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September 24, 1997

Antibiotic Therapy for Reduction of Infant Morbidity After Preterm Premature Rupture of the Membranes: A Randomized Controlled Trial

Author Affiliations

for the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network
From the University of Tennessee, Memphis (Dr Mercer and Ms Ramsey); University of Cincinnati, Cincinnati, Ohio (Dr Miodovnik); University of Oklahoma, Oklahoma City (Dr Thurnau); University of Alabama, Birmingham (Dr Goldenberg); George Washington University, Washington, DC (Ms Das and Dr Thom); University of Southern California, Los Angeles (Ms Rabello-and Dr Paul); Bowman Gray School of Medicine, Winston-Salem, NC (Dr Meis); University of Chicago, Chicago, Ill (Dr Moawad); Ohio State University, Columbus (Dr lams); Medical University of South Carolina, Charleston (Dr Van Dorsten); Wayne State University, Detroit, Mich (Dr Bottoms); University of Colorado, Denver (Dr Merenstein); University of Pittsburgh, Pittsburgh, Pa (Dr Roberts); and the National Institute of Child Health and Human Development, Bethesda, Md (Dr McNellis).

JAMA. 1997;278(12):989-995. doi:10.1001/jama.1997.03550120049032

Context.  —Intrauterine infection is thought to be one cause of preterm premature rupture of the membranes (PPROM). Antibiotic therapy has been shown to prolong pregnancy, but the effect on infant morbidity has been inconsistent.

Objective.  —To determine if antibiotic treatment during expectant management of PPROM will reduce infant morbidity.

Design.  —Randomized, double-blind, placebo-controlled trial.

Setting.  —University hospitals of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

Patients.  —A total of 614 of 804 eligible gravidas with PPROM between 24 weeks' and 0 days' and 32 weeks' and 0 days' gestation who were considered candidates for pregnancy prolongation and had not received corticosteroids for fetal maturation or antibiotic treatment within 1 week of randomization.

Intervention.  —Interavenous ampicillin (2-g dose every 6 hours) and erythromycin (250-mg dose every 6 hours) for 48 hours followed by oral amoxicillin (250-mg dose every 8 hours) and erythromycin base (333-mg dose every 8 hours) for 5 days vs a matching placebo regimen. Group B streptococcus (GBS) carriers were identified and treated. Tocolysis and corticosteroids were prohibited after randomization.

Main Outcome Measures.  —The composite primary outcome included pregnancies complicated by at least one of the following: fetal or infant death, respiratory distress, severe intraventricular hemorrhage, stage 2 or 3 necrotizing enterocolitis, or sepsis within 72 hours of birth. These perinatal morbidities were also evaluated individually and pregnancy prolongation was assessed.

Results.  —In the total study population, the primary outcome (44.1% vs 52.9%; P=.04), respiratory distress (40.5% vs 48.7%; P=.04), and necrotizing enterocolitis (2.3% vs 5.8%; P=.03) were less frequent with antibiotics. In the GBS-negative cohort, the antibiotic group had less frequent primary outcome (44.5% vs 54.5%; P=.03), respiratory distress (40.8% vs 50.6%; P=.03), overall sepsis (8.4% vs 15.6%; P=.01), pneumonia (2.9% vs 7.0%; P=.04), and other morbidities. Among GBS-negative women, significant pregnancy prolongation was seen with antibiotics (P<.001).

Conclusions.  —We recommend that women with expectantly managed PPROM remote from term receive antibiotics to reduce infant morbidity.

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