1. Chapter 31
Premature Rupture of the Membranes
Brian M. Mercer, MD
Rupture of the fetal membranes is an integral part of the normal par- TIMP-1, TIMP-3), and increased poly[ADP-ribose]polymerase (PARP)
turition process at term and is inevitable in the process of preterm cleavage.6,9 Term or preterm uterine contractions can also lead to mem-
birth. Spontaneous rupture of the membranes (SROM) at term and brane rupture resulting from increased bursting pressure due to
preterm can occur any time before or after the onset of contractions. increased intra-amniotic pressure and from “strain hardening” with
SROM before the onset of contractions is referred to as premature repeated uterine contractions. If the fetal membranes do not rupture
rupture of the membranes (PROM). Membrane rupture at term before labor, the work to cause membrane rupture at the internal cervi-
usually occurs as a result of a physiologic process of progressive mem- cal os decreases with advancing cervical dilatation because of the lack
brane weakening. Preterm PROM generally results from pathologic of anchoring to the supportive decidua and enhanced ability to stretch
weakening of the fetal membranes, which has several causes. Although with contractions.1
delivery after PROM may be required by the presence of advanced Preterm membrane rupture can arise through a number of path-
labor, intrauterine infection, vaginal bleeding due to placental abrup- ways that ultimately result in accelerated membrane weakening. Bacte-
tion, or non-reassuring fetal status, the physician often needs to make rial collagenases and proteases can directly cause fetal membrane tissue
the decision whether to actively pursue delivery or conservatively weakening.10 An increase in local host cytokines or an imbalance in the
manage the pregnancy. Management of PROM hinges on knowledge interaction between MMPs and TIMPs in response to microbial colo-
of gestational age, the neonatal risks related to immediate delivery, and nization can have similar effects.11 There is specific evidence linking
an understanding of the anticipated clinical course and relative risks urogenital tract infection and colonization with preterm PROM.
of intrauterine infection, abruptio placentae, and fetal distress or death Amniotic fluid cultures after PROM are frequently positive (25%
from umbilical cord accident or intrauterine infection with conserva- to 35%),12-19 and histologic evaluation in the setting of preterm
tive management. birth frequently has demonstrated acute inflammation and bacterial
contamination along the choriodecidual interface.20 Although these
findings may reflect ascending infection after PROM, it is likely
that ascending colonization and infection are directly involved in the
Physiology and pathogenesis of preterm PROM in many cases. Genital tract pathogens
that have been associated with PROM include Neisseria gonorrhoeae,
Pathophysiology of Chlamydia trachomatis, Trichomonas vaginalis, and group B β-hemo-
Membrane Rupture lytic streptococcus.20-26 Although group B streptococcus (GBS) bacte-
riuria has been associated with preterm PROM and low-birth-weight
The fetal membranes consist of the amnion, which lines the amniotic infants27 and an association between cervical colonization and preterm
cavity, and the thicker chorion, which adheres to the maternal decidua. PROM is possible,28 it does not appear that vaginal GBS carriage is
Initially, the amnion and chorion are separate layers. The amnionic sac associated with preterm PROM.29,30 Although there is a well-estab-
is visible on first trimester ultrasound scans until it fuses with the lished association between bacterial vaginosis and preterm birth,
chorion by the end of the 14th week of gestation. Subsequently, the including that related to preterm PROM,31,32 it remains unclear whether
amnion and chorion are connected by a collagen-rich connective tissue bacterial vaginosis merely identifies women with a predisposition to
layer, with the amnion represented by a single cuboidal epithelial abnormal genital tract colonization and inflammation, facilitates
amnion layer and subjacent compact and spongy connective tissue ascent of other bacteria to the upper genital tract, or is directly patho-
layers, and a thicker chorion consisting of reticular and trophoblastic genic and causative of membrane rupture. Physical effects related to
layers. Together, the amnion and chorion form a stronger unit than preterm contractions and prolapsing membranes with premature cer-
either layer individually. Physiologic membrane remodeling occurs vical dilatation can predispose the fetal membranes to rupture, as can
with advancing gestational age, reflecting changes in collagen content the increased intrauterine pressure seen with polyhydramnios.4,33 It is
and type, changes in intercellular matrix, and progressive cellular apop- likely that certain connective tissue disorders (e.g., Ehlers-Danlos syn-
tosis. These changes lead to structural weakening of the membranes, drome) can result in intrinsic weakening of the membranes. Clinical
which is more evident in the region of the internal cervical os.1-8 associations with preterm PROM include low socioeconomic status,
Membrane weakening can be stimulated by exposure to local lean maternal body mass (<19.8 kg/m2), nutritional deficiencies (e.g.,
matrix metalloproteinases (e.g., MMP-1, MMP-2, MMP-9), decreased copper, ascorbic acid), and prior cervical conization. During preg-
levels of membrane tissue inhibitors of matrix metalloproteinases (e.g., nancy, maternal cigarette smoking, cervical cerclage, second- and

2. 600 CHAPTER 31 Premature Rupture of the Membranes
third-trimester bleeding, pulmonary disease, prior episodes of preterm ing result at 22 to 24 weeks had a one-in-six chance (16.7%) of
labor or contractions, and uterine overdistention with polyhydramnios delivering a preterm infant because of PROM, and the combination
or multiple gestations have been linked to preterm PROM.4,33-45 of a prior preterm birth due to PROM, a short cervical length, and a
Although one or more risk factors may lead to membrane rupture, positive fetal fibronectin screening result increased the risk of delivery
the ultimate clinical cause of PROM is often not evident at delivery. at less than 35 weeks because of preterm PROM by 10.9-fold (25%
In some cases, factors leading to membrane rupture are subacute or versus 2.3%).46
chronic in nature. Women with a prior preterm birth have increased Unfortunately, despite knowledge of a broad range of potential risk
risk for preterm birth due to PROM in subsequent pregnancies, factors for preterm birth, we are able to predict only a small fraction
especially if the prior preterm delivery resulted from PROM.46 Asymp- of women destined to deliver preterm, and most preterm births due to
tomatic women with a short cervical length (<25 mm) remote from preterm labor or PROM occur in women considered to be at low risk
delivery are also at increased risk for subsequent preterm birth due to for these events. Ancillary tests such as fetal fibronectin screening or
preterm labor or PROM. Some women may have polymorphisms for transvaginal cervical sonography should be incorporated into routine
inflammatory proteins that alter their inflammatory response and practice only after effective interventions to prevent PROM have been
increase the risk for preterm birth.47,48 identified for those with an abnormal test result. Because most cases
of preterm PROM cannot be predicted or prevented, clinical efforts
continue to be focused on evaluation and treatment of women who
Prediction and Prevention present with symptoms of preterm PROM.
