Mercer Clin Perinatol 2004, Rpm Diagnosis And Management
Clin Perinatol 31 (2004) 765 – 782
Preterm premature rupture of the membranes:
diagnosis and management
Brian M. Mercer, MDa,b,*
Department of Reproductive Biology, Case Western Reserve University, Cleveland, OH, USA
Department of Obstetrics and Gynecology, MetroHealth Medical Center, Suite G240,
2500 MetroHealth Drive, Cleveland, OH 44109, USA
Premature rupture of the membranes (PROM) complicates approximately
8% of pregnancies: 3% of pregnancies deliver from PROM before term. Defined
as membrane rupture before the onset of labor, preterm PROM is responsible for
approximately one third of preterm deliveries.
Preterm PROM can result from various mechanisms, including physiologic
weakening associated with apoptosis (programmed cell death) near term;
dissolution of the amniochorionic matrix exacerbated by contraction-induced
shearing forces; ascending genital tract colonization/infection initiating a cytokine
cascade that enhances membrane apoptosis; protease production and dissolution
of the extracellular matrix; placental abruption with decidual thrombin expression
triggering thrombin–thrombin receptor interactions and increasing chorio-
decidual protease production; and membrane stretch that may increase amnio-
chorionic cytokine and protease release. Clinical risk factors for preterm PROM
include low socioeconomic status, low body mass index, prior preterm birth,
cigarette smoking, urinary tract infection, sexually transmitted disease, cervical
conization or cerclage, uterine overdistention, amniocentesis in the current
pregnancy, and prior preterm labor or symptomatic contractions in the current
pregnancy. In many cases, the ultimate cause of membrane rupture cannot be
The hallmarks of premature rupture of the membranes include brief latency
from membrane rupture to delivery, increased risk of intrauterine and neonatal
* Suite G240, MetroHealth Medical Center, 2500 MetroHealth Drive, Cleveland, OH 44109.
0095-5108/04/$ – see front matter D 2004 Elsevier Inc. All rights reserved.
766 B.M. Mercer / Clin Perinatol 31 (2004) 765–782
infection, and oligohydramnios. Few conditions carry a higher risk of delivery
soon after their onset. However, of those women with preterm PROM who are
amenable to conservative management, approximately half will remain pregnant
for at least 1 week after membrane rupture . The median and mean latency
periods increase with decreasing gestational age at membrane rupture, with
approximately 25% remaining undelivered at least 1 month after membrane
rupture when preterm PROM occurs before or near the limit of viability. A small
number of women (2.6% to 13%) [12,13], especially those with preterm PROM
subsequent to amniocentesis, can anticipate spontaneous resealing of the mem-
branes and restoration of a normal amniotic fluid volume. Clinical chorioamnio-
nitis is common after preterm PROM and, like latency, increases with decreasing
gestational age at membrane rupture. Abruptio placentae, amnionitis, and endo-
metritis complicate 4% to 12%, 13% to 60%, and 2% to 13% of pregnancies,
respectively, when membrane rupture occurs remote from term [14–21].
Although amnionitis and endometritis generally respond to delivery and par-
enteral antibiotic therapy, rare but serious complications such as maternal sepsis
and death can occur (b1%).
Neonatal complications relate primarily to the gestational age at which
membrane rupture and delivery occur. Respiratory distress syndrome (RDS) is
the most common serious complication after preterm PROM at any gestational
age. Other serious morbidities, including necrotizing enterocolitis, intraven-
tricular hemorrhage, sepsis, bronchopulmonary dysplasia, and retinopathy of
prematurity, decrease with advancing gestational age at delivery and are
uncommon with delivery after approximately 32 weeks, particularly if fetal
pulmonary maturity is present. Infants delivered preterm after PROM have a
twofold higher risk of sepsis than those delivered after preterm labor with intact
membranes . Although perinatal death is assured with delivery before the
limit of viability, perinatal mortality rapidly declines with each advancing week
of gestation at delivery until approximately 32 weeks’ gestation . After this
point there is little additional gain in neonatal survival with brief pregnancy
prolongation. Stillbirth resulting from umbilical cord compression, intrauterine
infection, or placental abruption complicates 1% to 2% of conservatively
managed cases. Persistent oligohydramnios, particularly when PROM occurs
before the limit of viability, inhibits alveolar development. With previable PROM
occurring before 18 to 20 weeks of gestation, lethal pulmonary hypoplasia may
ensue despite prolonged successful conservative management. Nonlethal
pulmonary hypoplasia leading to pulmonary complications such as pneumo-
thorax, pneumomediastinum, and high ventilatory pressures can occur with
prolonged membrane rupture and oligohydramnios after pre- or periviable
PROM. Prolonged oligohydramnios may also lead to restriction deformities
similar to those seen with Potter’s syndrome.
