, randomized studies, and meta-analyses of these
studies in particular. We included non-English publications, if pertinent. We searched the reference lists of
manuscripts identified, and selected those we judged relevant. Preconception care has been defined as a
set of interventions that aim to identify and modify risks to a woman’s health or pregnancy outcome through
prevention and management. It should occur any time any healthcare provider sees a reproductive age
woman. Personal and family history, physical exam, laboratory screening, reproductive plan, nutrition,
supplements, weight, exercise, vaccinations, and injury prevention should be reviewed in all women. Folic
acid 400 mcg per day, as well as proper diet and exercise should be encouraged. Women should receive the
influenza vaccine if planning pregnancy during flu season; the rubella and varicella vaccines if there’s no
evidence of immunity to these viruses; and tetanus/diphtheria/pertussis if lacking adult vaccination. Specific
interventions to reduce morbidity and mortality for both the woman and her baby should be offered to those
identified with chronic diseases, or exposed to teratogens or illicit substances. There are several interven-
tions that have been proven to effectively improve pregnancy outcome when provided as preconception
care. These should be consistently provided to reproductive-age women.
Target Audience: Obstetricians & Gynecologists, Family Physicians
Leaning Objectives: After completion of this educational activity, the participant should be better able to
assess potential benefits for women and their offspring that result from preconception care, translate specific
evidence-based preconception strategies into clinical practice, and select resources for practitioners and
patients that are print media or online related to preconception health.

Preconception care has ancient origins. Plutarch (46– the maidens to exercise [. . .], to the end that the fruit
120 CE) wrote that the ancient Spartans “[. . .] ordered they conceived might [. . .] take firmer root and find
better growth” (1). Preconception care is a set of inter-
Unless otherwise noted below, each faculty’s spouse/life part- ventions that aim to identify and modify biomedical,
ner (if any) has nothing to disclose. behavioral, and social risks to a woman’s health or
The authors have disclosed that they have no financial relation- pregnancy outcome through prevention and manage-
ships with or interests in any commercial companies pertaining to ment (2). This care has also been called prepregnancy,
this educational activity.
The Faculty and Staff in a position to control the content of Reprint requests to: Vincenzo Berghella, MD, Division of Maternal-
this CME activity have disclosed that they have no financial Fetal Medicine, Department of Obstetrics and Gynecology, Thomas
relationships with, or financial interests in, any commercial Jefferson University, 834 Chestnut Street, Suite 400, Philadelphia, PA
companies pertaining to this educational activity. 19107. E-mail: | 119
120 Obstetrical and Gynecological Survey

or interpregnancy care, or periconceptional medicine care visit within the prior year (5). Therefore, uni-
(3). The foundation of preconception care is prevention. versal preconception care can be achieved if health
Prevention of disease is the most effective form of care providers make it a priority and plan for it at
medicine, and health care should shift from the every opportunity (Table 1). The approach should be
delivery of procedure-based acute care to the pro- “every reproductive age woman, every time” (5).
vision of counseling-based preventive care (4,5). Increased awareness of preconception care should be
The first prenatal visit is “months too late!” (6). It accomplished through improved health resources,
usually happens after first trimester exposure to a public outreach, and advertising.
potential teratogen has already occurred. There are
about 1 billion reproductive age (usually defined as
15–44 year old) women worldwide. In the United CONTENT OF PRECONCEPTION CARE
States, as an example, only about half of pregnancies Every reproductive age woman should be asked at
are planned. Therefore, preconception care should every healthcare encounter: “Are you considering preg-
occur any time any healthcare provider sees a repro- nancy?” and “Could you possibly become pregnant?”
ductive age woman. As women get pregnant later in With these questions to initiate the dialogue, topics
life, disease prevalence and medication exposures pertinent to optimizing preconception health and there-
increase. Approximately 80% of reproductive age fore future maternal and perinatal outcome are dis-
US women have dental disease, 66% are obese or cussed. Topics to be discussed in preconception care are
overweight, 55% drink alcohol, 11% smoke, 9% listed in Table 2 (2,9). We have organized this manu-
have diabetes, 6% asthma, 3% hypertension, and 3% script to assist the practitioner, mimicking what would
cardiac disease (2). The incidences of many of these happen in a real preconception visit; first general health
conditions, even in pregnant women, are on the rise. screening with detection of specific risks, and then
Effectiveness of preventive interventions is best universal as well as individual interventions to optimize
assessed by randomized trials, so this review focuses pregnancy outcomes.
on such level I evidence, where available, as we have
described before (7,8). For example, the 2 leading TABLE 1
causes of death in the first year of life—birth defects Visits that are opportunities for preconception care
and disorders caused by preterm birth—can both be Adolescent (first gynecologic exam)
significantly reduced by preconception care. Any to a doctor during reproductive (15– 44) years
Annual ob-gyn
SOURCES AND STUDY SELECTION College—Graduate School health
Family planning, contraception prescribing, and counseling
We searched the Cochrane Library, MEDLINE, Pregnancy test (especially if negative)
and PUBMED from 1966 until January 2009. We Health maintenance
used the search terms “preconception,” “preconcep- Medical work
tion care,” “prepregnancy,” and “inter-pregnancy.” Emergency visit
We focused, as much as feasible, on randomized (Pre-)marriage
controlled studies, as well as meta-analyses of such
trials. We included non-English publications, if per-
tinent. We searched the reference lists of manuscripts TABLE 2
Topics to be reviewed in preconception care
identified, and selected those we judged relevant.
Review articles and book chapters are cited to pro- Risk assessment screening
Personal and family history, physical exam, and laboratory
vide readers additional details beyond the scope of
this review. Preventive health
Reproductive plan
Nutrition, supplements, weight, exercise
CARE Injury prevention
Specific individual issues/“exposures”
By age 25, about 50% of US women have had at Chronic diseases
least one birth. The highest fertility rate occurs in 25- Medications (teratogens)
to 30-year-old women. By age 44, ⬎85% have give Substance abuse/Environmental hazards and toxins
birth at least once. About 84% of reproductive-age Modified from MMWR Recomm Rep 2006;55(RR-6):1–23 and
women, when asked, answer that they had a health- Obstet Gynecol 2006;108:1615–1622.
Preconception Care Y CME Review Article 121

