Renal impairment associated with indomethacin treatment for patent ductus arteriosus in extremely preterm neonates - is postnatal age at start of treatment important?

Objective. To study serum creatinine (SCr) levels following indomethacin for patent ductus arteriosus (PDA) closure in extremely preterm neonates in relation to postnatal age at the start of treatment.Methods. This was a retrospective ( January 2000 - December 2002) analysis of data on preterm neonates ( gestation 529 weeks) who received indomethacin for PDA. Pre-existing renal malformation and/or impairment and high serum levels of nephrotoxic drugs were criteria for exclusion.Results. Indomethacin was commenced at postnatal age <7 days and >= 7 days in 60 ( group 1) and 30 ( group 2) neonates, respectively. The median (Q1, Q3) gestational age and birth weight for group 1 and group 2 neonates were 25 ( 23, 27) vs. 25 ( 24, 26) weeks and 740 ( 620, 909) vs. 780 ( 663, 966) grams, respectively. Postnatal age 57 days at start of indomethacin was associated with higher baseline (0.083 (0.074, 0.090) vs. 0.073 (0.054, 0.083) mmol/L, p = 0.001) and peak SCr levels (0.099 (0.089,0.109) vs. 0.090 (0.064, 0.104) mmol/L, p = 0.015). Logistic regression analysis controlling for gestational age and baseline SCr level indicated that postnatal age >= 7 days was a risk factor for elevated SCr after indomethacin (OR = 13.4, 95% CI: 3.8 - 46.6, p<0.001).Conclusion. Postnatal age >= 7 days at the start of indomethacin is a predictor of a significant rise in SCr in extremely preterm neonates.