Obstetrics and Gynecology - 2009

Editor-in-Chief
Rogerio A. Lobo, M.D.
Professor of Obstetrics & Gynecology,
College of Physicians and Surgeons
of Columbia University, New York, NY
 Chapter 9:
Obstetric
Complications
Errol R. Norwitz, MD, PhD
Men-Jean Lee, MD

Contents

1. Cervical Insufficiency

2. Preterm Labor

3. Post-term Pregnancy

4. Hypertensive Disorders of Pregnancy

5. Intrauterine Fetal Demise

6. Intrauterine Growth Restriction

7. Multiple Pregnancy

8. Premature Rupture of Membranes

9. Antepartum Hemorrhage

10. References

11. Questions

CHAPTER 9: OBSTETRIC COMPLICATIONS 217

1. Cervical Insufficiency
Cervical insufficiency (also known as cervical incom-
petence) is defined as a functional weakness of the
cervix resulting in a failure to carry a pregnancy to
term.1, 2 It complicates 0.1%-2% of all pregnancies,
and is estimated to be responsible for 15% of deliver-
ies between 16 and 28 weeks of gestation.3-5 The clas-
sic presentation is that of painless cervical dilatation
and shortening without evidence of uterine
contractions.6
Etiology
Some risk factors for cervical insufficiency are
described (Table 1), but most patients have no risk
factors.1, 2
The exact etiology of cervical insufficiency has not
been elucidated.6
Diagnosis
Cervical insufficiency is a clinical diagnosis charac-
terized by acute, painless dilatation of the cervix, usu-
ally in the mid-trimester (generally between 16-24
weeks), culminating in fetal membrane prolapse
and/or premature rupture of the membranes (PROM)
with resultant preterm and often previable delivery.
Table 1
Risk Factors for Cervical Insufficiency
Congenital
Müllerian abnormalities
(congenital cervical hypoplasia or aplasia)
In utero diethylstilbestrol (DES) exposure
218 OBSTETRICS AND GYNECOLOGY—2009
Management
Cervical cerclage has become the mainstay for the
management of cervical insufficiency. If the prior
preterm delivery was the result of preterm labor (docu-
mented active contractions) and not cervical insuffi-
ciency, cerclage placement is not indicated.2
Types of Cerclage
Prophylactic (elective) cervical cerclage is indicated
in women with a history of prior pregnancy loss and/or
preterm delivery with a history consistent with cervical
insufficiency, because the probability of recurrence of
cervical insufficiency in a subsequent pregnancy is
15%-30%.1, 7, 8 Prophylactic cervical cerclage is placed
most commonly at 13-16 weeks of gestation, at which
time the complication rate is low (<1%).2 Prophylactic
cerclage for diethylstilbestrol (DES) exposure (when
the patient was exposed in utero to DES taken by her
mother) alone remains controversial. Most clinicians
believe that a history of in utero DES exposure per se
(without a history of prior pregnancy loss) is not an
indication for prophylactic cerclage placement. Simi-
larly, elective cerclage has not been shown to be benefi-
cial in women with multiple pregnancies without a
prior history of cervical insufficiency.9-12
The primary indication for emergent (salvage, res-
cue) cervical cerclage is premature effacement and/or
dilatation of the cervix in the absence of labor prior to
28 weeks gestation. It is associated with a less than
50% success rate. Poor prognostic features include cer-
vical dilatation >4 cm and prolapsed membranes. In
Acquired
Cervical trauma (prior surgical or
obstetric trauma)
Connective tissue abnormalities
(Ehlers-Danlos syndrome)
general, most practitioners do not place an emergent
cerclage after fetal viability is reached (after 24
weeks), due to the inherent high risk of causing an
iatrogenic rupture of fetal membranes and accelerat-
ing the preterm delivery. An alternative plan of man-
agement in these pregnancies is bed rest for the dura-
tion of the pregnancy without cerclage placement.8
The benefit of cervical cerclage for asymptomatic cer-
vical shortening diagnosed either by digital examina-
tion or transvaginal ultrasound in women without a
prior history suggestive of cervical insufficiency
remains controversial.8 Although earlier studies sug-
gested that cerclage placement in women with an inci-
dental finding of a shortened cervix on ultrasound
examination may improve perinatal outcome, subse-
quent studies were unable to confirm these observa-
tions. In a recent multicenter randomized clinical trial,
47,123 women with singleton pregnancies were
screened by transvaginal cervical length measure-
ments at 22-24 weeks gestation. Cervical length was
shortened (≤15 mm) in 470 women. Of these, 253
(54%) participated in the study: 127 were randomized
to Shirodkar cerclage and 126 to expectant manage-
ment. Although cervical shortening was associated
with a high risk for preterm birth prior to 33 weeks,
placement of a cerclage did not reduce the risk of
early preterm birth (22% [28/127] in cerclage group
vs. 26% [33/126] in control group; P=0.44).13

Table 2

Contraindications to Cervical Cerclage

Maternal Factors Uteroplacental Factors Fetal Factors

Absolute contraindications

Uterine contractions / labor Rupture of fetal membranes Intrauterine fetal demise

Life-threatening maternal Unexplained vaginal bleeding Major fetal anomaly not

conditions that preclude (abruption) compatible with life
anesthesia

Intrauterine infection Gestational age >28 weeks

Relative contraindications

A mucopurulent cervical Placental previa Intrauterine fetal growth

discharge with membrane restriction
opacification

Positive Gram stain or culture on After the limit of fetal

amniotic fluid (because of a failure viability has been reached
rate ≥90%) (≥24 weeks gestation)

Fetal membranes prolapsing

through the cervical os (because of
the high incidence of preterm PROM)

Vaginal infection

CHAPTER 9: OBSTETRIC COMPLICATIONS 219

Contraindications. Contraindications to cerclage are
listed in Table 2. Intra-amniotic infection is an abso-
lute contraindication to cerclage placement,14, 15 and
the presence of bacteria on Gram stain or a positive
culture from preoperative amniocentesis is associated
with a failure rate of >90%. Preoperative amniocente-
sis in asymptomatic patients with cervical insuffi-
ciency may be considered prior to emergent cerclage
placement. Although ACOG supports cervical cer-
clage placement up to 28 weeks gestation, many prac-
titioners would not recommend cerclage placement
beyond the limit of fetal viability (≥24 weeks),
because the risk of complications outweighs the
potential benefit.7, 16 Furthermore, placement of a cer-
clage in a patient that is in preterm labor (actively con-
tracting) is contraindicated due to the risks of cervical
trauma and/or uterine rupture caused by maternal con-
tractions against a surgically sutured cervix.
Technical considerations. Once the decision has been
made to proceed with cerclage placement, a preopera-
tive ultrasound examination should be performed to
confirm fetal viability and exclude major structural
anomalies. Regional anesthesia is preferred to general
endotracheal anesthesia because of the decreased
maternal morbidity. Prophylactic tocolysis may be
used to inhibit transient uterine contractions associ-
ated with emergent cerclage placement, but there is no
objective evidence that tocolysis improves outcome.
Prophylactic broad-spectrum antibiotics are recom-
mended for emergent cerclage placement. However,
there are insufficient data to recommend routine use
of prophylactic antibiotics for elective cerclage place-
ment. If the fetal membranes are found to be prolaps-
ing through the external os, the risk of iatrogenic rup-
ture of the fetal membranes may be as high as 50%.
Trendelenburg position,17 retrograde filling of the
bladder,18 placement of a 30 mL Foley catheter
trancervically past the internal os and filling the bal-
loon,19 placement of a moistened sponge forceps into
the cervical os,20 and/or therapeutic amniocentesis21-23
can be used to reduce the fetal membranes prior to cer-
clage placement. In addition, the edges of the cervix
can be grasped by sponge forceps to build length to
the cervix for cerclage placement.24
Transvaginal cervical cerclage has been the mainstay
for the management of cervical insufficiency. There
are 2 basic types of transvaginal cerclage placement
techniques: Shirodkar and McDonald.25 The choice of
220 OBSTETRICS AND GYNECOLOGY—2009
cervical cerclage is best left to the discretion of the
obstetric care provider, especially in the setting of a
prophylactic cerclage. The selection of the type of cer-
clage placement for emergent cases may be limited by
the thickness and length of cervical tissue available
for suture placement. The choice of suture material
has evolved over the decades from fascia lata or silk to
currently a wide selection of non-absorbable sutures,
including Mersilene® tape (Dacron® tape), Prolene®
(monofilament), and Ethibond® (braided, coated
polyester).26 The choice of suture is based on practi-
tioner preference and choice of technique. Shirodkar
cerclage is a single suture placed submucosally
around the cervix at the level of the internal os after
surgically reflecting the bladder anteriorly and the rec-
tum posteriorly.27 The suture can be secured anteriorly
or posteriorly, and the mucosal incisions closed.
McDonald cerclage is 1 or more purse-string sutures
around the cervix placed without dissection of the
bladder or rectum.20 These 2 types of cerclage are
likely equally efficacious, but have never been tested
“head-to-head” in a well-designed clinical trial.
Transabdominal cerclage has not been compared
directly with transvaginal cerclage, and is a far more
invasive procedure requiring a laparotomy and subse-
quent cesarean delivery. Transabdominal cerclage
should therefore be reserved for women in whom a
prophylactic cerclage is indicated but technically
impossible to place transvaginally or that have failed
previous prophylactic transvaginal cerclage
placement.28, 29
Once a cerclage is in place, weekly or biweekly fol-
low-up visits for cervical examinations are probably
sufficient in the absence of clinical symptoms. Cervi-
cal assessment may be by simple bimanual examina-
tion or by ultrasound to assess the length of cervix,
any loosening of the suture or prolapse of membranes
through the suture, tearing of the cervix, loss of the
surgical knot, or loss of the suture. Modified bed rest
and “pelvic rest” (no coitus, tampons, or douching)
are usually recommended until a favorable gestational
age is reached, but without proven benefit. The cer-
clage is usually removed electively at 37 weeks gesta-
tion, but earlier removal may be necessary in the event
of premature uterine contractions. In the setting of
preterm PROM, evidence of amnionitis should
prompt immediate removal of the cerclage. In preterm
PROM without evidence of infection, the risk of pre-
mature delivery with removal must be weighed

against the risk of ascending infection with a foreign
body in place.30, 31
Complications. Complications of cervical cerclage
increase with increasing gestational age and cervical
dilatation (Table 3). Cervical cerclage is also associ-
ated with increased obstetric interventions, including
higher rates of admission to hospital, administration
of tocolytics, induction of labor, and cesarean deliv-
ery.5 Puerperal infection occurs in approximately 6%
of patients with cerclage, which is twice as common
as the incidence in gestational age-matched controls
without cerclage.5, 32 There is no demonstrable associa-
tion between the presence of a cerclage and preterm
PROM remote from placement.
Table 3
Complications of Cervical Cerclage
≤48 hours)
Short-term (≤
Premature rupture of fetal membranes
Excessive blood loss (may require blood transfusion)
Pregnancy loss (abortion)
Complications from anesthesia
2. Preterm Labor
Preterm (premature) labor refers to labor occurring
prior to 37 completed weeks of gestation. This should
be differentiated from preterm contractions without
documentation of cervical change (effacement and
dilatation). Preterm birth occurs in 7%-12% of all
deliveries, but accounts for over 85% of all perinatal
morbidity and mortality.33, 34
Etiology
Preterm labor represents a syndrome rather than a
diagnosis since the etiologies are varied. Preterm labor
may reflect a breakdown in the normal mechanisms
responsible for maintaining uterine quiescence, or a
short-circuiting or overwhelming of the normal partu-
rition cascade.5, 35 Up to 30% of preterm labor is
thought to result from intra-amniotic infection, and is
likely mediated through the interaction of cytokines
and eicosanoids.36, 37 Definitive diagnosis requires a
positive amniotic fluid culture, but amniotic fluid
markers of infection (such as interleukin-6, glucose,
and white blood cell count) may suggest the diagnosis.
Recently, thrombin has been shown to be a powerful
uterotonic agent providing a mechanism for preterm
labor resulting from placental abruption.
Diagnosis
Preterm labor is a clinical diagnosis characterized by
increasing intensity and frequency of uterine contrac-
Long-term (>48 hours)
Cervical laceration (3%-4%)
Chorioamnionitis (4%)
Cervical stenosis (1%)
Other rare complications (including
fetal growth restriction, fetal demise,
thrombophlebitis, placental abruption,
bladder pain, migration of suture)
CHAPTER 9: OBSTETRIC COMPLICATIONS 221
tions leading to effacement and dilatation of the
cervix, and culminating in expulsion of the products
of conception prior to 37 weeks of gestation.
Management
Screening
Several risk factors for preterm labor have been
described (Table 4). However, risk factor screening
alone will fail to identify over 50% of pregnancies that
deliver preterm.38, 39 As such, a number of modalities
have been developed in an attempt to identify women
at high-risk of preterm birth (Table 5).40-50 Currently,
the most reliable screening tests include serial sono-
graphic measurement of cervical length42, 43 and/or
measurement of fetal fibronectin (fFN) in cervicov-
aginal secretions.46-48
Clinical Management
In the setting of preterm labor, bed rest and hydration
are commonly recommended but without proven effi-
cacy.51 Pharmacologic tocolytic therapy remains the
cornerstone of modern management. Although a
number of alternative agents are now available (Table
6), only ritodrine hydrochloride has received approval
from the Food and Drug Administration (FDA) of the
United States (FDA) for the treatment of preterm
labor. The risks and benefits of the individual drugs
have been reviewed in detail elsewhere.35, 52-54 All of
the recommended agents appear equally effective in
delaying delivery for 24-48 hours, thereby creating a
window of opportunity for antenatal corticosteroid
administration. There is no good clinical evidence that
any of these agents can prolong pregnancy beyond 48
hours and prevent preterm delivery.55 Since no single
agent has a clear therapeutic advantage, the side-effect
profile of each of the drugs will often determine which
to use in a given clinical setting.
Intravenous magnesium sulfate as a continuous infu-
sion has a wide margin of safety and has traditionally
been regarded as the first-line agent for use in preterm
labor in North America. More recently, however, this
agent has fallen out of favor because of its potential
risk of maternal cardiopulmonary failure from over-
dose or neonatal rickets and neurologic injury from
prolonged or excessive use.56, 57 Adrenergic agonists
are commonly used (eg, subcutaneous terbutaline in
an injection, continuous infusion or oral administra-
222 OBSTETRICS AND GYNECOLOGY—2009
tion), but have a higher incidence of adverse effects,
including maternal tachycardia, EKG changes, and
hyperglycemia.55, 58, 59 Indomethacin, although effec-
tive, may be associated with fetal complications such
as oligohydramnios and premature closure of the duc-
tus arteriosus, as well as serious neonatal complica-
tions, such as patent ductus arteriosus that is refrac-
tory to pharmacological therapy, especially if given
shortly prior to delivery.60-63 Calcium channel block-
ers (nifedipine and amlodipine) are becoming
increasing popular agents for tocolysis, since they can
be orally administered, but maternal hypotension and
cardiac arrhythmias are a concern.64, 65 Promising
newer agents include oxytocin receptor antagonists
(used commonly in Europe) and selective cyclooxy-
genase-2 inhibitors.66, 67
A single course of antenatal glucocorticoids
decreases the incidence of respiratory distress syn-
drome (RDS), intraventricular hemorrhage (IVH),
and necrotizing enterocolitis (NEC) by 50%, and is
recommended for all pregnancies at high risk of
delivering before 34 weeks gestation with intact
membranes and before 32 weeks gestation with
preterm PROM.68-70 Maximal benefit is achieved 24-
48 hours after the initial dose. This effect lasts for 7
days, but it is unclear what happens thereafter.
Repeated courses of steroids are not generally recom-
mended, although a single rescue dose (or rescue
course) may be appropriate if the initial course was
administered prior to 28-30 weeks gestation.71, 72
Tocolysis should be continued until preterm labor has
been effectively halted, or empirically until 48 hours
after the first dose of corticosteroid. Maintenance
tocolytic (including terbutaline pump or chronic oral
tocolysis) therapy has not been shown to confer any
therapeutic benefit73, 74 and poses a risk of adverse side
effects. Similarly, concurrent use of 2 or more
tocolytic agents has not consistently been shown to be
more effective than a single agent and exposes the
parturient to cumulative risk of side effects, including
pulmonary edema.75, 76 The use of sequential therapy,
however, may be beneficial if initial therapy is unsuc-
cessful.77 Although effective in the setting of preterm
PROM, there is no role for broad-spectrum antibiotic
therapy to prolong latency in preterm labor with intact
membranes.78
Table 4

Risk Factors for Preterm Birth

Nonmodifiable Possibly Modifiable

Prior preterm birth Cigarette smoking

African American Illicit substance use (cocaine)

Age <18 or >40 years Absent prenatal care

Low socioeconomic status Poor nutrition

Cervical injury or anomaly Anemia

Uterine anomaly or fibroids Low prepregnancy weight

Excessive uterine activity Bacteriuria / urinary tract infection

Premature cervical dilation (>2 cm) Genital infection and/or gingival infection
or effacement (>80%)

Overdistended uterus (twins, polyhydramnios) Strenuous work

Vaginal bleeding High personal stress

CHAPTER 9: OBSTETRIC COMPLICATIONS 223

Table 5

Screening for Preterm Birth

Screening Modality Comment

Home uterine activity Although an increase in uterine activity is a prerequisite for

monitoring (HUAM) preterm labor, HUAM of women at low risk and high risk has not
been shown to reduce the incidence of preterm delivery.

Cervical evaluation
Serial digital examination
Serial digital evaluation of the cervix has not been shown to be
useful in predicting preterm delivery. An abnormal cervical find-
ing (shortening and/or dilatation) is associated with preterm
delivery in only 4% of low-risk women and 12%-20% of high-risk
women.