Cardiovascular risk factors
Preconception screening assessment for all reproductive age
Family history
women (age, 15– 44 yr)
History Dyslipidemia
Reason for visit Obesity
Health status: obstetrical, gynecological, medical, surgical, Diabetes mellitus
and family history Health/risk behaviors
Use of prescription, over-the-counter, complementary and Hygiene (including dental)
alternative medicines Injury prevention
Allergies (to medications or other) Safety belts and helmets
Tobacco, alcohol, other drug use Occupational hazards
Work-related exposures Recreational hazards
Dietary/nutrition assessment Firearms
Physical activity Hearing
Urinary and fecal incontinence Exercise and sports involvement
Physical examination Breast self-examination
Height, weight, body mass index (BMI) Vaccinations
Blood pressure See table 5
*Unless documented immunity.
Neck: adenopathy, thyroid †
HIV screening should be offered as routine to all women of
reproductive age, under an “opt-out” policy. Physicians should
Heart, lungs
be aware of and follow their states/countries HIV screening
Pelvic examination ‡
Annually or every other year beginning no later than age 21 yr;
every 2–3 yr after 3 consecutive negative test results if age 30 yr
Laboratory testing
or older with no history of cervical intraepithelial neoplasia 2 or 3,
Rubella titer*
immunosuppression, human immunodeficiency virus (HIV) infec-
Varicella titer*
tion, or diethylstilbestrol exposure in utero.
Human immunodeficiency virus (HIV) testing†
Modified from Obstet Gynecol 2006;108:1615–1622.
Cervical cytology‡
Chlamydia testing (if aged 25 yr or younger and sexually active)
Evaluation and counseling
Sexuality and reproductive planning
Discussion of a reproductive health plan
Contraceptive options for prevention of unwanted
pregnancy, including emergency contraception History, Exam, and Laboratory Screen
Genetic counseling
Sexually transmitted diseases Suggested preconception screening assessment is
Partner selection shown in Table 3 (9,10). A questionnaire should be
Barrier protection
Sexual function
completed ahead of time to review this extensive list
Fitness and nutrition (either on paper or online). History should be de-
Dietary/nutrition assessment tailed, especially when pertinent positives are de-
Exercise program tected. Prior inpatient and outpatient medical records
Folic acid supplementation (0.4 mg/d) should be reviewed. Women should be empowered
Calcium intake
Psychosocial evaluation
with easy access to their records (best if electronic), to
Abuse/neglect/violence (physical, sexual, emotional) facilitate multispecialty care coordination. Personal
Sexual practices medical record access is associated with increased ma-
Lifestyle/stress ternal control, satisfaction during pregnancy, and in-
Sleep disorders creased availability of antenatal records during hospital
Home and work (including satisfaction, and environmental
attendance (11).
Interpersonal/family relationships; social support Prior obstetrical and gynecological history, includ-
Depression (suicide) ing prior pregnancy complications, should be re-
Criminality viewed. Other reproductive issues should also be
Education assessed: fertility, including the possibility of as-
Language and culture
Health insurance status; coverage; access; public programs
sisted reproductive technology needs; sexuality (in
particular high-risk behaviors); contraception; part-
ner selection; and sexual function. Several social
issues need to be reviewed (Table 3).
122 Obstetrical and Gynecological Survey

