Chapter 31Premature Rupture of the Membranes Brian M. Mercer, MDRupture of the fetal membranes is an integral part of the normal par- TIMP-1, TIMP-3), and increased poly[ADP-ribose]polymerase (PARP)turition process at term and is inevitable in the process of preterm cleavage.6,9 Term or preterm uterine contractions can also lead to mem-birth. Spontaneous rupture of the membranes (SROM) at term and brane rupture resulting from increased bursting pressure due topreterm can occur any time before or after the onset of contractions. increased intra-amniotic pressure and from “strain hardening” withSROM before the onset of contractions is referred to as premature repeated uterine contractions. If the fetal membranes do not rupturerupture of the membranes (PROM). Membrane rupture at term before labor, the work to cause membrane rupture at the internal cervi-usually occurs as a result of a physiologic process of progressive mem- cal os decreases with advancing cervical dilatation because of the lackbrane weakening. Preterm PROM generally results from pathologic of anchoring to the supportive decidua and enhanced ability to stretchweakening of the fetal membranes, which has several causes. Although with contractions.1delivery after PROM may be required by the presence of advanced Preterm membrane rupture can arise through a number of path-labor, intrauterine infection, vaginal bleeding due to placental abrup- ways that ultimately result in accelerated membrane weakening. Bacte-tion, or non-reassuring fetal status, the physician often needs to make rial collagenases and proteases can directly cause fetal membrane tissuethe decision whether to actively pursue delivery or conservatively weakening.10 An increase in local host cytokines or an imbalance in themanage the pregnancy. Management of PROM hinges on knowledge interaction between MMPs and TIMPs in response to microbial colo-of gestational age, the neonatal risks related to immediate delivery, and nization can have similar effects.11 There is speciﬁc evidence linkingan understanding of the anticipated clinical course and relative risks urogenital tract infection and colonization with preterm PROM.of intrauterine infection, abruptio placentae, and fetal distress or death Amniotic ﬂuid cultures after PROM are frequently positive (25%from umbilical cord accident or intrauterine infection with conserva- to 35%),12-19 and histologic evaluation in the setting of pretermtive management. birth frequently has demonstrated acute inﬂammation and bacterial contamination along the choriodecidual interface.20 Although these ﬁndings may reﬂect ascending infection after PROM, it is likely that ascending colonization and infection are directly involved in thePhysiology and pathogenesis of preterm PROM in many cases. Genital tract pathogens that have been associated with PROM include Neisseria gonorrhoeae,Pathophysiology of Chlamydia trachomatis, Trichomonas vaginalis, and group B β-hemo-Membrane Rupture lytic streptococcus.20-26 Although group B streptococcus (GBS) bacte- riuria has been associated with preterm PROM and low-birth-weightThe fetal membranes consist of the amnion, which lines the amniotic infants27 and an association between cervical colonization and pretermcavity, and the thicker chorion, which adheres to the maternal decidua. PROM is possible,28 it does not appear that vaginal GBS carriage isInitially, the amnion and chorion are separate layers. The amnionic sac associated with preterm PROM.29,30 Although there is a well-estab-is visible on ﬁrst trimester ultrasound scans until it fuses with the lished association between bacterial vaginosis and preterm birth,chorion by the end of the 14th week of gestation. Subsequently, the including that related to preterm PROM,31,32 it remains unclear whetheramnion and chorion are connected by a collagen-rich connective tissue bacterial vaginosis merely identiﬁes women with a predisposition tolayer, with the amnion represented by a single cuboidal epithelial abnormal genital tract colonization and inﬂammation, facilitatesamnion layer and subjacent compact and spongy connective tissue ascent of other bacteria to the upper genital tract, or is directly patho-layers, and a thicker chorion consisting of reticular and trophoblastic genic and causative of membrane rupture. Physical effects related tolayers. Together, the amnion and chorion form a stronger unit than preterm contractions and prolapsing membranes with premature cer-either layer individually. Physiologic membrane remodeling occurs vical dilatation can predispose the fetal membranes to rupture, as canwith advancing gestational age, reﬂecting changes in collagen content the increased intrauterine pressure seen with polyhydramnios.4,33 It isand type, changes in intercellular matrix, and progressive cellular apop- likely that certain connective tissue disorders (e.g., Ehlers-Danlos syn-tosis. These changes lead to structural weakening of the membranes, drome) can result in intrinsic weakening of the membranes. Clinicalwhich is more evident in the region of the internal cervical os.1-8 associations with preterm PROM include low socioeconomic status, Membrane weakening can be stimulated by exposure to local lean maternal body mass (<19.8 kg/m2), nutritional deﬁciencies (e.g.,matrix metalloproteinases (e.g., MMP-1, MMP-2, MMP-9), decreased copper, ascorbic acid), and prior cervical conization. During preg-levels of membrane tissue inhibitors of matrix metalloproteinases (e.g., nancy, maternal cigarette smoking, cervical cerclage, second- and
600 CHAPTER 31 Premature Rupture of the Membranesthird-trimester bleeding, pulmonary disease, prior episodes of preterm ing result at 22 to 24 weeks had a one-in-six chance (16.7%) oflabor or contractions, and uterine overdistention with polyhydramnios delivering a preterm infant because of PROM, and the combinationor multiple gestations have been linked to preterm PROM.4,33-45 of a prior preterm birth due to PROM, a short cervical length, and a Although one or more risk factors may lead to membrane rupture, positive fetal ﬁbronectin screening result increased the risk of deliverythe ultimate clinical cause of PROM is often not evident at delivery. at less than 35 weeks because of preterm PROM by 10.9-fold (25%In some cases, factors leading to membrane rupture are subacute or versus 2.3%).46chronic in nature. Women with a prior preterm birth have increased Unfortunately, despite knowledge of a broad range of potential riskrisk for preterm birth due to PROM in subsequent pregnancies, factors for preterm birth, we are able to predict only a small fractionespecially if the prior preterm delivery resulted from PROM.46 Asymp- of women destined to deliver preterm, and most preterm births due totomatic women with a short cervical length (<25 mm) remote from preterm labor or PROM occur in women considered to be at low riskdelivery are also at increased risk for subsequent preterm birth due to for these events. Ancillary tests such as fetal ﬁbronectin screening orpreterm labor or PROM. Some women may have polymorphisms for transvaginal cervical sonography should be