Serial sonographic evaluation
Real-time sonographic evaluation of the cervix has demon-
strated an inverse correlation between cervical length and risk
of preterm delivery. If the cervical length is below the 10th per-
centile for gestational age, there is a 6-fold increased risk of
delivery prior to 35 weeks gestation.

Vaginal infection Vaginal infections (specifically bacterial vaginosis, Neisseria

gonorrhoea, Chlamydia trachomatis, Group B Streptococcus,
Ureaplasma urealyticum and Trichomonas vaginalis) have
been associated with preterm labor. However, screening and
treating for such organisms has not been demonstrated to
impact preterm birth.

Biochemical markers
Fetal fibronectin (fFN)
Elevated levels of fFN in cervicovaginal secretions are associ-
ated with premature delivery and may reflect separation of the
fetal membranes from the maternal decidua. The real value of
this test appears to lie in its negative predictive value (99% of
patients with a negative fFN test will not deliver within 7 days),
which may prevent unnecessary hospitalization. In a low-risk
population, the predictive value of a positive fFN test at 22-24
weeks gestation for spontaneous preterm delivery prior to 28
weeks and 37 weeks is only 13% and 36%, respectively.

Endocrine markers
Salivary estriol Progesterone withdrawal is not a prerequisite for labor in
the human and serum progesterone levels, andprogesterone/
17 ␤-estradiol ratios are not predictive of preterm labor. How-
ever, maternal salivary estriol can accurately identify activation
of the fetal hypothalamic-pituitary-adrenal axis that occurs prior
to the onset of labor, both at term and preterm. The detection of
elevated levels of estriol in maternal saliva (≥2.1 ng/mL) is pre-
dictive of delivery prior to 37 weeks gestation in a high-risk pop-
ulation with a sensitivity of 68%-87% and specificity of 77% (and
a false positive rate of 23%).

224 OBSTETRICS AND GYNECOLOGY—2009

 Table 6

Tocolytic Agents Commonly Used for the Management of Preterm Labor

Agent Administration Efficacy Major Maternal Major Fetal

(Dosage) Side Effects Side Effects

Magnesium sulfate IV (4-6 g bolus, then Effective Nausea, ileus, headache, weakness Decreased beat-to-beat variability
2-3 g/h infusion) Hypotension Neonatal drowsiness, hypotonia
Oral maintenance Not effective Pulmonary edema Ileus
(100-120 mcg Q4h) Cardiorespiratory arrest Congenital ricketic syndrome (with treatment >3 weeks)

␤-adrenergic agonists IV (2 mcg/min infusion, Effective Jitteriness, anxiety, restlessness, Fetal tachycardia
Terbutaline sulfate maximum 80 mcg/min) nausea, vomiting, rash Hypotension
SC (0.25 mcg Q20 min) Effective Cardiac dysrhythmias, myocardial Ileus
hypotension, tachycardia Hyperinsulinemia, hypoglycemia, hyperbilirubinemia
Oral maintenance (2.5-5 mcg Q4-6h) Effective Pulmonary edema Hypocalcemia
IV pump (0.05 mL/h) Not effective Paralytic ileus

Prostaglandin inhibitors
Indomethacin Oral (25-50 mcg Q4-6h) Effective Gastrointestinal effects (nausea, Transient oliguria, oligo-hydramnios
heartburn), headache, rash Premature closure of neonatal ductus
Rectal (100 mcg BID) Effective Interstitial nephritis arteriosus and persistent pulmonary hypertension
Increased bleeding time (most Necrotizing enterocolitis,
common with aspirin) intraventricular hemorrhage

Calcium channel blockers

Nifedipine Oral (20-30 mcg Q4-8h) Effective Hypotension, reflex tachycardia,
headache, nausea, flushing

Oxytocin antagonists
Atosiban IV (1 mM/min infusion) Effective Nausea, vomiting, headache, Inhibit lactation
chest pain, arthralgias

CHAPTER 9: OBSTETRIC COMPLICATIONS

The only tocolytic agent approved by the Food and Drug Administration of the U.S.
Efficacy is defined as proven benefit in delaying delivery by 24-48 hours as compared with placebo or standard control.

225
IM, intramuscular; IV, intravenous; SC, subcutaneous; TD, transdermal.
Modified from Norwitz ER, Robinson JN, Challis JRG. The control of labor. N Engl J Med. 1999;341:660-666.
3. Post-term Pregnancy
Post-term (prolonged) pregnancy refers to a preg-
nancy that has extended to or beyond a gestational age
of 42.0 weeks (294 days) from the first day of the last
menstrual period.79, 80 In the United States, around
10% of all singleton pregnancies continue beyond 42
weeks of gestation and 4% continue beyond 43
completed weeks in the absence of obstetric interven-
tion.79, 80 Post-term pregnancy should be differentiated
from a post-mature pregnancy, which is a distinct clin-
ical fetal syndrome consisting of a fetus that has wrin-
kled, peeling skin with a thin body, and meconium-
stained skin and nails that is diagnosed postnatally.81, 82
Etiology
Primiparity and prior post-term pregnancy are the
most common identifiable risk factors for a post-term
pregnancy. Rarely, post-term pregnancy may be asso-
ciated with placental sulfatase deficiency or fetal
anencephaly (in the absence of polyhydramnios).
Genetic predisposition may also play a role. However,
in the vast majority of cases, the cause of post-term
pregnancy is unknown.79
Diagnosis
Accurate pregnancy dating is critical to the diagnosis.
The incidence of post-term pregnancy depends upon
the patient population, including such factors as the
percentage of primigravid women, women with preg-
nancy complications, the prevalence of ultrasound
assessment of gestational age and the frequency of
spontaneous preterm birth. Local practice patterns,
such as the rates of scheduled cesarean delivery and
routine labor induction, will also affect the overall
incidence of post-term birth.
Complications
Post-term pregnancy is associated with both fetal
and maternal risks. Perinatal mortality (stillbirths
plus early neonatal deaths) at ≥42 weeks of gestation
is twice that at term (4-7 vs. 2-3 per 1000 deliveries)
and increases 4-fold at 43 weeks and 5- to 7-fold at
44 weeks.79, 80, 83 Chronic uteroplacental insuffi-
ciency, asphyxia and intrauterine infection all con-
tribute to the excess perinatal deaths. Post-term
infants are larger than term infants, with a higher
incidence of macrosomia (defined as an estimated
226 OBSTETRICS AND GYNECOLOGY—2009
fetal weight > 4500 g84 ) (2.5%-10% vs. 0.8%-
1%).85, 86 Complications associated with fetal macro-
somia include prolonged labor, cephalopelvic dis-
proportion and shoulder dystocia, with resultant
risks of orthopedic or neurologic injury.84 Post-term
pregnancies are also at increased risk of umbilical
cord compression from oligohydramnios, nonreas-
suring fetal antepartum or intrapartum assessment,
meconium aspiration, short-term neonatal complica-
tions (hypoglycemia, seizures) and long-term neuro-
logic sequelae.
Maternal risks of prolonged pregnancy include an
increase in labor dystocia (9%-12% vs. 2%-7% at
term), an increase in severe perineal injury (3.3% vs.
2.6% at term) and a doubling in the rate of cesarean
delivery.87-89 The latter is associated with higher risks
of complications such as endometritis, hemorrhage,
and thromboembolic disease.
Management
An accurately estimated date of delivery should be
calculated early in pregnancy. This may be based
upon a known last menstrual period in women with
regular, normal menstrual cycles and confirmatory
uterine sizing. Uncertainty in historical or physical
dating parameters should prompt ultrasound assess-
ment of gestational age.90
Post-term pregnancy is an accepted indication for
antenatal fetal monitoring. ACOG has recommended
that antepartum fetal surveillance be initiated after 42
weeks of gestation, without a specific recommenda-
tion regarding type of test or frequency.79, 80 Options for
evaluating fetal well-being include weekly or twice
weekly nonstress testing with amniotic fluid volume
assessment, the biophysical profile (BPP) or modified
BPP, the oxytocin challenge test or a combination of
these modalities; no single method has been shown to
be superior. Umbilical artery Doppler velocimetry
testing alone has not been shown to be beneficial in
monitoring the post-term fetus.79 It should be noted
that there is insufficient evidence to show that initiat-
ing antenatal surveillance between 40 and 42 weeks of
gestation improves pregnancy outcome or confers any
benefit to the fetus.79

Delivery is recommended when the risks to the fetus
by continuing the pregnancy are greater than those
faced by the neonate after birth. Both expectant man-
agement and labor induction are associated with low
complication rates in low-risk post-term gravida.91-93
Factors that need to be considered include gestational
age, results of antepartum fetal assessment, favorabil-
ity of the cervix, and maternal preference. Delivery
should be initiated immediately if there is evidence of
fetal compromise or oligohydramnios. There does
appear to be a small advantage to routine induction of
labor at 41 weeks gestation, regardless of parity or
method of induction.87, 88 In women with unfavorable
cervical exams, the routine use of preinduction cervi-
cal ripening has resulted in fewer failed and serial
inductions, lower fetal and maternal morbidity, a
shorter hospital stay, lower medical cost and possibly
a lower rate of cesarean delivery in the general obstet-
ric population. The post-term fetus is at increased risk
of intrapartum fetal heart rate abnormalities and pas-
sage of meconium. For this reason, continuous elec-
tronic fetal monitoring in labor is recommended for
such pregnancies.
4. Hypertensive Disorders
of Pregnancy
Hypertensive disorders of pregnancy are the second
most common cause of maternal death in the United
States (behind venous thromboembolic disease),
accounting for 15%-20% of all maternal deaths.94, 95
Hypertension is also associated with high perinatal
mortality and morbidity rates, primarily due to iatro-
genic prematurity.96 Hypertensive disorders of preg-
nancy can be classified into 4 categories:
1.) Chronic hypertension is defined as hypertension
prior to pregnancy and should also be considered in
parturients with a sustained BP ≥140/90 prior to 20
weeks gestation. Such pregnancies are at increased
risk of superimposed preeclampsia, uteroplacental
insufficiency and IUGR, placental abruption and still-
birth. Angiotensin converting enzyme (ACE)
inhibitors should be discontinued in pregnancy. These
drugs have not consistently been associated with an
increased risk of structural anomalies in the first
trimester over baseline, but exposure in the latter half
of pregnancy has been associated with progressive
and irreversible renal injury in the fetus, including
renal dysplasia and hypocalcified calvaria resulting
from the blockade of the conversion of angiotensin 1
to angiogensin 2 in the developing kidneys and low
fetal blood pressure on the fetal skull, respectively.97, 98
Because the perinatal mortality associated with mater-
nal chronic hypertension is increased above baseline
(6-25/1000 vs. 6.4/1000 in normotensive pregnan-
cies),99 antepartum fetal testing (weekly non-stress
tests, serial ultrasound examinations for fetal growth)
should be initiated after 32 weeks gestation. Delivery
should ideally be achieved by 40 weeks with a favor-
able cervix.
2.) Chronic hypertension with superimposed
preeclampsia is defined as pre-existing chronic hyper-
tension with worsening features during pregnancy,
and may be difficult to differentiate from preeclamp-
sia.
3.) Pregnancy-induced hypertension (PIH), also
known as transient hypertension or gestational non-
proteinuric hypertension, refers to persistent elevation
of BP ≥140/90 in the third trimester without evidence
of preeclampsia in a previously normotensive woman.
It is a diagnosis of exclusion. PIH likely represents an
exaggerated physiologic response of maternal cardio-
vascular system to pregnancy. It is rarely associated
with adverse maternal or fetal outcome, but may be
CHAPTER 9: OBSTETRIC COMPLICATIONS 227
difficult to distinguish from preeclampsia. PIH (but not
preeclampsia) is associated with an increased risk of
chronic hypertension in later life.
4.) Preeclampsia, also known as gestational protein-
uric hypertension, complicates 6%-8% of all pregnan-
cies.94, 100, 101 It is an idiopathic multisystem disorder
specific to human pregnancy and the puerperium.
More precisely, it is a disease of the placenta since it
occurs also in pregnancies where there is trophoblast
but no fetal tissue (complete molar pregnancies).
Preeclampsia is discussed in more detail below.
Etiology
The pathogenesis of preeclampsia remains poorly
understood. At present, 5 hypotheses are the subject of
intense investigation:100-103 (1.) genetic imprinting; (2.)
immune maladaption; (3.) placental ischemia; (4.)
generalized endothelial dysfunction; and (5.) defec-
tive-free fatty acid, lipoprotein and/or lipid peroxidase
metabolism. However, there is as yet no single unify-
ing theory that can account for all of the findings in
preeclampsia. Although the pathophysiology of
preeclampsia is not well understood, it is clear that the
blueprint for its development is laid down early in
pregnancy. It has been suggested that the pathologic
hallmark is a complete or partial failure of the second
wave of trophoblast invasion from 16-20 weeks of
gestation that, in normal pregnancies, causes destruc-
tion of the muscularis layer of the spiral arterioles.104-106
As pregnancy progresses, the metabolic demands of
the fetoplacental unit increase. Because of the abnor-
mally shallow invasion of the placenta in preeclampsia
and the lack of vascular remodeling, the spiral arteri-
oles are unable to dilate to accommodate the required
increase in blood flow, resulting in “placental dysfunc-
tion” that manifests clinically as preeclampsia. Recent
data suggest that excessive placental production of the
fms-like tyrosine kinase receptor (also known as solu-
ble Flt-1 [sFlt-1]), the soluble form of the vascular
endothelial growth factor (VEGF) receptor type I that
binds both circulating VEGF and placental growth fac-
tor, may be responsible for the widespread endothelial
injury that characterizes preeclampsia.107, 108 In this way,
sFlt-1 may be the elusive “toxemia factor” of
preeclampsia. Although attractive, this hypothesis
remains to be validated.
228 OBSTETRICS AND GYNECOLOGY—2009
Diagnosis
Preeclampsia is a clinical diagnosis encompassing 3
elements: (1.) new-onset hypertension (defined as a
sustained sitting BP ≥140/90 in a previously nor-
motensive woman); (2.) new-onset proteinuria (>300
mg/24 h or ≥1+ on a clean-catch urinalysis in the
absence of urinary infection); and (3.) nondependent
edema.100, 101 However, more recent consensus reports
have suggested eliminating edema as a criterion for
the diagnosis.109 A definitive diagnosis of preeclamp-
sia should only be made after 20 weeks gestation. Evi-
dence of gestational proteinuric hypertension prior to
20 weeks should raise the possibility of an underlying
molar pregnancy, collagen vascular disease, antiphos-
pholipid antibody syndrome, drug withdrawal, multi-
ple pregnancy, or chromosomal abnormality (trisomy)
in the fetus.
Preeclampsia is classified as either “mild” or “severe”
(there is no category of “moderate” preeclampsia). A
diagnosis of severe preeclampsia should be enter-
tained in women with new-onset proteinuric hyperten-
sion along with 1 or more of a series of complications
(Table 7). IUGR was excluded from the criteria in
2000 by the National High Blood Pressure in Preg-
nancy Working Group because of inconsistencies in
its definition, but was still included as a criterion for
the diagnosis of severe preeclampsia by ACOG in
2002.101 Mild preeclampsia includes all women with
preeclampsia, but without any features of severe dis-
ease.
Management
Timing of Delivery
Delivery is the only effective treatment for preeclamp-
sia. Delivery is recommended in women with mild
preeclampsia once a favorable gestational age has been
reached (>36-37 weeks) and in all women with severe
preeclampsia regardless of gestational age (with the
exception of severe preeclampsia due to proteinuria
alone or IUGR remote from term with good fetal test-
ing). There has also been a recent trend towards expec-
tant management of severe preeclampsia by BP criteria
alone <32 weeks gestation.110, 111 Every effort should be
made to delay delivery for 24-48 hours to administer
antenatal corticosteroids, if indicated.
Table 7

Diagnostic Features of Severe Preeclampsia

Symptoms

Symptoms of central nervous system dysfunction (blurred vision, scotomata, altered mental status, and/or
severe headache)

Symptoms of liver capsule distention or rupture (right upper quadrant and/or epigastric pain)

Signs

Severe elevations in BP (defined as BP ≥160/110 on 2 separate occasions at least 6 hours apart)

Pulmonary edema

Eclampsia (generalized seizures and/or unexplained coma in the setting of preeclampsia and in the absence of
other neurologic conditions)

Cerebrovascular accident

Cortical blindness

Fetal intrauterine growth restriction

Laboratory Findings

Proteinuria (>5 g/24 hours)

Renal failure or oliguria (<500 mL/24 hours)

Hepatocellular injury (serum transaminase levels ≥2 x normal)

Thrombocytopenia (<100,000 platelets/mm3)

Coagulopathy

HELLP (Hemolysis, elevated liver enzymes, low platelets) syndrome

Route of Delivery delivery, and fetal status and presentation. In general,

Severe preeclampsia does not mandate immediate
cesarean delivery. The decision of whether to proceed
with cesarean or induction of labor and attempted
vaginal delivery should be individualized based on
such factors as parity, gestational age, cervical exami-
nation (Bishop score), maternal desire for vaginal
less than one-quarter of women with severe
preeclampsia remote from term with an unfavorable
cervix will have a successful vaginal delivery.112, 113
Cervical ripening agents may be used if the cervix is
not favorable prior to induction, but prolonged induc-
tions should be avoided.