All couples should have a basic screen for family TABLE 4

history of heritable genetic disorders, with a pedigree to Preconception laboratory screening depending on risk factors
at least the second prior generation. Women belonging Personal history
to an ethnic group at increased risk for a recessive Age
⬎35: fasting glucose
condition (Table 4) should be offered appropriate Race
screening. Cystic fibrosis (CF) screening should be African American: fasting glucose; hemoglobin
offered to all couples planning a pregnancy, especially electrophoresis (for sickle cell disease)
those who have a family history of CF, or are repro- Hispanic: fasting glucose
ductive partners of individuals with CF (12). Women Native American: fasting glucose
Pacific islander: fasting glucose
with a specific indication for genetic testing should be Mediterranean: mean corpuscular volume (MCV) screening
referred for formal genetic counseling. (for thalassemia)
Physical examination details are shown in Table 3. Ethnic testing: Ashkenazi—familial dysautonomia; Tay-Sachs;
Pelvic examination may include cytologic and sexually Canavan; Fanconi anemia type C; Niemann-Pick
transmitted infection screening for women with certain disease type A; Bloom syndrome; Gaucher; glycogen
storage 1a; Maple syrup urine disease; Mucolipidosis type IV
risk factors. Laboratory tests are done routinely (Table Prior obstetrical history
3), and depending on risk factors (Table 4) (9,13). Prior birth of a newborn weighting more than 9 lbs or
⬎4500 gm (macrosomia): fasting glucose
History of gestational diabetes mellitus: fasting glucose
Prior unexplained fetal death: check autopsy and karyotype
Universal Preventive Health of fetal death; antiphospholipid antibody testing; fasting
Reproductive Health Plan Prior infant with congenital anomaly (if not screened in that
Asking a reproductive-age woman, and therefore pregnancy): fasting glucose
Prior recurrent unexplained early pregnancy loss:
inducing her to think about, her reproductive health antiphospholipid antibody testing; study of uterine
plan should be a priority of any medical visit (14). anatomy; parental karyotype
Such a plan should address the desire (or not) for Prior medical history
children, the optimal number, spacing and timing of Metabolic syndrome/obesity; family history of lipid or
pregnancies; contraception to achieve this plan; op- coronary disorders: cholesterol/lipid profile
Diabetes: lipid profile, hemoglobin A1c, cardiac and renal
portunities to improve her health and therefore a baseline function assessment, ophthalmologic exam
successful reproductive life; and age-related changes Hypertension: fasting glucose; baseline cardiac, renal, liver
in fertility (14). Having a reproductive health plan functions
reduces unintended pregnancies, age-related infertil- Multiple coronary heart disease risk factors (e.g., tobacco
ity, and fetal exposure to teratogens (2). Very few use, hypertension): lipid profile
High-density lipoprotein cholesterol level less than or equal
women know that a short interpregnancy interval to 35 mL/dL: fasting glucose
(e.g., ⬍6 months from the end of last pregnancy to Triglyceride level greater than or equal to 250 mg/dL:
the next conception) is associated with increases in fasting glucose
incidences of both small-for-gestational age and low- History of impaired glucose tolerance or impaired fasting
birth weight neonates (15). Folic acid depletion may glucose: fasting glucose
Chronic use of steroids: fasting glucose
be the cause for these increased risks (16). Education Polycystic ovary syndrome: fasting glucose
and contraception advice are necessary to aim for the History of vascular disease: fasting glucose
optimal 18 to 24 month interpregnancy interval goal. Marfan syndrome: echocardiogram for assessment of aortic
All women should be counseled that 2% to 3% of root; eye exam for lens
babies are born with minor (usually) or major anom- History of STD, drug abuse, etc.; HIV, Hep C
Recipients of blood from donors who later tested positive
alies. Screening and diagnostic options to detect an- for HCV infection: Hep C
euploidy and birth defects should be reviewed, and Recipients of blood or blood-component transfusion or
women should be encouraged to discuss their options organ transplant before July 1992: Hep C
in relation to their personal values. Recipients of clotting factor concentrates before 1987: Hep C
Chronic (long-term) hemodialysis: Hep C
History of transfusion from 1978 to 1985: HIV
Invasive cervical cancer: HIV
Nutrition, Weight, and Exercise HIV infection: STD screening; PPD
Medical risk factors known to increase risk of tuberculosis if
Lifelong habits of healthy diet and regular exercise infected: PPD
should be established preconceptionally (17). Proper Not sure if had varicella infection in past: varicella titer
diet and exercise can prevent several complications (continued)
Preconception Care Y CME Review Article 123

Physical examination
Overweight (BMI ⱖ25): fasting glucose
Social history Hypertension: fasting glucose
HIV or TB contact, IV drug use, etc.: TB testing Laboratory screening
History of injecting illegal drugs: HC; HIV; STD screening Persistently abnormal alanine aminotransferase levels: Hep C
(Chlamydia, Gonorrhea, syphilis, etc.); PPD Glycosuria: fasting glucose
Occupational percutaneous or mucosal exposure to
Hep C indicates hepatitis C; HIV, human immunodeficiency
HCV-positive blood: Hep C
syndrome; PPD, purified protein derivative; STDs, sexually trans-
More than one sexual partner since most recent HIV test or
mitted diseases.
a sex partner with more than one sexual partner since
Modified from Obstet Gynecol 2006;108:1615–1622.
most recent HIV test: HIV
Seeking treatment for STDs: HIV
History of prostitution: STD screening, HIV
Past or present sexual partner who is HIV positive or
bisexual or injects drugs: HIV
of pregnancy, including gestational diabetes, hyper-
Long-term residence or birth in an area with high
prevalence of HIV infection: HIV tensive complications, etc (18). Some general pre-
Adolescents who are or ever have been sexually active: HIV conception “common sense” nutritional advice
Adolescents entering detention facilities: HIV; STD screening includes thoroughly cooking all meat (beef, pork, or
Offer to women seeking preconception evaluation: HIV (all poultry) as well as seafood and shellfish, eating at
women should be screened)
History of multiple sexual partners or a sexual partner with
least 12 ounces of fish weekly but avoiding ⬎2
multiple contacts: STD screening serving/wk of shark, swordfish, King mackerel, or
Sexual contact with individuals with culture-proven STD: tilefish, all of which contain high concentrations of
STD screening mercury. Albacore (white) tuna has more mercury
History of repeated episodes of STDs: STD screening
Attendance at clinics for STDs: STD screening
than canned, light tuna (19). Other recommendations
All sexually active women aged 25 yr or younger: chlamydia include eating only pasteurized eggs and dairy prod-
All sexually active adolescents: gonorrhea ucts, washing raw fruits and vegetables before eating,
Close contact with individuals known or suspected to have and obtaining a minimum daily iodine intake of 150
tuberculosis: PPD mcg/d. Education about proper hand, food, and cook-
Born in country with high tuberculosis prevalence: PPD
Medically underserved: PPD
ing utensil hygiene is important, especially in devel-
Low income: PPD oping countries.
Alcoholism: PPD Body mass index (BMI) should be calculated at
Resident of long-term care facility (e.g., correctional institu- least annually for reproductive-age women (20). For
tions, mental institutions, nursing homes and facilities): PPD
Health professional working in high-risk health care
women whose BMI falls outside the normal range
facilities: PPD (19–25), preconception counseling is extremely im-
Family history portant. Women with low BMI should be screened
Family history of diabetes mellitus: fasting glucose for anorrhexia nervosa or bulimia. Overweight or
Family history of diabetes; history of gestational diabetes, obese women should have formal nutritional coun-
overweight/obese, hypertension, high-risk ethnic group
(Afro-American, Hispanic, Native American): fasting
seling, and should aim to not get pregnant until
glucose every 3 yr optimal weight is achieved through preconception
Family history suggestive of familial hyperlipidemia: lipid exercise and proper nutrition. Calorie and portion-
profile size control may be the most effective methods of
Family history of premature (age younger than 50 yr for
men, age younger than 60 yr for women) cardiovascular
sustained preconception weight loss. Postpartum in-
disease: lipid profile dividual counseling on diet and physical activity
Colorectal cancer or adenomatous polyps in first-degree increased the proportion of women returning to
relative younger than 60 yr or in 2 or more first-degree prepregnancy weight from 30% to 50% in 1 random-
relatives of any ages; family history of familial ized trial (21). An exercise routine that can be started
adenomatous polyposis or hereditary nonpolyposis colon
cancer: colonoscopy preconceptionally and safely continued in pregnancy
First-degree relative (i.e., mother, sister, or daughter) or may include yoga; brisk walking (including hiking
multiple other relatives who have a history of and backpacking); jogging; swimming; biking; cross-
premenopausal breast or breast or ovarian cancer: country skiing; and using fitness equipment such as
Family history of Marfan syndrome: echocardiogram for
an elliptical trainer, treadmill, or stationary bike.
assessment of aortic root; eye exam for lens Women should be given standard advice for engag-
Family history of breast cancer: mammography ing in regular physical activity for 30 to 60 minutes
Family history of thyroid disease: TSH per day for 5 or more days per week.
124 Obstetrical and Gynecological Survey

