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of membranes (ROM) prior to the onset of labor. Preterm premature rupture of membranes (PPROM) is ROM prior to 37 weeks' gestation. Spontaneous premature rupture of the membranes (SPROM) is ROM after or with the onset of labor. Prolonged ROM is any ROM that persists for more than 24 hours and prior to the onset of labor. At term, programmed cell death and activation of catabolic enzymes, such as collagenase and mechanical forces, result in ruptured membranes. Preterm PROM occurs probably due to the same mechanisms and premature activation of these pathways. However, early PROM also appears to be linked to underlying pathologic processes, most likely due to inflammation and/or infection of the membranes. Clinical factors associated with preterm PROM include low socioeconomic status, low body mass index, tobacco use, preterm labor history, urinary tract infection, vaginal bleeding at any time in pregnancy, cerclage, and amniocentesis.[1] Eighty-five percent of neonatal morbidity and mortality is a result of prematurity. PPROM is associated with 30-40% of preterm deliveries and is the leading identifiable cause of preterm delivery. PPROM complicates 3% of all pregnancies and occurs in approximately 150,000 pregnancies yearly in the United States. When PPROM occurs remote from term, significant risks of morbidity and mortality are present for both the fetus and the mother. Thus, the physician caring for the pregnant woman whose pregnancy has been complicated with PPROM plays an important role in management and needs to be familiar with potential complications and possible interventions to minimize risks and maximize the probability of the desired outcome. This article focuses on information the physician needs to achieve these goals.[2, 1, 3] For more information, see Medscape's Pregnancy Resource Center. For excellent patient education resources, visit eMedicine's Pregnancy and Reproduction Center. Also, see eMedicine's patient education article Labor Signs.
A new product, AmniSure, is being marketed with claims of positive and negative agreement with results of criterion standard for the diagnoses of PROM with 2 out of the 3 criteria that exceeds 95%. The use of this product in certain instances when a speculum examination cannot be performed may be of some use as an initial evaluation. Given the importance of the correct diagnoses, the associated morbidity with hospitalization and delivery prior to term in PROM reaching 34 weeks and beyond, the potential neonatal morbidity resulting from prematurity in cases of incorrect diagnoses of PROM; it is mandatory to confirm the diagnosis of PROM with pooling of amniotic fluid with some evidence of decreased or absence of amniotic fluid in all cases of suspected PROM. Most patients (90%) enter spontaneous labor within 24 hours when they experience ROM at term. The major question regarding management of these patients is whether to allow them to enter labor spontaneously or to induce labor. In large part, the management of these patients depends on their desires; however, the major maternal risk at this gestational age is intrauterine infection. The risk of intrauterine infection increases with the duration of ROM. Evidence supports the idea that induction of labor, as opposed to expectant management, decreases the risk of chorioamnionitis without increasing the cesarean delivery rate.[4, 5] Hannah et al studied 5041 women with PROM who were randomly assigned to induction of labor with intravenous oxytocin or vaginal prostaglandin E2 gel versus expectant management for as many as 4 days with induction of labor for complications.[6] They concluded that, in women with PROM, induction of labor and expectant management resulted in similar rates of cesarean delivery and neonatal infection. However, induction with oxytocin resulted in a lower risk of maternal infection (endometritis) when compared with expectant management. Additionally, the women in the study viewed induction of labor more favorably than expectant management. Other smaller studies have shown results with higher cesarean and/or operative delivery rates when the cervix was unfavorable. At term, infection remains the most serious complication associated with PROM for the mother and the neonate. The risk of chorioamnionitis with term PROM has been reported to be less than 10% and to increase to 40% after 24 hours of PROM.[7] This points out the importance of appropriate management strategies for PROM at term. Since risk of infection at term with ROM is small during the first 24 hours, expectant management and waiting for spontaneous labor may be considered in selected patients for the first 12-24 hours if a patient desires expectant management. The use of expectant management after the first 24 hours is questionable. Digital vaginal examinations should be avoided until labor is initiated; however, fetal presentation should be documented to avoid discovering malpresentation of the fetus long after admission for ROM. All patients with ROM should be asked to come to the hospital to ensure fetal well being. The neonatal risks of expectant management of PROM include infection, placental abruption, fetal distress, fetal restriction deformities and pulmonary hypoplasia, and fetal/neonatal death. Fetal death does occur in approximately 1% of patients with PROM after viability who have been expectantly managed[1] and in about 1:1000 term PROM[8] .
