HIGH-RISK PREGNANCY SERIES: AN EXPERT’S VIEW
We have invited select authorities to present background information on challenging clinical problems and practical information on diagnosis and treatment for use by practitioners.
Preterm Premature Rupture of the Membranes
Brian M. Mercer,
MD
Preterm premature rupture of membranes (PROM) af-fects over 120,000 pregnancies annually in the UnitedStatesandisassociatedwithsignificantmaternal,fetal,andneonatalrisk.ManagementofPROMrequiresanaccuratediagnosis as well as evaluation of the risks and benefits of continued pregnancy or expeditious delivery. An under-standing of gestational age–dependent neonatal morbidityand mortality is important in determining the potentialbenefits of conservative management of preterm PROM at any gestation. Where possible, the treatment of pregnan-cies complicated by PROM remote from term should bedirected towards conserving the pregnancy and reducing perinatal morbidity due to prematurity while monitoring closelyforevidenceofinfection,placentalabruption,labor,or fetal compromise due to umbilical cord compression.Current evidence suggests aggressive adjunctive antibiotic therapy to reduce gestational age–dependent and infec-tious infant morbidity. Similarly, review of evaluable data indicates that antenatal corticosteroid administration inthis setting enhances neonatal outcome without increasing the risk of perinatal infection. It is not clear that tocolysis inthe setting of preterm PROM remote from term reducesinfantmorbidity.WhenpretermPROMoccursnearterm,particularly if fetal pulmonary maturity is evident, thepatient is generally best served by expeditious delivery.(Obstet Gynecol 2003;101:178–93. © 2003 by The Amer-ican College of Obstetricians and Gynecologists.)
INTRODUCTIONIncidence and Clinical Importance
Preterm premature rupture of membranes (PROM) oc-curs in 3% of pregnancies and is responsible for approx-imatelyonethirdofallpretermbirths.PretermPROMisan important cause of perinatal morbidity and mortality, particularly because it is associated with brief latencyfrom membrane rupture to delivery, perinatal infection,and umbilical cord compression due to oligohydram-nios. Even with conservative management, 50–60% of women with preterm PROM remote from term willdeliver within 1 week of membrane rupture. Amnionitis(13–60%) and clinical abruptio placentae (4–12%) arecommonly associated with preterm PROM. The risk of thesecomplicationsincreaseswithdecreasinggestationalage at membrane rupture. The frequency and severity of neonatal complicationsafter preterm PROM vary with the gestational age atwhich rupture and delivery occur, and are increasedwith perinatal infection, abruptio placentae, and umbili-cal cord compression. Respiratory distress syndrome(RDS) is the most common serious complication after preterm PROM at any gestation. Other serious acutemorbidities including necrotizing enterocolitis, intraven-tricular hemorrhage, and sepsis are common with early preterm birth but relatively uncommon near term. Re-mote from term, serious perinatal morbidity that mayleadtolong-termsequelaeordeathiscommon.Figures1through 3 present recent gestational age–dependentmorbidity and mortality curves from a prospective com-munity-based evaluation of 8523 consecutive womendelivering at six hospitals in Shelby County, Tennessee between July 1997 and March 1998. In this evaluation,we found that 33% of live-born and resuscitated infantsdelivered at 23 weeks survived to discharge from hospi-tal (Figure 1). One-week increments in gestational agewere associated with impressive improvements in sur-vival when delivery occurred between 23 and 32 weeks’
From the Department of Obstetrics and Gynecology, MetroHealth Medical Center,Case Western Reserve University, Cleveland, Ohio.Support: The Prematurity Center of The Partnership for Women’s and Children’s Health (University of Tennessee, Memphis; Methodist Healthcare Foundation; LeBonheur Children’s Hospital; and the Tennessee Coordinated Care Network).Wewouldliketothankthefollowingindividualswho,inadditiontomembersofour Editorial Board, will serve as referees for this series: Dwight P. Cruikshank, MD,Ronald S. Gibbs, MD, Gary D. V. Hankins, MD, Philip B. Mead, MD,Kenneth L. Noller, MD, Catherine Y. Spong, MD, and Edward E. Wallach, MD.
