Preterm Premature (Prelabor) Rupture of Membranes

1/11/2016
Preterm premature (prelabor) rupture of membranes
Official reprint from UpToDate

www.uptodate.com 2016 UpToDate

Author
Patrick Duff, MD
Section Editor
Charles J Lockwood, MD, MHCM
Deputy Editor
Vanessa A Barss, MD, FACOG
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Dec 2015. | This topic last updated: Jan 04, 2016.
INTRODUCTION Premature rupture of membranes (PROM) refers to membrane rupture before the onset of
uterine contractions (also known as prelabor rupture of membranes); preterm PROM (PPROM) refers to PROM
before 370/7ths weeks of gestation.
The management of PPROM is among the most controversial issues in perinatal medicine. Points of contention
include:
Expectant management versus intervention

Use of tocolytics
Duration of administration of antibiotic prophylaxis
Timing of administration of antenatal corticosteroids
Methods of testing for maternal/fetal infection
Timing of delivery
Risk factors, diagnosis, and management of PPROM at 23 to 37 weeks of gestation will be discussed here. Issues
specifically relating to management of PROM prior to 23 weeks of gestation and at term are discussed separately.
(See "Midtrimester preterm premature rupture of membranes" and "Management of premature rupture of the fetal
membranes at term".)
INCIDENCE Preterm premature rupture of membranes (PPROM) occurs in 3 percent of pregnancies and is
responsible for, or associated with, approximately one-third of preterm births [1].
PATHOGENESIS The pathogenesis of spontaneous membrane rupture is not completely understood. The
strength and integrity of fetal membranes derive from extracellular membrane proteins, including collagens,
fibronectin, and laminin. Matrix metalloproteases (MMPs) decrease membrane strength by increasing collagen
degradation [2]. Tissue inhibitors of MMPs (TIMMPs) bind to MMPs and shut down proteolysis, thereby helping to
maintain membrane integrity [2,3]. A variety of pathologic events can disrupt this homeostasis and initiate a
cascade of biochemical changes that culminate in PROM. Although the pathway varies depending on the initiating
event, it is likely that all pathways lead to a final common pathway ending in membrane rupture. (See
"Pathogenesis of spontaneous preterm birth".)
CLINICAL FINDINGS
Risk factors Maternal physiologic, genetic, and environmental factors likely predispose to development of
preterm premature rupture of membranes (PPROM) in many cases. These risk factors are similar to those for
preterm labor (table 1), but most patients have no identifiable risk factors. (See "Risk factors for preterm labor and
delivery".)
A history of PPROM in a previous pregnancy, genital tract infection, antepartum bleeding, and cigarette smoking
have a particularly strong association with PPROM [4].
Previous PPROM Studies have consistently reported that a history of PPROM is a strong risk factor for
recurrence. As an example, the Preterm Prediction Study, a large prospective study conducted by the
National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU)
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Network, observed that women with a history of PPROM had a 13.5 percent rate of PPROM in a subsequent
pregnancy compared to 4.1 percent in women with no such history (RR 3.3, 95% CI 2.1-5.2) [5]. Others have
reported recurrence rates at high as 32 percent [6]. Women with a history of PPROM are at risk for recurrent
PPROM or preterm birth without PPROM [7,8].
Genital tract infection Genital tract infection is the single most common identifiable risk factor for
PPROM. Three lines of epidemiologic evidence strongly support this association: (1) women with PPROM are
significantly more likely than women with intact membranes to have pathogenic microorganisms in the
amniotic fluid, (2) women with PPROM have a significantly higher rate of histologic chorioamnionitis than
those who deliver preterm without PPROM, and (3) the frequency of PPROM is significantly higher in women
with certain lower genital tract infections (particularly bacterial vaginosis) than in uninfected women [3]. (See
"Bacterial vaginosis".)
The association between bacterial colonization of the lower genital tract and PPROM is not surprising. Many
of the microorganisms that colonize the lower genital tract have the capacity to produce phospholipases,
which can stimulate the production of prostaglandins and thereby lead to the onset of uterine contractions. In
addition, the host's immune response to bacterial invasion of the endocervix and/or fetal membranes leads to
the production of multiple inflammatory mediators that can cause localized weakening of the fetal membranes
and result in PPROM [3]. Genetic regulation of the host's immune and inflammatory response appears to play
a role in susceptibility and response to infections associated with PPROM. (See "Pathogenesis of
spontaneous preterm birth" and "Risk factors for preterm labor and delivery".)
Antepartum bleeding Antepartum bleeding in the first trimester is associated with a small but
statistically significant increase in the risk of PPROM [9]. Antepartum bleeding in more than one trimester
increases the risk of PPROM three- to seven-fold [4,10,11].
Cigarette smoking The risk of PPROM among smokers is increased two- to four-fold compared to
nonsmokers. The risk persists even after adjustment for other known risk factors for PPROM, including
infection. (See "Cigarette smoking and pregnancy".)
In addition, several genetic polymorphisms of genes related to infection, inflammation, and collagen degradation
have been identified as potential risk factors for PPROM.
Patient presentation The classic clinical presentation of PPROM is a sudden "gush" of clear or pale yellow
fluid from the vagina. However, many women describe intermittent or constant leaking of small amounts of fluid or
just a sensation of wetness within the vagina or on the perineum.
Findings on physical examination Direct observation of amniotic fluid coming out of the cervical canal or
pooling in the vaginal fornix is pathognomonic of PPROM. If amniotic fluid is not immediately visible, the woman can
be asked to push on her fundus, Valsalva, or cough to provoke leakage of amniotic fluid from the cervical os.
For patients who are not in active labor, examination of the cervix and vagina is performed using a sterile speculum.
Digital examination should be avoided because it may decrease the latency period (ie, time from rupture of
membranes to delivery) and increase the risk of intrauterine infection [12-14]. The cervix may appear dilated and/or
effaced and, rarely, prolapse of a fetal part or the umbilical cord may be detected.
Findings on ultrasonography Fifty to 70 percent of women with PPROM have low amniotic fluid volume on
initial sonography [15].
Clinical course The majority of pregnancies with PPROM deliver within one week of membrane rupture. In a
randomized trial of PPROM at 24 to 32 weeks, the median time to delivery of 239 group B streptococcal (GBS)
negative patients managed expectantly with prophylactic antibiotics was 6.1 days; 27 percent delivered within 48
hours, 56 percent delivered within 7 days, 76 percent delivered within 14 days, and 86 percent delivered within 21
days [16]. However, the duration of the latency period inversely correlates with gestational age at membrane rupture
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[17].
Cessation of fluid leakage is rare, except in women with PPROM related to amniocentesis. Sealing of membranes
is associated with a more favorable prognosis [18]. (See "Diagnostic amniocentesis", section on 'Leakage of
amniotic fluid'.)
The fetus and neonate are at greater risk of PPROM-related morbidity and mortality than the mother (table 2).
Prematurity-related morbidity varies with gestational age and is higher in the setting of chorioamnionitis [19]. Fetal
exposure to intrauterine inflammation has been associated with an increased risk of neurodevelopmental
impairment. (See "Incidence and mortality of the premature infant" and "Short-term complications of the premature
infant" and "Intraamniotic infection (chorioamnionitis)".)
Approximately one-third of women with PPROM develop potentially serious infections, such as intraamniotic
infection (chorioamnionitis and funisitis), endometritis, or septicemia. Endometritis is more common after cesarean
than vaginal delivery. The incidence of infection is higher at earlier gestational ages [20,21]. (See "Intraamniotic