The primary determinant of neonatal morbidity and mortality is gestational age at delivery, again stressing the importance of conservative management when possible. In general, prognosis is good after 32 weeks' gestation as long as no other complicating factor, such as congenital malformation or pulmonary hypoplasia, exists.
infections, in which case delivery and initiation of broad-spectrum antibiotics should be promptly facilitated. Ultrasonographic examination for amniotic fluid index and fetal growth and well being should be used liberally to ensure appropriateness of continued expectant management. While oligohydramnios, defined as an amniotic fluid index of less than 2 cm, has been associated with short latency and chorioamnionitis, it alone is not an indication for delivery when other means of surveillance are reassuring. White blood cell count is not predictive of outcome and does not need to be monitored other than to support clinical suspicion of chorioamnionitis. Digital cervical examinations should be avoided.[9] In a noncephalic presentation, especially with a dilated cervix, continuous monitoring should be considered to avoid missing the diagnosis of cord prolapse. Intra-amniotic infection should invoke prompt delivery. Practitioners should have a low threshold for diagnosing infection in a patient with PPROM as evidence clearly shows poor outcome in an infected neonate compared with a similar uninfected neonate.
are well informed and educated about the risks and the dismal prognosis for the neonate. Delivery is also appropriate when the mother is concerned about her own risks, especially when PPROM has occurred prior to 20 weeks' gestation. Incomplete abortion may be the appropriate term for the condition, as products of conception (the amniotic fluid) have passed the cervical opening and into the vagina in these cases. Other heroic measures such as amnioinfusion, tocolysis, and cervical plug to seal the membranes are unproven and should be considered in research protocols. Survival varies with gestational age at diagnosis (from 12% when diagnosed at 16-19 wk, to as much as 60% when diagnosed at 25-26 wk).[12] Until viability, maternal safety should be the primary concern.
Management of PPROM
The initial evaluation of premature preterm rupture of membranes (PPROM) should include a sterile speculum examination to document ROM. Cervical cultures including Chlamydia trachomatis and Neisseria gonorrhoeae and anovaginal cultures for Streptococcus agalactiae should be obtained. Maternal vital signs should be documented as well as continuous fetal monitoring initially to establish fetal status. Ultrasonographic documentation of gestational age, fetal weight, fetal presentation, and amniotic fluid index should be established. Digital examination should be avoided, but visual inspection of the cervix can accurately estimate cervical dilatation. Digital examination of the cervix with PPROM has been shown to shorten latency and increase risk of infections without providing any additional useful clinical information.[9] In certain circumstances, immediate delivery of the fetus with PPROM is indicated. These circumstances include chorioamnionitis, advanced labor, fetal distress, and placental abruption with nonreassuring fetal surveillance. If fetal lung maturity has been documented by either amniocentesis or collection of vaginal fluid, delivery should be facilitated. In a noncephalic fetus with advanced cervical dilatation (more than or equal to 3 cm), the risk of cord prolapse may also outweigh the benefits of expectant management and delivery should be considered. If after initial evaluation of the mother and fetus, they are both determined to be clinically stable, expectant management of PPROM may be considered to improve fetal outcome. The primary maternal risk with expectant management of PPROM is infection. This includes chorioamnionitis (13-60%), endometritis (2-13%), sepsis (< 1%), and maternal death (1-2 cases per 1000). Complications related to the placenta include abruption (4-12%) and retained placenta or postpartum hemorrhage requiring uterine curettage (12%).[2] The risks and potential benefits of expectant management should be discussed with the patient and her family, and informed consent should be obtained. The maternal and fetal status need to be reevaluated daily, and the safety and potential benefits of expectant management should be reassessed. If the condition remains stable, the immature fetus may benefit from expectant management, even if for a short period, to allow administration of steroids and antibiotics. Once maturity has been reached, the benefit from expectant management of PPROM is unclear and the risks of infection outweigh any potential benefits.
Amniocentesis can provide information about lung maturity accuracy and correctness of the diagnoses of PROM and infection. However, in most cases of PPROM, the amount of fluid is scant; thus, amniocentesis should be performed only by individuals with experience in performing difficult amniocentesis, and the appropriate risks with potential for fetal complications and the need for immediate delivery should be discussed with patients before attempting amniocentesis.