Supplements TABLE 5
Recommended preconception vaccinations
The preconception intervention with the most All reproductive age women
evidence-based data to support its efficacy is folic Planned pregnancy during flu season: influenza
acid supplementation. Folic acid supplementation is No evidence of immunity to rubella or varicella: MMR and/or
recommended, with a minimum of 400 mcg/d for all varicella
women (93% decrease in neural tube defects Tetanus/diphtheria/pertussis if lacking adult vaccination
[NTDs]), and 4 mg/d for women with prior children All girls and women 9 –26 yr old: HPV
with NTDs (69% decrease in recurrent NTDs) (22). All persons 18 yr and younger without immunity to hepatitis B
Supplementation should start at least one month infection: hepatitis B
before conception and continue until at least 28 days Occupational
after conception (time of neural tube closure). Given Health care workers: hepatitis B, influenza, MMR, varicella
Public safety workers who have exposure to blood in the
the unpredictability of planned conception, all repro- workplace: hepatitis B
ductive age women should be on folic acid supple- Students in schools of medicine, dentistry, nursing, laboratory
mentation from menarche to menopause. Women technology, and other allied health professions: hepatitis B
taking antiseizure medications, other drugs that Staff of institutions for the developmentally disabled: hepatitis B
might interfere with folic acid metabolism, those Individuals who work with HAV-infected nonhuman primates
or with HAV in a research laboratory setting: hepatitis A
with homozygous methylenetetrahydrofolate reduc- Military recruits: meningococcus
tase enzyme mutations, or those who are obese, may Microbiologists routinely exposed to Neisseria meningitidis
need higher doses of folic acid supplementation. As isolates: meningococcus
increases in baseline serum folate level are directly Social history/living situation
proportional with a decrease in the incidence of Individuals with more than one sexual partner in the previous
6 months: hepatitis B
NTD, some experts have advocated 5 mg of folic Household contacts and sexual partners of individuals with
acid per day as optimal universal supplementation chronic Hepatitis B infection: hepatitis B
(23). Folic acid supplementation may decrease the Inmates of correctional facilities: hepatitis B
risk of congenital anomalies other than NTDs (e.g., Clients of institutions for the developmentally disabled:
cardiac, facial clefts) (24). hepatitis B
Illegal-injected drug users: hepatitis B
The overall benefits or risks of fortifying basic Illegal drug users (injected and non-injected): hepatitis A
foods such as grains with added folate has been Exposure to environment where pneumococcal outbreaks
associated with a 140 to 200 mcg/d increase in sup- have occurred: pneumococcus
plementation, and a 20% to 50% decrease in inci- Native Alaskan/native American: pneumococcus
dence of NTD (25). Education with provision of Alcohol abuse: pneumococcus
Tobacco smoking: pneumococcus
printed material (22,26), computerized counseling Residents of long-term care facilities: influenza, pneumococcus
(27), and learner-centered nutrition education (28), First year college students living in dormitories: meningococcus
all increase the awareness of the folate/neural tube Travel/immigration
defects association, and the use of the folate supple- Individuals traveling to or working in countries that have high
ments. These interventions may be effective in or intermediate endemicity of hepatitis A: hepatitis A
International travelers who will be in countries with high or
increasing the prophylactic use of additional precon- intermediate prevalence of chronic Hepatitis B infection for
ception care activities. more than 6 months: hepatitis B
There is insufficient evidence to justify the routine Travel to areas hyperendemic or epidemic for Neisseria
use of other supplements in reproductive age women, meningitidis: meningococcus
except if a nutritional deficiency has been identified. Pulmonary conditions
Chronic pulmonary disorders, including asthma:
The use of certain supplements may be detrimental, pneumococcus
especially if excessive amounts of lipid-soluble vita- Cardiac conditions
mins such as vitamin A (⬎10,000 IU/d) are taken, Chronic cardiovascular disorders (e.g., CHF, cardiomyopathies):
since they can be teratogenic. All supplements, in- influenza, pneumococcus
cluding alternative and complementary medicines, Renal conditions
Chronic metabolic diseases, including renal dysfunction:
should be reviewed. influenza, pneumococcus
Nephrotic syndrome: pneumococcus
Vaccines End stage renal disease including those on dialysis: hepatitis B
Preconception vaccination for the prevention of
fetal and maternal disease is an important preconcep-
tion intervention (Table 5). Maternal immunity to
Preconception Care Y CME Review Article 125