Although recent studies have been encouraging, there remains no reliable
method for predicting and preventing preterm PROM. Hence the focus of clini-
cal practice remains the diagnosis and treatment of this condition. The clinical
assessment and management algorithms offered in this article are provided as
B.M. Mercer / Clin Perinatol 31 (2004) 765–782 767
possible approaches to the care of these patients. Individual circumstances should
also be considered when making management decisions after preterm PROM.
The diagnosis of membrane rupture is generally made clinically based on a
suspicious history, combined with physical examination and adjunctive laboratory
information as needed. The initial steps in confirming the diagnosis of membrane
rupture after a suspicious history are to perform a sterile speculum examination to
confirm the diagnosis, to evaluate cervical dilatation and effacement visually, and
to obtain appropriate cervical cultures (Chlamydia trachomatis and Neisseria
gonorrhea). In most cases membrane rupture can be confirmed by documentation
of fluid passing from the cervical os with visualization of a pool of fluid in the
posterior vaginal fornix, or with a high vaginal pH (nitrazine test: N6.0 to 6.5) or
arborization (ferning) of vaginal secretions from the posterior fornix when
observed on low-power microscopy. Although they are usually helpful, nitrazine
and ferning tests are not always accurate. A false-positive nitrazine test may occur
if there is blood, semen, alkaline antiseptics, or bacterial vaginosis present in the
vagina. Alternatively, if membrane rupture is chronic and little amniotic fluid is
present, the nitrazine test can be falsely negative. Causes of false-positive and
false-negative ferning tests include cervical mucus and prolonged leakage.
Alternate adjunctive tests such as vaginal prolactin, alpha-fetoprotein, human
chorionic gonadotropin (HCG), and fetal fibronectin have been suggested
[24–29]. These tests may be helpful if negative. However, a positive test is not
specific to the diagnosis of membrane rupture. Digital examination should be
avoided unless delivery is anticipated, because of the increased risk of infection
and the scant additional clinical information obtained with this procedure .
Anal vaginal cultures for group B Streptococcus (GBS) should be obtained
during initial assessment for PROM if they have not been obtained within
6 weeks. These are best obtained from immediately inside the hymeneal ring
and anal canal, rather than from the cervix and posterior fornix at speculum
examination. Cervical and high vaginal group B Streptococcus cultures are less
likely to be positive in the setting of maternal anovaginal carriage .
Should initial speculum examination be negative and a clinical suspicion of
membrane rupture persists, it may be helpful to repeat the speculum examination
after prolonged recumbency or to consider alternative measures. Ultrasound
evaluation may provide supportive information with the presence of oligohy-
dramnios without evident fetal urinary tract abnormalities or growth restriction.
The diagnosis of membrane rupture can be made unequivocally through
ultrasound-guided amnio-infusion of indigo carmine (1 mL in 9 mL of sterile
normal saline) followed by observation for passage of blue dye per vaginum onto
a perineal pad or at repeat speculum examination. A normal amniotic fluid
volume on ultrasound cannot exclude the diagnosis of membrane rupture. Should
testing be negative, other plausible causes of abnormal vaginal discharge such as
768 B.M. Mercer / Clin Perinatol 31 (2004) 765–782
urinary incontinence, vaginitis, cervicitis, mucous show, early labor, semen, and
vaginal douches should be considered.
On occasion, women with a normal amniotic fluid volume will present with a
suspicious history for membrane rupture but have negative speculum examina-
tion findings, only to return subsequently with gross membrane rupture. Whether
these women had initial transudation of a small amount of fluid across a
weakened membrane or minimal leakage around a firmly applied fetal presenting
part is unknown. However, women presenting with a suspicious history and
negative physical findings should be encouraged to return for re-evaluation
should their symptoms persist or recur.
