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Obstetrics and Gynecology - 2009

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


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


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 Cervical cerclage has become the mainstay for the
term.1, 2 It complicates 0.1%-2% of all pregnancies, management of cervical insufficiency. If the prior
and is estimated to be responsible for 15% of deliver- preterm delivery was the result of preterm labor (docu-
ies between 16 and 28 weeks of gestation.3-5 The clas- mented active contractions) and not cervical insuffi-
sic presentation is that of painless cervical dilatation ciency, cerclage placement is not indicated.2
and shortening without evidence of uterine
contractions.6 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

Some risk factors for cervical insufficiency are insufficiency, because the probability of recurrence of
described (Table 1), but most patients have no risk cervical insufficiency in a subsequent pregnancy is
factors.1, 2 15%-30%.1, 7, 8 Prophylactic cervical cerclage is placed
most commonly at 13-16 weeks of gestation, at which
The exact etiology of cervical insufficiency has not time the complication rate is low (<1%).2 Prophylactic
been elucidated.6 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

Cervical insufficiency is a clinical diagnosis charac- (without a history of prior pregnancy loss) is not an
terized by acute, painless dilatation of the cervix, usu- indication for prophylactic cerclage placement. Simi-
ally in the mid-trimester (generally between 16-24 larly, elective cerclage has not been shown to be benefi-
weeks), culminating in fetal membrane prolapse cial in women with multiple pregnancies without a
and/or premature rupture of the membranes (PROM) prior history of cervical insufficiency.9-12
with resultant preterm and often previable delivery.
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

Table 1

Risk Factors for Cervical Insufficiency

Congenital Acquired

Müllerian abnormalities Cervical trauma (prior surgical or

(congenital cervical hypoplasia or aplasia) obstetric trauma)

In utero diethylstilbestrol (DES) exposure Connective tissue abnormalities

(Ehlers-Danlos syndrome)


general, most practitioners do not place an emergent quent studies were unable to confirm these observa-
cerclage after fetal viability is reached (after 24 tions. In a recent multicenter randomized clinical trial,
weeks), due to the inherent high risk of causing an 47,123 women with singleton pregnancies were
iatrogenic rupture of fetal membranes and accelerat- screened by transvaginal cervical length measure-
ing the preterm delivery. An alternative plan of man- ments at 22-24 weeks gestation. Cervical length was
agement in these pregnancies is bed rest for the dura- shortened (≤15 mm) in 470 women. Of these, 253
tion of the pregnancy without cerclage placement.8 (54%) participated in the study: 127 were randomized
to Shirodkar cerclage and 126 to expectant manage-
The benefit of cervical cerclage for asymptomatic cer- ment. Although cervical shortening was associated
vical shortening diagnosed either by digital examina- with a high risk for preterm birth prior to 33 weeks,
tion or transvaginal ultrasound in women without a placement of a cerclage did not reduce the risk of
prior history suggestive of cervical insufficiency early preterm birth (22% [28/127] in cerclage group
remains controversial.8 Although earlier studies sug- vs. 26% [33/126] in control group; P=0.44).13
gested that cerclage placement in women with an inci-
dental finding of a shortened cervix on ultrasound
examination may improve perinatal outcome, subse-

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

Intrauterine infection Gestational age >28 weeks

Relative contraindications

A mucopurulent cervical Placental previa Intrauterine fetal growth

discharge with membrane restriction

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


Contraindications. Contraindications to cerclage are cervical cerclage is best left to the discretion of the
listed in Table 2. Intra-amniotic infection is an abso- obstetric care provider, especially in the setting of a
lute contraindication to cerclage placement,14, 15 and prophylactic cerclage. The selection of the type of cer-
the presence of bacteria on Gram stain or a positive clage placement for emergent cases may be limited by
culture from preoperative amniocentesis is associated the thickness and length of cervical tissue available
with a failure rate of >90%. Preoperative amniocente- for suture placement. The choice of suture material
sis in asymptomatic patients with cervical insuffi- has evolved over the decades from fascia lata or silk to
ciency may be considered prior to emergent cerclage currently a wide selection of non-absorbable sutures,
placement. Although ACOG supports cervical cer- including Mersilene® tape (Dacron® tape), Prolene®
clage placement up to 28 weeks gestation, many prac- (monofilament), and Ethibond® (braided, coated
titioners would not recommend cerclage placement polyester).26 The choice of suture is based on practi-
beyond the limit of fetal viability (≥24 weeks), tioner preference and choice of technique. Shirodkar
because the risk of complications outweighs the cerclage is a single suture placed submucosally
potential benefit.7, 16 Furthermore, placement of a cer- around the cervix at the level of the internal os after
clage in a patient that is in preterm labor (actively con- surgically reflecting the bladder anteriorly and the rec-
tracting) is contraindicated due to the risks of cervical tum posteriorly.27 The suture can be secured anteriorly
trauma and/or uterine rupture caused by maternal con- or posteriorly, and the mucosal incisions closed.
tractions against a surgically sutured cervix. McDonald cerclage is 1 or more purse-string sutures
around the cervix placed without dissection of the
Technical considerations. Once the decision has been bladder or rectum.20 These 2 types of cerclage are
made to proceed with cerclage placement, a preopera- likely equally efficacious, but have never been tested
tive ultrasound examination should be performed to “head-to-head” in a well-designed clinical trial.
confirm fetal viability and exclude major structural Transabdominal cerclage has not been compared
anomalies. Regional anesthesia is preferred to general directly with transvaginal cerclage, and is a far more
endotracheal anesthesia because of the decreased invasive procedure requiring a laparotomy and subse-
maternal morbidity. Prophylactic tocolysis may be quent cesarean delivery. Transabdominal cerclage
used to inhibit transient uterine contractions associ- should therefore be reserved for women in whom a
ated with emergent cerclage placement, but there is no prophylactic cerclage is indicated but technically
objective evidence that tocolysis improves outcome. impossible to place transvaginally or that have failed
Prophylactic broad-spectrum antibiotics are recom- previous prophylactic transvaginal cerclage
mended for emergent cerclage placement. However, placement.28, 29
there are insufficient data to recommend routine use
of prophylactic antibiotics for elective cerclage place- Once a cerclage is in place, weekly or biweekly fol-
ment. If the fetal membranes are found to be prolaps- low-up visits for cervical examinations are probably
ing through the external os, the risk of iatrogenic rup- sufficient in the absence of clinical symptoms. Cervi-
ture of the fetal membranes may be as high as 50%. cal assessment may be by simple bimanual examina-
Trendelenburg position,17 retrograde filling of the tion or by ultrasound to assess the length of cervix,
bladder,18 placement of a 30 mL Foley catheter any loosening of the suture or prolapse of membranes
trancervically past the internal os and filling the bal- through the suture, tearing of the cervix, loss of the
loon,19 placement of a moistened sponge forceps into surgical knot, or loss of the suture. Modified bed rest
the cervical os,20 and/or therapeutic amniocentesis21-23 and “pelvic rest” (no coitus, tampons, or douching)
can be used to reduce the fetal membranes prior to cer- are usually recommended until a favorable gestational
clage placement. In addition, the edges of the cervix age is reached, but without proven benefit. The cer-
can be grasped by sponge forceps to build length to clage is usually removed electively at 37 weeks gesta-
the cervix for cerclage placement.24 tion, but earlier removal may be necessary in the event
of premature uterine contractions. In the setting of
Transvaginal cervical cerclage has been the mainstay preterm PROM, evidence of amnionitis should
for the management of cervical insufficiency. There prompt immediate removal of the cerclage. In preterm
are 2 basic types of transvaginal cerclage placement PROM without evidence of infection, the risk of pre-
techniques: Shirodkar and McDonald.25 The choice of mature delivery with removal must be weighed


2. Preterm Labor

against the risk of ascending infection with a foreign Preterm (premature) labor refers to labor occurring
body in place.30, 31 prior to 37 completed weeks of gestation. This should
be differentiated from preterm contractions without
Complications. Complications of cervical cerclage documentation of cervical change (effacement and
increase with increasing gestational age and cervical dilatation). Preterm birth occurs in 7%-12% of all
dilatation (Table 3). Cervical cerclage is also associ- deliveries, but accounts for over 85% of all perinatal
ated with increased obstetric interventions, including morbidity and mortality.33, 34
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 Preterm labor represents a syndrome rather than a
as the incidence in gestational age-matched controls diagnosis since the etiologies are varied. Preterm labor
without cerclage.5, 32 There is no demonstrable associa- may reflect a breakdown in the normal mechanisms
tion between the presence of a cerclage and preterm responsible for maintaining uterine quiescence, or a
PROM remote from placement. 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.