Because PROM at term usually is part of the normal parturition
process, the focus of efforts has been on the prediction and prevention
of preterm birth caused by PROM. Prevention of preterm PROM
Clinical Course
would be particularly appealing because labor and intrauterine infec- PROM affects approximately 8% of pregnancies at term, and 95% of
tion or other complications necessitating delivery often ensue soon these women will deliver within 28 hours of membrane rupture.54
after membrane rupture occurs. The optimal way to prevent complica- Preterm PROM is also associated with brief latency from membrane
tions from preterm PROM is to prevent its occurrence. Potentially rupture to delivery; delivery within 1 week is the most common
modifiable risk factors for preterm PROM include cigarette smoking, outcome after preterm PROM at any gestational age. On average,
poor nutrition, urinary tract and sexually transmitted infections, acute latency increases with decreasing gestational age at membrane rupture.
pulmonary diseases, and severe polyhydramnios. When PROM occurs before 34 weeks’ gestation, 93% of women will
Other than treatment of infections, it is unknown whether correc- deliver within 1 week, and 50% to 60% of those who are managed
tion of these factors can avert this complication. Although most other conservatively will deliver within 1 week.55,56 With PROM near the
risk factors are fixed in that they cannot be removed or remedied in a limit of viability, 60% to 70% deliver within 1 week, but 1 in 5 will
particular woman, knowledge of risk can help to counsel women about have a latency of 4 or more weeks if they are managed conservatively.35
suspicious symptoms and the importance of timely evaluation if Although the likelihood of spontaneous resealing of the membranes
preterm PROM occurs. Broad-based preventive strategies such as pro- after preterm PROM is low (3% to 13%), the prognosis for those with
gesterone supplementation can be considered for those at risk due to PROM occurring after amniocentesis is much better, with 86% to 94%
less specific risk factors such as a history of spontaneous preterm resealing spontaneously.44,57,58 In a study of women with PROM after
birth49,50 (see Chapter 29). Although one study suggested that vitamin second-trimester amniocentesis, leakage stopped in most cases with
C supplementation had value in preventing preterm PROM (7.6% conservative management, although a normal fluid volume sometimes
versus 24.5%; P = .02), studies in which vitamin C was given alone or took time to re-accumulate (in a range of 8 to 51 days).58
with other supplements to women without prior preterm birth as a
risk factor indicate a trend toward increased preterm birth with such
treatments (relative risk [RR] = 1.38; 95% confidence interval [CI],
1.04 to 1.82).51,52 Vitamin C supplementation to prevent preterm birth
Complications after
due to PROM thus cannot be recommended until there is solid evi- Premature Rupture of
dence of benefit.
Perhaps the strongest risk factor for preterm PROM is a history of the Membranes
prematurity or PROM.53 Those with an early preterm birth have the
highest risk for a recurrence. A history of preterm birth after PROM Maternal Complications
confers a 3.3-fold increased risk for recurrent preterm birth due to the Chorioamnionitis complicates 9% of pregnancies with term PROM, a
same cause (13.5% versus 4.1%; P < .01) and a 13.5-fold higher risk risk that increases to 24% with membrane rupture lasting longer than
of subsequent delivery before 28 weeks (1.8% versus 0.13%; P < .01). 24 hours.59 The risk of intrauterine infection increases with the dura-
Because prior obstetric outcome has such a strong influence on tion of membrane rupture and with declining gestational age.54,55,60-62
subsequent pregnancy outcomes, it is useful to evaluate nulliparas Conservative management of PROM provides the opportunity for
separately from those with prior deliveries. When assessed at 22 to subclinical deciduitis to progress to overt infection and for ascending
24 weeks’ gestation, medical complications (e.g., pulmonary disease in infection to occur.20,54,55,62 Chorioamnionitis can complicate 13% to
pregnancy), work during pregnancy, low maternal body mass index 60% of cases when PROM occurs remote from term. Endometritis
(<19.8 kg/m2), and bacterial vaginosis are associated with preterm occurs in 2% to 13% of cases.63,64 Placental abruption is diagnosed in
birth due to PROM.46 Identification of a cervical length shorter than 4% to 12% of pregnancies complicated by PROM and can occur before
25 mm on transvaginal ultrasound also confers an increased risk of or after the onset of membrane rupture.34,65,66 Maternal sepsis (0.8%)
subsequent PROM in nulliparas and multiparas. In this study, nullipa- leading to death (0.14%) is a uncommon complication of preterm
ras with a short cervix and a positive cervicovaginal fibronectin screen- PROM occurring near the limit of viability.67

3. CHAPTER 31 Premature Rupture of the Membranes 601
reported outcomes of previable PROM may be optimistic because
Fetal Complications most studies have been retrospective and have included only patients
The risks to the fetus are primarily those related to intrauterine infec- amenable to conservative management.