CHAPTER 9: OBSTETRIC COMPLICATIONS 229

Treatment of Hypertension
The use of antihypertensive agents to control mildly
elevated BP in the setting of preeclampsia has not
been shown to alter the course of the disease, nor to
diminish perinatal morbidity or mortality, and may
even reduce birth weight. However, antihypertensive
agents should be administered to prevent a maternal
cerebrovascular accident (stroke) with severe hyper-
tension while effecting delivery. Most clinicians
would recommend initiation of antihypertensive ther-
apy for a systolic BP ≥160 mm Hg and/or diastolic BP
≥110 mm Hg, although these cut-offs have not been
tested prospectively.114, 115 Treatment options are sum-
marized in Table 8. Sodium restriction and diuretics
have no role in therapy. Restricted physical activity
(bed rest) can lower BP, although its efficacy for
improving perinatal outcome has not been proven.
Intrapartum Anesthesia
Neuraxial techniques (epidural, spinal) can be safely
administered in the setting of preeclampsia (in the
absence of thrombocytopenia) with close attention to
volume expansion and anesthetic technique.
Hypotension is a major concern, because preeclamp-
sia causes total body fluid overload but depleted
intravascular volume. Airway edema and exacerba-
tion of hypertension with intubation can complicate
induction of general anesthesia.
Seizure Prophylaxis
Seizure prophylaxis is generally initiated during labor
or while administering corticosteroids or
prostaglandins prior to planned delivery and contin-
ued until 24-48 hours postpartum, when the risk of
seizures is decreased.116 Magnesium sulfate is the drug
of choice to prevent seizures (eclampsia) in the setting
of mild or severe preeclampsia (Table 9).117, 118 The
incidence of seizures is much lower in women with
nonproteinuric mild hypertension (0.1% as compared
with 1%-2% for severe preeclampsia119), and it is safe
to withhold seizure prophylaxis in this setting. Mag-
nesium sulfate must be given intravenously or by
intramuscular injection, as it is not absorbed orally.
Because magnesium is renally excreted, infusion rates
should be decreased for maternal serum creatinine
levels of 1.0 mg/dL or higher.120
Postpartum Care
Preeclampsia and its complications resolve following
delivery, often within a few days. Permanent neuro-
230 OBSTETRICS AND GYNECOLOGY—2009
logic sequelae or renal failure are rare. Diuresis (>4
liters/day) often heralds clinical resolution. BP that
remains elevated more than 12 weeks postpartum are
unlikely to be related to preeclampsia. Patients with
severe hypertension (160/100 mmHg) can be treated
with oral antihypertensive medications until their 6-
week postpartum check, and then weaned off. If they
continue to require antihypertensive medication, they
should be referred to an internist for further
investigation.121, 122
Recurrence Risk and Prevention
The risk of recurrence of preeclampsia in a subse-
quent pregnancy is related to the severity and nature
of the presentation and to the gestational age at pre-
sentation.123 Preeclampsia is a disorder of placental
implantation and therefore not entirely preventable.
Despite promising early studies, low-dose aspirin
(acetylsalicylic acid [ASA]) and/or supplemental cal-
cium does not appear to prevent preeclampsia recur-
rence in either high- or low-risk parturients.124, 125 A
recent meta-analysis suggests that low-dose aspirin
(80 mg per day) may be useful in preventing
preeclampsia, but only in women with prior early,
severe preeclampsia.126 Moreover, low-dose aspirin in
low-risk women may increase their risk of placental
abruption. Women at high-risk for preeclampsia
should be seen early in pregnancy to establish accu-
rate pregnancy dating, and to perform baseline BP and
laboratory tests. Measurement of BP and urine protein
at regular intervals in the late second and third
trimesters is critical for timely diagnosis of
preeclampsia.
Table 8

Pharmacologic Management of Acute Hypertensive Crisisa

Drug Dosing Comment

Recommended first-line therapy

Hydralazine 5 mg IV push Q 10 min x 2 doses; then 10 mg Be aware of hypotension and

IV push Q 20 min as needed until blood potential to adversely affect
pressure has stabilized at 140-150/90-100 uteroplacental perfusion

Labetalol 10-20 mg IV push; repeat Q 10-20 min with Be aware of hypotension and poten-
doubling doses (not to exceed 80 mg in any tial to adversely affect uteroplacental
single dose) to a maximum of 300 mg total perfusion

Nifedipine 10 mg orally Q 30 min x 2 doses; then Sublingual nifedipine is best

10-20 mg orally Q 4-6 hourly avoidedb

Recommended therapy in women refractory to first-line agents

Sodium nitroprusside 0.5–3.0 mcg/kg/min IV infusion (not to Should be used only by someone
exceed 800 mcg/min) with critical care experience

Nitroglycerin 5 mg/min IV infusion, increase as required Relatively contraindicated in the

every 5 min to maximum dose of 100 mg/min setting of hypertensive encephalopathy
as it may increase cerebral blood flow
and intracranial pressure

a Adapted from Repke JT. Preeclampsia and hypertension. In: Repke JT, ed. Intrapartum Obstetrics. New York, NY: Churchill
Livingstone; 1996:271.
b Grossman E, Messerli FH, Grodzicki T, Kowey P. Should a moratorium be placed on sublingual nifedipine capsules
given for hypertensive emergencies and pseudoemergencies? JAMA. 1996;276:1328-1331.

Table 9

Prevention of Seizures in Parturients with Preeclampsia

Drug Loading Dose Maintenance Dose Therapeutic Level

Recommended first-line therapy

Magnesium sulfate 4-6 g IV over 10-20 min 2-3 g/h IV infusionb 4-8 mEq/La
10 g IM (5 g IM into each buttock) 5 g IM every 4 h as above

Recommended therapy in women refractory to magnesium sulfate

Phenytoin 1-1.5 g over 1 h (depending 250-500 mg Q 10-12 h 10-20 mcg/mL

on body weight) orally or IV

a Adapted from Repke JT. Preeclampsia and hypertension. In: Repke JT, ed. Intrapartum Obstetrics. New York, NY:
Churchill Livingstone;1996: 271.
b Grossman E, Messerli FH, Grodzicki T, Kowey P. Should a moratorium be placed on sublingual nifedipine capsules
given for hypertensive emergencies and pseudoemergencies? JAMA. 1996;276:1328-1331.

CHAPTER 9: OBSTETRIC COMPLICATIONS 231

5. Intrauterine Fetal Demise
Intrauterine fetal demise (IUFD)—also known as
stillbirth—is defined in the United States as fetal
demise after 20 weeks gestation and prior to deliv-
ery.127 In the United States, the stillbirth rate decreased
from 15.8 per 1000 total births in 1960 to 7.5 per 1000
births in 1990.99, 128 Risk factors for IUFD include
extremes of maternal age, multiple pregnancy, post-
term pregnancy, male fetus, fetal macrosomia and
maternal disease, such as pregestational diabetes, sys-
temic lupus erythematosus (SLE) and preeclamp-
sia.129, 130
Etiology
Causes of IUFD can be identified in only around 50%
of cases (Table 10). Pathologic examination of the
fetus and placenta/fetal membranes is the single most
useful test to identify a cause for the IUFD. Early
detection and appropriate management of underlying
maternal disorders (diabetes, preeclampsia) may
reduce the risk of IUFD.131, 132 Fetal karyotyping should
be considered in all cases of fetal death to identify
chromosomal abnormalities, particularly in cases with
documented fetal structural abnormalities. Approxi-
mately 6%-10% of stillborn fetuses have abnormal
karyotypes.133 Amniocentesis may be recommended
to salvage viable amniocytes for cytogenetic analysis
prior to delivery. Fetal-maternal hemorrhage (fetal
cells spilling into maternal circulation) occurs in all
pregnancies, but is usually minimal (<0.1 mL total
volume). In rare instances, fetal-maternal hemorrhage
may be massive, leading to fetal demise. The Klei-
hauer-Betke (acid elution) test allows an estimate of
the volume of fetal blood in the maternal circulation,
and should be drawn within 6 - 8 hours of the pur-
ported time of bleeding episode due to rapid clearance
of fetal cells from maternal circulation.134 Intra-amni-
otic infection resulting in fetal death is usually evident
on clinical exam. Placental membrane culture and
autopsy examination of the fetus, placenta/fetal mem-
branes and umbilical cord may be useful. Fetal x-rays
or MRI may sometimes be valuable if autopsy is
declined.135, 136
Diagnosis
The inability to identify fetal heart tones or the
absence of uterine growth may suggest the diagno-
sis. Ultrasound is the gold standard to confirm an
232 OBSTETRICS AND GYNECOLOGY—2009
IUFD by documenting the absence of fetal cardiac
activity. Other sonographic findings in later preg-
nancy may include scalp edema, overlapping
sutures and fetal maceration.
Management
Every effort should be made to avoid cesarean deliv-
ery in the setting of IUFD. As such, expectant man-
agement is often recommended. Latency (the period
from fetal demise to delivery) varies depending on the
underlying cause and gestational age. In general, the
earlier the gestational age, the longer the latency
period. Overall, >90% of women will go into sponta-
neous labor within 2 weeks of fetal death. However,
many women find the prospect of carrying a dead
fetus distressing and want the pregnancy terminated as
soon as possible. Management options include surgi-
cal dilatation and evacuation or induction of labor
with cervical ripening, if indicated. Around 20%-25%
of women who retain a dead singleton fetus for longer
than 3 weeks will develop disseminated intravascular
coagulopathy (DIC) due to excessive consumption of
clotting factors.137, 138 Therefore, delivery should be
effected within this time period.
Death of a Co-twin
The death of 1 twin confers an increased risk of major
morbidity to the surviving twin, including IUFD, neu-
rologic injury, multiorgan system failure, thrombosis,
distal limb necrosis, placental abruption and prema-
ture labor.99-101 The prognosis for the surviving twin is
dependent on the cause of death, gestational age,
chorionicity and time interval between death of the
first twin and delivery of the second. Dizygous twin
pregnancies do not share circulation, and the death of
1 twin may have little impact on the surviving twin.
The dead twin may be resorbed completely or become
compressed and incorporated into the membranes
(fetus papyraceus). DIC in the surviving fetus and/or
mother is rare.102 On the other hand, some degree of
shared circulation can be demonstrated in almost all
monozygous twin pregnancies, and death of 1 fetus in
this setting carries an increased risk of death of its co-
twin due to profound hypotension and/or purported
transfer of thromboplastic proteins from the dead fetus
to the live fetus.143 If it survives, the co-twin, has a 40%
risk of developing neurologic injury (multicystic

encephalomalacia), which may not be prevented by
immediate delivery.144, 145 Therefore, management of a
surviving co-twin depends on chorionicity and gesta-
tional age. Fetal surveillance (kickcharts, nonstress
testing, biophysical profile) should be instituted on a
regular basis, and delivery considered in the setting of
nonreassuring fetal testing or at a favorable gesta-
tional age.
Table 10
Causes of Intrauterine Fetal Demise (IUFD)
Maternal causes Uteroplacental causes
Underlying medical conditions Placental abruption
(diabetes mellitus, thyroid disease,
antiphospholipid antibody syndrome)
Preeclampsia Placenta previa
Isoimmunization Vasa previa
Illicit drug use (cocaine) Fetal-maternal hemorrhage
Antepartum drug / toxin exposure Cord accident
6. Intrauterine Growth Restriction
Birth weight is a function of both gestational age and
rate of fetal growth. Intrauterine growth restriction
(IUGR) refers to any fetus that fails to reach its full
growth potential. In the United States, 4%-8% of
fetuses are diagnosed with IUGR.146, 147 IUGR should
be differentiated from the term SGA (small for gesta-
tional age), a term commonly used by the pediatri-
cians to represent both constitutionally small
neonates that are healthy and the growth restricted
fetus that is at risk for poor perinatal outcomes.148
Etiology
IUGR likely represents the clinical end-point of many
different fetal, uteroplacental, and maternal condi-
tions (Table 11). Every attempt should be made to
determine the cause prior to delivery.
Diagnosis
The clinical diagnosis of IUGR is difficult, and physi-
cal examination alone will fail to identify over 50% of
IUGR fetuses. If the fundal height measurement is
significantly less than expected (<3-4 cm for gesta-
tional age), an ultrasound examination should be per-
formed. IUGR is a radiologic diagnosis that requires
either: (1.) an estimated fetal weight (EFW) <3rd per-
Fetal causes
Fetal chromosomal /
genetic anomalies
Fetal structural abnormalities
Intra-amniotic infection
Complications of multiple
pregnancies (including twin-to-twin
transfusion syndrome)
CHAPTER 9: OBSTETRIC COMPLICATIONS 233
centile (2 standard deviations from the mean) for ges-
tational age, or (2.) an EFW <10th percentile for gesta-
tional age along with evidence of fetal compromise
(usually oligohydramnios or abnormal umbilical
artery Doppler velocimetry).146,147,149 Fetuses who are
<10th percentile without evidence of compromise
should be referred to as SGA and not IUGR. Accurate
gestational age dating is clearly a prerequisite for the
diagnosis. A small calcified (Grade 3) placenta
detected on ultrasound examination in association
with a small biparietal circumference may also be sug-
gestive of an IUGR pregnancy.150
Complications
pregnancies should be followed on a regular basis to
exclude this complication.
IUGR fetuses can undergo vaginal delivery and
cesarean delivery should be reserved for the usual
obstetric indications. However, up to 50%-80% of
IUGR fetuses will show evidence of nonreassuring
fetal testing in labor requiring cesarean delivery.146
Timing of delivery also depends on the precise gesta-
tional age, any superimposed maternal conditions (eg,
severe preeclampsia), the presence or absence of
abnormal umbilical cord Dopplers (reversed end-
diastolic flow), whether or not there has been any
interval fetal growth over a 2- to 3-week period, and
whether or not the IUGR fetus is a singleton vs. a mul-

IUGR infants have higher rates of perinatal morbidity tiple gestation in which the other fetus(es) are growing
and mortality as compared with appropriate for gesta- appropriately.154 If a premature delivery <34 weeks is
tional age (AGA) fetuses for any given gestational anticipated, a course of antenatal corticosteroids may
age. Neonatal morbidity (meconium aspiration syn- be warranted. Note that antepartum fetal testing
drome, hypoglycemia, polycythemia, pulmonary (including the BPP and umbilical artery Doppler
hemorrhage) may be present in up to 50% of IUGR velocimetry) may temporarily worsen in the 24-48
neonates.146,147,149,151 Premature IUGR infants also have hours following steroid administration in some
difficulty with nutritional support, and many develop fetuses.155
feeding intolerance and failure to thrive in the
NICU.152 Long-term studies show a 2-fold increased
incidence of cerebral dysfunction (ranging from
minor learning disability to cerebral palsy) in IUGR
infants delivered at term, and an even higher incidence
if the infant was born preterm. Epidemiological stud-
ies also suggest that these infants may also be at higher
risk for developing chronic disease in adulthood such
as diabetes, hypertension, stroke and coronary heart
disease (the Barker Hypothesis).153

Management

Bed rest and low-dose aspirin have not been shown to

prevent IUGR in women at high risk; however, a
recent meta-analysis suggests that women with prior
history of an IUGR pregnancy with early severe
preeclampsia may benefit from empiric low-dose
aspirin therapy during subsequent pregnancies.126
Principles of management of IUGR pregnancies
include identification of women at high risk, early
antepartum diagnosis, attempts to identify etiology
(karyotype, infection, antiphospholipid antibody syn-
drome), regular (usually twice-weekly) fetal surveil-
lance and appropriate timing of delivery. IUGR may
be the first manifestation of preeclampsia, and such

234 OBSTETRICS AND GYNECOLOGY—2009

Table 11

Risk Factors for Intrauterine Growth Restriction (IUGR)

Maternal Causes

Demographic Drug / toxin Underlying medical

factors exposure conditions Infections

Prior IUGR infant Illicit drugs (cocaine) Hyperthyroidism Malaria

African American Cigarette smoking Hemoglobinopathies Rubella
Chemotherapy Chronic pulmonary disease Cytomegalovirus
Cyanotic heart disease HIV
Diabetes mellitus with Varicella
vascular disease
Anemia
Malnutrition

Uteroplacental Causes

Uteroplacental insufficiency Velamentous cord insertion

Chronic hypertension

Preeclampsia

Antiphospholipid antibody syndrome

Unexplained chronic proteinuria

Chronic placental abruption

Fetal Causes

Genetic factors Fetal structural anomalies Multiple pregnancy

Fetal chromosomal anomalies Cardiovascular anomalies Polyhydramnios /

(including trisomy 18>13>21 and
sex chomosome abnormalities)
Single gene defects (such as
phenylketonuria and dwarfism)
Bilateral renal agenesis oligohydramnios
Single umbilical artery sequence (including
twin-to-twin transfusion
syndrome)

