Maternal and Neonatal Factors Associated with Indomethacin-induced Ductal Closure in Extremely-Low-Birth-Weight Infants

Objective: The purpose of this study was to identify predictors of ductal closure in ELBW infants treated with indomethacin.

Methods: A single-center, retrospective cohort of ELBW infants treated with indomethacin for patent ductus arteriosus (PDA) were included. Predictors of PDA closure were identified using multivariable adjusted logistic regression.

Results: One hundred and five infants with a PDA were treated with indomethacin. Primary PDA closure with one course of indomethacin occurred in 61.9%. The rate of primary PDA closure was lower in infants with gestational age (GA) < 28 weeks compared to infants ≥ 28 weeks (58.1% vs 91.7%, p =0.03). Multivariable logistic regression model identified PDA size (OR 0.29, 95% CI 0.11-0.74, p =0.009) and exposure to antenatal indomethacin (OR 0.28, 95% CI 0.08–0.99, p =0.048) and magnesium (OR 0.31, 95% CI 0.12–0.82, p =0.019) as significant predictors for failure of ductal closure in infants treated with indomethacin. Infants with failed PDA closure were more likely to have moderate/severe bronchopulmonary dysplasia, severe intraventricular hemorrhage, and longer duration of hospitalization (p <0.05).

Conclusions: Large PDA and antenatal indomethacin and magnesium were predictors for failure of ductal closure with indomethacin. The negative association between antenatal indomethacin and magnesium on ductal closure with postnatal indomethacin warrants further investigation regarding routine use in mothers at risk for preterm delivery. Future studies focusing on developing predictive models to identify ideal candidates for indomethacin within the ELBW population could reduce the burden of the disease and improve overall outcomes.