Professional Documents
Culture Documents
Editor-in-Chief
Rogerio A. Lobo, M.D.
Professor of Obstetrics & Gynecology,
College of Physicians and Surgeons
of Columbia University, New York, NY
Chapter 9:
Obstetric
Complications
Errol R. Norwitz, MD, PhD
Men-Jean Lee, MD
Contents
1. Cervical Insufficiency
2. Preterm Labor
3. Post-term Pregnancy
7. Multiple Pregnancy
9. Antepartum Hemorrhage
10. References
11. Questions
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
Etiology
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
Diagnosis
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
Congenital Acquired
Table 2
Absolute contraindications
Relative contraindications
Vaginal infection
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%
Etiology
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.
Diagnosis
Table 3
≤48 hours)
Short-term (≤ Long-term (>48 hours)
Premature cervical dilation (>2 cm) Genital infection and/or gingival infection
or effacement (>80%)
Cervical evaluation
Serial digital examination Serial digital evaluation of the cervix has not been shown to be
useful in predicting preterm delivery. An abnormal cervical find-
ing (shortening and/or dilatation) is associated with preterm
delivery in only 4% of low-risk women and 12%-20% of high-risk
women.
Serial sonographic evaluation Real-time sonographic evaluation of the cervix has demon-
strated an inverse correlation between cervical length and risk
of preterm delivery. If the cervical length is below the 10th per-
centile for gestational age, there is a 6-fold increased risk of
delivery prior to 35 weeks gestation.
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%).
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
Oxytocin antagonists
Atosiban IV (1 mM/min infusion) Effective Nausea, vomiting, headache, Inhibit lactation
chest pain, arthralgias
225
IM, intramuscular; IV, intravenous; SC, subcutaneous; TD, transdermal.
Modified from Norwitz ER, Robinson JN, Challis JRG. The control of labor. N Engl J Med. 1999;341:660-666.
3. Post-term Pregnancy
Post-term (prolonged) pregnancy refers to a preg- 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.
Etiology
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
Management
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
Complications
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
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.
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-
Management
Symptoms
Symptoms of central nervous system dysfunction (blurred vision, scotomata, altered mental status, and/or
severe headache)
Symptoms of liver capsule distention or rupture (right upper quadrant and/or epigastric pain)
Signs
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
Laboratory Findings
Coagulopathy
Postpartum Care
Preeclampsia and its complications resolve following
delivery, often within a few days. Permanent neuro-
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
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
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
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
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.
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-
Management
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-
Etiology
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
Diagnosis
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
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
Etiology
Diagnosis
Table 10
IUGR infants have higher rates of perinatal morbidity tiple gestation in which the other fetus(es) are growing
and mortality as compared with appropriate for gesta- appropriately.154 If a premature delivery <34 weeks is
tional age (AGA) fetuses for any given gestational anticipated, a course of antenatal corticosteroids may
age. Neonatal morbidity (meconium aspiration syn- be warranted. Note that antepartum fetal testing
drome, hypoglycemia, polycythemia, pulmonary (including the BPP and umbilical artery Doppler
hemorrhage) may be present in up to 50% of IUGR velocimetry) may temporarily worsen in the 24-48
neonates.146,147,149,151 Premature IUGR infants also have hours following steroid administration in some
difficulty with nutritional support, and many develop fetuses.155
feeding intolerance and failure to thrive in the
NICU.152 Long-term studies show a 2-fold increased
incidence of cerebral dysfunction (ranging from
minor learning disability to cerebral palsy) in IUGR
infants delivered at term, and an even higher incidence
if the infant was born preterm. Epidemiological stud-
ies also suggest that these infants may also be at higher
risk for developing chronic disease in adulthood such
as diabetes, hypertension, stroke and coronary heart
disease (the Barker Hypothesis).153
Management
Maternal Causes
Uteroplacental Causes
Chronic hypertension
Preeclampsia
Fetal Causes
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.
Complications
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),
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
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
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.
Term PROM
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
Complications
Maternal complications include placenta accreta,
which refers to abnormal attachment of placental villi
to the uterine wall in which chorionic villi are directly
attached to the myometrium due to a poorly devel-
oped decidua basalis, and Nitabuch’s layer that nor-
mally separates the placenta from the uterine
myometrium.214 In the absence of placenta previa, pla-
centa accreta is rare (1 in 7000 pregnancies). How-
ever, it complicates 5%-15% of pregnancies with pla-
centa previa, 25% with previa and 1 prior cesarean,
and 60% with previa and 2 or more prior cesareans.215
Neonatal complications include preterm birth and
malpresentation. Fetal anemia may result from vasa
previa associated with a placenta previa, which is an
indication for an emergent delivery to prevent exsan-
guination of the fetus.216 Placenta previa is not associ-
ated with IUGR.217
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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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. 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.
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