tion, umbilical cord compression, and placental abruption. Fetal heart Fetal lung growth and development can be especially adversely
rate patterns consistent with umbilical cord compression due to affected when PROM occurs in the early phases of development.82-87
oligohydramnios are commonly seen after PROM.68 Umbilical cord With PROM occurring during the late pseudoglandular or canalicular
prolapse can occur after membrane rupture, particularly with fetal stage of pulmonary development, tracheobronchial collapse or loss of
malpresentation, which is more common with preterm gestations. intrinsic factors within the tracheobronchial fluid, or both, may lead
Fetal death occurs in 1% to 2% of cases of conservatively managed to failure of the terminal bronchioles and alveoli to develop, with
PROM.56 The reported incidence of fetal death after PROM at 16 to resultant failure of lung growth.88-91 Pulmonary hypoplasia develops
28 weeks ranges from 3.8% to 22%.36,69,70 This particularly high risk of over weeks after membrane rupture occurs. It is most accurately
fetal loss may reflect increased susceptibility to umbilical cord com- diagnosed pathologically based on radial alveolar counts and lung
pression and hypoxia or intrauterine infection, but it may also reflect weights.92,93 In surviving infants, pulmonary hypoplasia is suggested by
less aggressive obstetric interventions for fetal compromise before the a small chest circumference with severe respiratory distress or persis-
limit of viability. tent pulmonary hypertension and radiographic findings such as
small, well-aerated lungs with a bell-shaped chest and elevation of the
diaphragm.83,88
Neonatal Complications Overall, pulmonary hypoplasia becomes evident in 0% to 26.5% of
Gestational age at delivery is the primary determinant of the frequency infants (mean = 5.9%) delivering after PROM at 16 to 26 weeks’ gesta-
and severity of neonatal complications after PROM. Respiratory dis- tion. Early PROM before 20 weeks’ gestation carries the highest poten-
tress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, tial for lethal pulmonary hypoplasia (≈50% with PROM before 19
and sepsis are the most common serious acute morbidities, and they weeks’ gestation).83,86-88,94-96 With PROM at 15 to 16 weeks, an amniotic
are common with early preterm birth. Neonatal sepsis is twofold more fluid index of 2 cm or less, and a latency of 28 days, the risk of pulmo-
common after preterm PROM than after preterm birth due to preterm nary hypoplasia is estimated to be 74% to 82%.97 Lethal pulmonary
labor. Neonatal infection can manifest as congenital pneumonia, hypoplasia is uncommon with PROM after 24 to 26 weeks’ gestation
sepsis, meningitis, and late-onset bacterial or fungal infection. Early (0% to 1.4%) because there has been adequate alveolar development
preterm birth can lead to long-term complications, including chronic to support extrauterine life by this time.83,84,98 However, nonlethal pul-
lung disease, visual or hearing difficulties, mental retardation, monary hypoplasia increases the likelihood of pulmonary barotrauma,
developmental and motor delay, and cerebral palsy. In general, these including pneumothorax, pneumomediastinum, and the need for high
long-term morbidities are uncommon with delivery after about ventilatory pressures because of poor pulmonary compliance.83,98,99
32 weeks’ gestation.71,72 Cerebral palsy and periventricular leukomala- With prolonged oligohydramnios, restriction deformities can occur in
cia have been associated with amnionitis,73 and increased amniotic up to 27% of fetuses.67,83,98-101
fluid cytokines and fetal systemic inflammation have been associated
with preterm PROM, periventricular leukomalacia, and cerebral
palsy.74-76 This highlights the need for potential neonatal benefit
from delayed delivery if conservative management is to be attempted
Diagnosis
because this delay offers the opportunity for intrauterine infection to In more than 90% of cases, the diagnosis of PROM can be confirmed
develop. Alternatively, early gestational age at birth has been associated by clinical assessment, including the combination of history, clinical
with neonatal white matter damage (P < .001) after controlling for examination, and laboratory evaluation. Because optimal clinical care
other factors.77 Despite the described associations between PROM, requires an accurate diagnosis, attention should be paid to confirming
intrauterine infection or inflammation, and adverse neurologic out- the diagnosis when a suspicious history or ultrasound finding of oli-
comes, it has not been shown that immediate delivery after PROM can gohydramnios is identified. Other potentially confounding findings
prevent these morbidities. such as urine leakage, increased vaginal discharge with cervical dilata-
In the past, mid-trimester PROM, which encompasses membrane tion or membrane prolapse, cervical infection, passage of the mucous
rupture occurring at about 16 to 26 weeks’ gestation, was considered plug, and the presence of semen or vaginal douching should be
as a separate entity from preterm PROM because neonatal death considered.
usually could be anticipated with immediate delivery. With current A sterile speculum examination should be performed to provide
survival rates of about 25% to 85% after delivery at 23 to 26 weeks’ confirmatory evidence of membrane rupture and to inspect for cervi-
gestation, mid-trimester PROM is no longer a relevant clinical citis and for umbilical cord or fetal prolapse, to assess cervical dilata-
entity.71,72,78-80 Previable PROM occurring before the limit of viability tion and effacement, and to obtain cultures, including endocervical
(i.e., before 23 weeks’ gestation) is a special circumstance that places Neisseria gonorrhoeae and Chlamydia trachomatis, and anovaginal
the fetus in particular jeopardy. Immediate delivery will result in Streptococcus agalactiae (i.e., GBS), as appropriate. Initially, digital
neonatal death. Conservative management may result in fetal or cervical examination should be avoided unless imminent delivery is
neonatal loss before viability, and if viability is reached, delivery is anticipated because the needed information usually can be obtained
likely at an early gestational age, when the risks of long-term sequelae with visualization of the cervix. Digital examination can shorten
are highest. The neonatal survival rate after PROM occurring before latency between membrane rupture and delivery, and some studies
24 weeks has previously been reported to be approximately 30%, com- have shown it to introduce vaginal organisms into the cervical canal
pared with 57% for rupture at 24 to 26 weeks’ gestation.67 In a review and to increase the risk of infection.102-107
of 201 cases from 11 studies, the perinatal survival rate with conserva- The diagnosis of membrane rupture is confirmed by visualization
tive management of PROM before 23 weeks’ gestation was 21%, but of fluid passing from the cervical canal. If the diagnosis is not con-
there was similar survival after PROM at less than 20 weeks.81 These firmed on initial inspection, the pH of the vaginal side walls or pooled

4. 602 CHAPTER 31 Premature Rupture of the Membranes
vaginal fluid can be evaluated using Nitrazine paper, which turns blue of fluid across a weakened membrane or minimal leakage around a
at a pH above 6.0 to 6.5. Amniotic fluid usually has a pH of 7.1 to 7.3, firmly applied presenting fetal part. Women with a suspicious history
whereas normal vaginal secretions have a pH of about 4.5 to 6.0. Blood and initially negative testing should be encouraged to return for reeval-
or semen contamination, alkaline antiseptics, and bacterial vaginosis uation if symptoms are persistent or recurrent.
can cause false-positive Nitrazine test results. If further clarification is
needed, microscopic inspection can be performed for the presence of
arborized crystals (i.e., ferning) (Fig. 31-1) in an air-dried sample col-
lected from the vaginal side walls or pooled vaginal fluid. Ferning Management of Premature
results from the interaction of amniotic fluid proteins and salts. Cervi-
cal mucus should be avoided during sampling because it can also yield
Rupture of the Membranes
a ferning pattern on microscopy. The fern test is unaffected by meco- Management of PROM is based primarily on the estimated risks for
nium and vaginal pH, but it can be falsely positive if there is heavy fetal and neonatal complications with immediate delivery weighed
blood contamination.108,109 Prolonged leakage with minimal residual against the potential risks and benefits of conservative management to
fluid can lead to false-negative clinical, Nitrazine, and ferning test extend the pregnancy after membrane rupture (Fig. 31-2). The risks of
results. Re-examination after prolonged recumbency or alternate mea- maternal morbidity should also be considered, especially under the
sures can be considered if initial testing is negative. Assessment of circumstance of previable PROM.