Confined placental mosaicism

CHAPTER 9: OBSTETRIC COMPLICATIONS 235

7. Multiple Pregnancy
Multiple pregnancies complicate 1%-2% of all deliv-
eries and are becoming increasingly common, primar-
ily as a result of assisted reproductive technology
(ART). This is especially true of higher-order multiple
pregnancies (triplets and up) which now constitute
0.103% of all births.156 The vast majority (97%-98%)
of multiple gestations are twin pregnancies.
Diagnosis
Multiple pregnancy should be suspected in women at
high risk, women with excessive symptoms of preg-
nancy (such as nausea and vomiting), or uterine size
larger than expected. The overall incidence of dizy-
gous twinning in the U.S. is around 1 in 89 pregnan-
cies, and is influenced by a number of epidemiologic
factors, including a family or personal history of mul-
tiple pregnancy, advanced maternal age, multiparity,
African American, and ART.157 Monozygous twin-
ning, on the other hand, is a random event that occurs
in around 1 in 300 pregnancies (although the risk may
be increased 2- to 3-fold with in vitro fertilization).158
Ultrasound will confirm the diagnosis.
Zygosity and Chorionicity
80% of twin pregnancies are dizygous (derived from 2
separate embryos). Perinatal mortality is higher with
monozygous (30%-50%) than with dizygous twins
(10%-20%). Chorionicity refers to the arrangement of
membranes in multiple pregnancies. In monozygous
twinning, the timing of the cell division determines
the chorionicity. If the zygote divides within 3 days of
fertilization, the result is dichorionic/diamniotic pla-
centation (30% of all monozygous pregnancies); if the
division occurs between day 3 and day 8, the result is a
monochorionic/diamniotic pregnancy (65%);
between day 8 and day 13, a monochori-
onic/monoamniotic pregnancy ensues (<5%); and if
the division occurs on or after day 13, incomplete sep-
aration (conjoined twins) is the rule (<0.5%). Chori-
onicity correlates directly with perinatal mortality,
which is especially high with monochori-
onic/monoamniotic twins (65%-70%). Chorionicity
is determined most accurately by examination of the
membranes after delivery. Antenatal diagnosis is
more difficult.159-161 Typically, ultrasound examination
in the first half of the pregnancy can be performed to
evaluate the point at which the amniotic/chorionic
membranes arise from the placenta to determine if the
fetuses are dichorionic (twin peak or lamda sign) or
236 OBSTETRICS AND GYNECOLOGY—2009
monochorionic (no peak, but a thin filmy mem-
brane).162 Identification of separate sex fetuses or 2
separate placentae confirms dichorionic/diamniotic
placentation.
Complications
Overall, antepartum complications develop in 80% of
multiple pregnancies, compared with around 30% of
singleton gestations (Table 12).163 Preterm delivery is
the most common complication, and the risk of
preterm delivery increases as fetal number increases:
the average length of gestation is 40 weeks in single-
tons, 37 weeks in twins, 33 weeks in triplets, and 29
weeks in quadruplets.164 Fetal growth discordance
(defined as a ≥25% difference in EFW between
fetuses of the same pregnancy) occurs in 5%-15% of
twins and 30% of triplets, and is associated with a 6-
fold increase in perinatal mortality.165,166 Cord entan-
glement is rare (1 in 25,000 births), but may occur in
up to 70% of monochorionic/monoamniotic pregnan-
cies, and accounts for >50% of perinatal mortality in
this subgroup.163,167,168 Maternal complications include
an increased risk of gestational diabetes, preeclamp-
sia, anemia, cholestasis of pregnancy,169 cesarean
delivery (due primarily to malpresentation), and post-
partum hemorrhage.
Twin polyhydramnios/oligohydramnios
(“poly/oligo”) sequence results from an imbalance in
blood flow from the “donor” twin to the “recipient.”
Both twins are at risk for adverse events. Twin-to-twin
transfusion syndrome is a subset of polyhydram-
nios/oligohydramnios sequence seen in 15% of
monochorionic pregnancies,170, 171 and is due to unbal-
anced vascular communications between the fetal cir-
culations. One twin is usually appropriate for gesta-
tional age (AGA) while the other twin is usually
IUGR. The IUGR twin is typically in the oligohy-
dramniotic sac and is compressed against one edge of
the uterus, also known as the “stuck twin” syn-
drome.172 Following delivery, a difference in birth
weight of ≥20% or a difference in hematocrit of ≥5
g/dL confirms the diagnosis. The larger twin is often
polycythemic while the IUGR twin is anemic. Prog-
nosis depends on gestational age, severity, and under-
lying etiology. Overall perinatal mortality is 40%-
80%.173, 174 Treatment options include expectant man-
agement, serial amniocentesis of the polyhydramni-
otic sac, indomethacin (to decrease fetal urine output),
laser obliteration of the placental vascular communi-
cations or selective fetal reduction.175-178
Management
Gravidas with multiple gestations should be coun-
seled about the increased risk of preeclampsia,
preterm labor, postpartum hemorrhage, anemia, fetal
loss, fetal anomalies, IUGR, and cesarean delivery.
Principles of management include early diagnosis,
screening for fetal anomalies, determination of chori-
onicity, and regular antepartum follow-up (serial
ultrasound for growth at least every 3-4 weeks to
screen for discordant growth).179 Maternal serum
alpha-fetoprotein (MS-AFP) screening for multiple
gestation is a reliable screen for neural tube defects;
however, serum biochemical marker screening for
aneuploidy in the presence of more than one fetus is
not particularly reliable, due to the inherent structure
of the test parameters.180 Maternal plasma volume is
increased by 100%-200% with multiple gestation,
placing the gravida at higher risk for anemia. Addi-
tional folate and iron supplementation should be con-
sidered in multiple gestation. Multifetal pregnancies
are at higher risk for cesarean delivery. Patients should
be counseled about labor analgesia and anesthesia, the
possible need for emergent delivery, and the need for
multiple pediatric teams in the delivery room. There
Table 12
Complications of Multiple Pregnancy
Maternal complications Uteroplacental complications
Anemia Placenta previa
Hyperemesis gravidarum Preterm PROM
Gestational diabetes Cord entanglement
Preterm labor Postpartum hemorrhage
Cesarean delivery
are several management considerations specific to
multiple gestation, outlined below.
Multifetal Pregnancy Reduction
Overall, 10%-15% of higher-order multiple pregnan-
cies (triplets and up) will reduce spontaneously dur-
ing the first trimester.164 If not, the option of multifetal
pregnancy reduction to twins at 13-15 weeks should
be discussed. The benefits of reduction include
increased length of gestation, increased birth weight,
and reduced prematurity and perinatal mortality and
mortality.164, 181-183 The procedure-related loss rate prior
to 20 weeks may be as high as 15% (range: 5%-35%),
which is comparable to the background risk for
higher-order multiple pregnancies.164, 182-185 However,
the fetal loss rate increases with advancing gestation
at the time of the reduction. Multifetal pregnancy
reduction should be distinguished from selective fetal
reduction, in which one fetus is selectively terminated
because of a known structural or chromosomal
abnormality.186, 187
Screening for Congenital Anomalies
Using twin populations, maternal serum alpha-feto
protein (MS-AFP) and “quadruple panel” screening
(MS-AFP, estriol, hCG and activin A) has been stan-
Fetal complications
Fetal growth discordance
IUGR
IUFD of one or both twins
Congenital anomalies
Twin-to-twin transfusion syndrome
CHAPTER 9: OBSTETRIC COMPLICATIONS 237

dardized for twins as it is for singletons at 15-20
weeks.188, 189 In dizygous pregnancies, the risk of aneu-
ploidy (genetic abnormality) is independent for each
fetus. As such, the chance that 1 or both fetuses have a
karyotypic abnormality is greater than for a singleton.
Amniocentesis is recommended when the probability
of aneuploidy is equal to or greater than the proce-
dure-related pregnancy loss rate (estimated at 1 in
270).190, 191 In singleton pregnancies, this balance is
reached at a maternal age at delivery of 35 years. In
twin pregnancies, amniocentesis should be offered to
women at approximately 32 years of age.192, 193
Route of Delivery
The recommended route of delivery of twins depends
on presentation, gestational age (or EFW), concor-
dance, and maternal and fetal well-being. Prior
cesarean is not an absolute contraindication to vaginal
delivery of twins.194 Breech extraction of a nonvertex,
concordant second twin is a safe procedure,195, 196 but
should only be performed by an experienced obstetric
care provider. Preparation for a possible breech
extraction should include an ultrasound machine to
assist in evaluation of fetal heart rate and presentation,
specialized forceps to assist in delivery of the after-
coming head (Piper forceps), an experienced anesthe-
siologist and a uterine relaxant, such as intravenous
nitroglycerin or halothane by mask. Cesarean delivery
has traditionally been recommended for multiple
pregnancies in which the presenting fetus is not vertex
and for all higher-order multiple pregnancies,
although vaginal delivery may be appropriate in
selected patients.197
238 OBSTETRICS AND GYNECOLOGY—2009
8. Premature Rupture
of Membranes
PROM refers to rupture of the fetal membranes prior
to the onset of uterine contractions.198 It can be clas-
sified as term PROM (≥37 weeks) or preterm PROM
(<37 weeks). Latency (the time interval between
PROM and delivery) is dependent on several factors:
(1.) gestational age (at term, 50% of women with
PROM will go into spontaneous labor within 12 hours
and 95% within 72 hours; latency is generally longer
if PROM occurs preterm with 50% of women going
into labor within 24-48 hours and 70%-90% within 7
days)199; (2.) severity of oligohydramnios (severe
oligohydramnios is associated with shortened latency
period );200 and (3.) number of fetuses (twins have a
shorter latency period than singletons).201
Diagnosis
PROM is a clinical diagnosis with evidence of vaginal
pooling of amniotic fluid on sterile speculum exami-
nation, which is alkaline (vaginal fluid turns yellow
nitrazine paper blue) and demonstrates “ferning”
(microscopic crystallization) on drying. Evidence of
diminished amniotic fluid volume on ultrasound may
help to confirm the diagnosis, but is not a prerequisite
for the diagnosis. Sometimes a gush of fluid can be
observed to emanate from the cervix when a patient
coughs during a speculum exam. The fluid should also
be categorized as clear, blood-tinged, or meconium-
stained. Differential diagnosis includes leakage of
urine and vaginal discharge. If equivocal, an amnio-
centesis can be performed with instillation of indigo
carmine dye into the amniotic cavity (“amnio-dye
test”). Leakage of the dye into the vagina as evidenced
by staining of a tampon within 15-20 minutes will
confirm the diagnosis. The patient should be advised
that, after an hour or so, her urine may also stain blue.
Term PROM
Rupture of the membranes is a normal physiologic
event at term. Rupture of membranes at term prior to
the onset of uterine contractions (term PROM) occurs
in 8%-10% of term pregnancies.202 Contraindications
to expectant management in the setting of term
PROM include intra-amniotic infection, non-reassur-
ing fetal testing, vaginal bleeding and active labor. In
the absence of such contraindications, both expectant
management and immediate augmentation of labor
are acceptable options.203 Severe oligohydramnios
may be associated with umbilical cord compression in
labor leading to non-reassuring fetal testing and
cesarean delivery. In this setting, amnioinfusion with
saline has been shown to decrease the risk of cesarean
for non-reassuring fetal testing (but has not necessar-
ily been shown to improve perinatal outcome).
Preterm PROM
Preterm PROM complicates 2%-4% of singleton and
7%-10% of twin pregnancies. It is associated with
30%-40% of preterm births and 10% of all perinatal
mortality.204 Risk factors include prior preterm PROM,
unexplained vaginal bleeding, placental abruption
(seen in 10%-15% of women with preterm PROM,
but may be a result rather than a cause),205 cervical
insufficiency, vaginal or intra-amniotic infection,
amniocentesis, smoking, multiple pregnancy, polyhy-
dramnios, chronic steroid treatment, connective tissue
diseases (systemic lupus erythematosus, Ehlers-Dan-
los syndrome), anemia, low socioeconomic status and
unmarried marital status. Factors which are not associ-
ated with preterm PROM include coitus, cervical
examinations, maternal exercise and parity. The recur-
rence risk is 20%-30%.204
Complications
Neonatal complications are related primarily to pre-
maturity, including RDS, IVH, sepsis, pulmonary
hypoplasia (especially with preterm PROM <22
weeks) and skeletal deformities/limb strictures
(related to severity and duration of preterm PROM).
Overall, preterm PROM is associated with a 4-fold
increase in perinatal mortality and a 3-fold increase in
neonatal morbidity.204, 206 The fetus is at risk for devel-
oping chorioamnionitis, stillbirth from cord accident
or placental abruption, non-reassuring fetal heart rate
tracings or precipitous delivery. Maternal complica-
tions include increased rates of cesarean delivery,
intra-amniotic infection and postpartum endometritis.
Management
Management of preterm PROM should be individual-
ized. The risk of prematurity should be weighed
against the risk of expectant management, primarily
intra-amniotic infection.204, 206 Amniotic fluid can be
used to assess fetal lung maturity by testing for the
lethicin/sphingomyelin (L/S) ratio and presence of
phosphatidyl glycerol (PG). In the setting of expectant
management for preterm PROM, new onset uterine
contractions may portend the development of intra-
amniotic infection. Patients should be placed on
pelvic rest (no tampons, no douching, no sexual inter-
course). A screening sonogram should be performed
to determine fetal presentation as non-vertex presen-
tation places the fetus at risk for umbilical cord pro-
lapse. Hospitalization, bed rest and fetal surveillance
have been the mainstay of management of preterm
PROM.204 Areas of controversy in the management of
preterm PROM include:
1.) Tocolysis. Preterm PROM is a relative contraindi-
cation to tocolysis to prevent undue exposure of
fetuses to infected in utero environment, with subse-
quent postnatal risk of neurologic injury and cerebral
palsy.207 Tocolytic agents may delay delivery by 24-48
hours in the setting of intact membranes, but do not
appear to delay delivery or improve perinatal out-
come in pregnancies complicated by preterm
PROM.204
2.) Antibiotics. Prophylactic broad-spectrum antibi-
otic therapy has consistently been shown to prolong
latency in the setting of preterm PROM,208, 209 and this
appears to translate into an improvement in perinatal
outcome. There is currently no evidence to recom-
mend 1 antibiotic regimen over another. The most
commonly used antibiotic regimen is ampicillin and
erythromycin for 7 days.
3.) Antenatal corticosteroids. A single course of
antenatal glucocorticoids is recommended for all
pregnancies at high risk of delivering before 34 weeks
gestation with intact membranes and before 32 weeks
with preterm PROM with a view to decreasing the
incidence of RDS, IVH and NEC.68-70 The benefit of
antenatal corticosteroids in pregnancies complicated
by preterm PROM at 32-34 weeks gestation is not
clear.70
4.) Fetal surveillance. Fetuses in pregnancies com-
plicated by preterm PROM are at risk for ascending
infection, cord accident, placental abruption and (pos-
sibly) uteroplacental insufficiency. Amniocentesis
may be considered in the setting preterm PROM to
test for evidence of intra-amniotic infection and to
confirm fetal lung maturity with a view to affecting an
earlier delivery. In some cases, vaginal pooled amni-
otic fluid can be aspirated and tested for fetal lung
maturation. Loss of fetal breathing in the BPP was
CHAPTER 9: OBSTETRIC COMPLICATIONS 239

