The Risk of Necrotizing Enterocolitis After Indomethacin Tocolysis

Abstract

BACKGROUND: Postnatal indomethacin is reportedly associated with an increased incidence of necrotizing enterocolitis (NEC) in preterm infants. Because indomethacin readily crosses the placenta, we hypothesized that antenatal indomethacin (AI) would increase the risk for NEC in preterm infants. OBJECTIVE: The goal of this study was to explore the association between AI and NEC in preterm infants. METHODS: Medical records of preterm infants, 23 to 32 weeks' gestational age, without major congenital anomalies, were reviewed. Maternal and neonatal data were abstracted. Association of AI within 15 days before delivery (predictor variable) and classification of NEC according to modified Bell's stage 2a or higher in the first 15 days after delivery (early NEC [primary outcome variable]) was explored by using bivariate analyses, multivariate logistic regression, and propensity score analysis. RESULTS: Of 628 eligible infants, 63 received AI and 28 developed early NEC. AI exposure was significantly associated with multiple gestation, race, antenatal corticosteroids and magnesium sulfate, lower birth weight and gestational age, umbilical arterial catheter placement, respiratory distress syndrome, postnatal vasopressors and antibiotics, patent ductus arteriosus, sepsis, NEC, intraventricular hemorrhage, and mortality. On multivariate logistic regression controlling for covariates, AI was significantly associated with early NEC (adjusted odds ratio: 7.193 [95% confidence interval: 2.514–20.575]; number needed to harm: 5). The results remained significant when analyses were repeated using AI exposure within 5 days before delivery as a predictor variable; on analyses stratified according to gestational age; and on propensity score analysis. CONCLUSIONS: AI was associated with NEC in preterm infants in the first 15 days of life in this study, as were multiple other clinical factors.