cervicovaginal secretions for fetal fibronectin, prolactin, human cho-
rionic gonadotropin (hCG), and other markers may assist in the diag-
nosis of PROM. However, these tests usually are not more helpful than Initial Evaluation
the initial measures listed previously, because a positive test result After the diagnosis of membrane rupture is confirmed, the duration
may reflect decidual disruption rather than membrane rupture in of membrane rupture should be estimated to assist the pediatric
some cases and a negative test result cannot exclude the diagnosis caregivers with subsequent management decisions. Gestational age
unequivocally. is established based on the combination of menstrual dates, clinical
If the diagnosis remains unclear after initial evaluation, documen- history, and ultrasound findings, as appropriate. Fetal presentation is
tation of oligohydramnios by ultrasound, in the absence of fetal urinary assessed, and the patient is evaluated for labor, clinical findings of
tract malformations or significant growth restriction, is suggestive of intrauterine infection, and significant vaginal bleeding. Fetal well-
membrane rupture. Ultrasonographically guided amniocentesis with being is assessed by continuous heart rate monitoring if the limit of
infusion of indigo carmine dye (1 mL of dye in 9 mL of sterile normal viability has been reached. After preterm PROM, it is important to
saline), followed by observation for passage of blue fluid from the evaluate fetal growth and residual amniotic fluid volume by ultra-
vagina onto a perineal pad, can confirm or disprove the diagnosis of sound, and the potential of fetal abnormalities that can lead to poly-
membrane rupture. Amniocentesis in the setting of oligohydramnios hydramnios should be considered. Although narrowing of the biparietal
can be difficult, and particular attention should be paid to avoidance diameter (i.e., dolichocephaly) due to oligohydramnios or breech pre-
of the umbilical cord vessels, which can have the appearance of a thin, sentation can result in underestimation of gestational age and fetal
linear fluid space under this circumstance. weight, ultrasound usually is as reliable after PROM as it is with intact
Some women with a history suspicious for membrane rupture but membranes.110 Tables using fetal head circumference rather than bipa-
a negative speculum examination result and a normal amniotic fluid rietal diameter can be consulted as needed. GBS carrier status should
volume on ultrasound subsequently return with gross membrane be ascertained if available from culture results within 6 weeks or there
rupture. This pattern may reflect initial transudation of a small amount has been a positive urine culture in the current pregnancy, and the need
for intrapartum prophylaxis should be determined. In the absence of
available culture results, a risk factor–based approach should be used
for prevention of vertical transmission.111
If conservative management is planned, the patient should be cared
for in a facility with the ability to provide emergent delivery for pla-
cental abruption, fetal malpresentation, or fetal distress. The facility
should also have neonatal intensive care facilities and offer acute
neonatal resuscitation, because conservative management usually is
undertaken only if there is a significant risk of neonatal morbidity and
mortality with immediate delivery. Prenatal maternal transfer should
be undertaken early in the course of management if these resources
are not available. Because of the potential for acute complications,
outpatient management usually is not recommended when PROM
occurs after the limit of viability.
Term Premature Rupture of
the Membranes
FIGURE 31-1 Ferning. A typical ferning appearance is seen after a
There is no substantial fetal benefit to expectant management of preg-
swab from the posterior vaginal fornix was smeared on glass slide nancy after membrane rupture at 37 weeks’ gestation or later. Expect-
and the specimen allowed to air dry. The sample was obtained from a ant management of PROM at term was practiced in the 1980s and early
patient with premature rupture of the membranes. (Image courtesy of 1990s based on studies suggesting that immediate induction after term
Thomas Garite, University of California at Irvine, Orange, California.) PROM might increase the risks of infection and cesarean delivery.112-115

5. CHAPTER 31 Premature Rupture of the Membranes 603
Diagnosis confirmed
Fluid per cervical os or
vaginal pool with positive Nitrazine/ferning test or
indigo carmine amnio infusion
Ultrasound for gestational age, growth, anomalies as appropriate
Cervical cultures: Chlamydia, gonorrhea
Anovaginal culture: group B streptococcus
Urine culture: group B streptococcus
Initial and continuous monitoring for labor, fetal distress
Intrapartum group B
streptococcus prophylaxis,
Amnionitis, based on risk factors if no
abruptio placentae, Yes recent negative
fetal death, Deliver anovaginal culture
non-reassuring testing,
or advanced labor Broad-spectrum antibiotics
if amnionitis
No
Previable PROM Early Preterm PROM Preterm PROM Late Preterm PROM Term PROM
23 weeks 23-31 weeks 32-33 weeks 34-36 weeks 37 weeks
Documented fetal Yes
Initial monitoring pulmonary maturity
for infection,
labor, abruptio No
placentae
Immature testing
Initial bed rest or
to encourage fluid unavailable
resealing Conservative management
Modified bed rest/pelvic
rest to encourage
resealing, reduce infection
Evaluate for Consider conservative
persistent Serial evaluation for management for
oligohydramnios amnionitis, labor, corticosteroid benefit
and pulmonary abruption, fetal with concurrent
hypoplasia with well-being, growth antibiotic therapy,
serial ultrasound or
Administer corticosteroids expeditious delivery if
and antibiotics (NICHD previous antenatal
Re-counsel
protocol) short-term steroids and attempted
tocolysis latency 1 week
Induction If discharged
with before viability not planned
Deliver for amnionitis,
oxytocin, and remains non-reassuring fetal
PGE2 or pregnant, testing, abruption,
misoprostol, readmit at advanced labor 33 weeks
or fetal viability for 32 weeks
Deliver
dilatation and conservative Deliver at Expeditious Expeditious
Deliver at 34 weeks if 34 weeks after
evacuation management stable until then delivery delivery
steroids
Intrapartum group B streptococcus prophylaxis based on
risk factors if no recent negative anovaginal culture
Broad-spectrum antibiotics if amnionitis
FIGURE 31-2 Algorithm for management of premature rupture of the membranes (PROM). The algorithm includes several alternatives for
the approach to term and preterm PROM. NICHD, National Institute of Child Health and Human Development; PGE2, prostaglandin E2. (Adapted
from Mercer BM: Preterm premature rupture of the membranes. Obstet Gynecol 101:178-193, 2003.)

6. 604 CHAPTER 31 Premature Rupture of the Membranes
However, four large studies have since found that induction with oxy- conservative management of PROM is highlighted by the high inci-
tocin after term PROM does not increase the risks of maternal or neo- dence of recurrent variable decelerations found during intermittent
natal infections, nor does it make cesarean delivery more likely.54,116-118 monitoring (19.4%) among conservatively managed women. In this
In the largest study, oxytocin induction after term PROM reduced the study, documented fetal pulmonary maturity was a requirement for
duration of membrane rupture (17.2 versus 33.3 hours; P < .001) and enrollment, and neither group suffered any significant noninfectious
the frequencies of chorioamnionitis (4.0% versus 8.6%; P < .001) and neonatal morbidities. Specific attention to those enrolled at 32 to 33
postpartum febrile morbidity (1.9% versus 3.6%; P = .008), without weeks’ gestation revealed similar trends regarding brief latency,
increasing the risk of cesarean delivery (13.7% versus 14.1%) or neo- increased amnionitis, suspected neonatal sepsis, and antibiotic treat-
natal infections (2.0% versus 2.8%).54 Neonatal antibiotic therapy was ment with conservative management.130 Based on these findings, the
less common with immediate induction (7.5% versus 13.7%; P < .001), woman with PROM and documented fetal pulmonary maturity at 32
likely because of a lower concern regarding the potential for neonatal to 33 weeks’ gestation is at low risk for complications after immediate
infection with less frequent prolonged rupture of the membranes and delivery and increased risk with conservative management. Amniotic
less chorioamnionitis. Meta-analysis of studies comparing prostaglan- fluid studies documenting pulmonary maturity in this gestational age
din induction and conservative management in this setting has found range are useful to identify women who should be offered expeditious
shorter latency, decreased rates of chorioamnionitis, and less frequent delivery.