previously hailed as an early sign of intrauterine infec-
tion, but more recent studies have refuted this idea.210
In the absence of evidence of uteroplacental insuffi-
ciency, fetal surveillance has not been demonstrated to
reliably diagnose or predict intra-amniotic infection.
Fetal surveillance should therefore be instituted only
for the usual obstetric indications, such as fetal non-
stress testing (NST) to assess for variable decelera-
tions in the setting of oligohydramnios.
240 OBSTETRICS AND GYNECOLOGY—2009
9. Antepartum Hemorrhage
Antepartum hemorrhage is defined as vaginal bleed-
ing after 24 weeks gestation and before labor, and
complicates 4%-5% of all pregnancies. Placenta pre-
via (20%) and placental abruption (30%) are the most
common causes of antepartum hemorrhage. Other
causes include vasa previa, early labor and
lesions/lacerations of the lower genital tract.
Placenta Previa
Placenta previa refers to implantation of the placenta
over the cervical os in advance of the fetal presenting
part, and complicates 1 in 200 pregnancies.211 Risk
factors include multiparity, advanced maternal age,
prior placenta previa, prior cesarean delivery and
smoking. Placenta previa may be asymptomatic or
may present clinically with painless, bright-red vagi-
nal bleeding. Fetal malpresentation due to the inability
of the presenting part to engage the pelvis may further
suggest the diagnosis. Placenta previa is primarily a
sonographic diagnosis. Transvaginal sonogram can be
safely performed in the setting of abnormal placenta-
tion to quantify the distance from the leading edge of
the placenta to the internal os of the cervix. If the lead-
ing edge of the placenta crosses the cervical os, a com-
plete previa is diagnosed. If the leading edge of the
placenta is within 2 cm of the cervical os, a marginal
previa is diagnosed.212 Low-lying placenta is defined
as a placenta with its leading edge between 2-3 cm
from the internal cervical os. As the lower uterine seg-
ment develops with advancing gestational age, the
leading edge of the placenta may appear to “move”
further from the internal os.213
Complications
Maternal complications include placenta accreta,
which refers to abnormal attachment of placental villi
to the uterine wall in which chorionic villi are directly
attached to the myometrium due to a poorly devel-
oped decidua basalis, and Nitabuch’s layer that nor-
mally separates the placenta from the uterine
myometrium.214 In the absence of placenta previa, pla-
centa accreta is rare (1 in 7000 pregnancies). How-
ever, it complicates 5%-15% of pregnancies with pla-
centa previa, 25% with previa and 1 prior cesarean,
and 60% with previa and 2 or more prior cesareans.215
Neonatal complications include preterm birth and
malpresentation. Fetal anemia may result from vasa
previa associated with a placenta previa, which is an
indication for an emergent delivery to prevent exsan-
guination of the fetus.216 Placenta previa is not associ-
ated with IUGR.217
Management
The goal of antepartum management is to maximize
fetal maturation while minimizing risk to mother and
fetus. Blind digital vaginal examination should be
avoided in all women with antepartum hemorrhage
until placenta previa is excluded. Non-reassuring
fetal testing and excessive maternal hemorrhage are
contraindications to expectant management, and may
necessitate immediate cesarean delivery irrespective
of gestational age. However, most episodes of antena-
tal bleeding are not life-threatening. With careful
monitoring, delivery can be safely delayed in most
cases. Placenta previa may resolve with time due to
cephalic growth of the lower uterine segment, draw-
ing the leading edge of the placenta away from the
internal os, thereby allowing vaginal delivery to pro-
ceed. Indeed, only 5% of low-lying placentae iden-
tified by ultrasound at 14-20 weeks gestation persist to
term (although complete placenta previa is unlikely to
resolve).218 Cesarean delivery is generally performed
by 37 weeks gestation due to active maternal hemor-
rhage or concern over impending risk of maternal
hemorrhage. If elective delivery of an asymptomatic
patient is planned prior to 39 weeks gestation, it
should be done only after documentation of fetal lung
maturity.
Placental Abruption
Placental abruption refers to premature separation of
the placenta from the underlying maternal decidua,
and complicates 1 in 120 pregnancies.219, 220 Risk fac-
tors include hypertension, prior placental abruption,
trauma, smoking, cocaine, uterine anomaly or
fibroids, multiparity, advanced maternal age, preterm
PROM, bleeding diathesis and an overdistended
uterus (multifetal gestations, polyhydramnios).220 Pla-
cental abruption is a clinical diagnosis that may
include vaginal bleeding (80%), painful uterine con-
tractions (35%), and abdominal tenderness (70%),
with or without non-reassuring fetal testing (50%).
The amount of vaginal bleeding is not a reliable indi-
cator of the severity of the condition, because bleed-
ing may be concealed. A retroplacental collection of
≥300 mL is necessary for sonographic visualization,
and only 2% of placental abruptions can be visualized
on ultrasound. Serial measurements of fundal height
and abdominal girth are useful to monitor large retro-
placental blood collections.
Complications. Maternal complications include mor-
tality (due to hemorrhage, cardiac failure or renal fail-
ure [0.5%-5%]) and coagulopathy (10%). Fetal com-
plications include IUFD in 10%-35% of cases due pri-
marily to fetal hypoxia, exsanguination and/or com-
plications of prematurity. Chronic abruption is also
associated with an increased rate of congenital
anomalies and IUGR.219, 221
Management. Hospitalization is indicated to evalu-
ate maternal and fetal condition. Mode and timing
of delivery depends on the condition of the mother
and fetus, and on gestational age. In the setting of
hemodynamic instability, invasive monitoring and
immediate delivery may be necessary. If the abrup-
tion is mild and pregnancy is remote from term,
expectant management may be appropriate. Placen-
tal abruption is a relative contraindication to tocoly-
sis, particularly with beta-agonists that may cause
maternal tachycardia and increased pulse pressure
to the site of the abruption. The risk of cesarean
delivery is increased primarily due to fetal
compromise.
Vasa Previa
Vasa previa refers to the presence of fetal vessels
coursing through the membranes (velamentous inser-
tion) overlying the internal os ahead of presenting part
of the fetus. Vasa previa is usually asymptomatic, but
may present with painless bright-red vaginal bleed-
ing, often associated with diminished fetal movement.
Since bleeding is from the umbilical vessels and is
fetal in origin, fetal mortality is >75%, due primarily
to fetal exsanguination. Diagnosis is by the bedside
Apt test (hemoglobin alkaline denaturation test),
which involves adding 2-3 drops of an alkaline solu-
tion (NaOH) to 1 mL of blood. If the blood is mater-
nal, erythrocytes will rupture and the mixture will turn
brown. Fetal erythrocytes, on the other hand, are resis-
tant to rupture and the mixture will remain red. Emer-
gent cesarean delivery is indicated regardless of gesta-
tional age if the fetus is viable. Brisk vaginal bleeding
temporally related to spontaneous or artificial rupture
of the membranes, particularly in light of a placenta
previa or low-lying placenta, and acute changes in
fetal heart rate tracing, should prompt consideration of
this diagnosis.222
CHAPTER 9: OBSTETRIC COMPLICATIONS 241
10. References
1. Shortle B, Jewelewicz R. Cervical
incompetence. Fertil Steril. 1989;52(2):181-188.
2. ACOG Practice Bulletin. Cervical insufficiency.
Obstet Gynecol. 2003;102(5 Pt 1):1091-1099.
3. Harger JH. Cervical cerclage: patient selection,
morbidity, and success rates. Clin Perinatol.
1983;10(2):321-341.
4. Golan A, Barnan R, Wexler S, Langer R,
Bukovsky I, David MP. Incompetence of the
uterine cervix. Obstet Gynecol Surv.
1989;44(2):96-107.
5. ACOG Practice Bulletin. Clinical management
guidelines for obstetrician-gynecologist. Num-
ber 43, May 2003. Management of preterm
labor. Obstet Gynecol. 2003;101(5 Pt 1):
1039-1047.
6. Norman JE. Cervical function and prematurity.
Best Pract Res Clin Obstet Gynaecol. May
2007.
7. Althuisius SM, Dekker GA. A five century evo-
lution of cervical incompetence as a clinical
entity. Curr Pharm Des. 2005;11(6):687-697.
8. Althuisius SM, Dekker GA, Hummel P,
Bekedam DJ, van Geijn HP. Final results of the
Cervical Incompetence Prevention Randomized
Cerclage Trial (CIPRACT): therapeutic cer-
clage with bed rest versus bed rest alone. Am J
Obstet Gynecol. 2001;185(5):1106-1112.
9. Dor J, Shalev J, Mashiach S, Blankstein J, Serr
DM. Elective cervical suture of twin pregnan-
cies diagnosed ultrasonically in the first
trimester following induced ovulation. Gynecol
Obstet Invest. 1982;13(1):55-60.
10. Lazar P, Gueguen S, Dreyfus J, Renaud R, Pon-
tonnier G, Papiernik E. Multicentred controlled
trial of cervical cerclage in women at moderate
risk of preterm delivery. Br J Obstet Gynaecol.
1984;91(8):731-735.
242 OBSTETRICS AND GYNECOLOGY—2009
11. Rush RW, Isaacs S, McPherson K, Jones L,
Chalmers I, Grant A. A randomized controlled
trial of cervical cerclage in women at high risk of
spontaneous preterm delivery. Br J Obstet
Gynaecol. 1984;91(8):724-730.
12. Roman AS, Rebarber A, Pereira L, Sfakianaki
AK, Mulholland J, Berghella V. The efficacy of
sonographically indicated cerclage in multiple
gestations. J Ultrasound Med. 2005;24(6):763-
768; quiz 70-71.
13. To MS, Alfirevic Z, Heath VC, et al. Cervical
cerclage for prevention of preterm delivery in
women with short cervix: randomised controlled
trial. Lancet. 2004;363(9424):1849-1853.
14. Mays JK, Figueroa R, Shah J, Khakoo H,
Kaminsky S, Tejani N. Amniocentesis for selec-
tion before rescue cerclage. Obstet Gynecol.
2000;95(5):652-655.
15. Romero R, Gonzalez R, Sepulveda W, et al.
Infection and labor. VIII. Microbial invasion of
the amniotic cavity in patients with suspected
cervical incompetence: prevalence and clinical
significance. Am J Obstet Gynecol. 1992;167(4 :
1):1086-1091.
16. MacDougall J, Siddle N. Emergency cervical
cerclage. Br J Obstet Gynaecol.
1991;98(12):1234-1238.
17. Olatunbosun OA, Dyck F. Cervical cerclage
operation for a dilated cervix. Obstet Gynecol.
1981;57(2):166-170.
18. Scheerer LJ, Lam F, Bartolucci L, Katz M. A
new technique for reduction of prolapsed fetal
membranes for emergency cervical cerclage.
Obstet Gynecol. 1989;74(3:1):408-410.
19. Sher G. Congenital incompetence of the cervical
os: reduction of bulging membranes with a mod-
ified Foley catheter. J Reprod Med.
1979;22(3):165-167.
20. McDonald IA. Suture of the cervix for
inevitable miscarriage. J Obstet Gynaecol Br
Emp. 1957;64(3):346-350.
21. Goodlin RC. Cervical incompetence, hourglass
membranes, and amniocentesis. Obstet
Gynecol. 1979;54(6):748-750.
22. Ochi M, Ishikawa K, Itoh H, et al. [Aggressive
management of prolapsed fetal membranes ear-
lier than 26 weeks gestation by emergent
McDonald cerclage combined with amniocente-
sis and bladder overfilling]. Nippon Sanka
Fujinka Gakkai Zasshi. 1994;46(4):301-307.
23. Locatelli A, Vergani P, Bellini P, Strobelt N,
Arreghini A, Ghidini A. Amnioreduction in
emergency cerclage with prolapsed membranes:
comparison of two methods for reducing the
membranes. Am J Perinatol. 1999;16(2):73-77.
24. Daskalakis G, Papantoniou N, Mesogitis S,
Antsaklis A. Management of cervical insuffi-
ciency and bulging fetal membranes. Obstet
Gynecol. 2006;107(2 Pt 1):221-226.
25. Rozenberg P, Senat MV, Gillet A, Ville Y. Com-
parison of two methods of cervical cerclage by
ultrasound cervical measurement. J Matern
Fetal Neonatal Med. 2003;13(5):314-317.
26. Iams JD. Abnormal Cervical Competence. 5th
ed. Philadelphia: Saunders; 2004.
27. Shirodkar V. A new method of operative treat-
ment for habitual abortion in the second
trimester of pregnancy. Antiseptic. 1955;52:299.
28. Benson RC, Durfee RB. Transabdominal cer-
vico uterine cerclage during pregnancy for the
treatment of cervical incompetency. Obstet
Gynecol. 1965;25:145-155.
29. Novy MJ. Transabdominal cervicoisthmic cer-
clage: a reappraisal 25 years after its introduc-
tion. Am J Obstet Gynecol. 1991;164(6:1):1635-
1641; discussion 41-42.
30. McElrath TF, Norwitz ER, Lieberman ES,
Heffner LJ. Management of cervical cerclage
and preterm premature rupture of the mem-
branes: should the stitch be removed? Am J
Obstet Gynecol. 2000;183(4):840-846.
31. Jenkins TM, Berghella V, Shlossman PA, et al.
Timing of cerclage removal after preterm pre-
mature rupture of membranes: maternal and
neonatal outcomes. Am J Obstet Gynecol.
2000;183(4):847-852.
32. Final report of the Medical Research Coun-
cil/Royal College of Obstetricians and Gynae-
cologists multicentre randomised trial of cervi-
cal cerclage. MRC/RCOG Working Party on
Cervical Cerclage. Br J Obstet Gynaecol.
1993;100(6):516-523.
Preterm Labor
33. Rush RW, Keirse MJ, Howat P, Baum JD,
Anderson AB, Turnbull AC. Contribution of
preterm delivery to perinatal mortality. Br Med
J. 1976;2(6042):965-968.
34. Ananth CV, Vintzileos AM. Epidemiology of
preterm birth and its clinical subtypes. J Matern
Fetal Neonatal Med. 2006;19(12):773-82.
35. Norwitz ER, Robinson JN, Challis JR. The control
of labor. N Engl J Med. 1999;341(9):660-666.
36. Romero R, Avila C, Brekus CA, Morotti R. The
role of systemic and intrauterine infection in
preterm parturition. Ann NY Acad Sci.
1991;622:355-375.
37. Dudley DJ. Pre-term labor: an intra-uterine
inflammatory response syndrome? J Reprod
Immunol. 1997;36(1-2):93-109.
38. Creasy RK, Gummer BA, Liggins GC. System
for predicting spontaneous preterm birth. Obstet
Gynecol. 1980;55(6):692-695.
39. Mercer BM, Goldenberg RL, Das A, et al. The
preterm prediction study: a clinical risk assess-
ment system. Am J Obstet Gynecol.
1996;174(6):1885-1893; discussion 93-95.
CHAPTER 9: OBSTETRIC COMPLICATIONS 243
40. Iams JD, Johnson FF, O’Shaughnessy RW. A
prospective random trial of home uterine activ-
ity monitoring in pregnancies at increased risk of
preterm labor. Part II. Am J Obstet Gynecol.
1988;159(3):595-603.
41. Mortensen OA, Franklin J, Lofstrand T, Svan-
berg B. Prediction of preterm birth. Acta Obstet
Gynecol Scand. 1987;66(6):507-512.
42. Iams JD, Goldenberg RL, Meis PJ, et al. The
length of the cervix and the risk of spontaneous
premature delivery. National Institute of Child
Health and Human Development Maternal Fetal
Medicine Unit Network. N Engl J Med.
1996;334(9):567-572.
43. Heath VC, Southall TR, Souka AP, Elisseou A,
Nicolaides KH. Cervical length at 23 weeks of
gestation: prediction of spontaneous preterm
delivery. Ultrasound Obstet Gynecol.
1998;12(5):312-317.
44. Hillier SL, Nugent RP, Eschenbach DA, et al.
Association between bacterial vaginosis and
preterm delivery of a low-birth-weight infant.
The Vaginal Infections and Prematurity Study
Group. N Engl J Med. 1995;333(26):1737-1742.
45. Gibbs RS, Romero R, Hillier SL, Eschenbach
DA, Sweet RL. A review of premature birth and
subclinical infection. Am J Obstet Gynecol.
1992;166(5):1515-1528.
46. Lockwood CJ, Senyei AE, Dische MR, et al.
Fetal fibronectin in cervical and vaginal secre-
tions as a predictor of preterm delivery. N Engl J
Med. 1991;325(10):669-674.
47. Goldenberg RL, Mercer BM, Meis PJ, Copper
RL, Das A, McNellis D. The preterm prediction
study: fetal fibronectin testing and spontaneous
preterm birth. NICHD Maternal Fetal Medicine
Units Network. Obstet Gynecol.
1996;87(5:1):643-648.
48. Iams JD, Casal D, McGregor JA, et al. Fetal
fibronectin improves the accuracy of diagnosis
of preterm labor. Am J Obstet Gynecol.
1995;173(1):141-145.
244 OBSTETRICS AND GYNECOLOGY—2009
49. Goodwin TM. A role for estriol in human labor,
term and preterm. Am J Obstet Gynecol.
1999;180(1 Pt 3):S208-S213.
50. McGregor JA, Jackson GM, Lachelin GC, et al.
Salivary estriol as risk assessment for preterm
labor: a prospective trial. Am J Obstet Gynecol.
1995;173(4):1337-1342.
51. Goldenberg RL, Cliver SP, Bronstein J, Cutter
GR, Andrews WW, Mennemeyer ST. Bed rest in
pregnancy. Obstet Gynecol. 1994;84(1):131-
136.
52. Besinger RE, Niebyl JR. The safety and efficacy
of tocolytic agents for the treatment of preterm
labor. Obstet Gynecol Surv. 1990;45(7):415-
440.
53. Higby K, Xenakis EM, Pauerstein CJ. Do
tocolytic agents stop preterm labor? A critical
and comprehensive review of efficacy and
safety. Am J Obstet Gynecol. 1993;168(4):1247-
1256; discussion 56-59.
54. Hill WC. Risks and complications of tocolysis.
Clin Obstet Gynecol. 1995;38(4):725-745.
55. Hollander DI, Nagey DA, Pupkin MJ. Magne-
sium sulfate and ritodrine hydrochloride: a ran-
domized comparison. Am J Obstet Gynecol.
1987;156(3):631-637.
56. Witlin AG, Sibai BM. Magnesium sulfate ther-
apy in preeclampsia and eclampsia. Obstet
Gynecol. 1998;92(5):883-889.
57. Lamm CI, Norton KI, Murphy RJ, Wilkins IA,
Rabinowitz JG. Congenital rickets associated
with magnesium sulfate infusion for tocolysis. J
Pediatr. 1988;113(6):1078-1082.
58. Faidley CK, Dix PM, Morgan MA, Schechter E.
Electrocardiographic abnormalities during rito-
drine administration. South Med J.
1990;83(5):503-506.
59. Peterson A, Peterson K, Tongen S, et al. Glucose
intolerance as a consequence of oral terbutaline
treatment for preterm labor. J Fam Pract.
1993;36(1):25-31.
60. Vanhaesebrouck P, Thiery M, Leroy JG, et al.
Oligohydramnios, renal insufficiency, and ileal
perforation in preterm infants after intrauterine
exposure to indomethacin. J Pediatr.
1988;113(4):738-743.
61. Wiggins DA, Elliott JP. Oligohydramnios in
each sac of a triplet gestation caused by
Motrin®—fulfilling Kock’s postulates. Am J
Obstet Gynecol. 1990;162(2):460-461.
62. Suarez VR, Thompson LL, Jain V, et al. The
effect of in utero exposure to indomethacin on
the need for surgical closure of a patent ductus
arteriosus in the neonate. Am J Obstet Gynecol.
2002;187(4):886-888.
63. Itabashi K, Ohno T, Nishida H. Indomethacin
responsiveness of patent ductus arteriosus and
renal abnormalities in preterm infants treated
with indomethacin. J Pediatr. 2003;143(2):
203-207.
64. van Veen AJ, Pelinck MJ, van Pampus MG,
Erwich JJ. Severe hypotension and fetal death
due to tocolysis with nifedipine. BJOG.
2005;112(4):509-510.
65. Parasuraman R, Gandhi MM, Liversedge NH.
Nifedipine tocolysis associated atrial fibrillation
responds to DC cardioversion. BJOG.
2006;113(7):844-845.
66. Al-Omari WR, Al-Shammaa HB, Al-Tikriti
EM, Ahmed KW. Atosiban and nifedipine in
acute tocolysis: a comparative study. Eur J
Obstet Gynecol Reprod Biol. 2006;128
(1-2):129-134.
67. Stika CS, Gross GA, Leguizamon G, et al. A
prospective randomized safety trial of celecoxib
for treatment of preterm labor. Am J Obstet
Gynecol. 2002;187(3):653-660.
68. Effect of corticosteroids for fetal maturation on
perinatal outcomes. NIH Consensus Develop-
ment Panel on the Effect of Corticosteroids for
Fetal Maturation on Perinatal Outcomes. JAMA.
1995;273(5):413-418.
69. ACOG committee opinion. Antenatal corticos-
teroid therapy for fetal maturation. Number
147—December 1994. Committee on Obstetric
Practice. American College of Obstetricians and
Gynecologists. Int J Gynaecol Obstet.
1995;48(3):340-342.
70. Lee MJ, Davies J, Guinn D, et al. Single versus
weekly courses of antenatal corticosteroids in
preterm premature rupture of membranes.
Obstet Gynecol. 2004;103(2):274-281.
71. Committee on Obstetric P. ACOG committee
opinion: antenatal corticosteroid therapy for
fetal maturation. Obstet Gynecol.
2002;99(5:1):871-873.
72. Vermillion ST, Soper DE, Bland ML, Newman
RB. Effectiveness of antenatal corticosteroid
administration after preterm premature rupture
of the membranes. Am J Obstet Gynecol.
2000;183(4):925-929.
73. Rust OA, Bofill JA, Arriola RM, Andrew ME,
Morrison JC. The clinical efficacy of oral
tocolytic therapy. Am J Obstet Gynecol.
1996;175(4 Pt 1):838-842.
74. Guinn DA, Goepfert AR, Owen J, Wenstrom
KD, Hauth JC. Terbutaline pump maintenance
therapy for prevention of preterm delivery: a
double-blind trial. Am J Obstet Gynecol.
1998;179(4):874-878.
75. Ogburn PL Jr, Julian TM, Williams PP, Thomp-
son TR. The use of magnesium sulfate for tocol-
ysis in preterm labor complicated by twin gesta-
tion and betamimetic-induced pulmonary
edema. Acta Obstet Gynecol Scand.
1986;65(7):793-794.
CHAPTER 9: OBSTETRIC COMPLICATIONS 245
76. Ferguson JE, 2nd, Hensleigh PA, Kredenster D.
Adjunctive use of magnesium sulfate with rito-
drine for preterm labor tocolysis. Am J Obstet
Gynecol. 1984;148(2):166-171.
77. Valenzuela G, Cline S. Use of magnesium sul-
fate in premature labor that fails to respond to
betamimetic drugs. Am J Obstet Gynecol.
1982;143(6):718-719.
78. Gibbs RS, Eschenbach DA. Use of antibiotics to
prevent preterm birth. Am J Obstet Gynecol.
1997;177(2):375-380.
Post-term Pregnancy
79. ACOG Practice Bulletin. Clinical management
guidelines for obstetricians-gynecologists.
Number 55, September 2004 (replaces practice
pattern number 6, October 1997). Management
of Postterm Pregnancy. Obstet Gynecol.
2004;104(3):639-646.
80. ACOG criteria set. Postterm pregnancy. Number
10—August 1995. Committee on Quality
Assessment. American College of Obstetricians
and Gynecologists. Int J Gynaecol Obstet.
1996;53(1):89-90.
81. Barnes AC. Postmaturity syndrome; the obstetri-
cian’s role in management. Calif Med.
1956;85(5):289-292.
82. Clifford SH. Postmaturity clinical syndrome and
pathologic findings. AMA Am J Dis Child.
1953;86(3):319-321.
83. Feldman GB. Prospective risk of stillbirth.
Obstet Gynecol. 1992;79(4):547-553.
84. American College of Obstetricians and Gynecol-
ogists. ACOG Practice Bulletin No. 22. Fetal
Macrosomia. Washington, DC:ACOG, 2000.
85. Spellacy WN, Miller S, Winegar A, Peterson
PQ. Macrosomia—maternal characteristics and
infant complications. Obstet Gynecol.
1985;66(2):158-161.
246 OBSTETRICS AND GYNECOLOGY—2009
86. Rosen MG, Dickinson JC. Management of post-
term pregnancy. N Engl J Med.
1992;326(24):1628-1629.
87. Rand L, Robinson JN, Economy KE, Norwitz
ER. Post-term induction of labor revisited.
Obstet Gynecol. 2000;96(5:1):779-783.
88. Alexander JM, McIntire DD, Leveno KJ. Forty
weeks and beyond: pregnancy outcomes by
week of gestation. Obstet Gynecol.
2000;96(2):291-294.
89. Treger M, Hallak M, Silberstein T, Friger M,
Katz M, Mazor M. Post-term pregnancy: should
induction of labor be considered before 42
weeks? J Matern Fetal Neonatal Med.
2002;11(1):50-53.
90. American College of Obstetricians and Gynecol-
ogists. ACOG Practice Bulletin No. 10. Induc-
tion of Labor. Washington, DC:ACOG, 1999.
91. Crowley P. Interventions for preventing or
improving the outcome of delivery at or beyond
term. Cochrane Database Syst Rev.
2000(2):CD000170.
92. Hannah ME, Hannah WJ, Hellmann J, Hewson
S, Milner R, Willan A. Induction of labor as
compared with serial antenatal monitoring in
post-term pregnancy. A randomized controlled
trial. The Canadian Multicenter Post-term Preg-
nancy Trial Group. N Engl J Med.
1992;326(24):1587-1592.
93. A clinical trial of induction of labor versus
expectant management in postterm pregnancy.
The National Institute of Child Health and
Human Development Network of Maternal-
Fetal Medicine Units. Am J Obstet Gynecol.
1994;170(3):716-723.