infection (chorioamnionitis)" and "Postpartum endometritis".)
PPROM is also associated with increased risks of abruptio placentae and prolapse of the umbilical cord. Placental
abruption occurs in 2 to 5 percent of pregnancies complicated by PPROM [22-25]. The risk is increased seven- to
nine-fold in PPROM pregnancies in which intrauterine infection or oligohydramnios is present [23,24]. Placental
abruption may be the precipitating event for or a consequence of PPROM. (See "Placental abruption: Clinical
features and diagnosis", section on 'Pathogenesis and pathophysiology'.)
Fetal malpresentation is common, given the preterm gestational age and the frequent occurrence of reduced
amniotic fluid volume. The risk of cord prolapse is especially high (11 percent in one study [26]) in the setting of
both nonvertex fetal presentation and PPROM. Non-cephalic presentation may also increase the risk of abruption,
infection, and fetal death in utero [27]. (See "Umbilical cord prolapse" and "Placental abruption: Clinical features
and diagnosis".)
Early, severe, prolonged oligohydramnios can be associated with pulmonary hypoplasia, facial deformation, and
orthopedic abnormalities. Such complications are most likely when membrane rupture occurs at less than 23
weeks of gestation. (See "Midtrimester preterm premature rupture of membranes", section on 'Pediatric outcomes'.)
DIAGNOSIS The diagnosis of preterm premature rupture of membranes (PPROM) is clinical, and is generally
based on visualization of amniotic fluid in the vagina of a woman who presents with a history of leaking fluid.
Laboratory tests are used to confirm the clinical diagnosis when it is uncertain.
Laboratory confirmation of clinically suspected PPROM
Nitrazine and fern tests If PPROM is not obvious after visual inspection, the diagnosis can be confirmed by
testing the pH of the vaginal fluid, which is easily accomplished with Nitrazine paper. Amniotic fluid usually has a
pH range of 7.0 to 7.3 compared to the normally acidic vaginal pH of 3.8 to 4.2 (picture 1) [28].
False-negative and false-positive Nitrazine test results occur in up to 5 percent of cases [29,30]. False negative test
results can occur when leaking is intermittent or the amniotic fluid is diluted by other vaginal fluids. False positive
results can be due to the presence of alkaline fluids in the vagina, such as blood, seminal fluid, or soap. In addition,
the pH of urine can be elevated to near 8.0 if infected with Proteus species.
A second confirmatory test is the presence of arborization (ferning). Fluid from the posterior vaginal fornix is
swabbed onto a glass slide and allowed to dry for at least 10 minutes. Amniotic fluid produces a delicate ferning
pattern, in contrast to the thick and wide arborization pattern of dried cervical mucus (picture 2 and picture 3). Wellestrogenized cervical mucus or a fingerprint on the microscope slide may cause a false-positive fern test; false
negatives can be due to inadequate amniotic fluid on the swab or heavy contamination with vaginal discharge or
blood.
In the United Kingdom, an absorbent pad (AmnioSense) that changes color at pH >5.2 is used as a panty liner and
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marketed to pregnant women. In a study of 157 pregnant women, the sensitivity and specificity of this device for
diagnosis of membrane rupture were 98 and 65 percent, respectively [31].
AmniSure and Actim PROM Placental alpha microglobulin-1 protein assay (PAMG-1 [AmniSure]) and
insulin-like growth factor binding protein 1 (IGFBP-1 [Actim PROM]) are commercially available tests for diagnosis
of ROM. A 2013 meta-analysis of prospective observational or cohort studies investigating IGFBP-1 and PAMG1 tests for diagnosis of ROM concluded PAMG-1 (AmniSure) was more accurate than IGFBP-1 (Actim PROM) for
diagnosis of ROM in all patient populations (eg, known rupture status, uncertain rupture status) [32]. A subsequent
randomized trial reported similar findings [33].
Placental alpha microglobulin-1 protein assay (AmniSure) AmniSure is a rapid slide test that uses
immunochromatography methods to detect trace amounts of placental alpha microglobulin-1 protein in vaginal fluid.
An advantage of this test is that it is not affected by semen or trace amounts of blood.
The test is done by the provider at the point of care using a commercially available kit. A sterile swab is inserted
into the vagina for one minute, then placed into a vial containing a solvent for one minute, and then an AmniSure
test strip is dipped into the vial. The test result is revealed by the presence of one or two lines within the next 5 to
10 minutes (one visible line means a negative result for amniotic fluid, two visible lines is a positive result, no visible
lines is an invalid result). In large studies, sensitivity ranged from 94.4 to 98.9 percent and specificity ranged from
87.5 to 100 percent [34-38]. In one study, the authors hypothesized that false positive results in three patients
might have been due to a small leak that sealed over [35].
Given the relatively high cost of this test, we suggest limiting its use to cases where the diagnosis remains
uncertain after physical examination and Nitrazine and fern tests.
Insulin-like growth factor binding protein 1 (Actim PROM) Identification of insulin-like growth factor
binding protein 1 (IGFBP-1) also may be of value in confirming the diagnosis of PPROM in problematic cases. This
protein is secreted by decidual and placental cells and has a very high concentration in amniotic fluid compared to
other body fluids. An easy-to-use, immunochromatography dipstick method (eg, actim Prom) is available in some
countries for use at the bedside to detect IGFBP-1 in vaginal secretions. This test is popular in Europe, but is not
widely used in the United States. A positive test is denoted by the presence of two blue lines on the dipstick. The
test is not affected by the presence of infected vaginal secretions, urine, semen, or small amounts of blood.
The test is most accurate when applied as soon as possible after rupture of membranes. Sensitivity in detecting
ruptured membranes ranges from 95 to 100 percent, specificity ranges from 93 to 98 percent, and positive predictive
value approaches 98 percent [37,39-42]. The test is particularly helpful in identifying those women likely to deliver
within seven days.
Ultrasound examination In equivocal cases, ultrasound can be performed to look for a reduction in
amniotic fluid volume. If the patient has a normal amniotic fluid volume, it is very unlikely that she has experienced
rupture of membranes, even with a seemingly convincing history.
Other tests
Fetal fibronectin A negative fetal fibronectin result strongly supports absence of membrane rupture, but
a positive result only indicates disruption of the interface between chorion and decidua, which can occur with intact
membranes [43].
Alpha-fetoprotein Alpha-fetoprotein (AFP) in vaginal secretions suggestions the presence of amniotic
fluid [44-47]. In a pilot study, extraction of AFP from sanitary pads differentiated amniotic fluid, which has a high
AFP concentration, from other common secretions (vaginal discharge, urine, semen), which have low AFP levels
[47]. Sensitivity was 96.2 percent and specificity was 100 percent for diagnosis of PROM at an AFP cutoff of 3.88
ng/mL. Measurement of AFP is less costly than other commercially available tests for PROM, but blood in the
vagina can give false positive results.
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Instillation of dye In the past, clinicians performed the "tampon test" in problematic cases. Under
ultrasound guidance, 1 mL of indigo carmine dye in 9 mL of sterile saline was injected transabdominally into the
amniotic fluid, and a tampon was placed in the vagina. Twenty minutes later, the tampon was removed and
examined for blue staining, which indicated leakage of amniotic fluid. However, indigo carmine dye is no longer
available in the United States. Moreover, this invasive test is not always easy to perform in the presence of a
reduced amniotic fluid volume, and it can cause rupture of membranes. It has been replaced by non-invasive tests,
such as AmniSure and Actim PROM. (See 'AmniSure and Actim PROM' above.).
Differential diagnosis Other causes of vaginal/perineal wetness include urinary incontinence, vaginal