neonatal intensive care unit (NICU) admissions with no increase in If fetal pulmonary testing reveals an immature result or if amniotic
cesarean delivery rates with prostaglandin administration.119 Because fluid cannot be obtained for assessment, conservative management
oxytocin can more easily be discontinued, this choice is somewhat with antenatal corticosteroid administration for fetal maturation is an
more appealing, given similar efficacy for labor induction. appropriate choice. Concurrent antibiotic treatment should be given
In summary, available data indicate that women with PROM at to reduce the risk of intrauterine infection during conservative
term who are not in labor on arrival at the hospital should have labor management (discussed later). There are no data regarding optimal
induced, usually with an oxytocin infusion, to reduce the risk of mater- management after antenatal corticosteroid treatment is completed.
nal and neonatal complications. Caregivers should allow an adequate However, because conservative management increases the risks of
time for the latent phase of labor and minimize digital vaginal exami- chorioamnionitis and prolonged hospitalization and because it is
nations until the active phase of labor. unlikely that conservative management for less than 1 week will result
in further significant spontaneous fetal maturation, delivery should be
Preterm Premature Rupture of considered if elective delivery is planned within 7 days after antenatal
corticosteroid benefit has been achieved. If antenatal corticosteroids
the Membranes at 32 to 36 are not to be given to accelerate fetal pulmonary maturity after PROM
Weeks’ Gestation at 32 to 33 weeks, consideration should be given to the potential
Although infants born at 34 to 36 weeks’ gestation (i.e., late preterm benefits of expeditious delivery unless conservative management to
birth) have a higher risk of complications than term infants, severe extend latency for 1 or more weeks will be attempted. These decisions
acute morbidities and mortality are uncommon, and antenatal corti- should take into consideration local population-based risks of infec-
costeroids for fetal maturation are not typically recommended in this tion and neonatal morbidities.
gestational age range.71,120 Conservative management of PROM at 34
to 36 weeks prolongs pregnancy by only days, significantly increases Preterm Premature Rupture of
the risk of chorioamnionitis (16% versus 2%; P = .001), and reduces
umbilical cord pH (7.35 versus 7.25; P = .009), and it has not been
the Membranes at 23 to 31
shown to improve neonatal outcomes.121,122 For these reasons, women Weeks’ Gestation
presenting with late preterm PROM at 34 to 36 weeks should be Because delivery before 32 weeks’ gestation is associated with a high risk
actively delivered. for perinatal death, severe neonatal morbidities, and long-term sequelae,
With delivery at 32 to 33 weeks’ gestation, gestational age–depen- women with PROM between 23 and 31 weeks’ gestation usually should
dent neonatal morbidities, including respiratory distress syndrome, be managed expectantly to prolong pregnancy unless there is evidence
can occur, but the likelihood of survival is high, and chronic morbidi- of intrauterine infection, suspected placental abruption, advanced
ties are uncommon. Amniotic fluid can be collected from the vaginal labor, or a non-reassuring fetal heart rate pattern. Under certain addi-
pool at initial sterile speculum examination or by amniocentesis if tional circumstances, delivery may be appropriate despite an early ges-
vaginal fluid is not available. Each of the TDx/TdXFLx FLM II assay tational age at membrane rupture (e.g., fetal transverse lie and back up
(Abbott Laboratories, Abbott Park, IL), the lecithin-to-sphingomyelin with coexisting advanced cervical dilatation, human immunodeficiency
ratio (L/S ratio), and the phosphatidylglycerol (PG) test can predict virus infection, primary herpes simplex virus infection).
pulmonary maturity when performed on vaginal pool specimens.123-128 In women with conservatively managed PROM remote from term,
Modest reductions in the duration of neonatal hospital stay and hyper- a low initial amniotic fluid volume (amniotic fluid index <5.0 cm or
bilirubinemia with conservative management of PROM at 32 to 33 maximum vertical fluid pocket <2.0 cm) is associated with shorter
weeks’ gestation have been reported.122 Alternatively, conservative latency to delivery and increased neonatal morbidity (including respi-
management prolonged pregnancy only briefly (36 versus 14 hours; ratory distress syndrome) but not with increased maternal or neonatal
P < .001) in a randomized, controlled trial of conservative manage- infection after PROM.131 Despite this, the predictive value of a low
ment versus immediate induction after PROM at 32 to 36 weeks’ gesta- amniotic fluid volume for adverse outcomes is poor. A short cervical
tion. This limited benefit was offset by a 2.5-fold increased risk of length on endovaginal ultrasound after preterm PROM has been asso-
chorioamnionitis (27.7% versus 10.9%; P = .06), increased neonatal ciated with shorter latency to delivery.132-134 The latest study of cervical
sepsis workups (59.6% versus 28.3%; P =.003) and increased neonatal length in women with preterm PROM found that 83% of women
antibiotic treatment for suspected infection (78.7% versus 34.8%; P < delivered within 7 days if the initial cervical length was 1 to 10 mm,
.001).129 The potential for occult umbilical cord compression during compared with 18% for a cervical length more than 30 mm, but only

7. CHAPTER 31 Premature Rupture of the Membranes 605
41 women were evaluated.132 However, currently available studies of roid administration after preterm PROM has been extensively studied,
initial amniotic fluid volume and cervical length assessment in women generating several meta-analyses.145-147 Although early reviews pro-
with preterm PROM have insufficient power and consistency to guide duced conflicting conclusions about the utility of antenatal corticoste-
management. roid treatment after PROM, a later meta-analysis concluded that
Conservative management includes initial prolonged continuous antenatal glucocorticoids significantly reduce the risks of respiratory
fetal heart rate and maternal contraction monitoring to assess fetal distress syndrome (20% versus 35.4%), intraventricular hemorrhage
well-being and identify occult contractions and evidence of umbilical (7.5% versus 15.9%), and necrotizing enterocolitis (0.8% versus 4.6%),
cord compression. If initial testing results are reassuring, the patient without increasing the risks of maternal (9.2% versus 5.1%) or neo-
can be transferred to an inpatient unit or transferred to a facility natal (7.0% versus 6.6%) infections in women with preterm PROM.147
capable of emergent delivery and acute neonatal resuscitation for Multivariate analysis of prospective observational trials suggested a
modified bed rest. Because of the high risk of heart rate abnormalities benefit of antenatal corticosteroid use regardless of membrane
due to umbilical cord compression (32% to 76%), fetal assessment rupture.148 Three studies in which prophylactic antibiotics were given
should be performed at least daily for those with initially reassuring concurrent to antenatal corticosteroids found treatment to reduce