Preterm labor is a clinical diagnosis characterized by

increasing intensity and frequency of uterine contrac-

Table 3

Complications of Cervical Cerclage

≤48 hours)
Short-term (≤ Long-term (>48 hours)

Premature rupture of fetal membranes Cervical laceration (3%-4%)

Excessive blood loss (may require blood transfusion) Chorioamnionitis (4%)

Pregnancy loss (abortion) Cervical stenosis (1%)

Complications from anesthesia Other rare complications (including

fetal growth restriction, fetal demise,
thrombophlebitis, placental abruption,
bladder pain, migration of suture)


tions leading to effacement and dilatation of the tion), but have a higher incidence of adverse effects,
cervix, and culminating in expulsion of the products including maternal tachycardia, EKG changes, and
of conception prior to 37 weeks of gestation. 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-

Screening tions, such as patent ductus arteriosus that is refrac-

Several risk factors for preterm labor have been tory to pharmacological therapy, especially if given
described (Table 4). However, risk factor screening shortly prior to delivery.60-63 Calcium channel block-
alone will fail to identify over 50% of pregnancies that ers (nifedipine and amlodipine) are becoming
deliver preterm.38, 39 As such, a number of modalities increasing popular agents for tocolysis, since they can
have been developed in an attempt to identify women be orally administered, but maternal hypotension and
at high-risk of preterm birth (Table 5).40-50 Currently, cardiac arrhythmias are a concern.64, 65 Promising
the most reliable screening tests include serial sono- newer agents include oxytocin receptor antagonists
graphic measurement of cervical length42, 43 and/or (used commonly in Europe) and selective cyclooxy-
measurement of fetal fibronectin (fFN) in cervicov- genase-2 inhibitors.66, 67
aginal secretions.46-48
A single course of antenatal glucocorticoids
Clinical Management decreases the incidence of respiratory distress syn-
In the setting of preterm labor, bed rest and hydration drome (RDS), intraventricular hemorrhage (IVH),
are commonly recommended but without proven effi- and necrotizing enterocolitis (NEC) by 50%, and is
cacy.51 Pharmacologic tocolytic therapy remains the recommended for all pregnancies at high risk of
cornerstone of modern management. Although a delivering before 34 weeks gestation with intact
number of alternative agents are now available (Table membranes and before 32 weeks gestation with
6), only ritodrine hydrochloride has received approval preterm PROM.68-70 Maximal benefit is achieved 24-
from the Food and Drug Administration (FDA) of the 48 hours after the initial dose. This effect lasts for 7
United States (FDA) for the treatment of preterm days, but it is unclear what happens thereafter.
labor. The risks and benefits of the individual drugs Repeated courses of steroids are not generally recom-
have been reviewed in detail elsewhere.35, 52-54 All of mended, although a single rescue dose (or rescue
the recommended agents appear equally effective in course) may be appropriate if the initial course was
delaying delivery for 24-48 hours, thereby creating a administered prior to 28-30 weeks gestation.71, 72
window of opportunity for antenatal corticosteroid
administration. There is no good clinical evidence that Tocolysis should be continued until preterm labor has
any of these agents can prolong pregnancy beyond 48 been effectively halted, or empirically until 48 hours
hours and prevent preterm delivery.55 Since no single after the first dose of corticosteroid. Maintenance
agent has a clear therapeutic advantage, the side-effect tocolytic (including terbutaline pump or chronic oral
profile of each of the drugs will often determine which tocolysis) therapy has not been shown to confer any
to use in a given clinical setting. therapeutic benefit73, 74 and poses a risk of adverse side
effects. Similarly, concurrent use of 2 or more
Intravenous magnesium sulfate as a continuous infu- tocolytic agents has not consistently been shown to be
sion has a wide margin of safety and has traditionally more effective than a single agent and exposes the
been regarded as the first-line agent for use in preterm parturient to cumulative risk of side effects, including
labor in North America. More recently, however, this pulmonary edema.75, 76 The use of sequential therapy,
agent has fallen out of favor because of its potential however, may be beneficial if initial therapy is unsuc-
risk of maternal cardiopulmonary failure from over- cessful.77 Although effective in the setting of preterm
dose or neonatal rickets and neurologic injury from PROM, there is no role for broad-spectrum antibiotic
prolonged or excessive use.56, 57 Adrenergic agonists therapy to prolong latency in preterm labor with intact
are commonly used (eg, subcutaneous terbutaline in membranes.78
an injection, continuous infusion or oral administra-


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


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

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%).


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


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.

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- fetal weight > 4500 g84 ) (2.5%-10% vs. 0.8%-
nancy that has extended to or beyond a gestational age 1%).85, 86 Complications associated with fetal macro-
of 42.0 weeks (294 days) from the first day of the last somia include prolonged labor, cephalopelvic dis-
menstrual period.79, 80 In the United States, around proportion and shoulder dystocia, with resultant
10% of all singleton pregnancies continue beyond 42 risks of orthopedic or neurologic injury.84 Post-term
weeks of gestation and 4% continue beyond 43 pregnancies are also at increased risk of umbilical
completed weeks in the absence of obstetric interven- cord compression from oligohydramnios, nonreas-
tion.79, 80 Post-term pregnancy should be differentiated suring fetal antepartum or intrapartum assessment,
from a post-mature pregnancy, which is a distinct clin- meconium aspiration, short-term neonatal complica-
ical fetal syndrome consisting of a fetus that has wrin- tions (hypoglycemia, seizures) and long-term neuro-
kled, peeling skin with a thin body, and meconium- logic sequelae.
stained skin and nails that is diagnosed postnatally.81, 82
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.

Primiparity and prior post-term pregnancy are the 2.6% at term) and a doubling in the rate of cesarean
most common identifiable risk factors for a post-term delivery.87-89 The latter is associated with higher risks
pregnancy. Rarely, post-term pregnancy may be asso- of complications such as endometritis, hemorrhage,
ciated with placental sulfatase deficiency or fetal and thromboembolic disease.
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 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

Accurate pregnancy dating is critical to the diagnosis. uterine sizing. Uncertainty in historical or physical
The incidence of post-term pregnancy depends upon dating parameters should prompt ultrasound assess-
the patient population, including such factors as the ment of gestational age.90
percentage of primigravid women, women with preg-
nancy complications, the prevalence of ultrasound Post-term pregnancy is an accepted indication for
assessment of gestational age and the frequency of antenatal fetal monitoring. ACOG has recommended
spontaneous preterm birth. Local practice patterns, that antepartum fetal surveillance be initiated after 42
such as the rates of scheduled cesarean delivery and weeks of gestation, without a specific recommenda-
routine labor induction, will also affect the overall tion regarding type of test or frequency.79, 80 Options for
incidence of post-term birth. 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

Post-term pregnancy is associated with both fetal these modalities; no single method has been shown to
and maternal risks. Perinatal mortality (stillbirths be superior. Umbilical artery Doppler velocimetry
plus early neonatal deaths) at ≥42 weeks of gestation testing alone has not been shown to be beneficial in
is twice that at term (4-7 vs. 2-3 per 1000 deliveries) monitoring the post-term fetus.79 It should be noted
and increases 4-fold at 43 weeks and 5- to 7-fold at that there is insufficient evidence to show that initiat-
44 weeks.79, 80, 83 Chronic uteroplacental insuffi- ing antenatal surveillance between 40 and 42 weeks of
ciency, asphyxia and intrauterine infection all con- gestation improves pregnancy outcome or confers any
tribute to the excess perinatal deaths. Post-term benefit to the fetus.79
infants are larger than term infants, with a higher
incidence of macrosomia (defined as an estimated