Hypertensive Disorders of Pregnancy
94. Rochat RW, Koonin LM, Atrash HK, Jewett JF.
Maternal mortality in the United States: report
from the Maternal Mortality Collaborative.
Obstet Gynecol. 1988;72(1):91-97.
95. Berg CJ, Atrash HK, Koonin LM, Tucker M.
Pregnancy-related mortality in the United
States, 1987-1990. Obstet Gynecol.
1996;88(2):161-167.
96. Lin CC, Lindheimer MD, River P, Moawad AH.
Fetal outcome in hypertensive disorders of preg-
nancy. Am J Obstet Gynecol. 1982;142(3):255-
260.
97. Barr M, Jr. Teratogen update: angiotensin-con-
verting enzyme inhibitors. Teratology.
1994;50(6):399-409.
98. Quan A. Fetopathy associated with exposure to
angiotensin converting enzyme inhibitors and
angiotensin receptor antagonists. Early Hum
Dev. 2006;82(1):23-28.
99. Fretts RC. Etiology and prevention of stillbirth.
Am J Obstet Gynecol. 2005;193(6):1923-1935.
100. ACOG Practice Bulletin. Chronic hypertension
in pregnancy. ACOG Committee on Practice
Bulletins. Obstet Gynecol. 2001;98(1) suppl
177-185.
101. ACOG Practice Bulletin. Diagnosis and man-
agement of preeclampsia and eclampsia. Num-
ber 33, January 2002. American College of
Obstetricians and Gynecologists. Int J Gynaecol
Obstet. 2002;77(1):67-75.
102. Dekker GA, Sibai BM. Etiology and pathogene-
sis of preeclampsia: current concepts. Am J
Obstet Gynecol. 1998;179(5):1359-1375.
103. Redman CW, Sacks GP, Sargent IL. Preeclamp-
sia: an excessive maternal inflammatory
response to pregnancy. Am J Obstet Gynecol.
1999;180(2:1):499-506.
104. Meekins JW, Pijnenborg R, Hanssens M,
McFadyen IR, van Asshe A. A study of placental
bed spiral arteries and trophoblast invasion in
normal and severe pre-eclamptic pregnancies.
Br J Obstet Gynaecol. 1994;101(8):669-674.
105. Brosens IA, Robertson WB, Dixon HG. The role
of the spiral arteries in the pathogenesis of
preeclampsia. Obstet Gynecol Annu.
1972;1:177-191.
106. Cross JC, Werb Z, Fisher SJ. Implantation and
the placenta: key pieces of the development puz-
zle. Science. 1994;266(5190):1508-1518.
107. Maynard SE, Min JY, Merchan J, et al. Excess
placental soluble fms-like tyrosine kinase 1
(sFlt1) may contribute to endothelial dysfunc-
tion, hypertension, and proteinuria in
preeclampsia. J Clin Invest. 2003;111(5):649-
658.
108. Thadhani R, Mutter WP, Wolf M, et al. First
trimester placental growth factor and soluble
fms-like tyrosine kinase 1 and risk for
preeclampsia. J Clin Endocrinol Metab.
2004;89(2):770-775.
109. Report of the National High Blood Pressure
Education Program Working Group on High
Blood Pressure in Pregnancy. Am J Obstet
Gynecol. 2000;183(1):S1-S22.
110. Odendaal HJ, Pattinson RC, Bam R, Grove D,
Kotze TJ. Aggressive or expectant management
for patients with severe preeclampsia between
28-34 weeks gestation: a randomized controlled
trial. Obstet Gynecol. 1990;76(6):1070-1075.
111. Sibai BM, Mercer BM, Schiff E, Friedman SA.
Aggressive versus expectant management of
severe preeclampsia at 28 to 32 weeks gestation:
a randomized controlled trial. Am J Obstet
Gynecol. 1994;171(3):818-822.
112. Alexander JM, Bloom SL, McIntire DD, Leveno
KJ. Severe preeclampsia and the very low birth
weight infant: is induction of labor harmful?
Obstet Gynecol. 1999;93(4):485-488.
CHAPTER 9: OBSTETRIC COMPLICATIONS 247
113. Nassar AH, Adra AM, Chakhtoura N, Gomez-
Marin O, Beydoun S. Severe preeclampsia
remote from term: labor induction or elective
cesarean delivery? Am J Obstet Gynecol.
1998;179(5):1210-1213.
114. Sibai BM. Treatment of hypertension in preg-
nant women. N Engl J Med. 1996;335(4):
257-265.
115. Lindenstrom E, Boysen G, Nyboe J. Influence of
systolic and diastolic blood pressure on stroke
risk: a prospective observational study. Am J
Epidemiol. 1995;142(12):1279-1290.
116. Fontenot MT, Lewis DF, Frederick JB, et al. A
prospective randomized trial of magnesium sul-
fate in severe preeclampsia: use of diuresis as a
clinical parameter to determine the duration of
postpartum therapy. Am J Obstet Gynecol.
2005;192(6):1788-1793; discussion 93-94.
117. Which anticonvulsant for women with eclamp-
sia? Evidence from the Collaborative Eclampsia
Trial. Lancet. 1995;345(8963):1455-1463.
118. Coetzee EJ, Dommisse J, Anthony J. A ran-
domised controlled trial of intravenous magne-
sium sulphate versus placebo in the management
of women with severe pre-eclampsia. Br J
Obstet Gynaecol. 1998;105(3):300-303.
119. Douglas KA, Redman CW. Eclampsia in the
United Kingdom. BMJ. 1994;309(6966):1395-
1400.
120. Sibai BM. Diagnosis, prevention, and manage-
ment of eclampsia. Obstet Gynecol.
2005;105(2):402-410.
121. Sibai BM, Villar MA, Mabie BC. Acute renal
failure in hypertensive disorders of pregnancy.
Pregnancy outcome and remote prognosis in
thirty-one consecutive cases. Am J Obstet
Gynecol. 1990;162(3):777-783.
122. Sibai BM. Chronic hypertension in pregnancy.
Obstet Gynecol. 2002;100(2):369-377.
248 OBSTETRICS AND GYNECOLOGY—2009
123. Sibai BM, el-Nazer A, Gonzalez-Ruiz A. Severe
preeclampsia-eclampsia in young primigravid
women: subsequent pregnancy outcome and
remote prognosis. Am J Obstet Gynecol.
1986;155(5):1011-1016.
124. Sibai BM. Prevention of preeclampsia: a big dis-
appointment. Am J Obstet Gynecol.
1998;179(5):1275-1278.
125. Norwitz ER, Robinson JN, Repke JT. Preven-
tion of preeclampsia: is it possible? Clin Obstet
Gynecol. 1999;42(3):436-454.
126. Askie LM, Duley L, Henderson-Smart DJ,
Stewart LA. Antiplatelet agents for prevention
of pre-eclampsia: a meta-analysis of individual
patient data. Lancet. 2007;369(9575):1791-
1798.
Intrauterine Fetal Demise
127. Spong CY, Erickson K, Willinger M, Hankins
GD, Schulkin J. Stillbirth in obstetric practice:
report of survey findings. J Matern Fetal
Neonatal Med. 2003;14(1):39-44.
128. MacDorman MF, Hoyert DL, Martin JA, Mun-
son ML, Hamilton BE. Fetal and perinatal mor-
tality, United States, 2003. Natl Vital Stat Rep.
2007;55(6):1-17.
129. Huang DY, Usher RH, Kramer MS, Yang H,
Morin L, Fretts RC. Determinants of unex-
plained antepartum fetal deaths. Obstet Gynecol.
2000;95(2):215-221.
130. Froen JF, Arnestad M, Frey K, Vege A, Saugstad
OD, Stray-Pedersen B. Risk factors for sudden
intrauterine unexplained death: epidemiologic
characteristics of singleton cases in Oslo, Nor-
way, 1986-1995. Am J Obstet Gynecol.
2001;184(4):694-702.
131. Tenovuo A, Kero P, Piekkala P, Korvenranta H,
Erkkola R. Fetal and neonatal mortality of small-
for-gestational age infants. A 15-year study of
381 cases. Eur J Pediatr. 1988;147(6):613-615.
132. Spinillo A, Capuzzo E, Piazzi G, Nicola S,
Colonna L, Iasci A. Maternal high-risk factors
and severity of growth deficit in small for gesta-
tional age infants. Early Hum Dev.
1994;38(1):35-43.
133. Wapner RJ, Lewis D. Genetics and metabolic
causes of stillbirth. Semin Perinatol.
2002;26(1):70-74.
134. Kolialexi A, Tsangaris GT, Antsaklis A,
Mavroua A. Rapid clearance of fetal cells from
maternal circulation after delivery. Ann NY Acad
Sci. 2004;1022:113-118.
135. Brookes JS, Hagmann C. MRI in fetal necropsy.
J Magn Reson Imaging. 2006;24(6):1221-1228.
136. Cernach MC, Patricio FR, Galera MF, Moron
AF, Brunoni D. Evaluation of a protocol for
postmortem examination of stillbirths and
neonatal deaths with congenital anomalies.
Pediatr Dev Pathol. 2004;7(4):335-341.
137. Reid DE, Weiner AE, Roby CC, Diamond LK.
Maternal afibrinogenemia associated with long-
standing intrauterine fetal death. Am J Obstet
Gynecol. 1953;66(3):500-506.
138. Pritchard JA. Fetal death in utero. Obstet
Gynecol. 1959;14:573-580.
139. Carlson NJ, Towers CV. Multiple gestation com-
plicated by the death of one fetus. Obstet
Gynecol. 1989;73(5:1):685-9.
140. D’Alton ME, Newton ER, Cetrulo CL. Intrauter-
ine fetal demise in multiple gestation. Acta
Genet Med Gemellol (Roma). 1984;33(1):43-
49.
141. Bejar R, Vigliocco G, Gramajo H, et al. Antena-
tal origin of neurologic damage in newborn
infants. II. Multiple gestations. Am J Obstet
Gynecol. 1990;162(5):1230-1236.
142. Romero R, Duffy TP, Berkowitz RL, Chang E,
Hobbins JC. Prolongation of a preterm preg-
nancy complicated by death of a single twin in
utero and disseminated intravascular coagula-
tion. Effects of treatment with heparin. N Engl J
Med. 1984;310(12):772-774.
143. Benirschke K. Intrauterine death of a twin:
mechanisms, implications for surviving twin,
and placental pathology. Semin Diagn Pathol.
1993;10(3):222-231.
144. Szymonowicz W, Preston H, Yu VY. The surviv-
ing monozygotic twin. Arch Dis Child.
1986;61(5):454-458.
145. Ben-Shlomo I, Alcalay M, Lipitz S, Leibowitz
K, Mashiach S, Barkai G. Twin pregnancies
complicated by the death of one fetus. J Reprod
Med. 1995;40(6):458-462.
Intrauterine Growth Restriction
146. American College of Obstetricians and Gyne-
cologists. ACOG Practice Bulletin No. 12.
Intrauterine growth restriction. Washington, DC:
ACOG. 2000.
147. Lin CC, Santolaya-Forgas J. Current concepts of
fetal growth restriction: part I. Causes, classifica-
tion, and pathophysiology. Obstet Gynecol.
1998;92(6):1044-1055.
148. Clausson B, Gardosi J, Francis A, Cnattingius S.
Perinatal outcome in SGA births defined by cus-
tomised versus population-based birthweight
standards. Bjog. 2001;108(8):830-834.
149. Pollack RN, Divon MY. Intrauterine growth
retardation: definition, classification, and etiol-
ogy. Clin Obstet Gynecol. 1992;35(1):99-107.
150. Kazzi GM, Gross TL, Sokol RJ. Fetal biparietal
diameter and placental grade: predictors of
intrauterine growth retardation. Obstet Gynecol.
1983;62(6):755-759.
CHAPTER 9: OBSTETRIC COMPLICATIONS 249
151. Lin CC, Santolaya-Forgas J. Current concepts of
fetal growth restriction: part II. Diagnosis and
management. Obstet Gynecol. 1999;93(1):
140-146.
152. Lee MJ, Conner EL, Charafeddine L, Woods JR,
Jr., Priore GD. A critical birth weight and other
determinants of survival for infants with severe
intrauterine growth restriction. Ann NY Acad Sci.
2001;943:326-339.
153. Godfrey KM, Barker DJ. Fetal programming
and adult health. Public Health Nutr.
2001;4(2B):611-624.
154. Odibo AO, Quinones JN, Lawrence-Cleary K,
Stamilio DM, Macones GA. What antepartum
fetal test should guide the timing of delivery of
the preterm growth-restricted fetus? A decision-
analysis. Am J Obstet Gynecol.
2004;191(4):1477-1482.
155. Simchen MJ, Alkazaleh F, Adamson SL, et al.
The fetal cardiovascular response to antenatal
steroids in severe early-onset intrauterine
growth restriction. Am J Obstet Gynecol.
2004;190(2):296-304.
156. Mordel N, Ezra Y, Dorembus D, Benshushan A,
Schenker JG, Sadovsky E. Triplets are not so
rare any more. J Perinat Med. 1992;20(2):117-
122.
Multiple Gestation
157. Norwitz E. Multiple Pregnancies: Trends past,
present and future. Philadelphia, PA: WB Saun-
ders Company; 1998.
158. Derom C, Vlietinck R, Derom R, Van den
Berghe H, Thiery M. Increased monozygotic
twinning rate after ovulation induction. Lancet.
1987;1(8544):1236-1238.
159. Barss VA, Benacerraf BR, Frigoletto FD, Jr.
Ultrasonographic determination of chorion type
in twin gestation. Obstet Gynecol.
1985;66(6):779-783.
250 OBSTETRICS AND GYNECOLOGY—2009
160. Winn HN, Gabrielli S, Reece EA, Roberts JA,
Salafia C, Hobbins JC. Ultrasonographic criteria
for the prenatal diagnosis of placental chorionic-
ity in twin gestations. Am J Obstet Gynecol.
1989;161(6:1):1540-1542.
161. Scardo JA, Ellings JM, Newman RB. Prospec-
tive determination of chorionicity, amnionicity,
and zygosity in twin gestations. Am J Obstet
Gynecol. 1995;173(5):1376-1380.
162. Wood SL, St Onge R, Connors G, Elliot PD.
Evaluation of the twin peak or lambda sign in
determining chorionicity in multiple pregnancy.
Obstet Gynecol. 1996;88(1):6-9.
163. Kovacs BW, Kirschbaum TH, Paul RH. Twin
gestations: I. Antenatal care and complications.
Obstet Gynecol. 1989;74(3:1):313-317.
164. Haning RV, Jr., Seifer DB, Wheeler CA, Frish-
man GN, Silver H, Pierce DJ. Effects of fetal
number and multifetal reduction on length of in
vitro fertilization pregnancies. Obstet Gynecol.
1996;87(6):964-968.
165. Hendricks CH. Twinning in relation to birth
weight, mortality, and congenital anomalies.
Obstet Gynecol. 1966;27(1):47-53.
166. Erkkola R, Ala-Mello S, Piiroinen O, Kero P,
Sillanpaa M. Growth discordancy in twin preg-
nancies: a risk factor not detected by measure-
ments of biparietal diameter. Obstet Gynecol.
1985;66(2):203-206.
167. Peek MJ, McCarthy A, Kyle P, Sepulveda W,
Fisk NM. Medical amnioreduction with sulindac
to reduce cord complications in monoamniotic
twins. Am J Obstet Gynecol. 1997;176(2):334-
336.
168. Carr SR, Aronson MP, Coustan DR. Survival
rates of monoamniotic twins do not decrease
after 30 weeks gestation. Am J Obstet Gynecol.
1990;163(3):719-722.
169. Gonzalez MC, Reyes H, Arrese M, et al. Intra-
hepatic cholestasis of pregnancy in twin preg-
nancies. J Hepatol. 1989;9(1):84-90.
170. Fick AL, Feldstein VA, Norton ME, Wassel Fyr
C, Caughey AB, Machin GA. Unequal placental
sharing and birth weight discordance in mono-
chorionic diamniotic twins. Am J Obstet
Gynecol. 2006;195(1):178-183.
171. Danskin FH, Neilson JP. Twin-to-twin transfu-
sion syndrome: what are appropriate diagnostic
criteria? Am J Obstet Gynecol. 1989;161(2):
365-369.
172. Reisner DP, Mahony BS, Petty CN, et al. Stuck
twin syndrome: outcome in thirty-seven consec-
utive cases. Am J Obstet Gynecol.
1993;169(4):991-995.
173. Urig MA, Clewell WH, Elliott JP. Twin-twin
transfusion syndrome. Am J Obstet Gynecol.
1990;163(5 Pt 1):1522-1526.
174. Gonsoulin W, Moise KJ, Jr., Kirshon B, Cotton
DB, Wheeler JM, Carpenter RJ, Jr. Outcome of
twin-twin transfusion diagnosed before 28
weeks of gestation. Obstet Gynecol.
1990;75(2):214-216.
175. Ville Y, Hyett J, Hecher K, Nicolaides K. Prelim-
inary experience with endoscopic laser surgery
for severe twin-twin transfusion syndrome. N
Engl J Med. 1995;332(4):224-227.
176. Elliott JP, Urig MA, Clewell WH. Aggressive
therapeutic amniocentesis for treatment of twin-
twin transfusion syndrome. Obstet Gynecol.
1991;77(4):537-540.
177. Wittmann BK, Farquharson DF, Thomas WD,
Baldwin VJ, Wadsworth LD. The role of feticide
in the management of severe twin transfusion
syndrome. Am J Obstet Gynecol.
1986;155(5):1023-1026.
178. Senat MV, Deprest J, Boulvain M, Paupe A,
Winer N, Ville Y. Endoscopic laser surgery ver-
sus serial amnioreduction for severe twin-to-
twin transfusion syndrome. N Engl J Med.
2004;351(2):136-144.
179. ACOG Practice Bulletin #56: Multiple gesta-
tion: complicated twin, triplet, and high-order
multifetal pregnancy. Obstet Gynecol.
2004;104(4):869-883.
180. O’Brien JE, Dvorin E, Yaron Y, et al. Differen-
tial increases in AFP, hCG, and uE3 in twin
pregnancies: impact on attempts to quantify
Down syndrome screening calculations. Am J
Med Genet. 1997;73(2):109-112.
181. Melgar CA, Rosenfeld DL, Rawlinson K,
Greenberg M. Perinatal outcome after multifetal
reduction to twins compared with nonreduced
multiple gestations. Obstet Gynecol.
1991;78(5:1):763-767.
182. Boulot P, Hedon B, Pelliccia G, Peray P, Laffar-
gue F, Viala JL. Effects of selective reduction in
triplet gestation: a comparative study of 80 cases
managed with or without this procedure. Fertil
Steril. 1993;60(3):497-503.
183. Smith-Levitin M, Kowalik A, Birnholz J, et al.
Selective reduction of multifetal pregnancies to
twins improves outcome over nonreduced triplet
gestations. Am J Obstet Gynecol.
1996;175(4:1):878-882.
184. Evans MI, Dommergues M, Timor-Tritsch I, et