test results.68,135 Continuous monitoring may be appropriate for women respiratory distress syndrome (18.4% versus 43.6%; P = .03) perinatal
with intermittent fetal heart rate decelerations but otherwise reassur- mortality (1.3% versus 8.3%; P = .05), and composite morbidities
ing findings. Although the nonstress test and biophysical profile have (29.3% versus 48.6%; P < .05), with no increase in perinatal
the ability to confirm fetal well-being in the setting of preterm PROM, infections.149-151
fetal heart rate monitoring can identify variable and late decelerations The National Institutes of Health Consensus Development Panel
in addition to uterine activity. Biophysical profile testing may also be recommended a single course of antenatal corticosteroids for women
confounded by the presence of oligohydramnios but can be helpful if with PROM before 30 to 32 weeks’ gestation in the absence of intra-
the nonstress test is equivocal, particularly remote from term when the amniotic infection.152 Data regarding repeated weekly courses of
fetal heart rate pattern is less likely to be reactive. A nonreactive result antenatal corticosteroids after preterm PROM are conflicting. In a
for a nonstress test and a biophysical profile score of 6 or less within retrospective study that controlled for gestational age and other factors,
24 hours of delivery have been associated with perinatal infection.136,137 two or more courses of antenatal corticosteroids were associated with
A nonreactive nonstress test subsequent to an initially reactive result increased early neonatal sepsis (15.3% versus 2% for a single course or
should be considered suspicious. 1.5% for no courses; P < .001).153 In another retrospective analysis of
Conservative management requires surveillance for the devel- repeated antenatal corticosteroids, there was no reduction in respira-
opment of labor, abruptio placentae, and intrauterine infection. tory distress syndrome, but intraventricular hemorrhage and amnio-
Chorioamnionitis confers increased risks of perinatal mortality and nitis were less common, and there was a trend toward less sepsis.154
intraventricular hemorrhage, and it is diagnosed clinically by the pres- Respiratory distress syndrome was less common in another retrospec-
ence of maternal fever above 38.0 °C (100.4 °F) with uterine tenderness tive review of repeated courses of antenatal corticosteroids (34.9%
or with maternal or fetal tachycardia in the absence of another evident versus 45.2%) without an increase in neonatal sepsis (9.9% versus
source of infection.63 After the diagnosis of chorioamnionitis is made, 6.2%).155
delivery should be pursued and broad-spectrum antibiotics should be Based on current evidence that antenatal corticosteroids are effec-
initiated because treatment before delivery has been shown to decrease tive for induction of fetal pulmonary maturity without increasing the
the incidence of neonatal sepsis.138-140 Although evaluation of the mater- risk of infection and that most women will remain pregnant for the 24
nal white blood cell count can be helpful if clinical findings are equivo- to 48 hours needed to achieve corticosteroid benefit after PROM, a
cal, the counts can be artificially elevated within 5 to 7 days of antenatal single course of antenatal corticosteroids should be considered when
corticosteroid administration. If the diagnosis of chorioamnionitis is PROM occurs before 32 weeks’ gestation and for women with
suspected but additional confirmation is needed, amniocentesis may documented pulmonary immaturity at 32 to 33 weeks’ gestation.
yield helpful results.15,141,142 A glucose concentration below 16 to 20 mg/ Betamethasone (two doses of 12 mg IM, given 24 hours apart) or
dL (sensitivity and specificity of 80% to 90% for a positive culture) and dexamethasone (four doses of 6 mg IM, given 12 hours apart) is con-
a Gram stain positive for bacteria (sensitivity of 36% to 80% and speci- sidered appropriate. Repeated weekly antenatal corticosteroids are not
ficity of 80% to 97% for a positive culture) support the presence of recommended after preterm PROM. The benefits and risks of a single
intrauterine infection. The presence of leukocytes alone in amniotic rescue course remote from initial corticosteroid administration remain
fluid after PROM is not well correlated with intrauterine infection. to be determined.
Although a positive amniotic fluid culture supports clinical suspicion
of chorioamnionitis (sensitivity of 65% to 85% and specificity of 85%), Adjunctive Antibiotics
these results are not likely to be available before the diagnosis is clari- Antibiotic therapy is given during conservative management of
fied.17 One study suggested that determination of glucose levels from preterm PROM to treat or prevent ascending decidual infection to
vaginally collected amniotic fluid may be a simple and noninvasive prolong pregnancy and to reduce gestational age–dependent morbid-
method for identification of intra-amniotic infection.143 In this promis- ity while limiting the risk of neonatal infection. More than two dozen
ing study, a vaginal pool glucose value below 5 mg/dL had a 74.2% randomized clinical trials have been summarized in several meta-
accuracy rate for identifying women with a positive amniotic fluid analyses.56,156,157 In the latest one, antibiotic treatment after preterm
culture. Although research has found elevated amniotic fluid interleu- PROM significantly reduced chorioamnionitis (relative risk [RR] =
kin levels to be associated with early delivery and perinatal infectious 0.57); delivery within 48 hours (RR = 0.71) and within 7 days (RR =
morbidity,141 such testing is not available in most clinical laboratories. 0.80); and reduced infant morbidities, including neonatal infection
(RR = 0.68); and major cerebral abnormalities on ultrasound before
Antenatal Corticosteroids discharge (RR = 0.82) compared with placebo therapy.157 The need for
Respiratory distress syndrome is the most common acute morbidity surfactant administration (RR = 0.83) and oxygen therapy (RR = 0.88)
after conservatively managed preterm PROM.144 Antenatal corticoste- was also reduced. Antibiotics did not influence the risk of necrotizing

8. 606 CHAPTER 31 Premature Rupture of the Membranes
enterocolitis (RR = 1.14; CI, 0.66 to 1.97). Oral amoxicillin-clavulanic longation, less need for oxygen therapy, and fewer positive neonatal
acid treatment was associated with increased necrotizing enterocolitis blood cultures.157 This is not inconsistent with the NICHD-MFMU
(RR = 4.60; 95% CI, 1.98 to 10.72) in this analysis, but oral erythro- approach. Up to a 7-day course of parenteral and oral therapy using
mycin therapy was not (RR = 1.00; CI, 0.56 to 1.80).157 The study that ampicillin-amoxicillin and erythromycin is recommended for women
dominated this meta-analysis included women with PROM up to 36 undergoing conservative management of preterm PROM remote from
weeks’ gestation and included a population at low risk for necrotizing term. Shortages in intravenous and oral antibiotics have led to the need
enterocolitis overall (i.e., 0.5% among controls), and it was the only for alternative antibiotic choices. Oral ampicillin, erythromycin, and
one of 10 studies that found a significant increase in necrotizing azithromycin are likely appropriate alternatives if needed.