If the diagnosis of membrane rupture is confirmed, ultrasound should be
performed to assess gestational age (if needed), amniotic fluid volume, and fetal
growth and presentation and to evaluate for fetal malformations that could lead to
polyhydramnios and membrane rupture, if this evaluation has not been previously
performed (Fig. 1). The patient should initially be evaluated for evidence of
labor. Continuous uterine contraction monitoring is appropriate after 20 weeks
but may not be feasible before this gestation. Should the limit of viability have
been reached, fetal monitoring should be performed to assess for evident distress
due to umbilical cord compression, unless an active decision has been made not
to intervene for fetal benefit.
Subsequent management considerations will be dependent on the presence or
absence of factors necessitating delivery, the gestational age at membrane rupture,
and the presence of documented fetal pulmonary maturity. If the fetus is
potentially viable and clinical amnionitis, placental abruption, fetal death, a
nonreassuring fetal heart rate, or advanced labor are present, the patient is best
served by expeditious delivery, with cesarean delivery reserved for appropriate
clinical indications (see Fig. 1). Intrapartum group B Streptococcus prophylaxis
(penicillin unless the patient is allergic) should be given in the absence of a recent
negative anal vaginal culture, to reduce the risk of neonatal GBS sepsis . In the
presence of suspected chorioamnionitis, broad-spectrum intravenous antibiotics
(generally ampicillin and gentamicin) should be initiated before delivery. When
the diagnosis of amnionitis is unclear, amniocentesis can be helpful. A positive
gram stain, glucose value of less than 16 to 20 mg/dL, or positive amniotic fluid
culture is suggestive of intrauterine infection [32–34]. Amniotic fluid cytokines
(eg, interleukin-2, interleukin-6) are associated with intrauterine infection;
however, such testing is not currently routinely available for clinical practice.
In the absence of amnionitis, placental abruption, fetal death or distress, or
advanced labor, conservative management of the patient with preterm PROM
may be appropriate. In this circumstance, a gestational age–based approach to
management should be considered. The care-giver should be apprised of current
data regarding neonatal morbidity and mortality according to gestational age at
B.M. Mercer / Clin Perinatol 31 (2004) 765–782 769
Confirm the Diagnosis of Membrane Rupture
Fluid seen passing per cervical Os,
or vaginal pool with positive Nitrazine/Ferning test,
or positive Indigo-carmine amnio-infusion test
Cervical cultures: Chlamydia, Gonorrhea
Ano-vaginal culture: Group B streptococcus
Ultrasound for gestational age, amniotic fluid
Fetal growth, and anomalies as appropriate
Initial continuous monitoring for labor,
and for fetal distress if fetus is potentially viable
Diagnosis of: No evident diagnosis of:
Amnionitis, Abruptio placentae, Amnionitis, Abruptio placentae,
Fetal death, Non-reassuring testing, Fetal death, Non-reassuring testing,
or Advanced labor or Advanced labor
Gestational Age based
approach to management
Intrapartum group B streptococcus
prophylaxis if no recent
negative ano-vaginal culture
Broad spectrum antibiotics if
amnionitis See Figures 2, 3, and 4
Fig. 1. Algorithm for initial assessment and management of women presenting with preterm PROM.
delivery to make appropriate decisions about the potential benefits of conserva-
tive management as opposed to expeditious delivery .
Previable PROM (b23 weeks’ gestation)
The term bmidtrimester PROM,Q referring to delivery at or before 26 weeks’
gestation, has been used in the past and at one time appropriately denoted
membrane rupture before viability. Currently, however, women with membrane
rupture between 23 and 26 weeks’ gestation carry fetuses that have the potential
for survival. These patients are best cared for by following the scenario delineated
770 B.M. Mercer / Clin Perinatol 31 (2004) 765–782
later in this article for women with bPROM remote from term.Q When delivery
occurs immediately after previable PROM, intrapartum or neonatal death is
assured. Conservative management may lead to stillbirth or to the birth of a live
infant before or after the limit of potential neonatal viability.