al. Transabdominal versus transcervical and
transvaginal multifetal pregnancy reduction:
international collaborative experience of more
than one thousand cases. Am J Obstet Gynecol.
1994;170(3):902-909.
185. Evans MI, May M, Drugan A, Fletcher JC,
Johnson MP, Sokol RJ. Selective termination:
clinical experience and residual risks. Am J
Obstet Gynecol. 1990;162(6):1568-1572; dis-
cussion 72-75.
186. Malone FD, Craigo SD, Chelmow D, D’Alton
ME. Outcome of twin gestations complicated by
a single anomalous fetus. Obstet Gynecol.
1996;88(1):1-5.
CHAPTER 9: OBSTETRIC COMPLICATIONS 251
187. Evans MI, Goldberg JD, Dommergues M, et al.
Efficacy of second-trimester selective termina-
tion for fetal abnormalities: international collab-
orative experience among the world’s largest
centers. Am J Obstet Gynecol. 1994;171(1):
90-94.
188. Wald N, Cuckle H, Wu TS, George L. Maternal
serum unconjugated oestriol and human chori-
onic gonadotrophin levels in twin pregnancies:
implications for screening for Down’s syn-
drome. Br J Obstet Gynaecol. 1991;98(9):
905-908.
189. Neveux LM, Palomaki GE, Knight GJ, Haddow
JE. Multiple marker screening for Down syn-
drome in twin pregnancies. Prenat Diagn.
1996;16(1):29-34.
190. Tabor A, Philip J, Madsen M, Bang J, Obel EB,
Norgaard-Pedersen B. Randomised controlled
trial of genetic amniocentesis in 4606 low-risk
women. Lancet. 1986;1(8493):1287-1293.
191. Hook EB, Cross PK, Schreinemachers DM.
Chromosomal abnormality rates at amniocente-
sis and in live-born infants. JAMA.
1983;249(15):2034-2038.
192. Rodis JF, Egan JF, Craffey A, Ciarleglio L,
Greenstein RM, Scorza WE. Calculated risk of
chromosomal abnormalities in twin gestations.
Obstet Gynecol. 1990;76(6):1037-1041.
193. Meyers C, Adam R, Dungan J, Prenger V. Ane-
uploidy in twin gestations: when is maternal
age advanced? Obstet Gynecol.
1997;89(2):248-251.
194. Strong TH, Jr., Phelan JP, Ahn MO, Sarno AP,
Jr. Vaginal birth after cesarean delivery in the
twin gestation. Am J Obstet Gynecol.
1989;161(1):29-32.
195. Gocke SE, Nageotte MP, Garite T, Towers CV,
Dorcester W. Management of the nonvertex
second twin: primary cesarean section, external
version, or primary breech extraction. Am J
Obstet Gynecol. 1989;161(1):111-114.
252 OBSTETRICS AND GYNECOLOGY—2009
196. Davison L, Easterling TR, Jackson JC,
Benedetti TJ. Breech extraction of low-birth-
weight second twins: can cesarean section be
justified? Am J Obstet Gynecol.
1992;166(2):497-502.
197. Dommergues M, Mahieu-Caputo D, Mandel-
brot L, Huon C, Moriette G, Dumez Y. Deliv-
ery of uncomplicated triplet pregnancies: is the
vaginal route safer? A case-control study. Am J
Obstet Gynecol. 1995;172(2:1):513-517.
Preterm Premature Rupture of Membranes
198. Capeless EL, Mead PB. Management of
preterm premature rupture of membranes: lack
of a national consensus. Am J Obstet Gynecol.
1987;157(1):11-12.
199. Bengtson JM, VanMarter LJ, Barss VA, Greene
MF, Tuomala RE, Epstein MF. Pregnancy out-
come after premature rupture of the membranes
at or before 26 weeks gestation. Obstet Gynecol.
1989;73(6):921-927.
200. Park JS, Yoon BH, Romero R, et al. The rela-
tionship between oligohydramnios and the
onset of preterm labor in preterm premature rup-
ture of membranes. Am J Obstet Gynecol.
2001;184(3):459-462.
201. Bianco AT, Stone J, Lapinski R, Lockwood C,
Lynch L, Berkowitz RL. The clinical outcome
of preterm premature rupture of membranes in
twin versus singleton pregnancies. Am J Perina-
tol. 1996;13(3):135-138.
202. Duff P, Huff RW, Gibbs RS. Management of
premature rupture of membranes and unfavor-
able cervix in term pregnancy. Obstet Gynecol.
1984;63(5):697-702.
203. Hannah ME, Hodnett ED, Willan A, Foster GA,
Di Cecco R, Helewa M. Prelabor rupture of the
membranes at term: expectant management at
home or in hospital? The TermPROM Study
Group. Obstet Gynecol. 2000;96(4):533-538.
204. ACOG Practice Bulletin No. 80: premature rup-
ture of membranes. Clinical management
guidelines for obstetrician-gynecologists.
Obstet Gynecol. 2007;109(4):1007-1019.
205. Vintzileos AM, Campbell WA, Nochimson DJ,
Weinbaum PJ. Preterm premature rupture of the
membranes: a risk factor for the development of
abruptio placentae. Am J Obstet Gynecol.
1987;156(5):1235-1238.
206. Ohlsson A. Treatments of preterm premature
rupture of the membranes: a meta-analysis. Am
J Obstet Gynecol. 1989;160(4):890-906.
207. Wu YW, Colford JM, Jr. Chorioamnionitis as a
risk factor for cerebral palsy: A meta-analysis.
JAMA. 2000;284(11):1417-1424.
208. Mercer BM, Arheart KL. Antimicrobial therapy
in expectant management of preterm premature
rupture of the membranes. Lancet.
1995;346(8985):1271-1279.
209. Kenyon SL, Taylor DJ, Tarnow-Mordi W.
Broad-spectrum antibiotics for preterm,
prelabour rupture of fetal membranes: the
ORACLE I randomised trial. ORACLE Collab-
orative Group. Lancet. 2001;357(9261):979-
988.
210. Ghidini A, Salafia CM, Kirn V, Doria V, Spong
CY. Biophysical profile in predicting acute
ascending infection in preterm rupture of mem-
branes before 32 weeks. Obstet Gynecol.
2000;96(2):201-206.
Antepartum Hemorrhage
211. Sauer M, Parsons M, Sampson M. Placenta pre-
via: an analysis of three years’ experience. Am J
Perinatol. 1985;2(1):39-42.
212. Bhide A, Prefumo F, Moore J, Hollis B, Thila-
ganathan B. Placental edge to internal os dis-
tance in the late third trimester and mode of
delivery in placenta praevia. Bjog.
2003;110(9):860-864.
213. Predanic M, Perni SC, Baergen RN, Jean-Pierre
C, Chasen ST, Chervenak FA. A sonographic
assessment of different patterns of placenta pre-
via “migration” in the third trimester of preg-
nancy. J Ultrasound Med. 2005;24(6):773-780.
214. Gielchinsky Y, Mankuta D, Rojansky N, Laufer
N, Gielchinsky I, Ezra Y. Perinatal outcome of
pregnancies complicated by placenta accreta.
Obstet Gynecol. 2004;104(3):527-530.
215. Ananth CV, Smulian JC, Vintzileos AM. The
association of placenta previa with history of
cesarean delivery and abortion: a metaanalysis.
Am J Obstet Gynecol. 1997;177(5):1071-1078.
216. Oyelese Y, Smulian JC. Placenta previa, pla-
centa accreta, and vasa previa. Obstet Gynecol.
2006;107(4):927-941.
217. Wolf EJ, Mallozzi A, Rodis JF, Egan JF,
Vintzileos AM, Campbell WA. Placenta previa
is not an independent risk factor for a small for
gestational age infant. Obstet Gynecol.
1991;77(5):707-709.
218. Zelop CC, Bromley B, Frigoletto FD, Jr.,
Benacerraf BR. Second trimester sonographi-
cally diagnosed placenta previa: prediction of
persistent previa at birth. Int J Gynaecol Obstet.
1994;44(3):207-210.
219. Ananth CV, Wilcox AJ. Placental abruption and
perinatal mortality in the United States. Am J
Epidemiol. 2001;153(4):332-337.
220. 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(8):771-778.
221. Ananth CV, Berkowitz GS, Savitz DA, Lapinski
RH. Placental abruption and adverse perinatal
outcomes. JAMA. 1999;282(17):1646-1651.
222. Oyelese KO, Turner M, Lees C, Campbell S.
Vasa previa: an avoidable obstetric tragedy.
Obstet Gynecol Surv. 1999;54(2):138-145.
CHAPTER 9: OBSTETRIC COMPLICATIONS 253
11. Questions
1. A 27-year-old woman presents for her first prena-
tal visit at 8 weeks gestation. She has a number of
risk factors for cervical insufficiency. On review
of her medical and obstetrical history, you con-
clude that she is a good candidate for elective cer-
vical cerclage. Which of the following elements of
her history support this conclusion?
A. A history of in utero DES exposure.
B. 3 prior first trimester elective pregnancy ter-
minations.
C. A prior 20 week pregnancy loss
characterized by painless cervical dilatation.
D. A triplet pregnancy conceived through in
vitro fertilization.
2. A nulliparous woman presents at 18 weeks gesta-
tion complaining of a watery vaginal discharge.
Sterile speculum examination reveals a cervix
which is 1-2 cm dilated and 80% effaced. After
reviewing the respective risks and benefits, the
patient elects emergent cerclage placement over
bed rest. At the time of cerclage placement, how-
ever, you notice something which causes you to
cancel the procedure. Which of the following clin-
ical findings would explain this change in plans?
A. Evidence of uterine contractions.
B. Evidence of a vaginal yeast infection.
C. Fetal membranes visible through the open
cervical os.
D. A large cervical ectropion (cervical erosion).
3. A 36-year-old G7P1233 presents at 32-1/7 weeks
gestation complaining of increasing abdominal
pain and diminished fetal movement for 12 hours.
Bimanual examination shows her cervix to be 4
cm dilated and 90% effaced. Fetal cardiotocogra-
phy shows evidence of uterine contractions every
three minutes. Fetal heart rate tracing is formally
reactive, with a baseline of 140 bpm and no decel-
erations. A diagnosis of preterm labor is made.
254 OBSTETRICS AND GYNECOLOGY—2009
Regarding the management of preterm labor,
which of the following statements are true?
(More than 1 statement may be true.)
A. You should recommend strict bed rest and
aggressive intravenous hydration as these
interventions have been shown to prevent
preterm birth.
B. You should start IV magnesium sulfate as
this is the only drug approved by the FDA for
the treatment of preterm labor.
C. You should start broad-spectrum antibiotic
therapy as this has been shown to prolong
latency.
D. You should administer antenatal
corticosteroids.
4. A 28-year-old G4P3 is admitted to labor and
delivery at 29-3/7 weeks gestation with regular
painful uterine contractions every 3 minutes.
Bimanual examination shows her cervix to be
long and to admit a fingertip. Fetal heart rate
tracing is formally reactive with a baseline of
130 bpm. A diagnosis of preterm contractions is
made. She has had 3 prior spontaneous preterm
deliveries at 28-31 weeks gestation, and is very
concerned that this pregnancy will also end pre-
maturely. Which of the following statements
about screening for preterm labor are true?
(More than 1 statement may be true.)
A. Her history is highly predictive of preterm
birth. As such, no further screening tests are
available.
B. A negative test for fetal fibronectin (fFN) in
cervicovaginal secretions is reassuring.
C. Transvaginal sonography reveals a cervical
length of 3.6 cm. This finding should be
viewed as reassuring.
D. Given her increased risk of preterm birth, she
is a good candidate for home uterine activity
monitoring.
5. A 21-year-old G3P2 with two prior vaginal deliv-
eries is admitted to labor and delivery at 41-4/7
weeks gestation complaining of decreased fetal
movement. Fetal cardiotocography shows the
fetal heart rate to be formally reactive with a base-
line of 140 bpm, and the patient reports that she is
again feeling fetal movements. Bimanual exami-
nation shows her cervix to be 1 cm dilated and
80% effaced. Estimated fetal weight is 4,400 g. As
you are about to leave, she says: “My sister’s baby
died at 41 weeks. Why can’t you induce my labor
now, Doctor?” Which of the following statements
are true? (More than 1 statement may be true.)
A. Induction of labor is appropriate, because her
pregnancy is post-term.
B. Induction of labor is appropriate to minimize
maternal and fetal risks.
C. Induction of labor is appropriate for the indi-
cation of impending macrosomia.
D. Induction of labor will not increase her risk
of cesarean delivery.
6. A 43-year-old G1P0 presents to your office at 34-
5/7 weeks gestation complaining of a severe
headache and flashing lights in front of her eyes.
Her supine BP is 140/90 and there is 3+ protein-
uria. A diagnosis of preeclampsia is made. Which
of the following statements regarding the manage-
ment of preeclampsia are true? (More than 1 state-
ment may be true.)
A. She should be delivered immediately by
cesarean for a diagnosis of moderate
preeclampsia.
B. You should measure her BP sitting and not
lying.
C. You should start antihypertensive therapy in
an attempt to improve perinatal outcome.
D. Regional anesthesia is contraindicated.
7. A 36-year-old G6P2 calls the office complaining
of no fetal movement for 8 hours. She is at 37
weeks gestation. On arrival, you confirm an
IUFD. Which of the following statements regard-
ing the management of IUFD at term are true?
(More than 1 statement may be true.)
A. It is highly likely that a cause for the IUFD
can be identified after delivery.
B. Immediate induction of labor is indicated to
prevent coagulopathy.
C. Pathologic examination of the fetus and pla-
centa/fetal membranes is the single most use-
ful test to identify a cause for the IUFD.
D. A Kleihauer-Betke test should be sent to
identify fetomaternal hemorrhage.
8. An 18-year-old G1P0 presents for her first pre-
natal visit. She is complaining of severe morn-
ing sickness. On examination, uterine size is
greater than expected for gestational age. You
perform an ultrasound examination and confirm
a monochorionic/monoamniotic twin gestation.
Which of the following complications of
multiple gestations is specific to monochori-
onic/monoamniotic pregnancies?
A. Malpresentation.
B. Twin-to-twin transfusion syndrome.
C. Cord entanglement.
D. Preterm delivery.
9. A 27-year-old G3P1 with a strong family history of
multiple pregnancy presents for her first prenatal
visit at 12 weeks gestation. Ultrasound examination
confirms a monochorionic/diamniotic twin preg-
nancy. Which of the following statements regarding
twin pregnancy are true?
(More than 1 statement may be true.)
CHAPTER 9: OBSTETRIC COMPLICATIONS 255
 A. Monozygous twinning is not influenced by
epidemiologic or genetic factors.
B. 80% of twin pregnancies are dizygous.
C. Perinatal mortality is higher with monozy-
gous than with dizygous twins.
D. Perinatal mortality is highest with
monochorionic/monoamniotic twins.
10. A 30-year-old G4P2 presents at 19 weeks gesta-
tion with vaginal spotting. She has a history of 2
prior cesarean deliveries. Ultrasound examination
reveals a low-lying placenta covering the cervical
os. Fetal well-being is confirmed. Which of the
following statements regarding the management
of placenta previa are true? (More than 1 state-
ment may be true.)
A. There is a high probability that the placenta
will move away from the cervix as the preg-
nancy progresses.
B. Given placenta previa and 2 prior cesarean
deliveries, the likelihood of placenta acc-
reta is 25%.
C. Fetal nonstress testing is indicated after 32
weeks, because placenta previa is associated
with uteroplacental insufficiency and IUGR.
D. Pelvic examination should be deferred in all
patients presenting with antepartum hemor-
rhage until placenta previa can be excluded.
Answers
1. C.
A history suggestive of cervical insufficiency (ie,
acute, painless dilatation of the cervix usually in the
mid-trimester culminating in prolase and/or PROM
with resultant preterm and often previable delivery) is
the only proven indication for elective cervical cer-
clage. If the prior preterm delivery was the result of
preterm labor and not cervical insufficiency, cerclage
placement is not indicated. Prophylactic cerclage for
256 OBSTETRICS AND GYNECOLOGY—2009
DES exposure remains controversial. Most clinicians
believe that a history of in utero DES exposure alone
(without a history of prior pregnancy loss) is not an
indication for prophylactic cerclage placement. Simi-
larly, elective cerclage has not been shown to be bene-
ficial in women with multiple pregnancies without a
prior history of cervical insufficiency.