incorporated into routineinﬂammatory proteins that alter their inﬂammatory response and practice only after effective interventions to prevent PROM have beenincrease the risk for preterm birth.47,48 identiﬁed for those with an abnormal test result. Because most cases of preterm PROM cannot be predicted or prevented, clinical efforts continue to be focused on evaluation and treatment of women whoPrediction and Prevention present with symptoms of preterm PROM.Because PROM at term usually is part of the normal parturitionprocess, the focus of efforts has been on the prediction and preventionof preterm birth caused by PROM. Prevention of preterm PROM Clinical Coursewould be particularly appealing because labor and intrauterine infec- PROM affects approximately 8% of pregnancies at term, and 95% oftion or other complications necessitating delivery often ensue soon these women will deliver within 28 hours of membrane rupture.54after membrane rupture occurs. The optimal way to prevent complica- Preterm PROM is also associated with brief latency from membranetions from preterm PROM is to prevent its occurrence. Potentially rupture to delivery; delivery within 1 week is the most commonmodiﬁable risk factors for preterm PROM include cigarette smoking, outcome after preterm PROM at any gestational age. On average,poor nutrition, urinary tract and sexually transmitted infections, acute latency increases with decreasing gestational age at membrane rupture.pulmonary diseases, and severe polyhydramnios. When PROM occurs before 34 weeks’ gestation, 93% of women will Other than treatment of infections, it is unknown whether correc- deliver within 1 week, and 50% to 60% of those who are managedtion of these factors can avert this complication. Although most other conservatively will deliver within 1 week.55,56 With PROM near therisk factors are ﬁxed in that they cannot be removed or remedied in a limit of viability, 60% to 70% deliver within 1 week, but 1 in 5 willparticular woman, knowledge of risk can help to counsel women about have a latency of 4 or more weeks if they are managed conservatively.35suspicious symptoms and the importance of timely evaluation if Although the likelihood of spontaneous resealing of the membranespreterm PROM occurs. Broad-based preventive strategies such as pro- after preterm PROM is low (3% to 13%), the prognosis for those withgesterone supplementation can be considered for those at risk due to PROM occurring after amniocentesis is much better, with 86% to 94%less speciﬁc risk factors such as a history of spontaneous preterm resealing spontaneously.44,57,58 In a study of women with PROM afterbirth49,50 (see Chapter 29). Although one study suggested that vitamin second-trimester amniocentesis, leakage stopped in most cases withC supplementation had value in preventing preterm PROM (7.6% conservative management, although a normal ﬂuid volume sometimesversus 24.5%; P = .02), studies in which vitamin C was given alone or took time to re-accumulate (in a range of 8 to 51 days).58with other supplements to women without prior preterm birth as arisk factor indicate a trend toward increased preterm birth with suchtreatments (relative risk [RR] = 1.38; 95% conﬁdence interval [CI],1.04 to 1.82).51,52 Vitamin C supplementation to prevent preterm birth Complications afterdue to PROM thus cannot be recommended until there is solid evi- Premature Rupture ofdence of beneﬁt. Perhaps the strongest risk factor for preterm PROM is a history of the Membranesprematurity or PROM.53 Those with an early preterm birth have thehighest risk for a recurrence. A history of preterm birth after PROM Maternal Complicationsconfers a 3.3-fold increased risk for recurrent preterm birth due to the Chorioamnionitis complicates 9% of pregnancies with term PROM, asame cause (13.5% versus 4.1%; P < .01) and a 13.5-fold higher risk risk that increases to 24% with membrane rupture lasting longer thanof subsequent delivery before 28 weeks (1.8% versus 0.13%; P < .01). 24 hours.59 The risk of intrauterine infection increases with the dura-Because prior obstetric outcome has such a strong inﬂuence on tion of membrane rupture and with declining gestational age.54,55,60-62subsequent pregnancy outcomes, it is useful to evaluate nulliparas Conservative management of PROM provides the opportunity forseparately from those with prior deliveries. When assessed at 22 to subclinical deciduitis to progress to overt infection and for ascending24 weeks’ gestation, medical complications (e.g., pulmonary disease in infection to occur.20,54,55,62 Chorioamnionitis can complicate 13% topregnancy), work during pregnancy, low maternal body mass index 60% of cases when PROM occurs remote from term. Endometritis(<19.8 kg/m2), and bacterial vaginosis are associated with preterm occurs in 2% to 13% of cases.63,64 Placental abruption is diagnosed inbirth due to PROM.46 Identiﬁcation of a cervical length shorter than 4% to 12% of pregnancies complicated by PROM and can occur before25 mm on transvaginal ultrasound also confers an increased risk of or after the onset of membrane rupture.34,65,66 Maternal sepsis (0.8%)subsequent PROM in nulliparas and multiparas. In this study, nullipa- leading to death (0.14%) is a uncommon complication of pretermras with a short cervix and a positive cervicovaginal ﬁbronectin screen- PROM occurring near the limit of viability.67
CHAPTER 31 Premature Rupture of the Membranes 601 reported outcomes of previable PROM may be optimistic becauseFetal Complications most studies have been retrospective and have included only patientsThe risks to the fetus are primarily those related to intrauterine infec- amenable to conservative management.tion, umbilical cord compression, and placental abruption. Fetal heart Fetal lung growth and development can be especially adverselyrate patterns consistent with umbilical cord compression due to affected when PROM occurs in the early phases of development.82-87oligohydramnios are commonly seen after PROM.68 Umbilical cord With PROM occurring during the late pseudoglandular or canalicularprolapse can occur after membrane rupture, particularly with fetal stage of pulmonary development, tracheobronchial collapse or loss ofmalpresentation, which is more common with preterm gestations. intrinsic factors within the tracheobronchial ﬂuid, or both, may leadFetal death occurs in 1% to 2% of cases of conservatively managed to failure of the terminal bronchioles and alveoli to develop, withPROM.56 The reported incidence of fetal death after PROM at 16 to resultant failure of lung growth.88-91 Pulmonary hypoplasia develops28 weeks ranges from 3.8% to 22%.36,69,70 This particularly high risk of over weeks after membrane rupture occurs. It is most accuratelyfetal loss may reﬂect increased susceptibility to umbilical cord com- diagnosed pathologically based on radial alveolar counts and lungpression and hypoxia or intrauterine infection, but it may also reﬂect weights.92,93 In surviving infants, pulmonary hypoplasia is suggested byless aggressive obstetric interventions for fetal compromise before the a small chest circumference with severe