TABLE 5 Tetanus vaccination should remain up to date in

Continued reproductive age women, particularly in regions of
Endocrine conditions the world where maternal and neonatal tetanus is
Diabetes mellitus: influenza, pneumococcus prevalent (30). This has been shown to markedly
Hematologic/immunologic conditions
Prior transfusions: hepatitis A; hepatitis B
reduce the incidence of tetanus related to parturition.
Patients with clotting factor disorders (those who receive Due to increasing prevalence and the high morbidity
clotting factor concentrates): hepatitis A and mortality rates of neonatal pertussis, vaccination
Chronic illness, such as functional asplenia (e.g., sickle cell (in combination with tetanus and diphtheria) is rec-
disease) or splenectomy: pneumococcus ommended for all women and their partners of re-
Immunocompromised patients (e.g., HIV infection,
hematologic or solid malignancies, chemotherapy, steroid
productive age who have not been immunized in
therapy): pneumococcus their adult lives (since age 11 years) (31). It is well
Adults with anatomic or functional asplenia: pneumococcus, documented that 75% of cases of neonatal pertussis
meningococcus have a family member as the index case (32). Again,
Terminal complement component deficiencies: meningococcus through the concept of cocooning, the incidence of
Infectious conditions
Individuals with a recently acquired or recent evaluation for
neonatal pertussis can be reduced.
STD: hepatitis B Other vaccination recommendations based on med-
All clients in STD clinics: hepatitis B ical, occupational, or social risks are described in
HIV: hepatitis B, influenza, pneumococcus, consider Table 5.
GI/hepatic conditions Injury Prevention
Chronic liver disease: hepatitis A, hepatitis B, pneumococcus
Neurologic conditions The second leading cause of death in reproductive
Cerebrospinal fluid leaks: pneumococcus age women is accidents. Use of seat belts and hel-
Modified from Obstet Gynecol 2006;108:1615–1622. mets should be reviewed and strongly encouraged
where appropriate. Inquiry should be made regarding
occupational and recreational hazards. Possession
infections such as rubella and varicella should be and use of firearms should be evaluated.
assessed for potential vaccination of nonimmune
Specific Individual Issues
women, thus eliminating their risk for congenital
syndromes associated with these viruses. Vaccina- Chronic Diseases
tion with live-attenuated viruses should occur at least
The incidences of several medical disorders such
4 weeks before conception due to theoretical risk of
as obesity, diabetes mellitus, and hypertension are
live virus affecting the fetus.
high and on the rise in reproductive-age women.
Annual influenza vaccination for women and their
There is literature for evidence-based recommenda-
partners contemplating pregnancy will reduce the
tions on each disease or condition that can involve
chance of maternal prenatal infection, a time during
the reproductive age woman and affect her reproduc-
which higher morbidity has been documented. Influ-
tive health (3,8,10). Full review of each is behind the
enza vaccination for new mothers and other close
contacts of the newborn will reduce risk of infection
for the child who is unable to receive vaccination TABLE 6
until 6 months of age. Through this process of Preconception interventions for all women
“cocooning,” the newborn is protected from the high Intervention Prevention of
morbidity and mortality rates associated with influ-
Folic acid 400 ␮g/d* NTDs, possibly cardiac defects,
enza in the first year of life (29).
facial clefts
Hepatitis B vaccination should be offered to all Vaccinations Maternal/perinatal infection† (Table 5)
susceptible women of reproductive age in regions Proper diet and Obesity, diabetes, hypertensive diseases,
with intermediate and high rates of endemicity exercise and their consequences
(where ⱖ2% of the population is HBsAg positive). Screen for specific Table 7
risk factors
Perinatal transmission of hepatitis B results in 90%
chance of chronic infection in the newborn, which *Consider higher dose, especially for women taking anti-seizure
medications, other drugs which might interfere with folic acid
places the child at risk for future cirrhosis and hep-
metabolism, those with homozygous MTHFR enzyme mutations,
atocellular carcinoma. In regions of low prevalence, or those who are obese.
vaccination should be targeted to high risk groups †
By decreasing perinatal transmission, also decrease congen-
(Table 5). ital defects caused by infection.
126 Obstetrical and Gynecological Survey

scope of this review. In addition to recommendations ⫽ no increased risk (2%–3% baseline); 7%–9% ⫽
for all women (Table 6), we selected some common 15%; 9%–11% ⫽ 23%; ⬎11% ⫽ 25% (33). It has
conditions for brief preconception management re- been estimated that euglycemia (with normal HgB
view (Table 7). A1c) during the first trimester, which can only be
Diabetes is associated with an increased risk of achieved through attentive preconception counseling,
congenital anomalies, in particular cardiac and neural could prevent ⬎100,000 US pregnancy losses or
tube defects, if poorly-controlled in the first weeks of birth defects/year (2)! The benefits of preconception
pregnancy. The risk of congenital anomalies is re- diabetes care have been previously demonstrated
lated to long-term diabetic control, reflected in the (34,35) even in teenagers (36). Preconception care is
level of glycosylated hemoglobin (HgB A1c): ⬍7% also essential for counseling of the woman with