4. Hypertensive Disorders
of Pregnancy

Delivery is recommended when the risks to the fetus Hypertensive disorders of pregnancy are the second
by continuing the pregnancy are greater than those most common cause of maternal death in the United
faced by the neonate after birth. Both expectant man- States (behind venous thromboembolic disease),
agement and labor induction are associated with low accounting for 15%-20% of all maternal deaths.94, 95
complication rates in low-risk post-term gravida.91-93 Hypertension is also associated with high perinatal
Factors that need to be considered include gestational mortality and morbidity rates, primarily due to iatro-
age, results of antepartum fetal assessment, favorabil- genic prematurity.96 Hypertensive disorders of preg-
ity of the cervix, and maternal preference. Delivery nancy can be classified into 4 categories:
should be initiated immediately if there is evidence of
fetal compromise or oligohydramnios. There does 1.) Chronic hypertension is defined as hypertension
appear to be a small advantage to routine induction of prior to pregnancy and should also be considered in
labor at 41 weeks gestation, regardless of parity or parturients with a sustained BP ≥140/90 prior to 20
method of induction.87, 88 In women with unfavorable weeks gestation. Such pregnancies are at increased
cervical exams, the routine use of preinduction cervi- risk of superimposed preeclampsia, uteroplacental
cal ripening has resulted in fewer failed and serial insufficiency and IUGR, placental abruption and still-
inductions, lower fetal and maternal morbidity, a birth. Angiotensin converting enzyme (ACE)
shorter hospital stay, lower medical cost and possibly inhibitors should be discontinued in pregnancy. These
a lower rate of cesarean delivery in the general obstet- drugs have not consistently been associated with an
ric population. The post-term fetus is at increased risk increased risk of structural anomalies in the first
of intrapartum fetal heart rate abnormalities and pas- trimester over baseline, but exposure in the latter half
sage of meconium. For this reason, continuous elec- of pregnancy has been associated with progressive
tronic fetal monitoring in labor is recommended for and irreversible renal injury in the fetus, including
such pregnancies. 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-

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


difficult to distinguish from preeclampsia. PIH (but not
preeclampsia) is associated with an increased risk of

chronic hypertension in later life. Preeclampsia is a clinical diagnosis encompassing 3

elements: (1.) new-onset hypertension (defined as a
4.) Preeclampsia, also known as gestational protein- sustained sitting BP ≥140/90 in a previously nor-
uric hypertension, complicates 6%-8% of all pregnan- motensive woman); (2.) new-onset proteinuria (>300
cies.94, 100, 101 It is an idiopathic multisystem disorder mg/24 h or ≥1+ on a clean-catch urinalysis in the
specific to human pregnancy and the puerperium. absence of urinary infection); and (3.) nondependent
More precisely, it is a disease of the placenta since it edema.100, 101 However, more recent consensus reports
occurs also in pregnancies where there is trophoblast have suggested eliminating edema as a criterion for
but no fetal tissue (complete molar pregnancies). the diagnosis.109 A definitive diagnosis of preeclamp-
Preeclampsia is discussed in more detail below. 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-

The pathogenesis of preeclampsia remains poorly pholipid antibody syndrome, drug withdrawal, multi-
understood. At present, 5 hypotheses are the subject of ple pregnancy, or chromosomal abnormality (trisomy)
intense investigation:100-103 (1.) genetic imprinting; (2.) in the fetus.
immune maladaption; (3.) placental ischemia; (4.)
generalized endothelial dysfunction; and (5.) defec- Preeclampsia is classified as either “mild” or “severe”
tive-free fatty acid, lipoprotein and/or lipid peroxidase (there is no category of “moderate” preeclampsia). A
metabolism. However, there is as yet no single unify- diagnosis of severe preeclampsia should be enter-
ing theory that can account for all of the findings in tained in women with new-onset proteinuric hyperten-
preeclampsia. Although the pathophysiology of sion along with 1 or more of a series of complications
preeclampsia is not well understood, it is clear that the (Table 7). IUGR was excluded from the criteria in
blueprint for its development is laid down early in 2000 by the National High Blood Pressure in Preg-
pregnancy. It has been suggested that the pathologic nancy Working Group because of inconsistencies in
hallmark is a complete or partial failure of the second its definition, but was still included as a criterion for
wave of trophoblast invasion from 16-20 weeks of the diagnosis of severe preeclampsia by ACOG in
gestation that, in normal pregnancies, causes destruc- 2002.101 Mild preeclampsia includes all women with
tion of the muscularis layer of the spiral arterioles.104-106 preeclampsia, but without any features of severe dis-
As pregnancy progresses, the metabolic demands of ease.
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 Timing of Delivery

increase in blood flow, resulting in “placental dysfunc- Delivery is the only effective treatment for preeclamp-
tion” that manifests clinically as preeclampsia. Recent sia. Delivery is recommended in women with mild
data suggest that excessive placental production of the preeclampsia once a favorable gestational age has been
fms-like tyrosine kinase receptor (also known as solu- reached (>36-37 weeks) and in all women with severe
ble Flt-1 [sFlt-1]), the soluble form of the vascular preeclampsia regardless of gestational age (with the
endothelial growth factor (VEGF) receptor type I that exception of severe preeclampsia due to proteinuria
binds both circulating VEGF and placental growth fac- alone or IUGR remote from term with good fetal test-
tor, may be responsible for the widespread endothelial ing). There has also been a recent trend towards expec-
injury that characterizes preeclampsia.107, 108 In this way, tant management of severe preeclampsia by BP criteria
sFlt-1 may be the elusive “toxemia factor” of alone <32 weeks gestation.110, 111 Every effort should be
preeclampsia. Although attractive, this hypothesis made to delay delivery for 24-48 hours to administer
remains to be validated. antenatal corticosteroids, if indicated.


Table 7

Diagnostic Features of Severe Preeclampsia


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)


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)


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


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


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.


5. Intrauterine Fetal Demise

Intrauterine fetal demise (IUFD)—also known as IUFD by documenting the absence of fetal cardiac
stillbirth—is defined in the United States as fetal activity. Other sonographic findings in later preg-
demise after 20 weeks gestation and prior to deliv- nancy may include scalp edema, overlapping
ery.127 In the United States, the stillbirth rate decreased sutures and fetal maceration.
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 Every effort should be made to avoid cesarean deliv-
maternal disease, such as pregestational diabetes, sys- ery in the setting of IUFD. As such, expectant man-
temic lupus erythematosus (SLE) and preeclamp- agement is often recommended. Latency (the period
sia.129, 130 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-

