Preterm PROM: Prediction, Prevention, Principles
Preterm PROM: Prediction, Prevention, Principles
Preterm PROM: Prediction, Prevention, Principles
Preterm PROM:
Prediction,
Prevention, Principles
THADDEUS P. WATERS, MD and BRIAN MERCER, MD
MetroHealth Medical Center, Case Western Reserve University,
Cleveland, Ohio
Abstract: Preterm premature rupture of the membranes pregnancies in the United States. Preterm
remains difficult to predict accurately. The majority of PROM is a significant contributor to pre-
those suffering preterm premature rupture of the mem-
brane lack risk factors that might lead to preventative term birth and is a significant cause of
treatments. Its management is centered on an evaluation gestational age-dependent neonatal mor-
of the risks and benefits of attempted pregnancy pro- bidity and mortality. Optimally, preterm
longation compared with expeditious delivery. An un- PROM could be avoided through early
derstanding of the gestational age specific risks for identification of those at risk followed by
newborn morbidity and mortality is essential to estimate
the potential benefits of conservative management. effective interventions. However, as most
Once the diagnosis of membrane rupture remote from women who develop preterm PROM have
term is made, conservative management to reduce neo- no identifiable risk factors, current man-
natal complications is generally attempted while main- agement remains focused on interventions
taining vigilance for complications such as infection, to optimize outcomes once preterm PROM
umbilical cord compression, or abruption. Concurrent
antibiotic therapy and antenatal corticosteroid treat- is diagnosed. Management of women who
ment are typically administered to prolong pregnancy, develop preterm PROM requires an accu-
prevent infection, and reduce gestational age dependent rate diagnosis in addition to an individual
morbidities. Near and at term, particularly if fetal assessment of the benefits and risks of
pulmonary maturity has been confirmed, the patient is continuing pregnancy versus expedited de-
generally best served by expeditious delivery.
Key words: PROM, gestational age risk, complication, livery. This evaluation requires an under-
treatment standing of gestational age specific risks of
neonatal morbidity and mortality and the
potential benefits and risks of conservative
Introduction management.
Preterm premature rupture of the mem- In general, the approach to the patient
branes (preterm PROM or pPROM) with preterm PROM remote from term
complicates approximately 3% of all is one of continuing pregnancy to reduce
gestational age-dependent newborn compli-
Correspondence: Thaddeus P. Waters, MD, Metro- cations while maintaining vigilance for po-
Health Medical Center, Case Western, Reserve
University, 2500 MetroHealth Drive, Cleveland, OH. tential complications including intrauterine
E-mail: [email protected] infection, umbilical cord compression and
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308 Waters and Mercer
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Preterm PROM: Prediction, Prevention, Principles 309
solely focused on preterm PROM as a pri- risk of preterm PROM with treatment,13
mary outcome. Invariably, interventional whereas 2 others showed no benefit. No
trials use a reduction in preterm birth as a pooled risk was calculated due to study
primary outcome with some investigators heterogeneity. At this time, there seems to
reporting preterm PROM as a secondary be no role for routine screening and treat-
outcome. However, as preterm PROM is ment of asymptomatic bacterial vaginosis
a significant contributor to preterm birth, during pregnancy.
therapy, which consistently shows a re- In 2001, Woods et al14 proposed reac-
duction in the frequency of preterm birth tive oxygen species to be a potential con-
should be incorporated into the preven- tributor to preterm PROM. The authors
tion of preterm PROM. suggested that the process might be rever-
Although intuitively logical, attempts sible through antioxidant (Vitamins C
to reduce preterm PROM through mod- and E) supplementation. Although an
ification in adjustable risk factors, beyond initial investigation15 evaluating Vitamin
the treatment of urogenital infections, C supplementation alone showed promise
have not been proven to be effective. for preventing preterm PROM (7.6% vs.
Women with either urinary tract or sexu- 24.5%, P = 0.02), subsequent investiga-
ally transmitted infections should be trea- tions including a recent publication by
ted once identified. As heavy smoking is Spinnato et al16 have suggested an in-
associated with several poor outcomes, creased risk of preterm PROM with anti-
any reduction in tobacco use should be oxidant supplementation. This hypothesis
encouraged with the optimal goal of ces- was further rebuked by the finding of
sation. For women with symptomatic increased serum lutin concentrations (a
polyhydramnios, interventions at redu- potent antioxidant) among women with
cing the amniotic fluid volume, such as preterm PROM.17 At this time, routine
amnioreduction, can be performed. How- supplementation with antioxidants to
ever, it is unclear if this offers any real prevent preterm PROM is not recom-
benefit in reducing preterm PROM or mended.