discharge, and perspiration. These causes should be considered in women with negative clinical and laboratory
findings for PPROM.
If ultrasound is performed, a mild reduction of amniotic fluid volume is a nonspecific finding related to many
etiologies, including PPROM. On the other hand, the finding of anhydramnios or severe oligohydramnios, combined
with a characteristic history, is highly suggestive of rupture of membranes, although renal agenesis, obstructive
uropathy, or severe utero-placental insufficiency also can cause marked reductions in amniotic fluid volume. (See
"Assessment of amniotic fluid volume".)
MANAGEMENT Management of preterm premature rupture of membranes (PPROM) from 23 weeks to 37 weeks
will be discussed here. Issues specifically relating to management of previable PPROM and PROM at term are
reviewed separately. (See "Midtrimester preterm premature rupture of membranes" and "Management of premature
rupture of the fetal membranes at term".)
Initial approach The management of pregnancies complicated by PPROM is based upon consideration of
several factors, which are assessed upon presentation:
Gestational age
Presence or absence of maternal/fetal infection
Presence or absence of labor
Fetal presentation
Fetal well-being
Fetal lung maturity
Cervical status (by visual inspection)
Availability of neonatal intensive care
Some tests that can be useful in this assessment are listed in the table (table 3). Screening for GBS, sexually
transmitted infections, and possibly bacterial vaginosis is useful for guiding antibiotic therapy (discussed below),
but vaginal culture is not helpful since the vaginal flora is normally polymicrobial.
The key decision is whether to induce labor (or perform cesarean delivery) or to manage the pregnancy expectantly.
The immature fetus will benefit by prolongation of pregnancy that results in a significant reduction in gestational
age-related morbidity, but this benefit needs to balance with the risks of PPROM-associated complications and
their sequelae (table 2).
Expeditious delivery of women with PPROM is clinically appropriate if intrauterine infection, abruptio placentae,
nonreassuring fetal testing, or a high risk of cord prolapse is present or suspected. In each of these conditions, fetal
well-being can deteriorate with expectant management, and there are no therapeutic interventions available other
than delivery. (See "Placental abruption: Clinical features and diagnosis" and "Intraamniotic infection
(chorioamnionitis)" and "Umbilical cord prolapse".)
In the absence of these complications, we do not intervene to effect delivery prior to 34 weeks. Our simplified
algorithm for management of women with PPROM at 26 to 36 weeks is shown in the algorithm (algorithm 1). As
noted, most patients who are initially managed expectantly will be delivered at 34 weeks of gestation; in some,
delivery will be delayed until 36 weeks of gestation. A detailed analysis of the nuances of management is beyond
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the scope of this topic review; however, several aspects of management will be discussed.
The optimal time for intervention varies among institutions and depends on the balance between morbidity related to
prematurity and morbidity related to complications of PPROM. The American College of Obstetricians and
Gynecologists (ACOG) suggests delivery for all patients 34 weeks of gestation [48]. (See 'Timing of delivery for
expectantly managed pregnancies' below.)
Meta-analyses of randomized trials, and subsequent randomized trials, have not provided conclusive evidence
favoring induction or expectant management of PPROM between 28 and 37 weeks [49-53]. The complexity of
management decisions was illustrated by the Preterm Prelabour Rupture of the Membranes close to Term
(PPROMT) trial [49]. This multicenter, international randomized trial (65 centers in 11 countries) was focused
specifically on patients who developed PPROM between 34 and 366/7ths weeks of gestation and were randomly
assigned to immediate delivery (n = 924) or expectant management (n = 915). The trial found that rates of neonatal
sepsis (primary outcome) were 2 to 3 percent and did not differ significantly between the two groups. Infants in the
immediate delivery group were more likely to develop respiratory distress syndrome (8 versus 5 percent, relative risk
[RR] 1.6, 95% CI 1.1-2.3), require mechanical ventilation (12 versus 9 percent, RR 1.4, 95% CI 1.0-1.8), and spend
more time in the neonatal intensive care unit (six versus four days) than infants delivered to mothers in the
expectant management group. There was no difference between groups in the composite neonatal outcome of
sepsis, ventilation for 24 hours, or death. However, mothers assigned to expectant management were more likely
to develop antepartum or intrapartum bleeding (5 versus 3 percent), develop intrapartum fever (2 versus 1 percent),
and require use of therapeutic antibiotics (20 versus 16 percent). They also had a longer hospital stay (six versus
five days) and a lower frequency of cesarean delivery (19 versus 26 percent). This trial had several limitations that
preclude extrapolating these findings to contemporary populations in the United States. For example, the trial was
conducted over 10 years, during which obstetric and neonatal management has likely changed. In addition, the
study was conducted at many different facilities with different levels of resources and different management
strategies. Some patients were managed as outpatients, which is not done in the United States; there were no
clear criteria for determining the timing of delivery in the expectantly managed group; there were significant
variations in protocols for laboratory testing and administration of prophylactic antibiotics, and there were
inconsistencies in the use of corticosteroids.
Expectant management
Administration of antenatal corticosteroids A course of corticosteroids should be given to pregnancies
between 23 and 34 weeks of gestation. Data supporting this recommendation were provided by systematic reviews
of randomized trials [54,55] that showed neonatal death, respiratory distress syndrome (RDS), intraventricular
hemorrhage (IVH), necrotizing enterocolitis (NEC), and duration of neonatal respiratory support were significantly
reduced by antenatal glucocorticoid treatment, without an increase in either maternal or neonatal infection. Mean
risk reduction for these adverse events ranged from 30 to 60 percent.
A single course of rescue therapy is reasonable if the patient is clinically estimated to be at high risk of delivery
within the next seven days, at least two weeks have passed since the initial course of antenatal corticosteroids,
and the initial course was given at <28 weeks of gestation. (See "Antenatal corticosteroid therapy for reduction of
neonatal morbidity and mortality from preterm delivery", section on 'Evidence for salvage, rescue, booster therapy'.)
The effect of PPROM on fetal pulmonary maturation is unclear as studies have reported inconsistent results. This
discordancy may be due to failure to adjust for factors that affect neonatal respiratory function, such as mode of
delivery and presence or absence of labor, as well as gestational age, duration of latency, and comorbidities [56].
Antibiotic therapy Antibiotics are indicated to prolong latency and reduce the risk of early onset neonatal
group B streptococcal (GBS) infection, as well as for treatment of overt intraamniotic infection, if present. The
regimen of prophylactic antibiotics is given for seven days to pregnancies <34 weeks of gestation at the time of
membrane rupture.
Prophylaxis The rationale for antibiotic prophylaxis is that infection appears to be both a cause and
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consequence of PPROM. Infection may lead to spontaneous preterm labor or may be the indication for medicallyindicated preterm delivery. The goal of antibiotic therapy is to reduce the frequency of maternal and fetal infection
and thereby delay the onset of preterm labor (ie, prolong latency) and the need for preterm delivery. The importance
of reducing infection is underscored by studies suggesting a relationship between chorioamnionitis, duration of
membrane rupture, and development of cerebral palsy or neurodevelopmental impairment. (See "Intraamniotic
infection (chorioamnionitis)".)
A 2013 systematic review of 22 placebo-controlled randomized trials involving over 6800 women evaluated the use of