Causes of IUFD can be identified in only around 50% neous labor within 2 weeks of fetal death. However,
of cases (Table 10). Pathologic examination of the many women find the prospect of carrying a dead
fetus and placenta/fetal membranes is the single most fetus distressing and want the pregnancy terminated as
useful test to identify a cause for the IUFD. Early soon as possible. Management options include surgi-
detection and appropriate management of underlying cal dilatation and evacuation or induction of labor
maternal disorders (diabetes, preeclampsia) may with cervical ripening, if indicated. Around 20%-25%
reduce the risk of IUFD.131, 132 Fetal karyotyping should of women who retain a dead singleton fetus for longer
be considered in all cases of fetal death to identify than 3 weeks will develop disseminated intravascular
chromosomal abnormalities, particularly in cases with coagulopathy (DIC) due to excessive consumption of
documented fetal structural abnormalities. Approxi- clotting factors.137, 138 Therefore, delivery should be
mately 6%-10% of stillborn fetuses have abnormal effected within this time period.
karyotypes.133 Amniocentesis may be recommended
to salvage viable amniocytes for cytogenetic analysis Death of a Co-twin
prior to delivery. Fetal-maternal hemorrhage (fetal The death of 1 twin confers an increased risk of major
cells spilling into maternal circulation) occurs in all morbidity to the surviving twin, including IUFD, neu-
pregnancies, but is usually minimal (<0.1 mL total rologic injury, multiorgan system failure, thrombosis,
volume). In rare instances, fetal-maternal hemorrhage distal limb necrosis, placental abruption and prema-
may be massive, leading to fetal demise. The Klei- ture labor.99-101 The prognosis for the surviving twin is
hauer-Betke (acid elution) test allows an estimate of dependent on the cause of death, gestational age,
the volume of fetal blood in the maternal circulation, chorionicity and time interval between death of the
and should be drawn within 6 - 8 hours of the pur- first twin and delivery of the second. Dizygous twin
ported time of bleeding episode due to rapid clearance pregnancies do not share circulation, and the death of
of fetal cells from maternal circulation.134 Intra-amni- 1 twin may have little impact on the surviving twin.
otic infection resulting in fetal death is usually evident The dead twin may be resorbed completely or become
on clinical exam. Placental membrane culture and compressed and incorporated into the membranes
autopsy examination of the fetus, placenta/fetal mem- (fetus papyraceus). DIC in the surviving fetus and/or
branes and umbilical cord may be useful. Fetal x-rays mother is rare.102 On the other hand, some degree of
or MRI may sometimes be valuable if autopsy is shared circulation can be demonstrated in almost all
declined.135, 136 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

The inability to identify fetal heart tones or the to the live fetus.143 If it survives, the co-twin, has a 40%
absence of uterine growth may suggest the diagno- risk of developing neurologic injury (multicystic
sis. Ultrasound is the gold standard to confirm an


6. Intrauterine Growth Restriction

encephalomalacia), which may not be prevented by Birth weight is a function of both gestational age and
immediate delivery.144, 145 Therefore, management of a rate of fetal growth. Intrauterine growth restriction
surviving co-twin depends on chorionicity and gesta- (IUGR) refers to any fetus that fails to reach its full
tional age. Fetal surveillance (kickcharts, nonstress growth potential. In the United States, 4%-8% of
testing, biophysical profile) should be instituted on a fetuses are diagnosed with IUGR.146, 147 IUGR should
regular basis, and delivery considered in the setting of be differentiated from the term SGA (small for gesta-
nonreassuring fetal testing or at a favorable gesta- tional age), a term commonly used by the pediatri-
tional age. cians to represent both constitutionally small
neonates that are healthy and the growth restricted
fetus that is at risk for poor perinatal outcomes.148


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.


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-

Table 10

Causes of Intrauterine Fetal Demise (IUFD)

Maternal causes Uteroplacental causes Fetal causes

Underlying medical conditions Placental abruption Fetal chromosomal /

(diabetes mellitus, thyroid disease, genetic anomalies
antiphospholipid antibody syndrome)

Preeclampsia Placenta previa Fetal structural abnormalities

Isoimmunization Vasa previa Intra-amniotic infection

Illicit drug use (cocaine) Fetal-maternal hemorrhage Complications of multiple

pregnancies (including twin-to-twin
transfusion syndrome)

Antepartum drug / toxin exposure Cord accident


centile (2 standard deviations from the mean) for ges- pregnancies should be followed on a regular basis to
tational age, or (2.) an EFW <10th percentile for gesta- exclude this complication.
tional age along with evidence of fetal compromise
(usually oligohydramnios or abnormal umbilical IUGR fetuses can undergo vaginal delivery and
artery Doppler velocimetry).146,147,149 Fetuses who are cesarean delivery should be reserved for the usual
<10th percentile without evidence of compromise obstetric indications. However, up to 50%-80% of
should be referred to as SGA and not IUGR. Accurate IUGR fetuses will show evidence of nonreassuring
gestational age dating is clearly a prerequisite for the fetal testing in labor requiring cesarean delivery.146
diagnosis. A small calcified (Grade 3) placenta Timing of delivery also depends on the precise gesta-
detected on ultrasound examination in association tional age, any superimposed maternal conditions (eg,
with a small biparietal circumference may also be sug- severe preeclampsia), the presence or absence of
gestive of an IUGR pregnancy.150 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


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


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

Uteroplacental Causes

Uteroplacental insufficiency Velamentous cord insertion

Chronic hypertension


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

Confined placental mosaicism


7. Multiple Pregnancy

Multiple pregnancies complicate 1%-2% of all deliv- monochorionic (no peak, but a thin filmy mem-
eries and are becoming increasingly common, primar- brane).162 Identification of separate sex fetuses or 2
ily as a result of assisted reproductive technology separate placentae confirms dichorionic/diamniotic
(ART). This is especially true of higher-order multiple placentation.
pregnancies (triplets and up) which now constitute
0.103% of all births.156 The vast majority (97%-98%)
of multiple gestations are twin pregnancies.

Overall, antepartum complications develop in 80% of

multiple pregnancies, compared with around 30% of
singleton gestations (Table 12).163 Preterm delivery is

Multiple pregnancy should be suspected in women at the most common complication, and the risk of
high risk, women with excessive symptoms of preg- preterm delivery increases as fetal number increases:
nancy (such as nausea and vomiting), or uterine size the average length of gestation is 40 weeks in single-
larger than expected. The overall incidence of dizy- tons, 37 weeks in twins, 33 weeks in triplets, and 29
gous twinning in the U.S. is around 1 in 89 pregnan- weeks in quadruplets.164 Fetal growth discordance
cies, and is influenced by a number of epidemiologic (defined as a ≥25% difference in EFW between
factors, including a family or personal history of mul- fetuses of the same pregnancy) occurs in 5%-15% of
tiple pregnancy, advanced maternal age, multiparity, twins and 30% of triplets, and is associated with a 6-
African American, and ART.157 Monozygous twin- fold increase in perinatal mortality.165,166 Cord entan-
ning, on the other hand, is a random event that occurs glement is rare (1 in 25,000 births), but may occur in
in around 1 in 300 pregnancies (although the risk may up to 70% of monochorionic/monoamniotic pregnan-
be increased 2- to 3-fold with in vitro fertilization).158 cies, and accounts for >50% of perinatal mortality in
Ultrasound will confirm the diagnosis. this subgroup.163,167,168 Maternal complications include
an increased risk of gestational diabetes, preeclamp-
Zygosity and Chorionicity sia, anemia, cholestasis of pregnancy,169 cesarean
80% of twin pregnancies are dizygous (derived from 2 delivery (due primarily to malpresentation), and post-
separate embryos). Perinatal mortality is higher with partum hemorrhage.
monozygous (30%-50%) than with dizygous twins
(10%-20%). Chorionicity refers to the arrangement of Twin polyhydramnios/oligohydramnios
membranes in multiple pregnancies. In monozygous (“poly/oligo”) sequence results from an imbalance in
twinning, the timing of the cell division determines blood flow from the “donor” twin to the “recipient.”
the chorionicity. If the zygote divides within 3 days of Both twins are at risk for adverse events. Twin-to-twin
fertilization, the result is dichorionic/diamniotic pla- transfusion syndrome is a subset of polyhydram-
centation (30% of all monozygous pregnancies); if the nios/oligohydramnios sequence seen in 15% of
division occurs between day 3 and day 8, the result is a monochorionic pregnancies,170, 171 and is due to unbal-
monochorionic/diamniotic pregnancy (65%); anced vascular communications between the fetal cir-
between day 8 and day 13, a monochori- culations. One twin is usually appropriate for gesta-
onic/monoamniotic pregnancy ensues (<5%); and if tional age (AGA) while the other twin is usually
the division occurs on or after day 13, incomplete sep- IUGR. The IUGR twin is typically in the oligohy-
aration (conjoined twins) is the rule (<0.5%). Chori- dramniotic sac and is compressed against one edge of
onicity correlates directly with perinatal mortality, the uterus, also known as the “stuck twin” syn-
which is especially high with monochori- drome.172 Following delivery, a difference in birth
onic/monoamniotic twins (65%-70%). Chorionicity weight of ≥20% or a difference in hematocrit of ≥5
is determined most accurately by examination of the g/dL confirms the diagnosis. The larger twin is often
membranes after delivery. Antenatal diagnosis is polycythemic while the IUGR twin is anemic. Prog-
more difficult.159-161 Typically, ultrasound examination nosis depends on gestational age, severity, and under-
in the first half of the pregnancy can be performed to lying etiology. Overall perinatal mortality is 40%-
evaluate the point at which the amniotic/chorionic 80%.173, 174 Treatment options include expectant man-
membranes arise from the placenta to determine if the agement, serial amniocentesis of the polyhydramni-
fetuses are dichorionic (twin peak or lamda sign) or otic sac, indomethacin (to decrease fetal urine output),


laser obliteration of the placental vascular communi- are several management considerations specific to
cations or selective fetal reduction.175-178 multiple gestation, outlined below.