respiratory distress or persis-limit of viability. tent pulmonary hypertension and radiographic ﬁndings such as small, well-aerated lungs with a bell-shaped chest and elevation of the diaphragm.83,88Neonatal Complications Overall, pulmonary hypoplasia becomes evident in 0% to 26.5% ofGestational age at delivery is the primary determinant of the frequency infants (mean = 5.9%) delivering after PROM at 16 to 26 weeks’ gesta-and severity of neonatal complications after PROM. Respiratory dis- tion. Early PROM before 20 weeks’ gestation carries the highest poten-tress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, tial for lethal pulmonary hypoplasia (≈50% with PROM before 19and sepsis are the most common serious acute morbidities, and they weeks’ gestation).83,86-88,94-96 With PROM at 15 to 16 weeks, an amnioticare common with early preterm birth. Neonatal sepsis is twofold more ﬂuid index of 2 cm or less, and a latency of 28 days, the risk of pulmo-common after preterm PROM than after preterm birth due to preterm nary hypoplasia is estimated to be 74% to 82%.97 Lethal pulmonarylabor. Neonatal infection can manifest as congenital pneumonia, hypoplasia is uncommon with PROM after 24 to 26 weeks’ gestationsepsis, meningitis, and late-onset bacterial or fungal infection. Early (0% to 1.4%) because there has been adequate alveolar developmentpreterm birth can lead to long-term complications, including chronic to support extrauterine life by this time.83,84,98 However, nonlethal pul-lung disease, visual or hearing difﬁculties, mental retardation, monary hypoplasia increases the likelihood of pulmonary barotrauma,developmental and motor delay, and cerebral palsy. In general, these including pneumothorax, pneumomediastinum, and the need for highlong-term morbidities are uncommon with delivery after about ventilatory pressures because of poor pulmonary compliance.83,98,9932 weeks’ gestation.71,72 Cerebral palsy and periventricular leukomala- With prolonged oligohydramnios, restriction deformities can occur incia have been associated with amnionitis,73 and increased amniotic up to 27% of fetuses.67,83,98-101ﬂuid cytokines and fetal systemic inﬂammation have been associatedwith preterm PROM, periventricular leukomalacia, and cerebralpalsy.74-76 This highlights the need for potential neonatal beneﬁtfrom delayed delivery if conservative management is to be attempted Diagnosisbecause this delay offers the opportunity for intrauterine infection to In more than 90% of cases, the diagnosis of PROM can be conﬁrmeddevelop. Alternatively, early gestational age at birth has been associated by clinical assessment, including the combination of history, clinicalwith neonatal white matter damage (P < .001) after controlling for examination, and laboratory evaluation. Because optimal clinical careother factors.77 Despite the described associations between PROM, requires an accurate diagnosis, attention should be paid to conﬁrmingintrauterine infection or inﬂammation, and adverse neurologic out- the diagnosis when a suspicious history or ultrasound ﬁnding of oli-comes, it has not been shown that immediate delivery after PROM can gohydramnios is identiﬁed. Other potentially confounding ﬁndingsprevent these morbidities. such as urine leakage, increased vaginal discharge with cervical dilata- In the past, mid-trimester PROM, which encompasses membrane tion or membrane prolapse, cervical infection, passage of the mucousrupture occurring at about 16 to 26 weeks’ gestation, was considered plug, and the presence of semen or vaginal douching should beas a separate entity from preterm PROM because neonatal death considered.usually could be anticipated with immediate delivery. With current A sterile speculum examination should be performed to providesurvival rates of about 25% to 85% after delivery at 23 to 26 weeks’ conﬁrmatory evidence of membrane rupture and to inspect for cervi-gestation, mid-trimester PROM is no longer a relevant clinical citis and for umbilical cord or fetal prolapse, to assess cervical dilata-entity.71,72,78-80 Previable PROM occurring before the limit of viability tion and effacement, and to obtain cultures, including endocervical(i.e., before 23 weeks’ gestation) is a special circumstance that places Neisseria gonorrhoeae and Chlamydia trachomatis, and anovaginalthe fetus in particular jeopardy. Immediate delivery will result in Streptococcus agalactiae (i.e., GBS), as appropriate. Initially, digitalneonatal death. Conservative management may result in fetal or cervical examination should be avoided unless imminent delivery isneonatal loss before viability, and if viability is reached, delivery is anticipated because the needed information usually can be obtainedlikely at an early gestational age, when the risks of long-term sequelae with visualization of the cervix. Digital examination can shortenare highest. The neonatal survival rate after PROM occurring before latency between membrane rupture and delivery, and some studies24 weeks has previously been reported to be approximately 30%, com- have shown it to introduce vaginal organisms into the cervical canalpared with 57% for rupture at 24 to 26 weeks’ gestation.67 In a review and to increase the risk of infection.102-107of 201 cases from 11 studies, the perinatal survival rate with conserva- The diagnosis of membrane rupture is conﬁrmed by visualizationtive management of PROM before 23 weeks’ gestation was 21%, but of ﬂuid passing from the cervical canal. If the diagnosis is not con-there was similar survival after PROM at less than 20 weeks.81 These ﬁrmed on initial inspection, the pH of the vaginal side walls or pooled
602 CHAPTER 31 Premature Rupture of the Membranesvaginal ﬂuid can be evaluated using Nitrazine paper, which turns blue of ﬂuid across a weakened membrane or minimal leakage around aat a pH above 6.0 to 6.5. Amniotic ﬂuid usually has a pH of 7.1 to 7.3, ﬁrmly applied presenting fetal part. Women with a suspicious historywhereas normal vaginal secretions have a pH of about 4.5 to 6.0. Blood and initially negative testing should be encouraged to return for reeval-or semen contamination, alkaline antiseptics, and bacterial vaginosis uation if symptoms are persistent or recurrent.can cause false-positive Nitrazine test results. If further clariﬁcation isneeded, microscopic inspection can be performed for the presence ofarborized crystals (i.e., ferning) (Fig. 31-1) in an air-dried sample col-lected from the vaginal side walls or pooled vaginal ﬂuid. Ferning Management of Prematureresults from the interaction of amniotic ﬂuid proteins and salts. Cervi-cal mucus should be avoided during sampling because it can also yield Rupture of the Membranesa ferning pattern on microscopy. The fern test is unaffected by meco- Management of PROM is based primarily on the estimated risks fornium and vaginal pH, but it can be falsely positive if there is heavy fetal and neonatal complications with immediate delivery weighedblood contamination.108,109 Prolonged leakage with minimal residual against the potential risks and beneﬁts of conservative management toﬂuid can lead to false-negative