preventing preterm birth. Finally, activity In 2003, Meis et al18 published the
modification is often considered for findings of a randomized trial which iden-
patients at risk of preterm PROM or tified a significant reduction in recurrent
preterm birth, but little data supports spontaneous preterm birth for patients
its routine use.10 treated with weekly intramuscular 17 a-
Several trials have evaluated the bene- hydroxyprogesterone caproate. An addi-
fits of screening and treatment of bacterial tional investigation of vaginal progesterone
vaginosis in women at high risk and low supplementation found a similar benefit for
risk of preterm PROM. These trials were the prevention of preterm birth in high risk
recently summarized by 2 publications patients.19 Although neither investigation
by the United States Preventative Task reported outcomes specific to preterm
Force.11,12 For women at average risk of PROM, both included patients with an
preterm PROM (defined as representative earlier preterm birth due to PROM. Re-
sample of the general population), 4 trials cently, studies of omega 3 supplementa-
found no benefit from treatment of asymp- tion and cervical cerclage for the pre-
tomatic bacterial vaginosis in the reduction vention of preterm birth have had mixed
of preterm PROM; pooled risk reduction results.20,21 On the basis of the available
0.006 (95% CI, 0.030-0.018). For wo- data, weekly intramuscular progesterone
men defined as high risk (those with a should be used for patients with a history
history of a preterm delivery), the data of preterm PROM to reduce the risk of a
were mixed with 1 study noting a decreased recurrent preterm birth.
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310 Waters and Mercer
Recently, investigators have focused risks for fetal and neonatal complications
on the possible contribution of infectious with immediate delivery compared with
or inflammatory processes at sites distant the risks and benefits of conservative
from the female genital tract to preterm management.
birth and preterm PROM. Of particular For the patient with possible preterm
interest is maternal periodontal disease, PROM, the initial steps include confirma-
which if untreated and severe, can lead to tion of membrane rupture in addition to
increased levels of circulating proinflam- assessments of estimated gestational age,
matory cytokines and chemokines, and duration of membrane rupture, exclusion
potentially preterm birth. Although severe of maternal infection or abruption, and
untreated periodontal disease has been assessment of fetal well being. Cervico-
associated with preterm birth,6,7 no clear vaginal cultures should be obtained for
relationship with this condition and pre- Chlamydia trachomatis, Neisseria gonor-
term PROM has been elucidated. In addi- rhea, and anovaginal group B strepto-
tion, investigations aimed at treatment coccus cultures should be obtained. If
have been inconclusive.22 the patient is determined to have chor-
ioamnionitis or abruption, conservative
management is not advised. Fetal well
being should also be assessed by methods
General Management appropriate for gestational age. If a preg-
Considerations nancy is beyond the threshold of viability,
At term, approximately 8% of patients conservative management is not advised
will experience rupture of the membranes in the setting of nonreassuring fetal testing.
before the onset of labor. For these pa- At any gestational age, the management
tients, 95% will deliver within 28 hours of of PROM is guided by the gestational age
PROM.23 The clinical course of preterm at the time of membrane rupture. For the
PROM is also characterized by a brief patient at term, there is no substantial
period of latency from membrane rupture benefit of pregnancy prolongation in the
to delivery, with the duration of latency setting of PROM due to the relatively
increasing with decreasing gestational infrequent occurrence of significant neo-
age. For example, when PROM occurs natal complications at this gestational age.
before 34 weeks gestational age, 93% of Therefore, delivery should be undertaken
patients will deliver within 7 days com- in this situation. This is contrasted by the
pared with only 60% of those who present patient with preterm PROM between 23
with PROM near the threshold of viabili- to 31 weeks where there are significant
ty. As neonatal morbidities are closely risks of neonatal morbidities, long-term
correlated with gestational age at deliv- complications, and perinatal death from
ery, the optimal goal in the management premature delivery.24 In the absence of
of preterm PROM is to extend latency for significant contraindications to conserva-
those pregnancies that may benefit from tive management, including infection,
a delay in delivery. To achieve this goal, abruption, advanced labor, or nonreas-
preterm PROM requires accurate diagno- suring fetal testing, these patients are best
sis in addition to an understanding of the served with conservative management to
gestational age specific risks for neonatal prolong pregnancy.
morbidity and mortality. After the exclu- The management of patients with
sion of significant maternal complications preterm PROM between 32 weeks and
including infection, abruption, or cord pro- 36 weeks 6 days is not as clear-cut as those
lapse, the management of preterm PROM patients on the extremes of the gestational
is heavily determined on the estimation of age continuum. In a randomized trial of
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Preterm PROM: Prediction, Prevention, Principles 311
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312 Waters and Mercer
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