Preconception interventions for women with selected specific risk factors
Risk Factor/Population Intervention Prevention of
Smoking Smoking cessation PTB, LBW, etc.
Alcohol Avoid all alcohol intake Congenital anomalies, mental retardation
Other drugs of abuse Avoid all drugs of abuse PTB, IUGR, neonatal withdrawal, etc. (effect
depends on drug of abuse)
Teratogenic drugs Avoid teratogenic drugs (Table 8) Congenital anomalies
Supplements and over-the- Review and counsel: avoid excess of Congenital anomalies
counter medications recommended daily allowance (RDA)
Diabetes Hemoglobin A1C ⬍7%; screening for Congenital anomalies, length of NICU admission,
asymptomatic bacteriuria perinatal mortality and long-term health
consequences in infant; miscarriage; maternal
hospitalizations, maternal renal disease
Obesity Diet and exercise to achieve normal BMI; Infertility, fetal NTDs, PTB, CD, HTN-disorders,
screening for diabetes diabetes, VTE
Hypertension Avoid angiotensin-converting enzyme Congenital anomalies, HTN complications, CD,
inhibitors and angiotensin-receptor IUGR, placental abruption, PTB, perinatal death
blockers. If long-standing HTN, assess
for renal disease, ventricular
hypertrophy, and retinopathy
Hypothyroidism Thyroxine supplementation to maintain Infertility, maternal HTN, preeclampsia, abruption,
normal TSH (0.5–2.0 mcu/ml) anemia, PTB, LBW, fetal death, possibly
neurological problems in infant
Hyperthyroidism PTU (propylthiouracil) supplementation to Spontaneous pregnancy loss, PTB, preeclampsia,
maintain FT4 in high normal range, and fetal death, FGR, maternal congestive heart failure,
TSH in low normal range and thyroid storm; neonatal Graves’ disease
Seizure disorders Lowest dose of safest effective Congenital anomalies
anticonvulsant monotherapy; folic acid
4 mg/d
Asthma Management following National Asthma PTB, LBW, preeclampsia, perinatal mortality
Education and Prevention Program
Systemic lupus erythematosus ⱖ6 mo of quiescence on stable therapy HTN, preeclampsia, PTB, fetal death, IUGR, neonatal
HIV Initiate or modify antiviral agents with Perinatal HIV infection
goals of: (1) HIV-1 RNA viral load level
⬍1000 copies/mL or below the limit of
detection of the assay (2) avoid
teratogenic agents
PKU Low-phenylalanine diet PKU-related mental retardation
Sexually transmitted disease Screen at risk populations (Tables 3, 4) Ectopic pregnancy
(e.g., chlamydia)
Social issues (e.g., abuse, etc.) Counseling; referral to appropriate agency Physical and emotional trauma and their
PTB indicates preterm birth; LBW, low birth weight; IUGR, intrauterine growth restriction; NICU, neonatal intensive care unit; BMI,
body mass index; NTD, neural tube defects; CD, cesarean delivery; HTN, hypertension; VTE, venous thromboembolism; TSH,
thyroid-stimulating hormone; FT4, free thyroxine; HIV, human immunodeficiency virus; RNA, ribonucleic acid; PKU, phenyl ketonuria.
Preconception Care Y CME Review Article 127