antibiotics following PPROM before 37 weeks of gestation [57]. Compared to placebo/no treatment, antibiotic use
was associated with significant reductions in:
Chorioamnionitis (RR 0.66, 95% CI 0.46-0.96)
Babies born within 48 hours (RR 0.71, 95% CI 0.58-0.87) and 7 days (RR 0.79, 95% CI 0.71-0.89) of
randomization
Neonatal infection (RR 0.67, 95% CI 0.52-0.85),
Use of surfactant (RR 0.83, 95% CI 0.72-0.96),
Neonatal oxygen therapy (RR 0.88, 95% CI 0.81-0.96), and
Abnormal cerebral ultrasound scan prior to hospital discharge (RR 0.81, 95% CI 0.68-0.98)
Data were insufficient to determine whether any antibiotic regimen (drug, dose, duration) was better than another,
but amoxicillin-clavulanate appeared to be associated with an increased risk of neonatal necrotizing enterocolitis
(RR 4.72, 95% CI 1.57-14.23). The validity of this association requires further investigation in large trials, given the
wide confidence interval.
A 2008 meta-analysis was limited to PPROM before 34 weeks of gestation, and reported similar results [58].
Drug regimen A regimen with reasonable activity against the major pelvic pathogens should be used,
but the optimal regimen is unclear [59]. We recommend administering a seven-day course of antibiotic prophylaxis
to all women with PPROM who are managed expectantly. Our preference is ampicillin 2 g intravenously every 6
hours for 48 hours, followed by amoxicillin (500 mg orally three times daily or 875 mg orally twice daily) for an
additional five days. In addition, we recommend giving one dose of azithromycin (one gram orally) upon admission.
Ampicillin specifically targets group B streptococcus, many aerobic gram-negative bacilli, and some anaerobes.
Azithromycin specifically targets genital mycoplasmas, which can be important causes of chorioamnionitis in this
setting, and also provides coverage of Chlamydia trachomatis, which is an important cause of neonatal
conjunctivitis and pneumonitis.
This regimen is similar to that shown to be effective in the National Institute of Child Health and Human
Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network trial on antibiotic therapy for reduction of
infant morbidity after PPROM (intravenous ampicillin 2 g every 6 hours and erythromycin 250 mg every 6 hours for
48 hours followed by oral amoxicillin 250 mg every 8 hours and erythromycin 333 mg every 8 hours for five days)
[16]. We give azithromycin in lieu of a multiple-day course of erythromycin because of its ease of administration,
improved gastrointestinal tolerance, favorable cost profile, and similar efficacy. In a retrospective study of women
with PPROM given prophylaxis with ampicillin plus erythromycin or ampicillin plus azithromycin, the two regimens
resulted in similar pregnancy and neonatal outcomes (latency length; mean birth weight; rates of chorioamnionitis,
cesarean delivery, low Apgar score, neonatal sepsis, neonatal respiratory distress syndrome) [60]. The powder
formulation of azithromycin is less expensive than the tablets, but may not be as well tolerated.
A basic science investigation illustrates the importance of genital mycoplasmas in the pathogenesis of preterm
labor and helps to explain why drugs such as erythromycin and azithromycin may be valuable both in prolonging
the latent period and reducing the frequency of infection and injury in the baby [61]. In this study, 16 chronically
instrumented rhesus monkeys underwent intraamniotic inoculation with Ureaplasma parvum. Uterine contractions
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began soon after inoculation, at which time six monkeys received no treatment, five received intravenous
azithromycin for 10 days, and five received azithromycin plus dexamethasone and indomethacin for 10 days.
Azithromycin significantly prolonged gestation by approximately seven days, significantly decreased the
Ureaplasma colony count in the amniotic fluid, decreased the amniotic fluid concentration of proinflammatory
mediators, and decreased the magnitude of histologic lung injury. Interestingly, dexamethasone and indomethacin
did not further enhance the treatment effect of azithromycin.
Women with penicillin allergy If the patient's history suggests a "low risk" for anaphylaxis (eg,
isolated maculopapular rash without urticaria or pruritus), then we suggest cefazolin 1 g intravenously every 8 hours
for 48 hours, followed by cephalexin 500 mg orally four times daily for five days. These drugs provide coverage for
both GBS and E Coli, the two major causes of neonatal infection. We also give a single oral dose of azithromycin 1
g. (See "Penicillin allergy: Immediate reactions".)
If the patient's history suggests a "high risk" for anaphylaxis (eg, anaphylaxis, angioedema, respiratory distress,
urticaria, particularly if these symptoms occurred within 30 minutes of drug administration), we suggest clindamycin
900 mg intravenously every 8 hours for 48 hours plus gentamicin 7 mg/kg ideal body weight for two doses 24 hours
apart, followed by oral clindamycin 300 mg every eight hours for five days. We also give a single dose of
azithromycin 1 g.
Prophylactic antibiotics may exert selective pressures for emergence of drug-resistant microorganisms. In addition,
there is a theoretical concern that clinical infection may be more difficult to recognize or treat in patients who have
received prophylactic antibiotics. These problems have not been observed in women with PPROM receiving
antibiotic prophylaxis. Long-term adverse effects of antepartum prophylactic antibiotics for PPROM have not been
observed in children followed to age 7 years [62]. This finding is in contrast to the observation from the same
authors that, in patients with spontaneous preterm labor and intact membranes, the rate of cerebral palsy was
increased in children exposed to antibiotics in utero [63].
Chemoprophylaxis for GBS Chemoprophylaxis specifically for GBS disease is indicated if GBS test
results are positive or unknown and delivery is imminent, but is generally not given to women with recent (within five
weeks) negative GBS test results. The intravenous portion of the regimen described above for PPROM prophylaxis
(ampicillin 2 g intravenously every 6 hours for 48 hours) should provide adequate treatment for GBS-colonized
women who are in labor at the time of admission or who go into labor within 48 hours of admission. As noted, this
regimen of intravenous ampicillin, followed by oral amoxicillin, combined with azithromycin, is usually given for
seven days. After completion of this regimen, antibiotics should be discontinued. If the patients GBS culture is
positive, specific prophylaxis for GBS colonization should be resumed when the patient subsequently goes into
labor (algorithm 2) [64].
Testing to determine GBS status and guidelines for chemoprophylaxis are discussed in detail separately. (See
"Neonatal group B streptococcal disease: Prevention", section on 'Approach to threatened preterm delivery'.)
Use of tocolysis The principal indication for tocolysis in the setting of PPROM is to delay delivery for 48
hours to allow administration of corticosteroids. As a general rule, tocolytics should not be administered for more
than 48 hours. They also should not be administered to patients who are in advanced labor (>4 cm dilation) or who
have any findings suggestive of subclinical or overt chorioamnionitis. Other potential contraindications to tocolysis
include nonreassuring fetal testing, abruptio placentae, and significant risk of cord prolapse (eg, dilated cervix and
fetal malpresentation). (See "Inhibition of acute preterm labor".)
In a 2014 systematic review of randomized trials evaluating pregnancy outcomes of women with PPROM who
received or did not receive tocolytic therapy (prophylactic or therapeutic), tocolysis for pregnancies <34 weeks
resulted in fewer births within 48 hours (RR 0.59, 95% CI 0.34-1.00; four trials, n = 243 women), but an increase in
chorioamnionitis (RR 1.79, 95% CI 1.02-3.14; three trials, n = 168 women) and no significant improvement in
perinatal morbidity or mortality [65]. There are several limitations to these data, including the small number and size
of the trials, and patients did not consistently receive antenatal corticosteroids to reduce neonatal morbidity or
antibiotics to prolong latency, which diverges with current standards of care and may explain the lack of
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improvement in clinically important outcomes.

