Methods We conducted a secondary analysis of

Methods We conducted a secondary analysis of an extant cohort of 580 infants <32 weeks of gestational age. All infants in this study were part of a prospective, National Institutes of Health–funded study of the preterm microbiome and risk of NEC, sepsis, and death. Study infants were enrolled from 2 level III NICUs in Cincinnati, Ohio, and 1 level III NICU in Birmingham, Alabama, from 2009 to 2012. Enrollment criteria included delivery <32 weeks of gestation, being free of congenital anomalies, and survival free of NEC in the first week of life. One patient was excluded because of unknown maternal antibiotic status. Data collection followed the protocol of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network registry. Infants were enrolled immediately after delivery and were followed up until discharge, transfer, 120 days postpartum, or death. Maternal and infant data were abstracted from medical records. The institutional review boards at the 3 participating hospitals approved the study. Maternal antibiotic exposure was defined as antibiotic treatment within 72 hours before delivery. Indications for maternal antibiotic exposure included cesarean delivery, group B streptococci (GBS) prophylaxis, premature rupture of membranes, chorioamnionitis, and to prolong pregnancy (latency). Maternal antibiotic exposure did not include Fmoc-Ala-OMe synthesis given after the time of delivery or antibiotic initiated by surgeons during (but not before) cesarean delivery. Early empirical neonatal antibiotic exposure was defined as antibiotic treatment initiated within the first postnatal day without culture-identified infection. The duration of early antibiotic therapy was defined as the total number of continuous days of administration of antibiotics with sterile culture results. Empiric infant antibiotics used in this cohort were ampicillin and gentamicin, with empiric infant antibiotic exposure defined as either low (<5 days) or high (>5 days).3, 5, 6, 8 NEC was defined via Bell stage II or III criteria. Spontaneous intestinal perforation was excluded by including only cases of NEC that occurred after 7 days of life. LOS was defined as a positive blood, cerebrospinal fluid, urine, or sterile site culture after the third postnatal day. If patients were diagnosed with NEC or LOS or died after day 7 of their NICU course, they were considered positive for the combined outcome, NEC, sepsis or death (termed NSD).
Results Clinical and demographic characteristics of study infants and their mothers are presented in , compared by the number of maternal antibiotics used. Of the 580 infants included in the study, 362 (62.4%) were delivered to mothers who had received antibiotics in the 72 hours before delivery. Infant birth weight was similar across maternal antibiotic exposure groups, as was gestational age, infant sex, and race. The median gestational age at the time of delivery in both maternal exposure groups was 28 weeks. Pre-eclampsia was more common among mothers without antibiotic exposure (46.3% and 24.5% respectively, P < .001). Three hundred sixty-three infants (62.5%) were born via cesarean delivery, which was more common among mothers who were not exposed to antibiotics (P < .001). Antenatal corticosteroids were more regularly used in mothers who had antibiotic exposure (P < .001). Clinical chorioamnionitis was greater among mothers who received antibiotics (P < .001). Human milk feeding did not differ by maternal antibiotic exposure. Overall, 135 (23.2%) study infants received ≥5 days of postnatal empiric antibiotic. Infants who were born with prenatal antibiotic exposure were more likely to experience high postnatal empiric antibiotic exposure than infants without prenatal antibiotic exposure (P = .002). Among the 362 infants exposed to prenatal antibiotic, 100 (27.5%) had high postnatal antibiotic exposure, whereas among the 218 infants with no prenatal antibiotic exposure, 35 (16.0%) had high postnatal antibiotic exposure.