Management Multifetal Pregnancy Reduction

Gravidas with multiple gestations should be coun- Overall, 10%-15% of higher-order multiple pregnan-
seled about the increased risk of preeclampsia, cies (triplets and up) will reduce spontaneously dur-
preterm labor, postpartum hemorrhage, anemia, fetal ing the first trimester.164 If not, the option of multifetal
loss, fetal anomalies, IUGR, and cesarean delivery. pregnancy reduction to twins at 13-15 weeks should
Principles of management include early diagnosis, be discussed. The benefits of reduction include
screening for fetal anomalies, determination of chori- increased length of gestation, increased birth weight,
onicity, and regular antepartum follow-up (serial and reduced prematurity and perinatal mortality and
ultrasound for growth at least every 3-4 weeks to mortality.164, 181-183 The procedure-related loss rate prior
screen for discordant growth).179 Maternal serum to 20 weeks may be as high as 15% (range: 5%-35%),
alpha-fetoprotein (MS-AFP) screening for multiple which is comparable to the background risk for
gestation is a reliable screen for neural tube defects; higher-order multiple pregnancies.164, 182-185 However,
however, serum biochemical marker screening for the fetal loss rate increases with advancing gestation
aneuploidy in the presence of more than one fetus is at the time of the reduction. Multifetal pregnancy
not particularly reliable, due to the inherent structure reduction should be distinguished from selective fetal
of the test parameters.180 Maternal plasma volume is reduction, in which one fetus is selectively terminated
increased by 100%-200% with multiple gestation, because of a known structural or chromosomal
placing the gravida at higher risk for anemia. Addi- abnormality.186, 187
tional folate and iron supplementation should be con-
sidered in multiple gestation. Multifetal pregnancies
are at higher risk for cesarean delivery. Patients should
Screening for Congenital Anomalies

be counseled about labor analgesia and anesthesia, the Using twin populations, maternal serum alpha-feto
possible need for emergent delivery, and the need for protein (MS-AFP) and “quadruple panel” screening
multiple pediatric teams in the delivery room. There (MS-AFP, estriol, hCG and activin A) has been stan-

Table 12

Complications of Multiple Pregnancy

Maternal complications Uteroplacental complications Fetal complications

Anemia Placenta previa Fetal growth discordance

Hyperemesis gravidarum Preterm PROM IUGR

Gestational diabetes Cord entanglement IUFD of one or both twins

Preterm labor Postpartum hemorrhage Congenital anomalies

Cesarean delivery Twin-to-twin transfusion syndrome


8. Premature Rupture
of Membranes

dardized for twins as it is for singletons at 15-20 PROM refers to rupture of the fetal membranes prior
weeks.188, 189 In dizygous pregnancies, the risk of aneu- to the onset of uterine contractions.198 It can be clas-
ploidy (genetic abnormality) is independent for each sified as term PROM (≥37 weeks) or preterm PROM
fetus. As such, the chance that 1 or both fetuses have a (<37 weeks). Latency (the time interval between
karyotypic abnormality is greater than for a singleton. PROM and delivery) is dependent on several factors:
Amniocentesis is recommended when the probability (1.) gestational age (at term, 50% of women with
of aneuploidy is equal to or greater than the proce- PROM will go into spontaneous labor within 12 hours
dure-related pregnancy loss rate (estimated at 1 in and 95% within 72 hours; latency is generally longer
270).190, 191 In singleton pregnancies, this balance is if PROM occurs preterm with 50% of women going
reached at a maternal age at delivery of 35 years. In into labor within 24-48 hours and 70%-90% within 7
twin pregnancies, amniocentesis should be offered to days)199; (2.) severity of oligohydramnios (severe
women at approximately 32 years of age.192, 193 oligohydramnios is associated with shortened latency
period );200 and (3.) number of fetuses (twins have a
Route of Delivery shorter latency period than singletons).201

The recommended route of delivery of twins depends

on presentation, gestational age (or EFW), concor-

dance, and maternal and fetal well-being. Prior PROM is a clinical diagnosis with evidence of vaginal
cesarean is not an absolute contraindication to vaginal pooling of amniotic fluid on sterile speculum exami-
delivery of twins.194 Breech extraction of a nonvertex, nation, which is alkaline (vaginal fluid turns yellow
concordant second twin is a safe procedure,195, 196 but nitrazine paper blue) and demonstrates “ferning”
should only be performed by an experienced obstetric (microscopic crystallization) on drying. Evidence of
care provider. Preparation for a possible breech diminished amniotic fluid volume on ultrasound may
extraction should include an ultrasound machine to help to confirm the diagnosis, but is not a prerequisite
assist in evaluation of fetal heart rate and presentation, for the diagnosis. Sometimes a gush of fluid can be
specialized forceps to assist in delivery of the after- observed to emanate from the cervix when a patient
coming head (Piper forceps), an experienced anesthe- coughs during a speculum exam. The fluid should also
siologist and a uterine relaxant, such as intravenous be categorized as clear, blood-tinged, or meconium-
nitroglycerin or halothane by mask. Cesarean delivery stained. Differential diagnosis includes leakage of
has traditionally been recommended for multiple urine and vaginal discharge. If equivocal, an amnio-
pregnancies in which the presenting fetus is not vertex centesis can be performed with instillation of indigo
and for all higher-order multiple pregnancies, carmine dye into the amniotic cavity (“amnio-dye
although vaginal delivery may be appropriate in test”). Leakage of the dye into the vagina as evidenced
selected patients.197 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.


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 amniotic infection. Patients should be placed on
cesarean delivery. In this setting, amnioinfusion with pelvic rest (no tampons, no douching, no sexual inter-
saline has been shown to decrease the risk of cesarean course). A screening sonogram should be performed
for non-reassuring fetal testing (but has not necessar- to determine fetal presentation as non-vertex presen-
ily been shown to improve perinatal outcome). 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

Preterm PROM complicates 2%-4% of singleton and preterm PROM include:

7%-10% of twin pregnancies. It is associated with
30%-40% of preterm births and 10% of all perinatal 1.) Tocolysis. Preterm PROM is a relative contraindi-
mortality.204 Risk factors include prior preterm PROM, cation to tocolysis to prevent undue exposure of
unexplained vaginal bleeding, placental abruption fetuses to infected in utero environment, with subse-
(seen in 10%-15% of women with preterm PROM, quent postnatal risk of neurologic injury and cerebral
but may be a result rather than a cause),205 cervical palsy.207 Tocolytic agents may delay delivery by 24-48
insufficiency, vaginal or intra-amniotic infection, hours in the setting of intact membranes, but do not
amniocentesis, smoking, multiple pregnancy, polyhy- appear to delay delivery or improve perinatal out-
dramnios, chronic steroid treatment, connective tissue come in pregnancies complicated by preterm
diseases (systemic lupus erythematosus, Ehlers-Dan- PROM.204
los syndrome), anemia, low socioeconomic status and
unmarried marital status. Factors which are not associ- 2.) Antibiotics. Prophylactic broad-spectrum antibi-
ated with preterm PROM include coitus, cervical otic therapy has consistently been shown to prolong
examinations, maternal exercise and parity. The recur- latency in the setting of preterm PROM,208, 209 and this
rence risk is 20%-30%.204 appears to translate into an improvement in perinatal
outcome. There is currently no evidence to recom-
Complications mend 1 antibiotic regimen over another. The most
Neonatal complications are related primarily to pre- commonly used antibiotic regimen is ampicillin and
maturity, including RDS, IVH, sepsis, pulmonary erythromycin for 7 days.
hypoplasia (especially with preterm PROM <22
weeks) and skeletal deformities/limb strictures 3.) Antenatal corticosteroids. A single course of
(related to severity and duration of preterm PROM). antenatal glucocorticoids is recommended for all
Overall, preterm PROM is associated with a 4-fold pregnancies at high risk of delivering before 34 weeks
increase in perinatal mortality and a 3-fold increase in gestation with intact membranes and before 32 weeks
neonatal morbidity.204, 206 The fetus is at risk for devel- with preterm PROM with a view to decreasing the
oping chorioamnionitis, stillbirth from cord accident incidence of RDS, IVH and NEC.68-70 The benefit of
or placental abruption, non-reassuring fetal heart rate antenatal corticosteroids in pregnancies complicated
tracings or precipitous delivery. Maternal complica- by preterm PROM at 32-34 weeks gestation is not
tions include increased rates of cesarean delivery, clear.70
intra-amniotic infection and postpartum endometritis.
4.) Fetal surveillance. Fetuses in pregnancies com-
Management plicated by preterm PROM are at risk for ascending
Management of preterm PROM should be individual- infection, cord accident, placental abruption and (pos-
ized. The risk of prematurity should be weighed sibly) uteroplacental insufficiency. Amniocentesis
against the risk of expectant management, primarily may be considered in the setting preterm PROM to
intra-amniotic infection.204, 206 Amniotic fluid can be test for evidence of intra-amniotic infection and to
used to assess fetal lung maturity by testing for the confirm fetal lung maturity with a view to affecting an
lethicin/sphingomyelin (L/S) ratio and presence of earlier delivery. In some cases, vaginal pooled amni-
phosphatidyl glycerol (PG). In the setting of expectant otic fluid can be aspirated and tested for fetal lung
management for preterm PROM, new onset uterine maturation. Loss of fetal breathing in the BPP was
contractions may portend the development of intra-


9. Antepartum Hemorrhage

Antepartum hemorrhage is defined as vaginal bleed-

ing after 24 weeks gestation and before labor, and
previously hailed as an early sign of intrauterine infec- complicates 4%-5% of all pregnancies. Placenta pre-
tion, but more recent studies have refuted this idea.210 via (20%) and placental abruption (30%) are the most
In the absence of evidence of uteroplacental insuffi- common causes of antepartum hemorrhage. Other
ciency, fetal surveillance has not been demonstrated to causes include vasa previa, early labor and
reliably diagnose or predict intra-amniotic infection. lesions/lacerations of the lower genital tract.
Fetal surveillance should therefore be instituted only
for the usual obstetric indications, such as fetal non-
stress testing (NST) to assess for variable decelera-
Placenta Previa

tions in the setting of oligohydramnios. 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

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 Complications. Maternal complications include mor-
The goal of antepartum management is to maximize tality (due to hemorrhage, cardiac failure or renal fail-
fetal maturation while minimizing risk to mother and ure [0.5%-5%]) and coagulopathy (10%). Fetal com-
fetus. Blind digital vaginal examination should be plications include IUFD in 10%-35% of cases due pri-
avoided in all women with antepartum hemorrhage marily to fetal hypoxia, exsanguination and/or com-
until placenta previa is excluded. Non-reassuring plications of prematurity. Chronic abruption is also
fetal testing and excessive maternal hemorrhage are associated with an increased rate of congenital
contraindications to expectant management, and may anomalies and IUGR.219, 221
necessitate immediate cesarean delivery irrespective
of gestational age. However, most episodes of antena- Management. Hospitalization is indicated to evalu-
tal bleeding are not life-threatening. With careful ate maternal and fetal condition. Mode and timing
monitoring, delivery can be safely delayed in most of delivery depends on the condition of the mother
cases. Placenta previa may resolve with time due to and fetus, and on gestational age. In the setting of
cephalic growth of the lower uterine segment, draw- hemodynamic instability, invasive monitoring and
ing the leading edge of the placenta away from the immediate delivery may be necessary. If the abrup-
internal os, thereby allowing vaginal delivery to pro- tion is mild and pregnancy is remote from term,
ceed. Indeed, only 5% of low-lying placentae iden- expectant management may be appropriate. Placen-
tified by ultrasound at 14-20 weeks gestation persist to tal abruption is a relative contraindication to tocoly-
term (although complete placenta previa is unlikely to sis, particularly with beta-agonists that may cause
resolve).218 Cesarean delivery is generally performed maternal tachycardia and increased pulse pressure
by 37 weeks gestation due to active maternal hemor- to the site of the abruption. The risk of cesarean
rhage or concern over impending risk of maternal delivery is increased primarily due to fetal
hemorrhage. If elective delivery of an asymptomatic compromise.
patient is planned prior to 39 weeks gestation, it
should be done only after documentation of fetal lung
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
Placental Abruption

Placental abruption refers to premature separation of of the fetus. Vasa previa is usually asymptomatic, but
the placenta from the underlying maternal decidua, may present with painless bright-red vaginal bleed-
and complicates 1 in 120 pregnancies.219, 220 Risk fac- ing, often associated with diminished fetal movement.
tors include hypertension, prior placental abruption, Since bleeding is from the umbilical vessels and is
trauma, smoking, cocaine, uterine anomaly or fetal in origin, fetal mortality is >75%, due primarily
fibroids, multiparity, advanced maternal age, preterm to fetal exsanguination. Diagnosis is by the bedside
PROM, bleeding diathesis and an overdistended Apt test (hemoglobin alkaline denaturation test),
uterus (multifetal gestations, polyhydramnios).220 Pla- which involves adding 2-3 drops of an alkaline solu-
cental abruption is a clinical diagnosis that may tion (NaOH) to 1 mL of blood. If the blood is mater-
include vaginal bleeding (80%), painful uterine con- nal, erythrocytes will rupture and the mixture will turn
tractions (35%), and abdominal tenderness (70%), brown. Fetal erythrocytes, on the other hand, are resis-
with or without non-reassuring fetal testing (50%). tant to rupture and the mixture will remain red. Emer-
The amount of vaginal bleeding is not a reliable indi- gent cesarean delivery is indicated regardless of gesta-
cator of the severity of the condition, because bleed- tional age if the fetus is viable. Brisk vaginal bleeding
ing may be concealed. A retroplacental collection of temporally related to spontaneous or artificial rupture
≥300 mL is necessary for sonographic visualization, of the membranes, particularly in light of a placenta
and only 2% of placental abruptions can be visualized previa or low-lying placenta, and acute changes in
on ultrasound. Serial measurements of fundal height fetal heart rate tracing, should prompt consideration of
and abdominal girth are useful to monitor large retro- this diagnosis.222
placental blood collections.


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11. Questions

1. A 27-year-old woman presents for her first prena- Regarding the management of preterm labor,
tal visit at 8 weeks gestation. She has a number of which of the following statements are true?
risk factors for cervical insufficiency. On review (More than 1 statement may be true.)
of her medical and obstetrical history, you con-
clude that she is a good candidate for elective cer- A. You should recommend strict bed rest and
vical cerclage. Which of the following elements of aggressive intravenous hydration as these
her history support this conclusion? interventions have been shown to prevent
preterm birth.
A. A history of in utero DES exposure.
B. You should start IV magnesium sulfate as
B. 3 prior first trimester elective pregnancy ter- this is the only drug approved by the FDA for
minations. the treatment of preterm labor.