2. A.
The presence of uterine contractions suggests preterm
labor and not cervical insufficiency, and are an abso-
lute contraindication to cervical cerclage. Indeed, the
presence of persistent uterine contractions requires the
removal of any cerclage to avoid cervical laceration
and/or uterine rupture. Although intra-amniotic infec-
tion is an absolute contraindication to cerclage place-
ment, vaginal yeast infection is not. Cervical ectro-
pion represents a physiologic extrusion of columnar
epithelium out of the cervical canal under the influ-
ence of steroid hormones, and should not interfere
with cervical cerclage placement. If the fetal mem-
branes are found to be prolapsing through the external
os at the time of cerclage placement, the risk of iatro-
genic rupture of the fetal membranes may be as high
as 50%. Although this is not an absolute contraindica-
tion to cerclage placement, the surgeon should pro-
ceed with care. A number of techniques have been
described in an attempt to reduce the fetal membranes
prior to cerclage placement, including Trendelenburg
position, back-filling the bladder, placement of a 30
mL Foley catheter or moistened sponge forceps into
the cervical os, and/or therapeutic amniocentesis.
3. D.
You should administer antenatal corticosteroids. A
single course of antenatal corticosteroids decreases
the incidence of RDS, IVH, and (possibly) NEC by
50%, and is recommended for all pregnancies at high-
risk of delivering before 34 weeks gestation with
intact membranes and before 32 weeks with preterm
PROM. Maximal benefit is achieved 24-48 hours
after the initial dose. This effect lasts for 7 days, but it
is unclear what happens thereafter. Repeated courses
of steroids are not generally recommended. Bed rest is
recommended in up to 20% of all pregnancies, with an
estimated cost of >$250 million per year in the United
States alone. Despite these recommendations, there is
no proven benefit to bed rest in women at risk for
preterm labor. Intravenous hydration is also com-
monly recommended in the acute setting, but without
proven benefit. Broad-spectrum antibiotic therapy has
been shown to delay preterm birth and prolong
latency in the setting of preterm PROM < 34 weeks.
However, there is no consistent evidence of prolonged
latency in the setting of preterm labor with intact
membranes. As such, broad-spectrum antibiotics are
not recommended for this indication. Pharmacologic
tocolytic therapy remains the cornerstone of modern
management. Although a number of alternative
agents are now available for tocolysis, the only agent
that is approved by the FDA for the treatment of
preterm labor is ritodrine hydrochloride (which has
been off formulary in North America for over 10
years, because it is too dangerous to administer in
pregnancy). Although the ultimate goal of tocolysis is
to delay delivery to term, there is no reliable data to
suggest that any tocolytic agents are able to delay
delivery for longer than 24-48 hours. As such, the
most realistic goal of tocolysis is to delay delivery for
48 hours to allow administration of antenatal corticos-
teroids. No single tocolytic agent has a clear therapeu-
tic advantage. As such, the side effect profile of each
of the drugs will often determine which to use in a
given clinical setting. Magnesium sulfate (which acts
both to suppress nerve transmission to uterine smooth
muscle and to lower the concentration of intracellular
calcium within myometrial cells, which is necessary
for activation of the myosinactin contractile unit) has
traditionally been regarded as the first-line tocolytic
agent for use in preterm labor. More recent data sug-
gests that nifedipine (a calcium channel blocker) is
equally effective and safer, and can be administered
orally. In Europe, the first-line tocolytic agent is atosi-
ban, an oxytocin receptor antagonist.
4. B. and C.
It is clear from this patient’s history that she is at high
risk of preterm delivery. The screening tests currently
available for prediction of preterm birth fall into 5
broad categories:
1.) Risk factor scoring. A number of risk factors for
preterm labor have been identified. However,
reliance on risk factors alone will fail to identify
over 50% of pregnancies which deliver preterm,
and most women designated at risk will deliver at
term.
2.) Home uterine activity monitoring (HUAM). An
increase in uterine contractility is a prerequisite for
preterm labor. However, use of HUAM in women
at high risk does not reduce the incidence of
preterm delivery, but does lead to over-diagnosis
of preterm labor, increased obstetric intervention,
and increased cost.
3.) Assessment of cervical maturation. Serial digital
evaluation of the cervix is useful if the examina-
tion remains normal. However, an abnormal cervi-
cal finding (shortening and/or dilatation) is associ-
ated with preterm delivery in only 4% of low-risk
women and 12%-20% of high-risk women. Sono-
graphic evaluation of the cervix has demonstrated
a strong inverse correlation between cervical
length and preterm delivery. If the cervical length
is below the 10th percentile for gestational age, the
pregnancy is at a six-fold increased risk of deliv-
ery prior to 35 weeks gestation.
4.) Biochemical markers. Although a number of bio-
chemical markers have been associated with
preterm delivery, only fetal fibronectin (fFN) is
established as a screening test for preterm deliv-
ery. Elevated levels of fFN in cervicovaginal
secretions at 22-34 weeks gestation are associated
with premature delivery. The real value of this test
lies in its negative predictive value (99% of
patients with a negative fFN test will not deliver
within 7 days).
5.) Endocrine markers. The detection of elevated lev-
els of estriol in maternal saliva (≥2.1 ng/mL) is
predictive of delivery prior to 37 weeks gestation
in a high-risk population with a sensitivity of 68%-
87%, a specificity of 77% and a false positive rate
of 23%. Serial (weekly) measurments may be
more accurate in predicting pretermbirth than a
single measurement. This test is not currently
available in the United States.
5. B. and D.
Post-term (prolonged) pregnancy refers to a preg-
nancy that has extended to or beyond a gestational age
of 42.0 weeks (294 days) from the first day of the last
menstrual period. As such, this patient’s pregnancy is
currently at term, not post-term. Clearly, accurate
pregnancy dating is critical to the diagnosis. Post-term
pregnancy is associated with both fetal and maternal
CHAPTER 9: OBSTETRIC COMPLICATIONS 257
risks. Perinatal mortality (stillbirths plus early neona-
tal deaths) at ≥ 42 weeks of gestation is twice that at
term and increases 4-fold at 43 weeks and 5- to 7-fold
at 44 weeks. Chronic uteroplacental insufficiency,
asphyxia and intrauterine infection all contribute to
the excess perinatal deaths. Post-term infants are
larger than term infants, with a higher incidence of
macrosomia (defined as a sonographic EFW >4500
g). Complications associated with fetal macrosomia
include prolonged labor, cephalopelvic disproportion,
and shoulder dystocia with resultant risks of orthope-
dic or neurologic injury. Post-term pregnancies are at
increased risk of umbilical cord compression from
oligohydramnios, nonreassuring fetal antepartum or
intrapartum assessment, meconium aspiration, short-
term neonatal complications (hypoglycemia,
seizures) and long-term neurologic sequelae. For
these reasons, there does appear to be a small advan-
tage to routine induction of labor at 41 weeks gesta-
tion, regardless of parity or method of induction.
However, induction of labor for the indication of
“impending macrosomia” is not appropriate, and such
an approach has not been shown to decrease cesarean
delivery rates or improve perinatal outcome. Routine
induction of labor at 41 weeks will not increase the
cesarean rate for multipara and nullipara with a favor-
able cervical exam (although the cesarean delivery
rate of primipara with an unfavorable cervical exam is
likely to be increased).
6. B.
Preeclampsia is a clinical diagnosis encompassing 3
elements: 1.) new-onset hypertension (defined as a
sustained BP ≥140/90 in a previously normotensive
woman); 2.) new-onset proteinuria (>300 mg/24 h or
≥2+ on a clean-catch urinalysis in the absence of uri-
nary infection); and 3.) non-dependent edema
(although this is not a prerequisite for diagnosis). BP
should always be measured in the sitting position
using the 5th Korotkoff sound (disappearance of pul-
sation) to describe the diastolic BP. Preeclampsia is
classified as either “mild” or “severe” (there is no
moderate preeclampsia). This patient has severe
preeclampsia by symptoms (headache, visual
changes) and should be delivered immediately. How-
ever, immediate delivery need not necessarily mean
cesarean delivery. Cervical ripening agents may be
used if the cervix is not favorable prior to induction,
but prolonged inductions should be avoided. Regional
analgesia can be safely administered in the setting of
258 OBSTETRICS AND GYNECOLOGY—2009
preeclampsia (in the absence of thrombocytopenia)
with close attention to volume expansion and anes-
thetic technique. The use of antihypertensive agents to
control mildly elevated BP in the setting of
preeclampsia has not been shown to alter the course of
the disease nor to diminish perinatal morbidity or
mortality, and may indeed reduce uteroplacental per-
fusion. Moreover, the use of such agents may serve to
remove the most sensitive index of worsening
preeclampsia. For these reasons, antihypertensive
therapy is not recommended for mild-to-moderate
hypertension in the setting of preeclampsia.
7. C. and D.
Causes of unexplained IUFD at term can be identified
in only around 50% of cases. Pathologic examination
of the fetus and placenta/fetal membranes is the single
most useful test to identify a cause for the IUFD. Fetal
karyotyping should be considered in all cases of fetal
death to identify chromosomal abnormalities, particu-
larly in cases with documented fetal structural abnor-
malities. Fetal-maternal hemorrhage occurs in all
pregnancies, but is usually minimal. In rare instances,
fetal-maternal hemorrhage may be massive, leading
to fetal demise. The Kleihauer-Betke (acid elution)
test allows an estimate of the volume of fetal blood in
the maternal circulation and should be sent as soon as
possible since fetal cells are very rapidly cleared from
the maternal circulation. Intra-amniotic infection
resulting in fetal death is usually evident on clinical
exam. Placental culture and histologic examination of
the fetus, placenta/fetal membranes, and umbilical
cord may be useful. Immediate delivery is not neces-
sary. Overall, >90% of women will go into labor
within 2 weeks of fetal death. Around 20%-25% of
women that retain a dead singleton fetus for longer
than 3 weeks will develop disseminated intravascular
coagulopathy (DIC) due to excessive consumption of
clotting factors. Therefore, delivery should be
effected within this time period.
8. C.
Multiple pregnancy should be suspected in women at
high risk, excessive symptoms of pregnancy or uter-
ine size larger than expected. Overall, antepartum
complications develop in 80% of multiple pregnan-
cies as compared with around 30% of singleton gesta-
tions. Preterm delivery is the most common complica-
tion, and the risk of preterm delivery increases as fetal
number increases. Malpresentation is a common com-
plication of multiple pregnancies. Cord entanglement, perinatal mortality, which is especially high with
on the other hand, is specific to monochori- monochorionic/monoamniotic twins (65%-70%).
onic/monoamniotic pregnancies. Overall, it is a rare Chorionicity is determined most accurately by exami-
complication (1 in 25,000 births), but may occur in up nation of the membranes after delivery. Antenatal
to 70% of monochorionic/monoamniotic pregnancies diagnosis is more difficult. Identification of separate
and is thought to account for >50% of perinatal mor- sex fetuses or two separate placentae confirms
tality in this subgroup. Twin polyhydram- dichorionic/diamniotic placentation.
nios/oligohydramnios sequence results from an
imbalance in blood flow from the “donor” twin to the 10. A. and D.
“recipient.” Both twins are at risk for adverse events. Placenta previa refers to implantation of the placenta
Twin-to-twin transfusion is a subset of poly/oligo over the cervical os in advance of the fetal presenting
sequence seen in 15% of monochorionic pregnancies, part. In any patient presenting with antepartum hem-
and is due to unbalanced vascular communications orrhage, pelvic and/or rectal examinations should be
between the fetal circulations. Overall perinatal mor- avoided until placenta previa is excluded. Placenta
tality is 40%-80%. Treatment options include expec- previa is primarily a sonographic diagnosis. Placenta
tant management, serial amniocentesis, indomethacin previa may resolve with time, thereby permitting
(to decrease fetal urine output), laser obliteration of vaginal delivery. Indeed, only 5% of low-lying pla-
the placental vascular communications or selective centae identified by ultrasound at 14-20 weeks gesta-
fetal reduction. tion persist to term. Maternal complications include
placenta accreta, which refers to abnormal attachment
9. All are correct. of placental villi to the uterine wall. In the absence of
Of pregnancies with placenta previa, 25% with previa placenta previa, placenta accreta is rare. However, it
and 1 prior cesarean, and 60% with previa and 2 or complicates 5%-15% of pregnancies with placenta
more prior cesareans. Neonatal complications include previa, 25% with previa and 1 prior cesarean, and
preterm birth and malpresentation. However, placenta 60% with previa and 2 or more prior cesareans.
previa is not associated with IUGR. Elective cesarean Neonatal complications include preterm birth and
delivery is generally recommended at 36-37 weeks malpresentation. However, placenta previa is not
gestation. 80% of twin pregnancies are dizygous associated with IUGR. Elective cesarean delivery is
(derived from 2 separate embryos). Dizygous twin- generally recommended at 36-37 weeks gestation.
ning is influenced by a number of epidemiologic fac-
tors, including a family or personal history of multiple
pregnancy, advanced maternal age, multiparity,
African American, and ART. Monozygous twinning,
on the other hand, is a random event that occurs in
around 1 in 300 pregnancies (although the risk may be
increased 2- to 3-fold with in vitro fertilization). Peri-
natal mortality is higher with monozygous(30%-
50%) than with dizygous twins (10%-20%). Chorion-
icity refers to the arrangement of membranes in multi-
ple pregnancies. In monozygous twinning, the timing
of the cell division determines the chorionicity. If the
zygote divides within 3 days of fertilization, the result
is dichorionic/diamniotic placentation (30% of all
monozygous pregnancies); if the division occurs
between day 3 and day 8, the result is a monochori-
onic/diamniotic pregnancy (65%); between day 8 and
day 13, a monochorionic/ monoamniotic pregnancy
ensues (<5%); and if the division occurs on or after
day 13, incomplete separation (conjoined twins) is the
rule (<0.5%). Chorionicity correlates directly with

CHAPTER 9: OBSTETRIC COMPLICATIONS 259

260 OBSTETRICS AND GYNECOLOGY—2009