Supplemental progesterone Progesterone supplementation is not beneficial in women with PPROM in the
current pregnancy. In two placebo-controlled, randomized trials of women with PPROM at 20 to 30 weeks of
gestation, weekly injection of hydroxyprogesterone caproate did not extend the latent period before delivery or
reduce perinatal morbidity [66,67].
In women who are on supplemental progesterone because of a prior pregnancy with preterm delivery related to
preterm labor or PPROM, we discontinue the medication upon diagnosis of PPROM. (See "Progesterone
supplementation to reduce the risk of spontaneous preterm birth", section on 'Preterm premature rupture of
membranes'.)
Hospitalization versus home care We hospitalize women with PPROM who have a viable fetus from the
time of diagnosis until delivery, with few exceptions. Activity is limited to using the bathroom and sitting up in a
bedside chair. Thromboprophylaxis in the form of sequential compression devices should be provided to all
hospitalized pregnant women at bedrest [68]. We also administer prophylactic doses of enoxaparin (1 mg/kg/day)
to patients who have additional risk factors for deep vein thrombosis.
There have been only two randomized trials evaluating the safety of outpatient versus inpatient management of
women with PPROM [69,70]. The smaller trial included only 21 women with PPROM as part of a larger study of
antenatal day care versus in-hospital care [70]. The larger trial, which included 67 women with PPROM, randomly
assigned one group to expectant management at home and the other to expectant management in the hospital
[69]. Both groups were managed similarly with bedrest, recording of temperature and pulse every six hours, daily
charting of fetal movements, twice-weekly nonstress tests (NSTs) and complete blood count, and weekly
ultrasound and visual examination of the cervix. Only 18 percent of the women met the strict safety criteria used for
inclusion (table 4) and three women managed at home delivered unexpectedly at outside hospitals.
A meta-analysis found no significant differences in maternal or neonatal outcomes between the hospital and home
care groups, although the home group had lower maternal costs [71]. However, these small trials did not have
sufficient statistical power to detect meaningful differences between groups. A small retrospective study also
observed no significant differences in maternal or neonatal outcomes for hospital versus home care, but the small
number of patients and lack of a standardized protocol are major limitations to interpreting the results [72].
Further study to determine the safety of this approach is warranted before a policy of outpatient management can
be recommended. In particular, the possibility and risks of a delay in diagnosis of maternal infection, cord prolapse,
and precipitous labor and delivery need to be addressed [26,69].
Maternal monitoring Women with PPROM should be monitored for signs of infection; however, there is no
consensus as to the best approach. At a minimum, routine clinical parameters (eg, maternal temperature, uterine
tenderness and contractions, maternal and fetal heart rate) should be monitored. Periodically monitoring white
blood cell counts or other markers for inflammation/infection has not been proven useful [73].
Amniocentesis to obtain amniotic fluid for Gram stain, culture, leukocyte esterase, and glucose concentration is
more controversial. We do not routinely perform amniocentesis to screen for intraamniotic infection in
asymptomatic women. If the clinical diagnosis of chorioamnionitis is uncertain and we need more information to
decide about expectant management, then we perform amniocentesis to rule out infection. However, if there is
insufficient amniotic fluid to sample, which occurs in at least 50 percent of patients, then the diagnosis of
chorioamnionitis will have to be based on clinical examination and indirect testing such as identification of an
abnormal peripheral white blood cell count. An in-depth discussion of the diagnosis and management of
intraamniotic infection can be found separately. (See "Intraamniotic infection (chorioamnionitis)".)
Fetal monitoring Some type of fetal surveillance is generally employed (eg, kick counts, NSTs, biophysical
profile [BPP]) to provide the clinician and patient some assurance of fetal well-being [74]. At our center, we perform
a daily NST. If the NST is not reassuring, we perform a BPP. However, none of these tests has good sensitivity for
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predicting fetal infection, even when performed daily (sensitivity of daily NST and BPP: 39 and 25 percent,
respectively [75]). There is no consensus among experts regarding the optimum type and frequency of testing.
Three randomized trials (n = 275 women) that attempted to determine whether testing leads to an improvement in
perinatal outcome did not report convincing evidence of improvement or harm, but were of low quality [76]. In the
largest trial (n = 135 women), women with PPROM were randomly assigned to either a daily NST or a BPP and
neither test had good sensitivity for predicting maternal or fetal infection [75].
Low amniotic fluid volume is associated with an increased risk of umbilical cord compression and shorter latency,
but, as with other tests, the value of fetal heart rate testing or the BPP score for prediction of adverse fetal/neonatal
outcome in this setting is low [15].
Similarly, Doppler surveillance is not useful for monitoring fetal status in PPROM [77-79].
Special situations
Women with HSV, HIV, or cerclage Expectant management of women with PPROM and genital
herpes simplex virus (HSV) or human immunodeficiency virus (HIV) infection is controversial, and opinions about
the best course of action diverge widely. These issues are discussed separately. (See "Genital herpes simplex
virus infection and pregnancy" and "Prenatal evaluation and intrapartum management of the HIV-infected woman in
resource-rich settings".)
Expectant management of women with PPROM and a cerclage is also reviewed elsewhere. (See "Transvaginal
cervical cerclage", section on 'Removal of cerclage after PPROM'.)
Meconium stained fluid Studies of term and preterm PROM patients have generally reported that those
with meconium-stained amniotic fluid have higher rates of both overt and subclinical chorioamnionitis and positive
amniotic fluid cultures [80-82]. Meconium release predisposes to infection by enhancing the growth of bacteria and
lowering phagocytic capacity of neutrophils [83]. However, it is also possible that in some cases meconium-like
staining is actually pigment associated with decidual hemorrhage (abruption).
Patients with PPROM and meconium-stained amniotic fluid should be evaluated for signs of chorioamnionitis. In the
absence of these signs, meconium alone is not an indication for intervention.
Tissue sealants A variety of tissue sealants (eg, fibrin glue, gelatin sponge) has shown some success in
stopping leakage in case reports. Neither the safety nor the efficacy of these sealants has been established. Tissue
sealants are discussed in more detail separately. (See "Midtrimester preterm premature rupture of membranes",
section on 'Repair of leaks'.)
Amnioinfusion A 2014 systematic review and meta-analysis compared pregnancy outcome in patients
who received antepartum transabdominal amnioinfusion versus those who received usual care for management of
PPROM in the third trimester (five randomized trials, n = 241 pregnancies) [84]. Transabdominal amnioinfusion
resulted in statistical reductions in neonatal death, sepsis/infection, and pulmonary hypoplasia, but the data for
each outcome were limited to one to two very small trials of low to moderate quality.
To better understand whether amnioinfusion is beneficial in PPROM, more and better information is needed about
the effects of specific amnioinfusion protocols, selection of patients (eg, gestational age at rupture of membranes),
and other interventions (type, dose, and duration of antibiotics; use of corticosteroids) on perinatal outcome. Until
better data are available to support a change in practice, we recommend not performing antepartum amnioinfusion
on patients with PPROM.
Twin pregnancy The management of PPROM in twin pregnancies is similar to that in singletons.
Diagnosis and treatment of overt infection Overt chorioamnionitis is usually easily diagnosed clinically
because of maternal fever, particularly when associated with leukocytosis, maternal and fetal tachycardia, uterine
tenderness, and/or malodorous amniotic fluid. Diagnosis of subclinical chorioamnionitis requires amniocentesis to
identify microorganisms in the amniotic fluid (gram stain and culture) and document an abnormally low amniotic
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fluid glucose concentration. A rapid test for interleukin-6 (IL-6), which is perhaps the most sensitive marker for
microbial invasion of the amniotic cavity, is available in some countries [85]. (See "Intraamniotic infection
(chorioamnionitis)", section on 'Diagnosis of clinical chorioamnionitis'.)
Women who develop overt infection require therapy with therapeutic, rather than prophylactic, antibiotics. (See
"Intraamniotic infection (chorioamnionitis)", section on 'Antibiotics'.)
Women with PPROM who have an identifiable genital tract infection (eg, gonorrhea, chlamydia, bacterial vaginosis)
that would not be eliminated by a prophylactic antibiotic regimen should receive antibiotics that specifically target
the infection. (See individual topic reviews on each infection).
Delivery
Magnesium sulfate for neuroprotection Magnesium sulfate is administered prior to delivery according to
standard clinical protocols for fetal neuroprotection (eg, pregnancies at least 24 but <32 weeks of gestation at risk
of imminent delivery). (See "Neuroprotective effects of in utero exposure to magnesium sulfate".)
Timing of delivery for expectantly managed pregnancies Our approach to timing delivery of women with
PPROM is summarized in the table (table 5). In general, prematurity is the greatest risk to the fetus with
uncomplicated PPROM at less than 34 weeks of gestation. Therefore, we manage pregnancies at this gestational
age expectantly in the absence of complications (eg, infection, abruption, cord prolapse, unstable fetal
presentation, nonreassuring fetal assessment).
When the pregnancy reaches 34 weeks, we usually induce labor without testing for fetal lung maturity. However, if
there is uncertainty about the patients gestational age, we attempt to aspirate amniotic fluid from the vaginal vault
to test for fetal lung maturity. We use the lamellar body count as our initial screen for fetal lung maturity. If this test
is immature, we perform a lecithin/sphingomyelin (L/S) ratio. (See "Assessment of fetal lung maturity".) If testing
shows a low risk of neonatal respiratory problems, we initiate delivery because we believe the risks of prematurity
are small in this setting compared to the risk of developing maternal or fetal complications during expectant
management [86]. If we cannot aspirate fluid or testing suggests a high risk of neonatal respiratory problems, we
continue to manage the patient expectantly until 36 weeks of gestation (by best estimate), at which time we
proceed with delivery without resampling the fluid. Earlier delivery would be indicated if the patient developed clinical
evidence of infection or abruption, preterm labor, or nonreassuring tests of fetal well-being.
Method of delivery In the absence of contraindications to labor and vaginal birth, most patients will deliver
by spontaneous or induced vaginal delivery [87]. Cesarean delivery is performed for standard indications; otherwise,
labor is induced. We perform a digital cervical examination to determine whether cervical ripening has occurred. If
the cervix is favorable, oxytocin is administered for induction according to standard protocols. Once cervical
ripening has occurred, we prefer to use oxytocin over prostaglandins because oxytocin is more easily titrated.
Unfavorable cervix Misoprostol is also effective for inducing labor, and may be advantageous in women
with an unfavorable cervix. A meta-analysis including 15 randomized trials of women with term PROM reported the
rate of vaginal delivery in 12 and 24 hours was similar after administration of misoprostol or oxytocin [88]. Whether
misoprostol was advantageous in the subgroup of women with an unfavorable cervix is unknown since this was not
evaluated. The optimum dose and route of misoprostol administration have also not been determined. Prostaglandin
E2 is a reasonable alternative [89]. There is minimal information on the safety of mechanical methods of cervical
ripening in PROM [90]. We do not use these methods (eg, Foley bulb) due to concern that introducing a foreign
body might increase the risk of infection. (See "Techniques for ripening the unfavorable cervix prior to induction",
section on 'Prostaglandin E1 (misoprostol)'.)
Management of the newborn (See "Clinical features, evaluation, and diagnosis of sepsis in term and late
preterm infants", section on 'Maternal risk factors'.)
FUTURE PREGNANCIES As discussed above, a history of PPROM is a strong risk factor for recurrence (see
'Risk factors' above). We suggest progesterone supplementation for these women in future pregnancies. In studies
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of women with prior preterm birth that included both patients with intact and ruptured membranes, progesterone
supplementation in subsequent pregnancies reduced the risk of recurrent preterm birth. (See "Progesterone
supplementation to reduce the risk of spontaneous preterm birth", section on 'Spontaneous singleton preterm birth
in prior pregnancy'.)
In addition, PPROM may be related to cervical insufficiency in some cases. In future pregnancies, sonographic
measurement of cervical length and placement of a cerclage if cervical length is <25 mm before 24 weeks of
gestation can reduce the risk of recurrent preterm birth. (See "Cervical insufficiency", section on 'Candidates for
ultrasound surveillance and possible ultrasound-indicated cerclage'.)
INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and
Beyond the Basics. The Basics patient education pieces are written in plain language, at the 5th to 6th grade
reading level, and they answer the four or five key questions a patient might have about a given condition. These
articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the
Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the
10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with
some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these
topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on
patient info and the keyword(s) of interest.)
Basics topics (see "Patient information: Preterm premature rupture of membranes (The Basics)")
SUMMARY AND RECOMMENDATIONS
Preterm premature rupture of membranes (PPROM) refers to rupture of fetal membranes prior to labor in
pregnancies <370/7ths weeks. It occurs in 3 percent of pregnancies and is responsible for one-third of preterm
births. (See 'Introduction' above and 'Incidence' above.)
PPROM in a previous pregnancy is associated with at least a three-fold increase in risk of PPROM in the
subsequent pregnancy. (See 'Risk factors' above.)
The diagnosis of PPROM is clinical, based on visualization of amniotic fluid in the vagina of a woman who
presents with a history of leaking fluid. Laboratory tests (eg, Nitrazine and fern or Amnisure) are used for
confirmation in cases of clinical uncertainty. (See 'Diagnosis' above.)
The fetus/neonate is at greater risk of PPROM-related morbidity and mortality than the mother (table 2). (See
'Clinical course' above.)
A clinical history suggestive of PPROM should be confirmed by visual inspection or diagnostic testing to
exclude other causes of wetness, such as urinary incontinence, vaginal discharge, and perspiration. (See
'Diagnosis' above.)
Management The management of women with PPROM is based upon consideration of several factors,
including gestational age, the availability of neonatal intensive care, the presence or absence of maternal/fetal
infection, the presence or absence of labor or abruptio placentae, the stability of the fetal presentation and fetal
heart rate tracing pattern, the probability of fetal lung maturity, and cervical status (algorithm 1). (See 'Management'
above.)
Expeditious delivery of women with PPROM is clinically appropriate if intrauterine infection, abruptio
placentae, nonreassuring fetal testing, or a high risk of cord prolapse is present or suspected. (See 'Initial
approach' above.)
For stable patients with PPROM <34 weeks, we suggest expectant management (Grade 2B). (See 'Initial
approach' above.) In addition:
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We recommend administering a course of antenatal corticosteroids to enhance fetal lung maturation in

