Multiple courses of indomethacin and neonatal outcomes in premature infants.

The objective of this retrospective cohort study was to determine patent ductus arteriosus (PDA) closure rate with multiple short courses (three doses) of postnatal indomethacin and compare neonatal outcomes in infants who received two versus three courses of indomethacin for PDA closure. Infants <34 weeks' gestational age born between January 2000 and December 2004 at the University of Maryland Medical Center and who received two or more short courses of indomethacin were included. Outcome measures were ductal closure rate and neonatal outcomes. Of 61 infants who were identified to have received two or more courses of indomethacin, 26 infants closed their ductus after the second course (response rate, 42%). Of the 35 infants who failed ductal closure after two courses, 11 infants had their ductus ligated and 23 received a third course of indomethacin. Of 23 who received a third course, 10 closed their ductus (response rate, 43%). There was no significant difference in the incidence of chronic lung disease, severe retinopathy of prematurity, necrotizing enterocolitis, renal function, or mortality between infants who received two and those who received three courses of indomethacin. Infants exposed to three courses of indomethacin had a statistically nonsignificant increased incidence of periventricular leukomalacia (p = 0.08; adjusted odds ratio = 4.8; 95% CI, 0.8-30) and remained in the hospital for a longer duration (p = 0.02) compared to infants exposed to two courses of indomethacin. We conclude that multiple courses of indomethacin may be associated with a ductal closure. However, the requirement for a third course may be associated with an increased risk of periventricular leukomalacia.