clinical, Nitrazine, and ferning test extend the pregnancy after membrane rupture (Fig. 31-2). The risks ofresults. Re-examination after prolonged recumbency or alternate mea- maternal morbidity should also be considered, especially under thesures can be considered if initial testing is negative. Assessment of circumstance of previable PROM.cervicovaginal secretions for fetal ﬁbronectin, prolactin, human cho-rionic gonadotropin (hCG), and other markers may assist in the diag-nosis of PROM. However, these tests usually are not more helpful than Initial Evaluationthe initial measures listed previously, because a positive test result After the diagnosis of membrane rupture is conﬁrmed, the durationmay reﬂect decidual disruption rather than membrane rupture in of membrane rupture should be estimated to assist the pediatricsome cases and a negative test result cannot exclude the diagnosis caregivers with subsequent management decisions. Gestational ageunequivocally. is established based on the combination of menstrual dates, clinical If the diagnosis remains unclear after initial evaluation, documen- history, and ultrasound ﬁndings, as appropriate. Fetal presentation istation of oligohydramnios by ultrasound, in the absence of fetal urinary assessed, and the patient is evaluated for labor, clinical ﬁndings oftract malformations or signiﬁcant growth restriction, is suggestive of intrauterine infection, and signiﬁcant vaginal bleeding. Fetal well-membrane rupture. Ultrasonographically guided amniocentesis with being is assessed by continuous heart rate monitoring if the limit ofinfusion of indigo carmine dye (1 mL of dye in 9 mL of sterile normal viability has been reached. After preterm PROM, it is important tosaline), followed by observation for passage of blue ﬂuid from the evaluate fetal growth and residual amniotic ﬂuid volume by ultra-vagina onto a perineal pad, can conﬁrm or disprove the diagnosis of sound, and the potential of fetal abnormalities that can lead to poly-membrane rupture. Amniocentesis in the setting of oligohydramnios hydramnios should be considered. Although narrowing of the biparietalcan be difﬁcult, and particular attention should be paid to avoidance diameter (i.e., dolichocephaly) due to oligohydramnios or breech pre-of the umbilical cord vessels, which can have the appearance of a thin, sentation can result in underestimation of gestational age and fetallinear ﬂuid space under this circumstance. weight, ultrasound usually is as reliable after PROM as it is with intact Some women with a history suspicious for membrane rupture but membranes.110 Tables using fetal head circumference rather than bipa-a negative speculum examination result and a normal amniotic ﬂuid rietal diameter can be consulted as needed. GBS carrier status shouldvolume on ultrasound subsequently return with gross membrane be ascertained if available from culture results within 6 weeks or thererupture. This pattern may reﬂect initial transudation of a small amount has been a positive urine culture in the current pregnancy, and the need for intrapartum prophylaxis should be determined. In the absence of available culture results, a risk factor–based approach should be used for prevention of vertical transmission.111 If conservative management is planned, the patient should be cared for in a facility with the ability to provide emergent delivery for pla- cental abruption, fetal malpresentation, or fetal distress. The facility should also have neonatal intensive care facilities and offer acute neonatal resuscitation, because conservative management usually is undertaken only if there is a signiﬁcant risk of neonatal morbidity and mortality with immediate delivery. Prenatal maternal transfer should be undertaken early in the course of management if these resources are not available. Because of the potential for acute complications, outpatient management usually is not recommended when PROM occurs after the limit of viability. Term Premature Rupture of the MembranesFIGURE 31-1 Ferning. A typical ferning appearance is seen after a There is no substantial fetal beneﬁt to expectant management of preg-swab from the posterior vaginal fornix was smeared on glass slide nancy after membrane rupture at 37 weeks’ gestation or later. Expect-and the specimen allowed to air dry. The sample was obtained from a ant management of PROM at term was practiced in the 1980s and earlypatient with premature rupture of the membranes. (Image courtesy of 1990s based on studies suggesting that immediate induction after termThomas Garite, University of California at Irvine, Orange, California.) PROM might increase the risks of infection and cesarean delivery.112-115
CHAPTER 31 Premature Rupture of the Membranes 603 Diagnosis confirmed Fluid per cervical os or vaginal pool with positive Nitrazine/ferning test or indigo carmine amnio infusion Ultrasound for gestational age, growth, anomalies as appropriate Cervical cultures: Chlamydia, gonorrhea Anovaginal culture: group B streptococcus Urine culture: group B streptococcus Initial and continuous monitoring for labor, fetal distress Intrapartum group B streptococcus prophylaxis, Amnionitis, based on risk factors if no abruptio placentae, Yes recent negative fetal death, Deliver anovaginal culture non-reassuring testing, or advanced labor Broad-spectrum antibiotics if amnionitis No Previable PROM Early Preterm PROM Preterm PROM Late Preterm PROM Term PROM 23 weeks 23-31 weeks 32-33 weeks 34-36 weeks 37 weeks Documented fetal Yes Initial monitoring pulmonary maturity for infection, labor, abruptio No placentae Immature testing Initial bed rest or to encourage fluid unavailable resealing Conservative management Modified bed rest/pelvic rest to encourage resealing, reduce infection Evaluate for Consider conservative persistent Serial evaluation for management for oligohydramnios amnionitis, labor, corticosteroid benefit and pulmonary abruption, fetal with concurrent hypoplasia with well-being, growth antibiotic therapy, serial ultrasound or Administer corticosteroids expeditious delivery if and antibiotics (NICHD previous antenatal Re-counsel protocol) short-term steroids and attempted tocolysis latency 1 week Induction If discharged with before viability not planned Deliver for amnionitis, oxytocin, and remains non-reassuring fetal PGE2 or pregnant, testing, abruption, misoprostol, readmit at advanced labor 33 weeks or fetal viability for 32 weeks Deliver dilatation and conservative Deliver at Expeditious Expeditious Deliver at 34 weeks if 34 weeks after evacuation management stable until then delivery delivery steroids Intrapartum group B streptococcus prophylaxis based on risk factors if no recent negative anovaginal culture Broad-spectrum antibiotics if amnionitisFIGURE 31-2 Algorithm for management of premature rupture of the membranes (PROM). The algorithm includes several alternatives forthe approach to term and preterm PROM. NICHD, National Institute of Child Health and Human Development; PGE2, prostaglandin E2. (Adaptedfrom Mercer BM: Preterm premature rupture of the membranes. Obstet Gynecol 101:178-193, 2003.)