conditions severe enough to make a successful preg- electrocardiogram, and ophthalmological exam, and
nancy extremely unlikely. The diabetic woman with ophthalmological exam are suggested, especially in
either ischemic heart disease, untreated proliferative women with long-standing, high-risk, or severe hyper-
retinopathy, creatinine clearance ⬍50 mL/min, pro- tension. It is important to identify cardiovascular risk
teinuria ⬎2 gm/24 h, creatinine ⬎2 mg/dL, uncon- factors, any reversible cause of hypertension, and assess
trolled hypertension, or gastropathy should be told for target organ damage or cardiovascular disease. If
not to get pregnant before the above conditions can hypertension is newly diagnosed and has not been eval-
be improved, and counseled regarding adoption if the uated previously, a medical consult may be indicated to
conditions cannot be improved (37). The frequency assess for any of these factors. Secondary hypertension,
of fetal/infant and maternal morbidity and mortality target organ damage (left ventricular dysfunction, reti-
are reduced in diabetic women seeking consultation nopathy, dyslipidemia, microvascular disease, prior
in preparation for pregnancy, but unfortunately only stroke), maternal age ⬎40, previous pregnancy loss,
about a third of these women receive such consulta- systolic blood pressure ⱖ180, or diastolic blood pres-
tion (38). The preconception consultation affords the sure ⱖ110 mm Hg are associated with higher risks in
opportunity to screen for vascular consequences of pregnancy. Abnormalities should be addressed and
the diabetes, with ophthalmologic, EKG, and renal managed appropriately. If, for example, serum creati-
evaluation via a 24-hour urine collection for total nine is ⬎1.4 mg/dL, the woman should be aware of
protein and creatinine clearance, and determine an- increased risks in pregnancy (pregnancy loss, reduced
cillary pregnancy risks. A thyroid-stimulating hor- birth weight, preterm birth, and accelerated deteriora-
mone should be checked, as 40% of young women tion of maternal renal disease). Even mild renal disease
with type 1 diabetes have hypothyroidism. Prolifer- (creatinine, 1.1–1.4 mg/dL) with uncontrolled hyperten-
ative retinopathy should be treated with laser before sion is associated with 10-fold higher risk of fetal loss.
pregnancy. Diabetes evaluation should emphasize Preconception prevention can be enormously effective.
the importance of tight glycemic control, with nor- Exercise for 30 minutes 3 times per week in all women
malization of the HgB A1C to at least ⬍7%. To with hypertension, and weight reduction if overweight
achieve euglycemia, diet, glucose monitoring, and are recommended. Restriction of sodium intake to the
exercise are always used and stressed. If euglycemia same ⬍2.4 gm sodium daily intake recommended for
is not achieved with these means, oral hypoglycemic essential hypertension is beneficial in nonpregnant
agents or insulin are utilized, and their regimens adults. If antihypertensive medical therapy is necessary,
should be refined preconceptionally. Of the oral hy- angiotensin-converting enzyme (ACE) inhibitors and
poglycemic agents, glyburide and glucophage can be angiotensin-II (AII) receptor antagonists should be dis-
used, and probably continued during pregnancy. The continued as they are associated with birth defects, fetal
original safety data available for glyburide showed growth restriction, oligohydramnios, neonatal renal fail-
that it did not cross the placenta in appreciable ure, and neonatal death in pregnancy. Other antihyper-
amounts (39), but recent data have shown a 70% level tensive agents should be used at the lowest effective
in umbilical blood compared to maternal blood (40). dose, and are probably safe if started preconceptionally
The other oral hypoglycemic agents should not be and continued in pregnancy.
used for preconception glycemic control, as there is Regarding seizures, conception should be deferred
not sufficient evidence for their safety and efficacy in until they are well controlled on minimum dose of
pregnancy. A common regimen currently used by medication. Monotherapy is preferable. Recently,
diabetologists is long-acting (e.g., glargine) and lamotrigine has been reported to be both first-line
short-acting (e.g., lispro insulin). There is growing therapy for nonpregnant adults for partial seizures,
evidence that this is a safe and effective regimen in (41,42) and associated with a low incidence of major
pregnancy, too. Women compliant with insulin malformations (43). The best choice is the antiepi-
pumps should continue this regimen. leptic drug (AED) that best controls the seizures. The
Hypertension is associated with several maternal AEDs are usually Food and Drug Administration
(worsening hypertension; superimposed preeclampsia; category C (human risk unknown, but none proven
severe preeclampsia; eclampsia; hemolysis, elevated yet) except for the following AEDs, which are
liver function texts, low platelets (HELLP) syndrome; known potential teratogens: carbamazepine, primi-
cesarean delivery) and fetal (growth restriction; done, phenytoin, and valproate (Table 8). These 4
oligohydramnios; placental abruption; preterm birth; AEDs should therefore be avoided if possible, by
perinatal death) risks in pregnancy. Serum creatinine, using a different therapy beginning in the precon-
24 hour urine for total protein and creatinine clearance, ception period. Women who have been seizure-
128 Obstetrical and Gynecological Survey

TABLE 8 preconception care, and can save and ameliorate sig-

Teratogens nificantly the health of a future offspring. Great re-
Prescribed drugs sources exist on the web for up-to-date teratologic
Androgens and testosterone derivatives (e.g., danazol) information (47–49).
Angiotensin-converting enzyme (ACE) inhibitors (e.g.,
enalapril, captopril) and angiotensin II receptor blockers Substance Abuse/Environmental Hazards/Toxins
Coumadin derivatives (e.g., warfarin)
Carbamazepine Tobacco smoking during pregnancy is associated
Diethylstilbestrol with increased risks of several complications. The
Folic acid antagonists (methotrexate and aminopterin) benefits of smoking cessation are tremendous: pre-
HMG-CoA reductase inhibitors (statins)
vention of 10% of perinatal deaths, 35% of low
Phenytoin weight births, and 15% of preterm deliveries (50).
Primidone Smoking even only 1 to 5 cigarettes per day is
Streptomycin and kanamycin associated with a 55% higher incidence of low birth
Tetracycline weight compared to nonsmokers. Reproductive-age
Thalidomide and leflunomide
Trimethadione and paramethadione
women should be informed of other smoking-related
Valproic acid diseases, such as ischemic heart disease, lung and
Vitamin A above RDA, and its derivatives (e.g., isotretinoin, other cancers, other lung diseases and pneumonia,
etretinate, and retinoids) stroke, and congestive heart failure. Major risk
Chemicals groups for smoking are women ⬍25 years old with
less than a high-school education. Smoking makes a
Drugs of abuse major contribution to disparities in mortality (51).
Alcohol Smoking cessation programs are based mostly on
Cocaine oral and written advice at each prenatal visit regard-
Infections ing the risk of smoking for mother and baby, and
plan to quit. These programs are associated with a
Syphilis 6% increase in smoking cessation, and decreases in
Toxoplasmosis incidences of low birth weight (by 19%) and preterm
Varicella birth (by 16%) (52). Support and reward techniques
Radiation to help quit smoking are one of the best form of
Modified from Lancet 2007;369:970–971 and Neurology 2008; evidence-based medicine, supported by over 20 high
71:706–707. quality randomized trials. The “5 A’s” for screening
and interventions to prevent smoking in pregnancy
free for ⱖ2 years with a normal EEG may be are Ask, Advise, Assess, Assist, and Arrange (53).
eligible to stop anticonvulsant therapy after con- Counseling with behavioral and educational inter-
sulting with a neurologist (44). ventions is associated with highest cessation rates.
Pregnancy is a unique opportunity for medical inter-
vention with frequent visits and may be the only time
Detailed discussion regarding prescribed and over smoking women seek medical attention. Most phar-
the counter medications needs to occur at the precon- macotherapies are also effective preconceptionally,
ception visit. The indication, safety, effectiveness, but contraindicated or with uncertain safety and
and necessity of each drug needs to be reviewed. efficacy during pregnancy. Nicotine replacement
Many women and their doctors often stop efficacious therapies (patch, gum, and bupropion) are safe and
and necessary medications as soon as the woman effective in reproductive-age women, but there is
finds out she is pregnant, compromising the health of insufficient evidence for recommending them in
both the woman and her baby. The majority of pre- pregnant smokers. Nicotine replacement therapy is
scribed medications are safe in pregnancy, even in associated with known adverse fetal effects and nic-
the first trimester, as they have not been shown to be otine is detected in breast milk. Possibly the best
teratogens. Only a few drugs, chemicals, infections, prevention of the adverse effect of smoking to preg-
or radiation are proven teratogens (Table 8) (45,46). nancy is achieved by avoidance of sales of tobacco to
These should be avoided, except in rare circum- young people, prohibition of smoking in public
stances (e.g., the woman with mechanical cardiac places, increase in tobacco taxation, workplace
valves who accepts the teratogenic risk of warfarin). smoking cessation programs, and banning of tobacco
This medication counseling is often a crucial part of sponsorship of sporting and cultural events.
Preconception Care Y CME Review Article 129