pregnancies less than 34 weeks of gestation (Grade 1A). (See 'Administration of antenatal
corticosteroids' above.)
We recommend prophylactic antibiotics (Grade 1A). Our preference is to give ampicillin 2 g
intravenously every 6 hours for 48 hours, followed by amoxicillin (500 mg orally three times daily or 875
mg orally twice daily) for an additional five days. In addition, we give one dose of azithromycin (one gram
orally) at the time of admission and repeat the dose five days later. (See 'Prophylaxis' above and
'Management' above.)
For patients with confirmed gestational age, we suggest delivery at 34 weeks of gestation without
assessment of pulmonary maturity (Grade 2C). If gestational age is uncertain, we attempt to confirm
lung maturity before delivery. If amniotic fluid cannot be obtained or the test result demonstrates lung
immaturity, we suggest delivery at 36 weeks, assuming the mother and fetus are stable (Grade 2C).
(See 'Timing of delivery for expectantly managed pregnancies' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
Topic 6754 Version 77.0
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GRAPHICS
Risk factors for preterm birth
No partner
Low socioeconomic status
Anxiety
Depression
Life events (divorce, separation, death)
Abdominal surgery during pregnancy
Occupational issues (upright posture, use of industrial machines, physical exertion, mental or
environmental stress related to work or working conditions)
Multiple gestation
Polyhydramnios
Uterine anomaly, including diethylstilbestrol-induced changes in uterus and leiomyomas
Preterm premature rupture of membranes
History of second trimester abortion
History of cervical surgery
Premature cervical dilatation or effacement (short cervical length)
Sexually transmitted infections
Systemic infection, pyelonephritis, appendicitis, pneumonia
Bacteriuria
Periodontal disease
Placenta previa
Placental abruption
Vaginal bleeding, especially in more than one trimester
Previous preterm delivery
Substance abuse
Smoking
Maternal age (<18 or >40)
African-American race
Poor nutrition and low body mass index
Inadequate prenatal care
Anemia (hemoglobin <10 g/dL)
Excessive uterine contractility
Low level of educational achievement
Maternal first degree family history of spontaneous preterm birth, especially if the pregnant
woman herself was born preterm
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Fetal anomaly
Fetal growth restriction
Environmental factors (eg, heat, air pollution)
Graphic 68992 Version 7.0
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Pregnancy complications associated with preterm premature rupture

