Gestational Age-Dependent Variations in Effects of Prophylactic Indomethacin on Brain Injury and Intestinal Injury.

Objective To evaluate the impact of prophylactic indomethacin on early death ( Study design Multicenter retrospective cohort study of neonates (N=12515) born at 230 to 286 weeks’ GA, admitted to neonatal intensive care units participating in the Canadian Neonatal Network who received prophylactic indomethacin started within the first 12 hours after birth. Univariate and multivariate analysis compared the composite outcomes of early death or severe neurological injury and early death or spontaneous intestinal perforation. Results Of 12515 eligible neonates, 1435 (11.5%) were exposed to prophylactic indomethacin; recipients were of lower GA and birth weight and had higher severity of illness (Score for Neonatal Acute Physiology, SNAPII-PE score) on admission compared with non-recipients. After adjusting for confounders, prophylactic indomethacin was associated with reduced odds of early death or severe neurological injury and early death or spontaneous intestinal perforation in neonates born at 23 to 24 weeks’ GA. However, prophylactic indomethacin was associated with increased odds of early mortality or spontaneous intestinal perforation for neonates born at 26 to 28 weeks’ GA. Conclusions Prophylactic indomethacin use was associated with benefit in neonates born at 23 to 24 weeks GA, but with harm at 26 to 28 weeks GA. Given the observation of significantly improved survival, a randomized controlled trial is needed to investigate the effect of prophylactic indomethacin in babies born at 23 to 25 weeks’ GA.