When PROM occurs before the limit of viability, gestational age assignment is
of particular importance. Because the likelihood of error in ultrasound estimation
of gestational age increases as pregnancy advances, the earliest available
ultrasound should be obtained for confirmation of gestational dating. A bbest
gestational ageQ determination should be made based on the earliest available
ultrasound and menstrual history. These patients should be counseled with a
realistic appraisal of potential neonatal outcomes and made aware of the
availability of obstetric monitoring and neonatal intensive care facilities should
delivery occur after the limit of potential viability. Because neonatal survival and
morbidity in the periviable period continue to improve, attempts should be made
to provide the most up-to-date information about potential perinatal outcomes.
As for maternal morbidity, conservative management of midtrimester PROM
is associated with a high risk of chorioamnionitis (39%), endometritis (14%),
abruptio placentae (3%), and retained placenta with postpartum hemorrhage
requiring curettage (12%) [13,35]. The risk of stillbirth during conservative
management of midtrimester PROM is approximately 15%, higher than the 1% to
2% risk seen later in pregnancy. This greater risk may reflect fetal susceptibility
to umbilical cord compression and intrauterine infection, or it may reflect
nonintervention for fetal distress in the previable period. Although there are
currently inadequate data to provide estimates of maternal morbidity and fetal
mortality related to conservative management of PROM at less than 23 weeks’
gestation, the risks are probably higher than those stated above.
Given the grave fetal and neonatal prognosis, some women will not wish to
assume the maternal risks associated with conservative management of previable
PROM. Expeditious delivery can be accomplished by labor induction with high
dose oxytocin or with vaginal prostaglandin E2 or oral or vaginal prostaglandin
E1 (Misoprostol), or by dilatation and evacuation (Fig. 2). Intracervical laminaria
placement before oxytocin therapy or prostaglandin induction may be helpful.
The optimal treatment approach to achieve delivery in this circumstance will
depend on patient factors (eg, gestational age, evident amnionitis, prior cesarean
delivery), as well as on physician experience and facilities available for induction
or dilatation and evacuation.
Should the patient elect conservative management, she should be monitored
initially for the development of infection, labor, or placental abruption. Strict
pelvic rest and modified bed rest with bathroom privileges should be encouraged,
to enhance the potential for membrane resealing and reduce the potential for
ascending infection. Given the current lack of data establishing the superiority of
either approach, initial inpatient or outpatient monitoring may be appropriate,
depending on clinical circumstances. For those women with previable PROM
remote from the limit of viability, serial ultrasound is recommended to evaluate
for fetal pulmonary growth and for persistent oligohydramnios. Fetal pulmonary
B.M. Mercer / Clin Perinatol 31 (2004) 765–782 771
Previable PROM (<23 weeks gestation)
Initial monitoring for development of Infection,
Labor, Abruptio placentae
Initial bed-rest to encourage resealing
Evaluate for persistent oligohydramnios
and pulmonary hypoplasia with serial ultrasound
Induction with Oxytocin, PgE2 or
Re-counsel based on clinical course and available
ultrasound findings regarding persistent
oligohydramnios and pulmonary hypoplasia
Dilatation & Evacuation
If discharged before viability and remains
pregnant, consider readmission at limit of fetal
for ongoing conservative management
Modified bed-rest and pelvic rest to encourage
resealing, reduce infection
Administer Antenatal Corticosteroids for Fetal
Serial evaluation for Amnionitis, Labor, Abruption,
Fetal well-being, Growth
Deliver for Amnionitis, Non-reassuring Fetal
Testing, Abruption, Advanced labor
Consider Delivery at 34 weeks gestation
Intrapartum group B streptococcus prophylaxis
if no recent negative ano-vaginal culture
Broad spectrum antibiotics if Amnionitis
Fig. 2. Management algorithm for women presenting with preterm PROM before the current limit of
potential viability (b23 weeks, 0 days of gestation).
growth can be estimated by a variety of techniques, including measurement of the
thoracic/abdominal circumference ratio, chest circumference, and pulmonary
length. A declining thoracic/abdominal circumference ratio in the setting of
persistent oligohydramnios is highly predictive of lethal pulmonary hypoplasia in
this setting [36–39]. When this finding is identified before the limit of viability, it
772 B.M. Mercer / Clin Perinatol 31 (2004) 765–782
may be helpful in assisting the patient in the decision between continued
conservative management and delivery.