of membranes (PPROM)
Pregnancy complication
Potential consequences
for offspring
Intrauterine infection
Neonatal sepsis
Potential maternal
consequences
Postpartum endometritis
Long-term
neurodevelopmental
abnormalities, particularly
cerebral palsy
Umbilical cord compression
Fetal asphyxia
Oligohydramnios
Limb restriction deformities

and pulmonary hypoplasia
(primarily with severe
oligohydramnios in the early
to mid second trimester).
These complications are rare
when membrane rupture
occurs after 23 weeks.
Fetal malpresentation
Cesarean delivery
Umbilical cord prolapse
Fetal asphyxia
Cesarean delivery
Abruptio placentae
Fetal asphyxia
Cesarean delivery
Coagulopathy
Preterm birth
Morbidity of prematurity,
including respiratory
abnormalities, intraventricular
hemorrhage, necrotizing
enterocolitis, retinopathy of
prematurity, patent ductus
arteriosus
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pH of vaginal discharge using nitrazine paper
(A) normal, (B) bac terial vaginosis, (C) pregnant woman with
premature rupture of membranes.
Reproduced with permission from Aron Schuftan, MD. Copyright Aron
Schuftan, MD.
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Ferning of amniotic fluid
(A) Typic al ferning pattern of dried amniotic fluid (400).