604 CHAPTER 31 Premature Rupture of the MembranesHowever, four large studies have since found that induction with oxy- conservative management of PROM is highlighted by the high inci-tocin after term PROM does not increase the risks of maternal or neo- dence of recurrent variable decelerations found during intermittentnatal infections, nor does it make cesarean delivery more likely.54,116-118 monitoring (19.4%) among conservatively managed women. In thisIn the largest study, oxytocin induction after term PROM reduced the study, documented fetal pulmonary maturity was a requirement forduration of membrane rupture (17.2 versus 33.3 hours; P < .001) and enrollment, and neither group suffered any signiﬁcant noninfectiousthe frequencies of chorioamnionitis (4.0% versus 8.6%; P < .001) and neonatal morbidities. Speciﬁc attention to those enrolled at 32 to 33postpartum febrile morbidity (1.9% versus 3.6%; P = .008), without weeks’ gestation revealed similar trends regarding brief latency,increasing the risk of cesarean delivery (13.7% versus 14.1%) or neo- increased amnionitis, suspected neonatal sepsis, and antibiotic treat-natal infections (2.0% versus 2.8%).54 Neonatal antibiotic therapy was ment with conservative management.130 Based on these ﬁndings, theless common with immediate induction (7.5% versus 13.7%; P < .001), woman with PROM and documented fetal pulmonary maturity at 32likely because of a lower concern regarding the potential for neonatal to 33 weeks’ gestation is at low risk for complications after immediateinfection with less frequent prolonged rupture of the membranes and delivery and increased risk with conservative management. Amnioticless chorioamnionitis. Meta-analysis of studies comparing prostaglan- ﬂuid studies documenting pulmonary maturity in this gestational agedin induction and conservative management in this setting has found range are useful to identify women who should be offered expeditiousshorter latency, decreased rates of chorioamnionitis, and less frequent delivery.neonatal intensive care unit (NICU) admissions with no increase in If fetal pulmonary testing reveals an immature result or if amnioticcesarean delivery rates with prostaglandin administration.119 Because ﬂuid cannot be obtained for assessment, conservative managementoxytocin can more easily be discontinued, this choice is somewhat with antenatal corticosteroid administration for fetal maturation is anmore appealing, given similar efﬁcacy for labor induction. appropriate choice. Concurrent antibiotic treatment should be given In summary, available data indicate that women with PROM at to reduce the risk of intrauterine infection during conservativeterm who are not in labor on arrival at the hospital should have labor management (discussed later). There are no data regarding optimalinduced, usually with an oxytocin infusion, to reduce the risk of mater- management after antenatal corticosteroid treatment is completed.nal and neonatal complications. Caregivers should allow an adequate However, because conservative management increases the risks oftime for the latent phase of labor and minimize digital vaginal exami- chorioamnionitis and prolonged hospitalization and because it isnations until the active phase of labor. unlikely that conservative management for less than 1 week will result in further signiﬁcant spontaneous fetal maturation, delivery should bePreterm Premature Rupture of considered if elective delivery is planned within 7 days after antenatal corticosteroid beneﬁt has been achieved. If antenatal corticosteroidsthe Membranes at 32 to 36 are not to be given to accelerate fetal pulmonary maturity after PROMWeeks’ Gestation at 32 to 33 weeks, consideration should be given to the potentialAlthough infants born at 34 to 36 weeks’ gestation (i.e., late preterm beneﬁts of expeditious delivery unless conservative management tobirth) have a higher risk of complications than term infants, severe extend latency for 1 or more weeks will be attempted. These decisionsacute morbidities and mortality are uncommon, and antenatal corti- should take into consideration local population-based risks of infec-costeroids for fetal maturation are not typically recommended in this tion and neonatal morbidities.gestational age range.71,120 Conservative management of PROM at 34to 36 weeks prolongs pregnancy by only days, signiﬁcantly increases Preterm Premature Rupture ofthe risk of chorioamnionitis (16% versus 2%; P = .001), and reducesumbilical cord pH (7.35 versus 7.25; P = .009), and it has not been the Membranes at 23 to 31shown to improve neonatal outcomes.121,122 For these reasons, women Weeks’ Gestationpresenting with late preterm PROM at 34 to 36 weeks should be Because delivery before 32 weeks’ gestation is associated with a high riskactively delivered. for perinatal death, severe neonatal morbidities, and long-term sequelae, With delivery at 32 to 33 weeks’ gestation, gestational age–depen- women with PROM between 23 and 31 weeks’ gestation usually shoulddent neonatal morbidities, including respiratory distress syndrome, be managed expectantly to prolong pregnancy unless there is evidencecan occur, but the likelihood of survival is high, and chronic morbidi- of intrauterine infection, suspected placental abruption, advancedties are uncommon. Amniotic ﬂuid can be collected from the vaginal labor, or a non-reassuring fetal heart rate pattern. Under certain addi-pool at initial sterile speculum examination or by amniocentesis if tional circumstances, delivery may be appropriate despite an early ges-vaginal ﬂuid is not available. Each of the TDx/TdXFLx FLM II assay tational age at membrane rupture (e.g., fetal transverse lie and back up(Abbott Laboratories, Abbott Park, IL), the lecithin-to-sphingomyelin with coexisting advanced cervical dilatation, human immunodeﬁciencyratio (L/S ratio), and the phosphatidylglycerol (PG) test can predict virus infection, primary herpes simplex virus infection).pulmonary maturity when performed on vaginal pool specimens.123-128 In women with conservatively managed PROM remote from term,Modest reductions in the duration of neonatal hospital stay and hyper- a low initial amniotic ﬂuid volume (amniotic ﬂuid index <5.0 cm orbilirubinemia with conservative management of PROM at 32 to 33 maximum vertical ﬂuid pocket <2.0 cm) is associated with shorterweeks’ gestation have been reported.122 Alternatively, conservative latency to delivery and increased neonatal morbidity (including respi-management prolonged pregnancy only brieﬂy (36 versus 14 hours; ratory distress syndrome) but not with increased maternal or neonatalP < .001) in a randomized, controlled trial of conservative manage- infection after PROM.131 Despite this, the predictive value of a lowment versus immediate induction after PROM at 32 to 36 weeks’ gesta- amniotic ﬂuid volume for adverse outcomes is poor. A short cervicaltion. This limited beneﬁt was offset by a 2.5-fold increased risk of length on endovaginal ultrasound after preterm PROM has been asso-chorioamnionitis (27.7% versus 10.9%; P = .06), increased neonatal ciated with shorter latency to delivery.132-134 The latest study of cervicalsepsis workups (59.6% versus 28.3%; P =.003) and increased neonatal length in women with preterm PROM found that 83% of womenantibiotic treatment for suspected infection (78.7% versus 34.8%; P < delivered within 7 days if the initial cervical length was 1 to 10 mm,.001).129 The potential for occult umbilical cord compression during compared with 18% for a cervical length more than 30 mm, but only
