Indomethacin dose-interruption and maternal chorioamnionitis are risk factors for indomethacin treatment failure in preterm infants with patent ductus arteriosus

Abstract

Background: Indomethacin has been used as the primary pharmacotherapeutic agent for the closure of patent ductus arteriosus (PDA) in preterm infants. However, it is commonly observed that infants often respond differently to indomethacin treatment with some requiring multiple courses of the drug and subsequently surgical ligation. Objectives: To explore common variables that could be associated with failure of a primary course of indomethacin for PDA in preterm infants.Methods: We examined 83 preterm infants who received intravenous indomethacin for PDA treatment from 2010 to 2013. We identified those who failed primary pharmacotherapy and required subsequent courses or surgical ligation. A number of perinatal/neonatal variables in the infants with and without primary indomethacin failure were compared initially for univariate analysis. Following the univariate analysis, those variables which had a significant difference between the two groups were selected to carry out logistic regression analysis to find out independent risk factors for indomethacin failure. Results: Of 77 infants analyzed, 36 (46.7%) had a primary indomethacin failure and nine infants (11.7%) underwent surgical ligation. Univariate analysis revealed that infants with primary indomethacin failure were significantly more preterm, were more likely to be males, did not receive a complete course of antenatal corticosteroids, their mothers had clinical chorioamnionitis and indomethacin dose interruption was documented during clinical care. The multivariate logistic regression analysis showed that dose interruption (odds ratio [OR]: 27.14; 95% confidence interval [CI]: 5.94, 124.07) and clinical chorioamnionitis (OR: 7.80; 95% CI: 1.73, 35.00) were independent risk factors for indomethacin failure. Conclusion: Indomethacin dose interruption and clinical chorioamnionitis appear to be independent risk factors for primary indomethacin failure in preterm infants.