Although it is appealing to consider broad-spectrum antibiotic therapy for
pregnancy prolongation and reduction of infection (see later discussion) after
previable PROM, no specific data are available. A number of novel treatments for
membrane sealing after previable PROM have been studied (eg, serial
amnioinfusion, membrane plugging with Gelfoam or fibrin-platelet-cryoprecipi-
tate plugs, and indwelling transcervical infusion catheter) [40–42]. However, the
maternal and fetal risks and benefits associated with these interventions have not
yet been determined. Further research is needed before membrane sealing is
incorporated into clinical practice.
Once the patient with previable PROM reaches the limit of viability, many
physicians will admit her to the hospital for ongoing bed rest. The purpose of
admission at this time is to allow for early diagnosis and intervention for
infection, abruption, labor, and nonreassuring fetal heart rate patterns. Because
these women remain at high risk for early delivery, administration of antenatal
corticosteroids for fetal maturation may be appropriate at this time. It is not clear
that delayed administration of broad-spectrum antibiotics for pregnancy pro-
longation will assist this population.
Preterm PROM remote from term (23 to 316 weeks’ gestation)
In the absence of evident infection, abruption, advanced labor, or fetal com-
promise, the patient with preterm PROM between 23 and 31 weeks’ gestation is
generally best served by conservative management to prolong pregnancy and
reduce gestational age–dependent morbidity (Fig. 3). The decision whether to
delay or expedite delivery should be based on the potential neonatal benefits of
prolonged latency and the concurrent maternal and fetal/neonatal risks associated
with conservative management. Women undergoing conservative management of
preterm PROM remote from term should generally be managed in hospital to
facilitate the early detection and management of amnionitis, vaginal bleeding,
nonreassuring fetal heart-rate patterns, and labor. Such management should be
undertaken in a facility capable of providing emergent care to the mother and
newborn. Should obstetric or neonatal facilities not exist at the presenting
hospital, the patient should be transferred to a facility capable of providing her
with care after initial assessment and before the onset of acute complications.
Digital examinations should be avoided when possible, to reduce the risk of
intrauterine infection and enhanced latency. Uterine contraction and fetal heart-
rate assessment should be performed at least once daily to assess for occult
contractions, fetal well-being, and umbilical cord compression. Additional testing
may be appropriate and necessary based on these findings. Biophysical profile
testing is an alternative to fetal nonstress testing for assessment of fetal well-being
B.M. Mercer / Clin Perinatol 31 (2004) 765–782 773
Preterm PROM remote from term (230 - 31 6 weeks gestation)
Modified bed-rest and pelvic rest to encourage resealing,
and reduce infection
Administer Antenatal Corticosteroids for Fetal Maturation
Serial evaluation for Amnionitis, Labor, Abruption,
Fetal well-being, Growth
Deliver for Amnionitis, Non-reassuring Fetal Testing, Abruption,
Consider Delivery at 34 weeks gestation
Intrapartum group B streptococcus prophylaxis
if no recent negative ano-vaginal culture
Broad spectrum antibiotics if Amnionitis
Fig. 3. Management algorithm for women presenting with preterm PROM remote from term
(23 weeks, 0 days–31 weeks, 6 days).
and may be helpful if the nonstress test is not reactive. However, this test does not
provide the opportunity to evaluate for periodic heart-rate changes and occult
uterine activity. Because pregnancy and inactivity are risk factors for throm-
boembolic complications, preventative measures such as leg exercises, anti-
embolic stockings, and prophylactic doses of subcutaneous heparin may be of
value during conservative management with bed rest.
The combination of fever (z38.08C or 100.48F) with uterine tenderness or
maternal or fetal tachycardia in the absence of another evident source of infection
is suggestive of intrauterine infection and should lead to consideration of deliv-
ery. Some patients will not demonstrate classical symptomatology of amnionitis.
Increasing uterine discomfort or menstrual cramps may be an early finding.