CHAPTER 31 Premature Rupture of the Membranes 60541 women were evaluated.132 However, currently available studies of roid administration after preterm PROM has been extensively studied,initial amniotic ﬂuid volume and cervical length assessment in women generating several meta-analyses.145-147 Although early reviews pro-with preterm PROM have insufﬁcient power and consistency to guide duced conﬂicting conclusions about the utility of antenatal corticoste-management. roid treatment after PROM, a later meta-analysis concluded that Conservative management includes initial prolonged continuous antenatal glucocorticoids signiﬁcantly reduce the risks of respiratoryfetal heart rate and maternal contraction monitoring to assess fetal distress syndrome (20% versus 35.4%), intraventricular hemorrhagewell-being and identify occult contractions and evidence of umbilical (7.5% versus 15.9%), and necrotizing enterocolitis (0.8% versus 4.6%),cord compression. If initial testing results are reassuring, the patient without increasing the risks of maternal (9.2% versus 5.1%) or neo-can be transferred to an inpatient unit or transferred to a facility natal (7.0% versus 6.6%) infections in women with preterm PROM.147capable of emergent delivery and acute neonatal resuscitation for Multivariate analysis of prospective observational trials suggested amodiﬁed bed rest. Because of the high risk of heart rate abnormalities beneﬁt of antenatal corticosteroid use regardless of membranedue to umbilical cord compression (32% to 76%), fetal assessment rupture.148 Three studies in which prophylactic antibiotics were givenshould be performed at least daily for those with initially reassuring concurrent to antenatal corticosteroids found treatment to reducetest results.68,135 Continuous monitoring may be appropriate for women respiratory distress syndrome (18.4% versus 43.6%; P = .03) perinatalwith intermittent fetal heart rate decelerations but otherwise reassur- mortality (1.3% versus 8.3%; P = .05), and composite morbiditiesing ﬁndings. Although the nonstress test and biophysical proﬁle have (29.3% versus 48.6%; P < .05), with no increase in perinatalthe ability to conﬁrm fetal well-being in the setting of preterm PROM, infections.149-151fetal heart rate monitoring can identify variable and late decelerations The National Institutes of Health Consensus Development Panelin addition to uterine activity. Biophysical proﬁle testing may also be recommended a single course of antenatal corticosteroids for womenconfounded by the presence of oligohydramnios but can be helpful if with PROM before 30 to 32 weeks’ gestation in the absence of intra-the nonstress test is equivocal, particularly remote from term when the amniotic infection.152 Data regarding repeated weekly courses offetal heart rate pattern is less likely to be reactive. A nonreactive result antenatal corticosteroids after preterm PROM are conﬂicting. In afor a nonstress test and a biophysical proﬁle score of 6 or less within retrospective study that controlled for gestational age and other factors,24 hours of delivery have been associated with perinatal infection.136,137 two or more courses of antenatal corticosteroids were associated withA nonreactive nonstress test subsequent to an initially reactive result increased early neonatal sepsis (15.3% versus 2% for a single course orshould be considered suspicious. 1.5% for no courses; P < .001).153 In another retrospective analysis of Conservative management requires surveillance for the devel- repeated antenatal corticosteroids, there was no reduction in respira-opment of labor, abruptio placentae, and intrauterine infection. tory distress syndrome, but intraventricular hemorrhage and amnio-Chorioamnionitis confers increased risks of perinatal mortality and nitis were less common, and there was a trend toward less sepsis.154intraventricular hemorrhage, and it is diagnosed clinically by the pres- Respiratory distress syndrome was less common in another retrospec-ence of maternal fever above 38.0 °C (100.4 °F) with uterine tenderness tive review of repeated courses of antenatal corticosteroids (34.9%or with maternal or fetal tachycardia in the absence of another evident versus 45.2%) without an increase in neonatal sepsis (9.9% versussource of infection.63 After the diagnosis of chorioamnionitis is made, 6.2%).155delivery should be pursued and broad-spectrum antibiotics should be Based on current evidence that antenatal corticosteroids are effec-initiated because treatment before delivery has been shown to decrease tive for induction of fetal pulmonary maturity without increasing thethe incidence of neonatal sepsis.138-140 Although evaluation of the mater- risk of infection and that most women will remain pregnant for the 24nal white blood cell count can be helpful if clinical ﬁndings are equivo- to 48 hours needed to achieve corticosteroid beneﬁt after PROM, acal, the counts can be artiﬁcially elevated within 5 to 7 days of antenatal single course of antenatal corticosteroids should be considered whencorticosteroid administration. If the diagnosis of chorioamnionitis is PROM occurs before 32 weeks’ gestation and for women withsuspected but additional conﬁrmation is needed, amniocentesis may documented pulmonary immaturity at 32 to 33 weeks’ gestation.yield helpful results.15,141,142 A glucose concentration below 16 to 20 mg/ Betamethasone (two doses of 12 mg IM, given 24 hours apart) ordL (sensitivity and speciﬁcity of 80% to 90% for a positive culture) and dexamethasone (four doses of 6 mg IM, given 12 hours apart) is con-a Gram stain positive for bacteria (sensitivity of 36% to 80% and speci- sidered appropriate. Repeated weekly antenatal corticosteroids are notﬁcity of 80% to 97% for a positive culture) support the presence of recommended after preterm PROM. The beneﬁts and risks of a singleintrauterine infection. The presence of leukocytes alone in amniotic rescue course remote from initial corticosteroid administration remainﬂuid after PROM is not well correlated with intrauterine infection. to be determined.Although a positive amniotic ﬂuid culture supports clinical suspicionof chorioamnionitis (sensitivity of 65% to 85% and speciﬁcity of 85%), Adjunctive Antibioticsthese results are not likely to be available before the diagnosis is clari- Antibiotic therapy is given during conservative management ofﬁed.17 One study suggested that determination of glucose levels from preterm PROM to treat or prevent ascending decidual infection tovaginally collected amniotic ﬂuid may be a simple and noninvasive prolong pregnancy and to reduce gestational age–dependent morbid-method for identiﬁcation of intra-amniotic infection.143 In this promis- ity while limiting the risk of neonatal infection. More than two dozening study, a vaginal pool glucose value below 5 mg/dL had a 74.2% randomized clinical trials have been summarized in several meta-accuracy rate for identifying women with a positive amniotic ﬂuid analyses.56,156,157 In the latest one, antibiotic treatment after pretermculture. Although research has found elevated amniotic ﬂuid interleu- PROM signiﬁcantly reduced chorioamnionitis (relative risk [RR] =kin levels to be associated with early delivery and perinatal infectious 0.57); delivery within 48 hours (RR = 0.71) and within 7 days (RR =morbidity,141 such testing is not available in most clinical laboratories. 0.80); and reduced infant morbidities, including neonatal infection (RR = 0.68); and major cerebral abnormalities on ultrasound beforeAntenatal Corticosteroids discharge (RR = 0.82) compared with placebo therapy.157 The need forRespiratory distress syndrome is the most common acute morbidity surfactant administration (RR = 0.83) and oxygen therapy (RR = 0.88)after conservatively managed preterm PROM.144 Antenatal corticoste- was also reduced. Antibiotics did not inﬂuence the risk of necrotizing