Revised guidelines from the Centers for Disease Control and Prevention (CDC) recommend that women with preterm PROM who are not in labor should receive intravenous group B streptococcus (GBS) coverage for at least the first 48 hours of preterm PROM latency prophylaxis, until the GBS test results obtained on admission are available.[15] However, GBS test results should not affect the duration of antibiotic therapy. If the patient completes the full 7-day course of antibiotic prophylaxis has no evidence of infection or labor, intrapartum GBS prophylaxis can be managed based on the results of the baseline GBS test at the time of preterm PROM, unless 5 weeks have passed. This is because a negative GBS test result is considered valid for 5 weeks.[16, 17]
A single course of corticosteroids is recommended for pregnant women 24-34 weeks' gestation who are at risk of preterm delivery within 7 days. A single course of antenatal corticosteroids is recommended for women with PROM before 32 weeks' gestation to reduce the risks of respiratory distress syndrome, perinatal mortality, and other morbidities. If pulmonary immaturity is documented, corticosteroid treatment at 32-33 weeks of completed gestation may be beneficial. Corticosteroid use before fetal age of viability is not recommended, as sparse data exists on the efficacy. A single rescue course of antenatal corticosteroids may be considered if the antecedent treatment was given more than 2 weeks prior, the gestational age is less than 32 6/7 weeks, and the woman is judged by the clinician to be likely to give birth within the next week. However, regularly scheduled repeat courses or more than 2 courses are not recommended. Further research regarding the risks and benefits, optimal dose, and timing of a single rescue course of steroid treatment is needed.
Tocolytics
The most common cause of labor in the setting of PPROM is underlying chorioamnionitis. The use of tocolysis in that setting is not justified. No data indicate that administering tocolysis benefits the neonate.[20] In one study, prophylactic tocolysis was found to briefly prolong latency. In another study by Jazayeri et al, latency was shorter when magnesium sulfate was given.[21] The use of tocolysis, unlike corticosteroids and antibiotics, should be considered only when a clear clinical benefit exists, such as in transport of the mother to a tertiary institution with a NICU. Many large clinical studies have evaluated neuroprotective benefits from exposure to magnesium sulfate in preterm neonates. The studies show a reduction in cerebral palsy in surviving infants who were exposed to magnesium. None of the individual studies found a benefit with regard to their primary outcome. However, available evidence suggests that magnesium sulfate given before anticipated early preterm birth reduces the risk of cerebral palsy in surviving infants. Physicians electing to use magnesium sulfate for fetal neuroprotection should develop specific guidelines regarding inclusion criteria, treatment regimens, concurrent tocolysis, and monitoring in accordance with one of the larger trials. In these studies, 12-24 hours of exposure was used with either a 4- or 6-g bolus and a maintenance dose of 1-2 g. These findings should be discussed with patients undergoing expectant management of PROM.[22] The use of tocolysis for 48 hours to administer steroids and allow acceleration of fetal lung maturity has been proposed and is being used by some obstetricians. No data support the efficacy of this practice and, as such, when used in this manner, the lack of evidence to support this practice should be discussed with patients to allow informed consent prior to the use of tocolytics and the potential complications and side effects.
Summary
PPROM is a common complication of pregnancy occurring in about 3% of all pregnancies. The obstetrician needs to be familiar with appropriate management of PPROM. High-risk consultation with a maternal-fetal medicine subspecialist should be considered in all cases to ensure appropriate current therapy is instituted. In general, the following guidelines should be followed:
ROM diagnosis needs to be confirmed. Digital vaginal examinations should be avoided. Ultrasonography should be performed to confirm gestational age, estimated fetal weight, presentation, amniotic fluid index, and fetal anatomy if not already fully evaluated. Antibiotics need to be given based on present evidence. See Medical Treatment. Corticosteroids should be given to accelerate lung maturity between 24 and 34 weeks. Informed consent should be obtained for expectant management versus delivery with careful documentation in the chart. In PPROM, the rule should be hospitalization after viability in an institution where care for a premature neonate can be provided. Maternal health is the primary indicator for the need to deliver. Any evidence of infection or maternal instability due to complications of PPROM, such as bleeding,
requires careful evaluation and determination of the appropriateness of expectant management. Fetal monitoring should be performed at least daily until delivery, and fetal well being and growth should be evaluated periodically with ultrasonography. After 32 weeks and certainly after 34 weeks' gestation, the appropriateness of expectant management of PPROM should be reevaluated individually for each case. PROM at term should be managed by delivery unless reasons exist to consider waiting for spontaneous labor. Large enough studies to document neonatal safety of expectant management of PROM at term do not exist