enterocolitis with antibiotic therapy.158 The meta-analysis found treat- Adjunctive antibiotic administration to prolong latency must be
ment with “all penicillins” (excluding amoxicillin-clavulanic acid) distinguished from intrapartum prophylaxis to prevent vertical trans-
versus placebo to be associated with fewer births within 48 hours and mission of GBS from mother to baby.111 Known GBS carriers and those
7 days of PROM, less overall maternal infection and chorioamnionitis, who deliver before carrier status can be determined should receive
less neonatal infection, fewer positive neonatal blood cultures, and intrapartum prophylaxis to prevent vertical transmission, regardless of
fewer major intracranial cerebral ultrasound abnormalities. Because of prior antibiotic treatments. Women with a diagnosis of chorioamnio-
the increased risk of neonatal necrotizing enterocolitis with amoxicil- nitis should receive broad-spectrum intrapartum antibiotic therapy.
lin-clavulanate, the study authors recommended erythromycin as a
better choice, even though benefits were limited to reduction in deliv- Tocolysis
ery at 48 hours, fewer positive neonatal blood cultures, and a reduced Evidence from prospective studies of tocolysis after PROM is similar
need for oxygen therapy. to that from studies of tocolysis for preterm labor with intact
In a clinical trial with adequate power to evaluate antibiotic therapy membranes.162-167 After preterm PROM, prophylactic tocolysis with β-
during conservative management of women with preterm PROM agonists before the onset of contractions can prolong pregnancy briefly.
before 32 weeks’ gestation, the National Institutes of Child Health and Therapeutic tocolysis administered only after contractions occur has
Human Development Maternal Fetal Medicine Units (NICHD- not been shown to be effective in prolonging latency. In a retrospective
MFMU) Research Network assigned women with PROM to initial comparison of aggressive tocolysis with limited treatment for contrac-
aggressive intravenous therapy for 48 hours (2 g of ampicillin IV every tions only during the first 48 hours, aggressive therapy was not associ-
6 hours and 250 mg of erythromycin IV every 6 hours) followed by ated with longer latency (3.8 versus 4.5 days; P = .16).167 A report from
oral therapy for 5 days (250 mg of amoxicillin PO every 8 hours and the Collaborative Study on Antenatal Steroids suggested tocolytic
333 mg of enteric-coated erythromycin base PO every 8 hours) to use after PROM was associated with subsequent neonatal respiratory
provide limited-duration, broad-spectrum antimicrobial coverage distress syndrome, but the biologic mechanism for this association is
before delivery.144,159 GBS screening was performed. GBS carriers were unclear.168
treated with ampicillin for 1 week and again in labor, and they were Overall, the available prospective studies have not found tocolytic
analyzed separately. Antibiotic treatment increased the likelihood of treatment after PROM to increase or prevent neonatal morbidities
continued pregnancy after 7 days of treatment by twofold. Benefit after PROM. Tocolytic therapy has not been studied when antenatal
persisted for 3 weeks after randomization despite discontinuation of corticosteroids and antibiotics were administered concurrently, and
antibiotics at 7 days. Babies born to women treated with ampicillin it remains plausible that prophylactic tocolysis could delay delivery
plus erythromycin had a reduced incidence of one or more major long enough to allow antibiotic suppression of subclinical decidual
infant morbidities (53% versus 44% rate of composite morbidity, infection and for corticosteroid effects on the fetus. Pending further
including death, respiratory distress syndrome, early sepsis, severe study in this area, tocolytic therapy should not be considered an
intraventricular hemorrhage, and severe necrotizing enterocolitis; P < expected practice after preterm PROM, but it may be appropriate in
.05). Antibiotic therapy also significantly reduced individual gesta- pregnancies at high risk for neonatal complications with early preterm
tional age–dependent morbidities, including respiratory distress syn- birth.
drome (40.5% versus 48.7%), patent ductus arteriosus (11.7% versus
20.2%), chronic lung disease (bronchopulmonary dysplasia: 20.5% Cervical Cerclage
versus 13.0%), and stage 3 or 4 necrotizing enterocolitis (2.3% versus Preterm PROM complicates about one fourth of pregnancies with a
5.8%), with P values of 0.05 or less for each. Chorioamnionitis was cervical cerclage and one half of pregnancies requiring an emergent
reduced with the study’s antibiotics (23% versus 32.5%; P = .01), and cerclage.43,169,170 Because no prospective studies have been performed
neonatal sepsis (8.4% versus 15.6%; P = .009) and pneumonia (2.9% regarding management of preterm PROM with a cerclage in situ, rec-
versus 7.0%; P = .04) were reduced for those who were not GBS carri- ommendations reflect the data available from retrospective cohorts.
ers. The antibiotic study group had less neonatal GBS sepsis (0% versus The risk of adverse perinatal outcomes does not appear to be different
1.5%; P = .03). Two other studies have attempted to determine whether when PROM occurs with a cerclage or without one, provided the cer-
antibiotic therapy of shorter duration could provide similar benefit, clage is removed on admission after PROM.171-172
but the studies lacked size and power to demonstrate equivalent Several small studies comparing pregnancies of preterm PROM in
effectiveness.160,161 which the cerclage was retained or removed have yielded consistent
In summary, broad-spectrum antibiotic (ampicillin-amoxicillin patterns.173-175 No study has found cerclage retention after PROM to
plus erythromycin) therapy for women with preterm PROM before 32 reduce the frequency or severity of infant morbidities after preterm
weeks’ gestation prolongs pregnancy sufficiently to reduce neonatal PROM, and each has demonstrated statistically insignificant trends
gestational age–dependent morbidities and reduce the frequencies of toward increased maternal infectious morbidity with only brief preg-
maternal and neonatal infections.144 An alternative conclusion from nancy prolongation. One study found increased infant mortality and
the latest meta-analysis is that penicillins other than amoxicillin- mortality due to sepsis with cerclage retention after PROM.173 One
clavulanic acid are an acceptable treatment for preterm PROM and study that compared different practices at two institutions found
that the benefits of erythromycin are limited to brief pregnancy pro- longer latencies with cerclage retention, but this finding could reflect

9. CHAPTER 31 Premature Rupture of the Membranes 607
population or practice differences at these institutions rather than the specific neonatal outcomes after previable PROM is extremely difficult
effect of cerclage retention.174 because it is not possible to predict extended latency, the ultimate
Because cerclage retention after PROM has not been shown to gestational age at delivery, or the degree of neonatal pulmonary hypo-
improve perinatal outcomes and there are potential risks related to plasia at the time of initial presentation with PROM.