Although maternal white blood cell count may increase in the setting of
amnionitis, such test results may be artificially elevated if antenatal corticosteroids
have been administered within 5 to 7 days. Alternatively, an increasing white
blood cell count in the presence of suspicious clinical findings may be useful in
identifying patients who require closer observation—including continuous
contraction and fetal monitoring—or who require delivery. If the clinical diagnosis
is not sufficiently clear, additional information can be gained with amniocentesis,
provided an adequate amniotic fluid pocket is accessible. When amniocentesis is
performed, care should be taken to avoid inadvertent sampling of the umbilical
774 B.M. Mercer / Clin Perinatol 31 (2004) 765–782
cord. Color flow ultrasound may be helpful in differentiating a small amniotic
fluid pocket from umbilical-cord arterial or venous flow.
Women managed conservatively with preterm PROM remote from term
should be administered antenatal corticosteroids for fetal maturation if they have
not previously received corticosteroids in the current pregnancy. This inter-
vention has been demonstrated to reduce the risk of intraventricular hemorrhage,
and it is supported by the National Institute of Health Consensus Conference and
by the American College of Obstetricians and Gynecologists [43,44]. Recent
randomized clinical trials have evaluated antenatal corticosteroid administration
concurrent with antibiotic administration. Lewis et al  found a reduction in
respiratory distress (18.4% versus 43.6%, P = 0.03) with antenatal corticosteroid
administration. Although a second trial found no increase or decrease in infant
morbidity with antenatal corticosteroids, patients who received antenatal steroids
and remained pregnant for at least 24 hours had a lower incidence of perinatal
death (1.3% versus 8.3%, P = 0.05) with antenatal corticosteroid administration
. A recent meta-analysis has supported the beneficial effects of antenatal
corticosteroid administration in this setting for the reduction of respiratory
distress (20% versus 35.4%), intraventricular hemorrhage (7.5% versus 15.9%),
and necrotizing enterocolitis (0.8% versus 4.6%), without significant increased
risks of maternal infection (9.2% versus 5.1%) or neonatal infection (7.0% versus
Antibiotic prophylaxis and treatment
The benefits of narrow-spectrum intrapartum prophylaxis against vertical
transmission of group B Streptococcus before preterm birth are well established.
Intrapartum treatment is recommended for known group B Streptococcus–
carriers, those of unknown carrier status, and those without a recent culture
(ie, within 6 weeks of delivery) . Adjunctive antibiotic therapy during
conservative management of preterm PROM remote from term is given to treat
or prevent ascending subclinical decidual infection, to prolong pregnancy, to
reduce infectious morbidity, and to offer the opportunity to reduce neonatal
infectious and gestational age–dependent morbidity. This intervention has been
the subject of many randomized prospective trials. Several meta-analyses have
confirmed the efficacy of aggressive, limited-duration, broad-spectrum antibiotic
therapy for reduction of infant morbidity in this setting. Intravenous therapy
(48 hours) with ampicillin (2 g IV every 6 hours) and erythromycin (250 mg IV
every 6 hours), followed by limited-duration oral therapy (5 days) with amoxi-
cillin (250 mg by mouth every 8 hours) and enteric-coated erythromycin base
(333 mg by mouth every 8 hours) is recommended . Although alternative
antibiotic treatments have not been specifically studied, recent shortages in anti-
B.M. Mercer / Clin Perinatol 31 (2004) 765–782 775
biotic availability have necessitated them. Oral ampicillin, erythromycin, and
azithromycin, as needed, are likely appropriate alternatives to the therapy described.
A recent large multicenter study suggested that broad-spectrum antibiotic
therapy might increase the risk of necrotizing enterocolitis (1.9% versus 0.5%,
P = 0.001) . Neonates in this study were at low risk for necrotizing
enterocolitis compared with neonates in other trials, partially because of the
inclusion of many women near term (32 to 36 weeks’ gestation) who might have
been better served by expeditious delivery. Furthermore, the findings are at
variance with those of the National Institute for Child and Human Development-
Maternal-Fetal Medicine Unit (NICHD-MFMU) trial indicating a reduced stage–
2 to 3 necrotizing enterocolitis with aggressive antibiotic therapy in a higher-risk
population . Overall, review of the literature reveals no consistent pattern to
indicate an increased risk of necrotizing enterocolitis with broad-spectrum
antibiotic therapy in this setting. Several recent studies have attempted to
determine whether shorter-duration antibiotic treatment (b7 days) is appropriate
during conservative management with preterm PROM [50,51]. These studies are
of inadequate size and power to evaluate equivalency regarding infant morbidity
or latency. Currently, the 7-day NICHD-MFMU protocol is recommended.