Numerous recreational drug exposures have ad- care, and its screening and interventions as routine as
verse pregnancy effects. This list is extensive and those for prenatal care.
includes but is not limited to common recreational We believe physicians of all specialties should be
drugs such as alcohol, cannabinoids, cocaine, heroin, aware of these evidence-based recommendations
and methamphetamines. Working to ensure that (Tables 1–8). Organizations representing family and
women with substance abuse issues engage in safe internal medicine, obstetrics and gynecology, nurse
sex practices and family planning is a constant chal- midwifery, nursing, public health, diabetes, neurol-
lenge, and these women are disproportionately over- ogy, cardiology, and many other associations have
represented among women with unplanned pregnancies. supported recommendations in preconception care.
Unfortunately, practitioners seldom implement them,
Current Evidence, Future Research, and Needs
(59) even if this is an opportunity to optimize the
for Preconception Care
health of the woman independently of whether she
Evidence supports specific preconception interven- becomes pregnant (5). Only 1 out of 6 ob-gyns or
tions in all women (Table 6), and in women with family physicians provide preconception care to the
specific risk factors (Table 7). There is less evidence majority of women for whom they provide prenatal
to support comprehensive preconception screening, care (60). Preconception care is based on the specific
counseling, and intervention, and more research is risks identified, and individualized care. No single
needed in this area. A standardized form improves pill ensures preconception health and a successful
the completeness of preconception screening, which pregnancy. Once a preconception plan is in place,
necessitates time and commitment (54). The form further preconception care may be necessary every
should be given (or mailed) and filled out by all time a new risk (disease, medication, etc.) arises.
women of reproductive age before any medical visit Preconception care is a process to care, not just a
(Table 1). This standardized preconception form single office visit. Pregnancy is a temporary condi-
must be integrated into the permanent record of all tion, not a disease. As there are 2 patients in one,
reproductive-age women. In a nonrandomized study, special precautions are necessary. Maternal physiol-
preconception care decreased the number of unin- ogy is different than nonpregnant adult physiology.
tended pregnancies (55). In a randomized trial, An entire field, maternal-fetal medicine, is dedicated
women assigned to be screened with a preconception to the care of pregnancies with maternal or fetal
risk survey were found to have an average of 9 risks problems, and these specialists are particularly adept at
factors, supporting the facts that even low risk directing best practices for preconception counseling.
women may benefit from preconception screening As the preconception woman can have numerous
(56). General-practitioner initiated preconception different medical problems affecting different spe-
counseling not only can decrease adverse pregnancy cialties, preconception care needs to be multidisci-
outcomes, but also reduces anxiety in reproductive plinary care, and occur in close collaborations
age women (57). between the different fields involved. Preconception
Despite its great effectiveness, not all health care care only occurs if all practitioners, including pri-
plans cover preconception care. One clear necessity mary and specialty care, either directly implement or
is a political will and need for funding and insurance appropriately refer for implementation of effective
coverage for preconception care. Further research is preconception screening and intervention. The worse
needed to determine the best content of preconcep- scenario is the belief that a positive pregnancy test is
tion care and the most effective ways to implement a good reason to stop “all medicines” and to stop
its use (56,58). treating diseases. Prevent panic: get women ready for
a healthy pregnancy before contraception is stopped.
Moreover, reproductive-age women should be
aware of these evidence-based recommendations
The time that people should start caring for a preg- (Tables 6, 7), through their doctors but also through
nancy is not after, but before it happens. Evidence- public awareness campaigns. Several on line re-
based medicine and science support preconception sources are available (61–64). Women and their part-
care as effective in improving maternal and infant ners should take more responsibility for their care and
health. A preconception visit (or often more than the future health of their offspring, and implement the
one) should be standard primary care, as stated by the health and lifestyle changes recommended. Preconcep-
Centers for Disease Control and Prevention in 2006 tion counseling offers the opportunity for improved
(2). It should be as routine, if not more so, as prenatal cooperation with women, increased planned pregnan-
130 Obstetrical and Gynecological Survey

cies, and decreased terminations of pregnancy. It also 7. Berghella V. Obstetric Evidence Based Guidelines. London,
United Kingdom: Informa Healthcare, 2007.
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for the mother, fewer anomalies for the fetus, etc. A don, United Kingdom: Informa Healthcare, 2007.
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