606 CHAPTER 31 Premature Rupture of the Membranesenterocolitis (RR = 1.14; CI, 0.66 to 1.97). Oral amoxicillin-clavulanic longation, less need for oxygen therapy, and fewer positive neonatalacid treatment was associated with increased necrotizing enterocolitis blood cultures.157 This is not inconsistent with the NICHD-MFMU(RR = 4.60; 95% CI, 1.98 to 10.72) in this analysis, but oral erythro- approach. Up to a 7-day course of parenteral and oral therapy usingmycin therapy was not (RR = 1.00; CI, 0.56 to 1.80).157 The study that ampicillin-amoxicillin and erythromycin is recommended for womendominated this meta-analysis included women with PROM up to 36 undergoing conservative management of preterm PROM remote fromweeks’ gestation and included a population at low risk for necrotizing term. Shortages in intravenous and oral antibiotics have led to the needenterocolitis overall (i.e., 0.5% among controls), and it was the only for alternative antibiotic choices. Oral ampicillin, erythromycin, andone of 10 studies that found a signiﬁcant increase in necrotizing azithromycin are likely appropriate alternatives if needed.enterocolitis with antibiotic therapy.158 The meta-analysis found treat- Adjunctive antibiotic administration to prolong latency must bement with “all penicillins” (excluding amoxicillin-clavulanic acid) distinguished from intrapartum prophylaxis to prevent vertical trans-versus placebo to be associated with fewer births within 48 hours and mission of GBS from mother to baby.111 Known GBS carriers and those7 days of PROM, less overall maternal infection and chorioamnionitis, who deliver before carrier status can be determined should receiveless neonatal infection, fewer positive neonatal blood cultures, and intrapartum prophylaxis to prevent vertical transmission, regardless offewer major intracranial cerebral ultrasound abnormalities. Because of prior antibiotic treatments. Women with a diagnosis of chorioamnio-the increased risk of neonatal necrotizing enterocolitis with amoxicil- nitis should receive broad-spectrum intrapartum antibiotic therapy.lin-clavulanate, the study authors recommended erythromycin as abetter choice, even though beneﬁts were limited to reduction in deliv- Tocolysisery at 48 hours, fewer positive neonatal blood cultures, and a reduced Evidence from prospective studies of tocolysis after PROM is similarneed for oxygen therapy. to that from studies of tocolysis for preterm labor with intact In a clinical trial with adequate power to evaluate antibiotic therapy membranes.162-167 After preterm PROM, prophylactic tocolysis with β-during conservative management of women with preterm PROM agonists before the onset of contractions can prolong pregnancy brieﬂy.before 32 weeks’ gestation, the National Institutes of Child Health and Therapeutic tocolysis administered only after contractions occur hasHuman Development Maternal Fetal Medicine Units (NICHD- not been shown to be effective in prolonging latency. In a retrospectiveMFMU) Research Network assigned women with PROM to initial comparison of aggressive tocolysis with limited treatment for contrac-aggressive intravenous therapy for 48 hours (2 g of ampicillin IV every tions only during the ﬁrst 48 hours, aggressive therapy was not associ-6 hours and 250 mg of erythromycin IV every 6 hours) followed by ated with longer latency (3.8 versus 4.5 days; P = .16).167 A report fromoral therapy for 5 days (250 mg of amoxicillin PO every 8 hours and the Collaborative Study on Antenatal Steroids suggested tocolytic333 mg of enteric-coated erythromycin base PO every 8 hours) to use after PROM was associated with subsequent neonatal respiratoryprovide limited-duration, broad-spectrum antimicrobial coverage distress syndrome, but the biologic mechanism for this association isbefore delivery.144,159 GBS screening was performed. GBS carriers were unclear.168treated with ampicillin for 1 week and again in labor, and they were Overall, the available prospective studies have not found tocolyticanalyzed separately. Antibiotic treatment increased the likelihood of treatment after PROM to increase or prevent neonatal morbiditiescontinued pregnancy after 7 days of treatment by twofold. Beneﬁt after PROM. Tocolytic therapy has not been studied when antenatalpersisted for 3 weeks after randomization despite discontinuation of corticosteroids and antibiotics were administered concurrently, andantibiotics at 7 days. Babies born to women treated with ampicillin it remains plausible that prophylactic tocolysis could delay deliveryplus erythromycin had a reduced incidence of one or more major long enough to allow antibiotic suppression of subclinical decidualinfant morbidities (53% versus 44% rate of composite morbidity, infection and for corticosteroid effects on the fetus. Pending furtherincluding death, respiratory distress syndrome, early sepsis, severe study in this area, tocolytic therapy should not be considered anintraventricular hemorrhage, and severe necrotizing enterocolitis; P < expected practice after preterm PROM, but it may be appropriate in.05). Antibiotic therapy also signiﬁcantly reduced individual gesta- pregnancies at high risk for neonatal complications with early pretermtional age–dependent morbidities, including respiratory distress syn- birth.drome (40.5% versus 48.7%), patent ductus arteriosus (11.7% versus20.2%), chronic lung disease (bronchopulmonary dysplasia: 20.5% Cervical Cerclageversus 13.0%), and stage 3 or 4 necrotizing enterocolitis (2.3% versus Preterm PROM complicates about one fourth of pregnancies with a5.8%), with P values of 0.05 or less for each. Chorioamnionitis was cervical cerclage and one half of pregnancies requiring an emergentreduced with the study’s antibiotics (23% versus 32.5%; P = .01), and cerclage.43,169,170 Because no prospective studies have been performedneonatal sepsis (8.4% versus 15.6%; P = .009) and pneumonia (2.9% regarding management of preterm PROM with a cerclage in situ, rec-versus 7.0%; P = .04) were reduced for those who were not GBS carri- ommendations reﬂect the data available from retrospective cohorts.ers. The antibiotic study group had less neonatal GBS sepsis (0% versus The risk of adverse perinatal outcomes does not appear to be different1.5%; P = .03). Two other studies have attempted to determine whether when PROM occurs with a cerclage or without one, provided the cer-antibiotic therapy of shorter duration could provide similar beneﬁt, clage is removed on admission after PROM.171-172but the studies lacked size and power to demonstrate equivalent Several small studies comparing pregnancies of preterm PROM ineffectiveness.160,161 which the cerclage was retained or removed have yielded consistent In summary, broad-spectrum antibiotic (ampicillin-amoxicillin patterns.173-175 No study has found cerclage retention after PROM toplus erythromycin) therapy for women with preterm PROM before 32 reduce the frequency or severity of infant morbidities after pretermweeks’ gestation prolongs pregnancy sufﬁciently to reduce neonatal PROM, and each has demonstrated statistically insigniﬁcant trendsgestational age–dependent morbidities and reduce the frequencies of toward increased maternal infectious morbidity with only brief preg-maternal and neonatal infections.144 An alternative conclusion from nancy prolongation. One study found increased infant mortality andthe latest meta-analysis is that penicillins other than amoxicillin- mortality due to sepsis with cerclage retention after PROM.173 Oneclavulanic acid are an acceptable treatment for preterm PROM and study that compared different practices at two institutions foundthat the beneﬁts of erythromycin are limited to brief pregnancy pro- longer latencies with cerclage retention, but this ﬁnding could reﬂect
