BACKGROUND: The relationship between early antibiotic exposure, necrotizing enterocolitis (NEC), and growth faltering (GF) in extremely preterm infants is unknown. METHODS: We evaluated the association between peripartum and postnatal antibiotic exposure in the first week after birth with NEC and GF in this secondary analysis of Preterm Erythropoietin Neuroprotection Trial subjects. NEC was defined as Bell's stage ≥ IIA
GF was defined as decreased weight, length, or head circumference (HC) z-score from birth to discharge of <
-0.8. Multivariable analyses were adjusted with maternal and infant factors. RESULTS: A total of 891 infants survived the first week and were included in the NEC analyses, while 828 infants survived to discharge and were included in the growth analyses. For every 1-day increase in infant antibiotic exposure during the first week after birth, there was a significantly increased adjusted hazard of NEC (aHR/day 1.14 [1.01-1.28], p = 0.034). Antibiotics for 3-4 days and 5-7 days total in the first week were associated with increased odds of weight GF (aOR 1.90 [1.21-2.99], aOR 2.32 [1.44-3.74]), length GF (aOR 1.76 [1.22-2.59], aOR 1.88 [1.26-2.80]), and HC GF (aOR 1.75 [1.08-2.84], aOR 1.87 [1.14-3.08]). CONCLUSION: Increased antibiotic exposure in the first week after birth was associated with NEC and GF risk. IMPACT: In this post-hoc analysis of a large multi-site trial, we found infant antibiotic exposure in the first week after birth was associated with an increased hazard of necrotizing enterocolitis in the extremely preterm infant after adjusting for maternal and infant factors. First week antibiotic exposure in the extremely preterm infant was associated with an increased odds of weight, linear, and head circumference growth faltering after adjusting for maternal and infant factors. These findings encourage the judicious use of early antibiotics in extremely preterm infants.