C. A prior 20 week pregnancy loss C. You should start broad-spectrum antibiotic

characterized by painless cervical dilatation. therapy as this has been shown to prolong
D. A triplet pregnancy conceived through in
vitro fertilization. D. You should administer antenatal

2. A nulliparous woman presents at 18 weeks gesta-

tion complaining of a watery vaginal discharge. 4. A 28-year-old G4P3 is admitted to labor and
Sterile speculum examination reveals a cervix delivery at 29-3/7 weeks gestation with regular
which is 1-2 cm dilated and 80% effaced. After painful uterine contractions every 3 minutes.
reviewing the respective risks and benefits, the Bimanual examination shows her cervix to be
patient elects emergent cerclage placement over long and to admit a fingertip. Fetal heart rate
bed rest. At the time of cerclage placement, how- tracing is formally reactive with a baseline of
ever, you notice something which causes you to 130 bpm. A diagnosis of preterm contractions is
cancel the procedure. Which of the following clin- made. She has had 3 prior spontaneous preterm
ical findings would explain this change in plans? deliveries at 28-31 weeks gestation, and is very
concerned that this pregnancy will also end pre-
A. Evidence of uterine contractions. maturely. Which of the following statements
about screening for preterm labor are true?
B. Evidence of a vaginal yeast infection. (More than 1 statement may be true.)

C. Fetal membranes visible through the open

cervical os. A. Her history is highly predictive of preterm
birth. As such, no further screening tests are
D. A large cervical ectropion (cervical erosion). available.

B. A negative test for fetal fibronectin (fFN) in

3. A 36-year-old G7P1233 presents at 32-1/7 weeks cervicovaginal secretions is reassuring.
gestation complaining of increasing abdominal
pain and diminished fetal movement for 12 hours. C. Transvaginal sonography reveals a cervical
Bimanual examination shows her cervix to be 4 length of 3.6 cm. This finding should be
cm dilated and 90% effaced. Fetal cardiotocogra- viewed as reassuring.
phy shows evidence of uterine contractions every
three minutes. Fetal heart rate tracing is formally D. Given her increased risk of preterm birth, she
reactive, with a baseline of 140 bpm and no decel- is a good candidate for home uterine activity
erations. A diagnosis of preterm labor is made. monitoring.


5. A 21-year-old G3P2 with two prior vaginal deliv- 7. A 36-year-old G6P2 calls the office complaining
eries is admitted to labor and delivery at 41-4/7 of no fetal movement for 8 hours. She is at 37
weeks gestation complaining of decreased fetal weeks gestation. On arrival, you confirm an
movement. Fetal cardiotocography shows the IUFD. Which of the following statements regard-
fetal heart rate to be formally reactive with a base- ing the management of IUFD at term are true?
line of 140 bpm, and the patient reports that she is (More than 1 statement may be true.)
again feeling fetal movements. Bimanual exami-
nation shows her cervix to be 1 cm dilated and A. It is highly likely that a cause for the IUFD
80% effaced. Estimated fetal weight is 4,400 g. As can be identified after delivery.
you are about to leave, she says: “My sister’s baby
died at 41 weeks. Why can’t you induce my labor B. Immediate induction of labor is indicated to
now, Doctor?” Which of the following statements prevent coagulopathy.
are true? (More than 1 statement may be true.)
C. Pathologic examination of the fetus and pla-
centa/fetal membranes is the single most use-
A. Induction of labor is appropriate, because her ful test to identify a cause for the IUFD.
pregnancy is post-term.
D. A Kleihauer-Betke test should be sent to
B. Induction of labor is appropriate to minimize identify fetomaternal hemorrhage.
maternal and fetal risks.

C. Induction of labor is appropriate for the indi- 8. An 18-year-old G1P0 presents for her first pre-
cation of impending macrosomia. natal visit. She is complaining of severe morn-
ing sickness. On examination, uterine size is
D. Induction of labor will not increase her risk greater than expected for gestational age. You
of cesarean delivery. perform an ultrasound examination and confirm
a monochorionic/monoamniotic twin gestation.
Which of the following complications of
6. A 43-year-old G1P0 presents to your office at 34- multiple gestations is specific to monochori-
5/7 weeks gestation complaining of a severe onic/monoamniotic pregnancies?
headache and flashing lights in front of her eyes.
Her supine BP is 140/90 and there is 3+ protein- A. Malpresentation.
uria. A diagnosis of preeclampsia is made. Which
of the following statements regarding the manage- B. Twin-to-twin transfusion syndrome.
ment of preeclampsia are true? (More than 1 state-
ment may be true.) C. Cord entanglement.

A. She should be delivered immediately by D. Preterm delivery.

cesarean for a diagnosis of moderate
9. A 27-year-old G3P1 with a strong family history of
B. You should measure her BP sitting and not multiple pregnancy presents for her first prenatal
lying. visit at 12 weeks gestation. Ultrasound examination
confirms a monochorionic/diamniotic twin preg-
C. You should start antihypertensive therapy in nancy. Which of the following statements regarding
an attempt to improve perinatal outcome. twin pregnancy are true?
(More than 1 statement may be true.)
D. Regional anesthesia is contraindicated.


A. Monozygous twinning is not influenced by DES exposure remains controversial. Most clinicians
epidemiologic or genetic factors. believe that a history of in utero DES exposure alone
(without a history of prior pregnancy loss) is not an
B. 80% of twin pregnancies are dizygous. indication for prophylactic cerclage placement. Simi-
larly, elective cerclage has not been shown to be bene-
C. Perinatal mortality is higher with monozy- ficial in women with multiple pregnancies without a
gous than with dizygous twins. prior history of cervical insufficiency.

D. Perinatal mortality is highest with 2. A.

monochorionic/monoamniotic twins. The presence of uterine contractions suggests preterm
labor and not cervical insufficiency, and are an abso-
lute contraindication to cervical cerclage. Indeed, the
10. A 30-year-old G4P2 presents at 19 weeks gesta- presence of persistent uterine contractions requires the
tion with vaginal spotting. She has a history of 2 removal of any cerclage to avoid cervical laceration
prior cesarean deliveries. Ultrasound examination and/or uterine rupture. Although intra-amniotic infec-
reveals a low-lying placenta covering the cervical tion is an absolute contraindication to cerclage place-
os. Fetal well-being is confirmed. Which of the ment, vaginal yeast infection is not. Cervical ectro-
following statements regarding the management pion represents a physiologic extrusion of columnar
of placenta previa are true? (More than 1 state- epithelium out of the cervical canal under the influ-
ment may be true.) ence of steroid hormones, and should not interfere
with cervical cerclage placement. If the fetal mem-
A. There is a high probability that the placenta branes are found to be prolapsing through the external
will move away from the cervix as the preg- os at the time of cerclage placement, the risk of iatro-
nancy progresses. genic rupture of the fetal membranes may be as high
as 50%. Although this is not an absolute contraindica-
B. Given placenta previa and 2 prior cesarean tion to cerclage placement, the surgeon should pro-
deliveries, the likelihood of placenta acc- ceed with care. A number of techniques have been
reta is 25%. described in an attempt to reduce the fetal membranes
prior to cerclage placement, including Trendelenburg
C. Fetal nonstress testing is indicated after 32 position, back-filling the bladder, placement of a 30
weeks, because placenta previa is associated mL Foley catheter or moistened sponge forceps into
with uteroplacental insufficiency and IUGR. the cervical os, and/or therapeutic amniocentesis.