CHAPTER 31 Premature Rupture of the Membranes 607population or practice differences at these institutions rather than the speciﬁc neonatal outcomes after previable PROM is extremely difﬁculteffect of cerclage retention.174 because it is not possible to predict extended latency, the ultimate Because cerclage retention after PROM has not been shown to gestational age at delivery, or the degree of neonatal pulmonary hypo-improve perinatal outcomes and there are potential risks related to plasia at the time of initial presentation with PROM.leaving the cerclage in situ, removal is recommended when PROM For women who decide that the risks of conservative managementoccurs, particularly if the indication for initial cerclage placement was exceed the potential beneﬁts, delivery can usually be accomplishednot strong. While deferred removal might enhance pregnancy prolon- with vaginal prostaglandin E2, oral or vaginal prostaglandin E1 (i.e.,gation for corticosteroid administration, the risks and beneﬁts of this misoprostol), with a high-dose oxytocin infusion, or by dilatation andapproach have not been determined. evacuation. The optimal approach depends on the patient’s character- istics (e.g., gestational age, evident amnionitis, prior cesarean delivery)Maternal Herpes Simplex Virus Infection and preference, the available facilities, and the physician’s experienceNeonatal herpes simplex infection most commonly results from direct with these techniques.maternal-fetal transmission at delivery, but hematogenous transmis- Data to guide the management for women who choose conservativesion can occur to the fetus in utero in some cases. Neonatal infection management of previable PROM are lacking. There is no consensusrates after primary and secondary maternal infections occur in 34% to about the advantages of inpatient versus outpatient management.80% and 1% to 5% of cases, respectively,176,177 and infection can result Initial inpatient evaluation may include strict bed and pelvic rest toin mortality rates of 50% to 60% and serious sequelae in up to 50% enhance the opportunity for resealing and for early identiﬁcation ofof survivors.178,179 infection and placental abruption. Women who are discharged should Based on two case series including a total of 35 women with an be advised to abstain from intercourse and limit physical activity. Theyactive maternal genital herpesvirus infection, it has been generally should return immediately in case of fever, abdominal pains, suspi-accepted that increasing latency after membrane rupture of more than cious vaginal discharge, or any vaginal bleeding. Hospitalization for4 to 6 hours increases risk of neonatal infection and that cesarean the duration of amniotic ﬂuid leakage may be appropriate in somedelivery should be performed expeditiously to prevent fetal infection circumstances. Discharged patients are typically readmitted to hospitalin this setting.180-182 However, a case series of women with conserva- after the limit of viability has been reached to allow early interventiontively managed PROM before 32 weeks’ gestation coincident to active for infection, placental abruption, labor, and non-reassuring fetal heartrecurrent herpes simplex virus lesions suggests that conservative man- rate patterns. Administration of antenatal corticosteroids for fetalagement may be considered.183 Antenatal corticosteroids and antibiot- maturation at this time is appropriate.ics were not administered, and antiviral therapy was inconsistent in After an initial ultrasound assessment, repeated evaluation can bethis series. Cesarean delivery was performed for women with active performed every 1 to 2 weeks to determine whether there is re-accu-lesions at the time of delivery. After latencies ranging from 1 to 35 days, mulation of amniotic ﬂuid and to evaluate lung growth. Persistent,none of the 26 infants developed neonatal herpes infection (CI, 0% to severe oligohydramnios after PROM before 20 weeks is the strongest10.4%). predictor of subsequent lethal pulmonary hypoplasia. Serial fetal bio- Based on these data, conservative management of PROM com- metric evaluation (e.g., lung length, chest circumference), ratios toplicated by recurrent maternal herpes simplex virus infection may adjust for overall fetal size (thoracic to abdominal circumference, tho-be appropriate if membrane rupture occurs remote from term and racic circumference to femur length) and Doppler studies of fetal pul-the potential for mortality or serious sequelae with delivery is consid- monary artery and ductus arteriosus waveform modulation with fetalered to be high. Antiviral therapy (e.g., acyclovir) during conserva- breathing movements can demonstrate whether fetal pulmonarytive management can reduce viral shedding and the frequency of growth has occurred over time. These results have a high predictiverecurrence. value for neonatal mortality due to pulmonary hypoplasia.88,96,185-190 If pulmonary hypoplasia becomes evident before the limit of viability orPreviable Premature Rupture of there is persistent, severe oligohydramnios, the patient may choose to reconsider her decision regarding ongoing expectant management.the Membranes before 23 Treatments to seal the membrane defect or restore normal amnioticWeeks’ Gestation ﬂuid volume include transabdominal amnioinfusion and membraneAlthough the cause is often not apparent, clinical antecedents can be sealing with ﬁbrin, platelet, cryoprecipitate, or gel-foam plugs. Thesehelpful in determining the likely outcomes in some cases of previable methods are described in a review.191 The maternal risks and fetalPROM. Membrane rupture after amniocentesis is associated with ces- beneﬁts of these interventions have not been adequately evaluated, andsation of leakage and subsequent successful pregnancy outcomes in there are inadequate data to recommend that any of these approachesmost cases. Alternatively, previable PROM in a pregnancy complicated be incorporated into routine clinical practice.by persistent second-trimester bleeding, oligohydramnios, or an ele-vated level of maternal serum α-fetoprotein more likely reﬂects anabnormality of placentation, which carries a poor prognosis. The patient with previable PROM and no other indication for Summaryimmediate delivery should be counseled regarding the risks and bene- When term or preterm PROM occurs, there is the potential for signiﬁ-ﬁts of expectant management, including a realistic appraisal of poten- cant perinatal morbidity and mortality, which can be reduced by con-tial fetal and neonatal outcomes according to the available information sidered and timely obstetric interventions. Expeditious delivery of thefor gestational age–appropriate outcomes.71,72,184 In addition to the patient with term and late preterm PROM can reduce the risk of peri-maternal risks of conservative management previously delineated, natal infections without increasing the likelihood of operative delivery.muscle wasting, bone demineralization, and deep venous thrombosis Conservative management of PROM remote from term can reducecan also occur with prolonged bed rest, and there are signiﬁcant ﬁnan- infectious and gestational age–dependent morbidities. Regardless ofcial and social implications of prolonged hospitalization. Prediction of management approach, infants delivered after early preterm or previ-
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