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gestation. Among infants surviving to discharge, RDS(more than 24 hours’ oxygen requirement or ventilationin the absence of other evident cause of respiratorycompromise) was the most common acute morbidity atany gestational age (Figure 2). Among surviving infants,intraventricular hemorrhage and necrotizing enterocoli-tis were rare when delivery occurred after 32 weeks.Blood- or cerebrospinal culture–proven sepsis declinedrapidly among those delivering between 27 and 30weeks, with a modest decline in sepsis for each weekgained thereafter. Although this study did not have theopportunity to measure long-term morbidity, retinopa-thy of prematurity and bronchopulmonary dysplasiaoccurred almost uniformly among survivors born at 23weeks, and were almost never seen with delivery at orafter 32 weeks (Figure 3). These findings were similar toa recent multicenter observational study of women de-livering infants who weighed less than 1000 g.
In thatstudy, 15 of 40 live-born singletons delivered at 23weeks’ gestation survived (37.5%). However, two thirdsof survivors suffered major morbidities potentially asso-ciated with long-term morbidity (any of the following:grades 3 to 4 intraventricular hemorrhage, grades 3 to 4retinopathy of prematurity, necrotizing enterocolitis re-quiring surgery, oxygen dependence at 120 days or atdischarge, or seizures). Current data specific to infantsdelivering after preterm PROM are not available. How-ever, it has been found that perinatal sepsis is two-foldmore common in the setting of preterm PROM than preterm birth after preterm labor with intact mem- branes.
Definitions
Premature rupture of the membranes is defined as spon-taneous membrane rupture that occurs before the onsetof labor. When spontaneous membrane rupture occurs before 37 weeks’ gestation, it is referred to as pretermPROM. The term “latency” refers to the time frommembrane rupture to delivery. “Conservative” manage-ment is defined as treatment directed at continuing the
Figure 1.
Survival by gestational age among live-born resuscitated infants. Results of a community-based evaluation of8523 deliveries, 1997–1998, Shelby County, Tennessee. Curves smoothed by 2-point average.
Mercer. Treatment of Preterm PROM. Obstet Gynecol 2003.
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Treatment of Preterm PROM
pregnancy. Preterm PROM that occurs at or before 26weeks’ gestation complicates 0.6–0.7% of pregnancies,and has been defined as “midtrimester PROM.” Al-though the delineation of midtrimester PROM was clin-ically relevant in the 1970s and 1980s, the limit of fetalviability has progressively declined over the past 3 de-cades. As such it is currently more clinically relevant todifferentiate preterm PROM into “previable PROM,”which occurs before the limit of viability (less than 23weeks), “preterm PROM remote from term” (from via- bility to about 32 weeks’ gestation), and “pretermPROM near term” (approximately 32–36 weeks’ gesta-tion). When previable PROM occurs, immediate deliv-ery will lead to neonatal death. Conservative manage-ment may lead to previable or periviable birth, but mayalso lead to extended latency and delivery of a poten-tially viable infant. Immediate delivery after pretermPROMremotefromtermisassociatedwithahighriskof significant perinatal morbidity and mortality that de-creases with advancing gestational age at delivery. Alter-natively, with preterm PROM near term, expeditiousdelivery of a noninfected and nonasphyxiated infant isassociated with a high likelihood of survival and a lowrisk of severe morbidity.
Pathophysiology
Premature rupture of membranes is multifactorial in na-ture. In any given patient, one or more pathophysiologic processes may be evident. Choriodecidual infection or in-flammationappearstoplayanimportantroleinetiologyof preterm PROM, especially at early gestational ages.
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De-creased membrane collagen content has been demon-stratedinthesettingofpretermPROMandwithincreasing gestational age.
In support of this, increases in amnioticfluid matrix metalloproteases (1, 8, and 9) as well as de-creases in tissue inhibitors of matrix metalloproteases (1and 2) have been identified among women with pretermPROM.
Other factors associated with preterm PROMincludelowersocioeconomicstatus,cigarettesmoking,sex-ually transmitted infections, prior cervical conization, prior preterm delivery, prior preterm labor in the current preg-nancy, uterine distention (eg, twins, hydramnios), cervicalcerclage,amniocentesis,andvaginalbleedinginpregnancy.Each of these may be associated with preterm PROMthroughmembranestretchordegradation,localinflamma-tion, or a weakening of maternal resistance to ascending bacterial colonization. In many cases, the ultimate cause of premature membrane rupture is unknown.
Figure 2.
Acute morbidity by gestational age among surviving infants. Results of a community-based evaluation of 8523deliveries, 1997
–
1998, Shelby County, Tennessee. Curves smoothed by 2-point average.
Mercer. Treatment of Preterm PROM. Obstet Gynecol 2003.
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