A small number of studies exist on which to base practice regarding tocolysis
during conservative management of preterm PROM remote from term [52–56].
Overall, there does not appear to be an increase in maternal or fetal risk with
tocolysis during conservative management. Neither prophylactic nor therapeutic
tocolysis in this setting has been demonstrated to reduce infant morbidity. Hence,
tocolytic administration should not be an expected practice. However, because
several of these studies have suggested that short-term tocolytic therapy may
enhance initial pregnancy prolongation at 24 to 48 hours, it is worth considering
that tocolytic therapy concurrent with antenatal corticosteroid treatment for fetal
maturation and antibiotic treatment to suppress infection and prolong pregnancy
might enhance the effects of both steroid and antibiotic treatment. This area
warrants further research to determine whether the hypothesized benefits exist.
Premature rupture of the membranes complicates approximately one in four
pregnancies with a cervical cerclage in situ. Retrospective studies suggest that
when cerclage is removed on admission after preterm PROM, the risk of adverse
perinatal outcome is no higher than for those women admitted with preterm
PROM and no cerclage [57,58]. Studies comparing cerclage retention or removal
after preterm PROM have been small and have yielded conflicting results
[59–61]. Individually, these studies suggest trends toward increased maternal
infection with retained cerclage; however, no study has reached significance. One
study found increased overall infant mortality and death related to sepsis with
776 B.M. Mercer / Clin Perinatol 31 (2004) 765–782
cerclage retention, despite brief pregnancy prolongation . Another study
comparing practices at different institutions found significant pregnancy pro-
longation with cerclage retention . Although they are intriguing, the results of
this study may reflect patient population or practice differences, rather than
differences solely related to cerclage retention. No study has found a significant
reduction in infant morbidity with cerclage retention after preterm PROM. Hence,
it appears prudent to remove the cerclage when PROM occurs either remote from
or near term. Should a decision be made to retain the cerclage during attempts to
enhance fetal maturation with antenatal steroids, concurrent antibiotic admin-
istration should be considered to reduce the risk of infection. Furthermore,
consideration should be given to removal of the stitch after antenatal steroid
benefit has been reached at 24 to 48 hours.
Preterm PROM near term (32 to 366 weeks’ gestation)
When preterm PROM occurs at 34 to 36 weeks’ gestation, the risk of severe
acute neonatal morbidity and mortality with expeditious delivery is low.
Conversely, conservative management at 34 to 36 weeks has been associated
with an eightfold increase in amnionitis (16% versus 2%, P = 0.001) and only
brief prolongation of latency and maternal hospitalization (5.2 days versus
2.6 days, P = 0.006), without significant reduction in perinatal morbidity related
to prematurity . Hence these women are best served by expeditious delivery
with labor induction, in the absence of contraindication to labor or vaginal
delivery (Fig. 4). Intrapartum group B Streptococcus prophylaxis should be given
in the absence of a recent negative anal-vaginal culture. Broad-spectrum
antibiotics should be given intravenously if there is a suspicion of amnionitis.
A number of investigators have evaluated the clinical applicability of fetal
pulmonary maturity testing in the setting of preterm PROM. Shaver et al 
found lecithin-shingomyelin (L/S) ratios to be similar whether collected from
vaginal pool or at amniocentesis. Vaginally collected phosphatidylglycerol (PG)
determinations have been found to be highly predictive of fetal pulmonary
maturity, with a similar negative predictive value (34% RDS) to that seen from
amniocentesis specimens in the face of an immature test . The surfactant/
albumin ratio has also been demonstrated to be predictive of pulmonary maturity
or immaturity when obtained from vaginal pool or amniocentesis specimens
[65,66]. Nonpulmonary phospholipids in blood may lower a mature result to an
immature value but are unlikely to increase an immature result to a mature value
[67,68]. Hence, a mature L/S ratio should be reassuring if there is blood con-
tamination. Blood contamination can falsely lower the TDX-FLM assay result,
but a mature result reliably predicts fetal pulmonary maturity . Meconium
staining can falsely elevate an L/S ratio, but not the PG test . Clinically, if
there is blood or meconium present in the vaginal pool specimen, serious
consideration should be given to delivery rather than conservative management.
