ANTIBIOTIC-THERAPY FOR REDUCTION OF INFANT MORBIDITY AFTER PRETERM PREMATURE RUPTURE OF THE MEMBRANES - A RANDOMIZED CONTROLLED TRIAL

Context.-Intrauterine infection is thought to be one cause of preterm premature rupture of the membranes (PPROM). Antibiotic therapy has bee n shown to prolong pregnancy, but the effect on infant morbidity has b een inconsistent. Objective.-To determine if antibiotic treatment duri ng expectant management of PPROM will reduce infant morbidity. Design. -Randomized, double-blind, placebo-controlled trial. Setting.-Universi ty hospitals of the National Institute of Child Health and Human Devel opment 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 pr egnancy prolongation and had not received corticosteroids for fetal ma turation or antibiotic treatment within 1 week of randomization. Inter ventions.-Intravenous ampicillin (2-g dose every 6 hours) and erythrom ycin (250-mg dose every 6 hours) for 48 hours followed by oral amoxici llin (250-mg dose every 8 hours) and erythromycin base (333-mg dose ev ery 8 hours) for 5 days vs a matching placebo regimen, Group B strepto coccus (GBS) carriers were identified and treated, Tocolysis and corti costeroids 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 distres s, severe intraventricular hemorrhage, stage 2 or 3 necrotizing entero colitis, or sepsis within 72 hours of birth, These perinatal morbiditi es were also evaluated individually and pregnancy prolongation was ass essed. 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), an d necrotizing enterocolitis (2.3% vs 5.8%; P=.03) were less frequent w ith antibiotics. In the GBS-negative cohort, the antibiotic group had less frequent primary outcome (44.5% vs 54.5%; P=.03), respiratory dis tress (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-nega tive women, significant pregnancy prolongation was seen with antibioti cs (P<.001). Conclusions.-We recommend that women with expectantly man aged PPROM remote from term receive antibiotics to reduce infant morbi dity.