leaving the cerclage in situ, removal is recommended when PROM For women who decide that the risks of conservative management
occurs, particularly if the indication for initial cerclage placement was exceed the potential benefits, delivery can usually be accomplished
not strong. While deferred removal might enhance pregnancy prolon- with vaginal prostaglandin E2, oral or vaginal prostaglandin E1 (i.e.,
gation for corticosteroid administration, the risks and benefits of this misoprostol), with a high-dose oxytocin infusion, or by dilatation and
approach have not been determined. evacuation. The optimal approach depends on the patient’s character-
istics (e.g., gestational age, evident amnionitis, prior cesarean delivery)
Maternal Herpes Simplex Virus Infection and preference, the available facilities, and the physician’s experience
Neonatal herpes simplex infection most commonly results from direct with these techniques.
maternal-fetal transmission at delivery, but hematogenous transmis- Data to guide the management for women who choose conservative
sion can occur to the fetus in utero in some cases. Neonatal infection management of previable PROM are lacking. There is no consensus
rates after primary and secondary maternal infections occur in 34% to about the advantages of inpatient versus outpatient management.
80% and 1% to 5% of cases, respectively,176,177 and infection can result Initial inpatient evaluation may include strict bed and pelvic rest to
in mortality rates of 50% to 60% and serious sequelae in up to 50% enhance the opportunity for resealing and for early identification of
of survivors.178,179 infection and placental abruption. Women who are discharged should
Based on two case series including a total of 35 women with an be advised to abstain from intercourse and limit physical activity. They
active maternal genital herpesvirus infection, it has been generally should return immediately in case of fever, abdominal pains, suspi-
accepted that increasing latency after membrane rupture of more than cious vaginal discharge, or any vaginal bleeding. Hospitalization for
4 to 6 hours increases risk of neonatal infection and that cesarean the duration of amniotic fluid leakage may be appropriate in some
delivery should be performed expeditiously to prevent fetal infection circumstances. Discharged patients are typically readmitted to hospital
in this setting.180-182 However, a case series of women with conserva- after the limit of viability has been reached to allow early intervention
tively managed PROM before 32 weeks’ gestation coincident to active for infection, placental abruption, labor, and non-reassuring fetal heart
recurrent herpes simplex virus lesions suggests that conservative man- rate patterns. Administration of antenatal corticosteroids for fetal
agement may be considered.183 Antenatal corticosteroids and antibiot- maturation at this time is appropriate.
ics were not administered, and antiviral therapy was inconsistent in After an initial ultrasound assessment, repeated evaluation can be
this series. Cesarean delivery was performed for women with active performed every 1 to 2 weeks to determine whether there is re-accu-
lesions at the time of delivery. After latencies ranging from 1 to 35 days, mulation of amniotic fluid and to evaluate lung growth. Persistent,
none of the 26 infants developed neonatal herpes infection (CI, 0% to severe oligohydramnios after PROM before 20 weeks is the strongest
10.4%). predictor of subsequent lethal pulmonary hypoplasia. Serial fetal bio-
Based on these data, conservative management of PROM com- metric evaluation (e.g., lung length, chest circumference), ratios to
plicated by recurrent maternal herpes simplex virus infection may adjust for overall fetal size (thoracic to abdominal circumference, tho-
be appropriate if membrane rupture occurs remote from term and racic circumference to femur length) and Doppler studies of fetal pul-
the potential for mortality or serious sequelae with delivery is consid- monary artery and ductus arteriosus waveform modulation with fetal
ered to be high. Antiviral therapy (e.g., acyclovir) during conserva- breathing movements can demonstrate whether fetal pulmonary
tive management can reduce viral shedding and the frequency of growth has occurred over time. These results have a high predictive
recurrence. value for neonatal mortality due to pulmonary hypoplasia.88,96,185-190 If
pulmonary hypoplasia becomes evident before the limit of viability or
Previable Premature Rupture of there is persistent, severe oligohydramnios, the patient may choose to
reconsider her decision regarding ongoing expectant management.
the Membranes before 23 Treatments to seal the membrane defect or restore normal amniotic
Weeks’ Gestation fluid volume include transabdominal amnioinfusion and membrane
Although the cause is often not apparent, clinical antecedents can be sealing with fibrin, platelet, cryoprecipitate, or gel-foam plugs. These
helpful in determining the likely outcomes in some cases of previable methods are described in a review.191 The maternal risks and fetal
PROM. Membrane rupture after amniocentesis is associated with ces- benefits of these interventions have not been adequately evaluated, and
sation of leakage and subsequent successful pregnancy outcomes in there are inadequate data to recommend that any of these approaches
most cases. Alternatively, previable PROM in a pregnancy complicated be incorporated into routine clinical practice.
by persistent second-trimester bleeding, oligohydramnios, or an ele-
vated level of maternal serum α-fetoprotein more likely reflects an
abnormality of placentation, which carries a poor prognosis.
The patient with previable PROM and no other indication for
Summary
immediate delivery should be counseled regarding the risks and bene- When term or preterm PROM occurs, there is the potential for signifi-
fits of expectant management, including a realistic appraisal of poten- cant perinatal morbidity and mortality, which can be reduced by con-
tial fetal and neonatal outcomes according to the available information sidered and timely obstetric interventions. Expeditious delivery of the
for gestational age–appropriate outcomes.71,72,184 In addition to the patient with term and late preterm PROM can reduce the risk of peri-
maternal risks of conservative management previously delineated, natal infections without increasing the likelihood of operative delivery.
muscle wasting, bone demineralization, and deep venous thrombosis Conservative management of PROM remote from term can reduce
can also occur with prolonged bed rest, and there are significant finan- infectious and gestational age–dependent morbidities. Regardless of
cial and social implications of prolonged hospitalization. Prediction of management approach, infants delivered after early preterm or previ-

10. 608 CHAPTER 31 Premature Rupture of the Membranes
able PROM are at high risk for perinatal complications, many of which 19. Carroll SG, Papaioannou S, Davies ET, Nicolaides KH: Maternal assess-
cannot be avoided with current technologies and management algo- ment in the prediction of intrauterine infection in preterm prelabor amni-
rithms. Attention to early diagnosis and management of complications orrhexis. Fetal Diagn Ther 10:290-296, 1995.
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infection in pregnancy: Intervention with indomethacin and delayed
ampicillin-sulbactam therapy. Am J Obstet Gynecol 169:708-712,
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11. CHAPTER 31 Premature Rupture of the Membranes 609
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