B.M. Mercer / Clin Perinatol 31 (2004) 765–782 777
Preterm PROM near term (320 - 366 weeks gestation)
320 - 336 weeks 340-366 weeks
Immature Testing or Fluid Documented fetal
Unavailable pulmonary maturity
for Antenatal Corticosteroid
benefit, with Concurrent
Delivery after Delivery at Expeditious Expeditious Expeditious
24 - 48 hours 34 weeks delivery delivery delivery
Intrapartum group B streptococcus prophylaxis
if no recent negative ano-vaginal culture
Broad spectrum antibiotics if Amnionitis
Fig. 4. Management algorithm for women presenting with preterm PROM near term (32 weeks,
0 days–36 weeks, 6 days).
When preterm PROM occurs at 32 to 336 weeks’ gestation, fetal pulmonary
maturity assessment can be helpful in determining the approach to management.
In the presence of fetal pulmonary maturity documented by either vaginal pool
sampling or amniocentesis after 32 weeks, there is little risk of severe neonatal
morbidity with expeditious delivery . Given the increased risk of amnionitis,
the potential for occult cord compression, and the scant additional latency
accrued with conservative management after preterm PROM near term, this
strategy is likely to lead to more morbidity than expeditious delivery, assuming
fetal pulmonary maturity is documented. Women with documented fetal
pulmonary maturity after preterm PROM at 32 to 336 weeks’ gestation are best
served by expeditious delivery with intrapartum antibiotic administration, as
When amniotic fluid testing reveals an immature result, or when amniotic
fluid is unavailable after preterm PROM at 32 to 336 weeks’ gestation, conser-
vative management may be appropriate. No studies specifically address this
778 B.M. Mercer / Clin Perinatol 31 (2004) 765–782
subset of women. However, the following principles may be helpful. The infant
delivered with documented pulmonary immaturity is at an increased risk of
respiratory distress and other complications. Antenatal corticosteroids have been
demonstrated to benefit populations at high risk for fetal immaturity, and
antibiotic treatment in the setting of preterm PROM has been shown to reduce the
risk of infectious morbidity. Given these general principles, conservative
management with antenatal corticosteroid administration and concurrent anti-
biotic therapy may be appropriate. Because no data address the potential risks and
benefits of delaying delivery after antenatal corticosteroid benefit has been
achieved, either delivery 24 to 48 hours after corticosteroid administration or
conservative management to 34 weeks’ gestation should be considered accept-
able. All three studies that prospectively evaluated preterm PROM near term
found significant increases in perinatal infection and only brief pregnancy
prolongation subsequent to conservative management [62,71,72]. Expeditious
delivery should be considered unless the fetus is considered to be at significant
risk for gestational age–dependent morbidity, in which case measures should be
taken to reduce the risk of infection and enhance fetal maturation. If antenatal
corticosteroids and antibiotics are not to be administered in this setting, the
women may be better served by expeditious delivery with appropriate intra-
partum antibiotic therapy.
Preterm PROM is a common and significant cause of preterm birth and
perinatal morbidity and mortality. The obstetric caregiver has the opportunity
significantly to alter pregnancy and perinatal outcome for women suffering from
this complication. Although management is often predetermined by the presence
of clinical infection, vaginal bleeding, labor, or nonreassuring fetal heart-rate
pattern on admission, a gestational age–based approach to the management of the
stable patient with preterm PROM offers the potential to reduce perinatal
infectious and gestational age–dependent morbidity for patients amenable to
conservative management. Gestational age–appropriate counseling, incorporating
both the obstetric and the neonatal caregiver, may be helpful in preparing the
patient for potential complications. Early transfer to a facility capable of
providing urgent obstetric and neonatal intensive care is important should ade-
quate local facilities not be available. Regardless of management approach, this
population is at high risk for perinatal complications, many of which cannot be
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