(B, C) Urine and amniotic fluid c an be distinguished by mic rosc opic examination of a
droplet of the fluid spread and dried on a mic rosc ope slide. The proteins in amniotic
fluid give the appearanc e of ferning (B) that is not observed with urine (C).
(D) Ferning pattern from amniotic fluid.
Reproduced with permission from:
(A) Courtesy of Dr. Dwight Rouse.
(B) McClatchey KD. Clinical Laboratory Medicine, 2nd Edition. Philadelphia: Lippincott Williams &
Wilkins, 2002.
(C) McClatchey KD. Clinical Laboratory Medicine, 2nd Edition. Philadelphia: Lippincott Williams &
Wilkins, 2002.
(D) Beckmann CRB, Ling FW, Smith RP, et al. Obstetrics and Gynecology, 5th Edition.
Philadelphia: Lippincott Williams & Wilkins, 2006.
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Ferning of cervical mucus
(A) Ferning of c ervic al muc us.

(B) A ferning pattern of c ervic al muc us oc c urs with high estrogen levels.
(C) Inc omplete ferning during sec retory phase of c yc le.
Reproduced with permission from:
(A) Lexikon Medizin, 3rd Edition. Munich, Germany: Urban & Schwarzenburg, 1993.
(B) Scott JR. Danforth's Obstetrics and Gynecology, 6th Edition. Philadelphia: J.B. Lippincott,
1990.
(C) Scott JR. Danforth's Obstetrics and Gynecology, 6th Edition. Philadelphia: J.B. Lippincott,
1990.
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Evaluation of pregnancies with preterm premature rupture of

membranes
Diagnostic tests (one of the following):
Nitrazine and fern
Placental alpha microglobulin-1 protein assay (AmniSure)
Assessments to consider after confirmation of membrane rupture:

Complete blood count
Test for fetal lung maturity (eg, lamellar body count in amniotic fluid, lecithin sphingomyelin
ratio)
Rectovaginal culture for group B streptococcus
Ultrasound examination for fetal growth, position, residual amniotic fluid volume, fetal
anatomy, and biophysical profile
Cardiotocography to monitor fetal heart rate (including a nonstress test) and frequency of
uterine contractions
Nucleic acid amplification test or culture for Neisseria gonorrhoeae and Chlamydia
trachomatis
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Algorithm for management of patients with PPROM at 23 to 34

weeks of gestation
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CDC algorithm for screening for GBS in PROM before

37 weeks of gestation
CDC: Centers for Disease Control and Prevention; GBS: Group B

streptococcus; PROM: premature rupture of membranes.
* If patient has undergone vaginal-rectal GBS culture within the preceding
5 weeks, the results of that culture should guide management. GBScolonized women should receive intrapartum antibiotic prophylaxis. No
antibiotics are indicated for GBS prophylaxis if a vaginal-rectal screen
within 5 weeks was negative.
Antibiotics given for latency in the setting of pPROM that include
ampicillin 2 g intravenously (IV) once, followed by 1 g IV every 6 hours for
at least 48 hours are adequate for GBS prophylaxis. If other regimens are
used, GBS prophylaxis should be initiated in addition.
GBS prophylaxis should be discontinued at 48 hours for women with
pPROM who are not in labor. If results from a GBS screen performed on
admission become available during the 48-hour period and are negative,
GBS prophylaxis should be discontinued at that time.
Unless subsequent GBS culture prior to delivery is positive.
A negative GBS screen is considered valid for 5 weeks. If a patient with
pPROM is entering labor and had a negative GBS screen >5 weeks prior,
she should be rescreened and managed according to this algorithm at
that time.
Reproduced from: Centers for Disease Control and Prevention. Prevention of
Perinatal Group B Streptococcal Disease. Revised Guidelines from CDC, 2010.
MMWR 2010; 59:No. RR-10.
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Suggested criteria for home management of women with PPROM

Reliable patient
Dependable transportation and telephone service
Lives near hospital
Evaluation in hospital for 72 hours before discharge home
Patient to check her pulse and temperature every 6 hours and notify physician if temperature
>98.6 degrees F (37 degrees C) or pulse >100 beats/minute
Fetal kick counts daily and notify physician if fewer than 10 fetal movements in a two hour
period
Nonstress test and complete blood count twice a week
Weekly ultrasound
Cephalic presentation
No evidence of infection or labor
Presence of a vertical amniotic fluid pocket >2 cm on ultrasound
Adapted from: data in Bartfield MC, Carlan SJ. Clin Obstet Gynecol 1998; 41:503.
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Corticosteroid and antibiotic management of PPROM in the absence of

labor
Week of
gestation when
PPROM occurs
24 to 32 weeks
Plan
Expectant
management if no
Corticosteroids*
Yes
evidence of
chorioamnionitis or
fetal compromise
>32 but <34 weeks
Deliver if fetal lung

maturity can be
documented or there
is evidence of an
intraamniotic
infection clinically or
on amniocentesis;
Antibiotics
Yes and GBS
prophylaxis at
delivery if indicated
Yes, if there is
evidence of fetal lung
immaturity or fetal
lung status is
unknown
Yes, if expectant
management and
GBS prophylaxis at
delivery if indicated
No
GBS prophylaxis
begun on admission
and continued until
delivery
otherwise expectant
management
with delivery at 34
weeks
34 weeks
Deliver
* A single course of corticosteroids is given. If contractions begin and there are no

contraindications to tocolysis, tocolytics can be given for 48 hours during which time a course of
corticosteroids is also administered.
Broad spectrum, see text for possible regimens. GBS prophylaxis is given at delivery if indicated
because of positive or unknown GBS culture results.
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Disclosures
Disclosures: Patrick Duff, MD Nothing to disclose. Charles J Lockw ood, MD, MHCM Consultant/Advisory Boards: Celula [Aneuploidy
screening (Prenatal and cancer DNA screening tests in development)]. Vanessa A Barss, MD, FACOG Nothing to disclose.
Contributor disclosures are review ed for conflicts of interest by the editorial group. When found, these are addressed by vetting through
a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced
content is required of all authors and must conform to UpToDate standards of evidence.
Conflict of interest policy
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Preterm premature (prelabor) rupture of membranes

Official reprint from UpToDate

Preterm premature (prelabor) rupture of membranes

Expectant management versus intervention

Preterm premature (prelabor) rupture of membranes

Preterm premature (prelabor) rupture of membranes

Preterm premature (prelabor) rupture of membranes

Preterm premature (prelabor) rupture of membranes

Preterm premature (prelabor) rupture of membranes

Preterm premature (prelabor) rupture of membranes

Preterm premature (prelabor) rupture of membranes

Preterm premature (prelabor) rupture of membranes

improvement in clinically important outcomes.

Preterm premature (prelabor) rupture of membranes

Preterm premature (prelabor) rupture of membranes

Preterm premature (prelabor) rupture of membranes

Preterm premature (prelabor) rupture of membranes

We recommend administering a course of antenatal corticosteroids to enhance fetal lung maturation in

Preterm premature (prelabor) rupture of membranes

Preterm premature (prelabor) rupture of membranes

Preterm premature (prelabor) rupture of membranes

Pregnancy complications associated with preterm premature rupture

Limb restriction deformities

Umbilical cord prolapse

Graphic 88802 Version 2.0

Preterm premature (prelabor) rupture of membranes

pH of vaginal discharge using nitrazine paper

Preterm premature (prelabor) rupture of membranes

Ferning of amniotic fluid

(A) Typic al ferning pattern of dried amniotic fluid (400).

Preterm premature (prelabor) rupture of membranes

Ferning of cervical mucus

(A) Ferning of c ervic al muc us.

Preterm premature (prelabor) rupture of membranes

Evaluation of pregnancies with preterm premature rupture of

Assessments to consider after confirmation of membrane rupture:

Preterm premature (prelabor) rupture of membranes

Algorithm for management of patients with PPROM at 23 to 34

Graphic 64412 Version 6.0

Preterm premature (prelabor) rupture of membranes

CDC algorithm for screening for GBS in PROM before

CDC: Centers for Disease Control and Prevention; GBS: Group B

Preterm premature (prelabor) rupture of membranes

Graphic 60841 Version 6.0

Preterm premature (prelabor) rupture of membranes

Suggested criteria for home management of women with PPROM

Preterm premature (prelabor) rupture of membranes

Corticosteroid and antibiotic management of PPROM in the absence of

Deliver if fetal lung

* A single course of corticosteroids is given. If contractions begin and there are no

Preterm premature (prelabor) rupture of membranes

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