D. Pelvic examination should be deferred in all 3. D.

patients presenting with antepartum hemor- You should administer antenatal corticosteroids. A
rhage until placenta previa can be excluded. 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

1. C. after the initial dose. This effect lasts for 7 days, but it
A history suggestive of cervical insufficiency (ie, is unclear what happens thereafter. Repeated courses
acute, painless dilatation of the cervix usually in the of steroids are not generally recommended. Bed rest is
mid-trimester culminating in prolase and/or PROM recommended in up to 20% of all pregnancies, with an
with resultant preterm and often previable delivery) is estimated cost of >$250 million per year in the United
the only proven indication for elective cervical cer- States alone. Despite these recommendations, there is
clage. If the prior preterm delivery was the result of no proven benefit to bed rest in women at risk for
preterm labor and not cervical insufficiency, cerclage preterm labor. Intravenous hydration is also com-
placement is not indicated. Prophylactic cerclage for monly recommended in the acute setting, but without


proven benefit. Broad-spectrum antibiotic therapy has 2.) Home uterine activity monitoring (HUAM). An
been shown to delay preterm birth and prolong increase in uterine contractility is a prerequisite for
latency in the setting of preterm PROM < 34 weeks. preterm labor. However, use of HUAM in women
However, there is no consistent evidence of prolonged at high risk does not reduce the incidence of
latency in the setting of preterm labor with intact preterm delivery, but does lead to over-diagnosis
membranes. As such, broad-spectrum antibiotics are of preterm labor, increased obstetric intervention,
not recommended for this indication. Pharmacologic and increased cost.
tocolytic therapy remains the cornerstone of modern
management. Although a number of alternative 3.) Assessment of cervical maturation. Serial digital
agents are now available for tocolysis, the only agent evaluation of the cervix is useful if the examina-
that is approved by the FDA for the treatment of tion remains normal. However, an abnormal cervi-
preterm labor is ritodrine hydrochloride (which has cal finding (shortening and/or dilatation) is associ-
been off formulary in North America for over 10 ated with preterm delivery in only 4% of low-risk
years, because it is too dangerous to administer in women and 12%-20% of high-risk women. Sono-
pregnancy). Although the ultimate goal of tocolysis is graphic evaluation of the cervix has demonstrated
to delay delivery to term, there is no reliable data to a strong inverse correlation between cervical
suggest that any tocolytic agents are able to delay length and preterm delivery. If the cervical length
delivery for longer than 24-48 hours. As such, the is below the 10th percentile for gestational age, the
most realistic goal of tocolysis is to delay delivery for pregnancy is at a six-fold increased risk of deliv-
48 hours to allow administration of antenatal corticos- ery prior to 35 weeks gestation.
teroids. No single tocolytic agent has a clear therapeu-
tic advantage. As such, the side effect profile of each 4.) Biochemical markers. Although a number of bio-
of the drugs will often determine which to use in a chemical markers have been associated with
given clinical setting. Magnesium sulfate (which acts preterm delivery, only fetal fibronectin (fFN) is
both to suppress nerve transmission to uterine smooth established as a screening test for preterm deliv-
muscle and to lower the concentration of intracellular ery. Elevated levels of fFN in cervicovaginal
calcium within myometrial cells, which is necessary secretions at 22-34 weeks gestation are associated
for activation of the myosinactin contractile unit) has with premature delivery. The real value of this test
traditionally been regarded as the first-line tocolytic lies in its negative predictive value (99% of
agent for use in preterm labor. More recent data sug- patients with a negative fFN test will not deliver
gests that nifedipine (a calcium channel blocker) is within 7 days).
equally effective and safer, and can be administered
orally. In Europe, the first-line tocolytic agent is atosi- 5.) Endocrine markers. The detection of elevated lev-
ban, an oxytocin receptor antagonist. els of estriol in maternal saliva (≥2.1 ng/mL) is
predictive of delivery prior to 37 weeks gestation
4. B. and C. in a high-risk population with a sensitivity of 68%-
It is clear from this patient’s history that she is at high 87%, a specificity of 77% and a false positive rate
risk of preterm delivery. The screening tests currently of 23%. Serial (weekly) measurments may be
available for prediction of preterm birth fall into 5 more accurate in predicting pretermbirth than a
broad categories: single measurement. This test is not currently
available in the United States.
1.) Risk factor scoring. A number of risk factors for
preterm labor have been identified. However, 5. B. and D.
reliance on risk factors alone will fail to identify Post-term (prolonged) pregnancy refers to a preg-
over 50% of pregnancies which deliver preterm, nancy that has extended to or beyond a gestational age
and most women designated at risk will deliver at of 42.0 weeks (294 days) from the first day of the last
term. 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


risks. Perinatal mortality (stillbirths plus early neona- preeclampsia (in the absence of thrombocytopenia)
tal deaths) at ≥ 42 weeks of gestation is twice that at with close attention to volume expansion and anes-
term and increases 4-fold at 43 weeks and 5- to 7-fold thetic technique. The use of antihypertensive agents to
at 44 weeks. Chronic uteroplacental insufficiency, control mildly elevated BP in the setting of
asphyxia and intrauterine infection all contribute to preeclampsia has not been shown to alter the course of
the excess perinatal deaths. Post-term infants are the disease nor to diminish perinatal morbidity or
larger than term infants, with a higher incidence of mortality, and may indeed reduce uteroplacental per-
macrosomia (defined as a sonographic EFW >4500 fusion. Moreover, the use of such agents may serve to
g). Complications associated with fetal macrosomia remove the most sensitive index of worsening
include prolonged labor, cephalopelvic disproportion, preeclampsia. For these reasons, antihypertensive
and shoulder dystocia with resultant risks of orthope- therapy is not recommended for mild-to-moderate
dic or neurologic injury. Post-term pregnancies are at hypertension in the setting of preeclampsia.
increased risk of umbilical cord compression from
oligohydramnios, nonreassuring fetal antepartum or 7. C. and D.
intrapartum assessment, meconium aspiration, short- Causes of unexplained IUFD at term can be identified
term neonatal complications (hypoglycemia, in only around 50% of cases. Pathologic examination
seizures) and long-term neurologic sequelae. For of the fetus and placenta/fetal membranes is the single
these reasons, there does appear to be a small advan- most useful test to identify a cause for the IUFD. Fetal
tage to routine induction of labor at 41 weeks gesta- karyotyping should be considered in all cases of fetal
tion, regardless of parity or method of induction. death to identify chromosomal abnormalities, particu-
However, induction of labor for the indication of larly in cases with documented fetal structural abnor-
“impending macrosomia” is not appropriate, and such malities. Fetal-maternal hemorrhage occurs in all
an approach has not been shown to decrease cesarean pregnancies, but is usually minimal. In rare instances,
delivery rates or improve perinatal outcome. Routine fetal-maternal hemorrhage may be massive, leading
induction of labor at 41 weeks will not increase the to fetal demise. The Kleihauer-Betke (acid elution)
cesarean rate for multipara and nullipara with a favor- test allows an estimate of the volume of fetal blood in
able cervical exam (although the cesarean delivery the maternal circulation and should be sent as soon as
rate of primipara with an unfavorable cervical exam is possible since fetal cells are very rapidly cleared from
likely to be increased). the maternal circulation. Intra-amniotic infection
resulting in fetal death is usually evident on clinical
6. B. exam. Placental culture and histologic examination of
Preeclampsia is a clinical diagnosis encompassing 3 the fetus, placenta/fetal membranes, and umbilical
elements: 1.) new-onset hypertension (defined as a cord may be useful. Immediate delivery is not neces-
sustained BP ≥140/90 in a previously normotensive sary. Overall, >90% of women will go into labor
woman); 2.) new-onset proteinuria (>300 mg/24 h or within 2 weeks of fetal death. Around 20%-25% of
≥2+ on a clean-catch urinalysis in the absence of uri- women that retain a dead singleton fetus for longer
nary infection); and 3.) non-dependent edema than 3 weeks will develop disseminated intravascular
(although this is not a prerequisite for diagnosis). BP coagulopathy (DIC) due to excessive consumption of
should always be measured in the sitting position clotting factors. Therefore, delivery should be
using the 5th Korotkoff sound (disappearance of pul- effected within this time period.
sation) to describe the diastolic BP. Preeclampsia is
classified as either “mild” or “severe” (there is no 8. C.
moderate preeclampsia). This patient has severe Multiple pregnancy should be suspected in women at
preeclampsia by symptoms (headache, visual high risk, excessive symptoms of pregnancy or uter-
changes) and should be delivered immediately. How- ine size larger than expected. Overall, antepartum
ever, immediate delivery need not necessarily mean complications develop in 80% of multiple pregnan-
cesarean delivery. Cervical ripening agents may be cies as compared with around 30% of singleton gesta-
used if the cervix is not favorable prior to induction, tions. Preterm delivery is the most common complica-
but prolonged inductions should be avoided. Regional tion, and the risk of preterm delivery increases as fetal
analgesia can be safely administered in the setting of 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