Does indomethacin exposure increase risk for chronic kidney disease in very low birth weight infants?

Objective: To determine the association between indomethacin exposure and risk for chronic kidney disease defined by hypertension in very low birth weight (VLBW) infants. Study design: Retrospective chart review including VLBW infants admitted from January 2011-December 2014 at the University of Colorado Level III Neonatal Intensive Care Unit (NICU). Data collected included: indomethacin administration, presence of hypertension, and clinically relevant confounders. The primary outcome was hypertension at discharge. Logistic regression was performed to determine association between indomethacin and hypertension while controlling for confounding variables. Result: 503 VLBW infants were admitted to the NICU during study time period (19.4% of admissions). 202 infants were excluded (death, congenital anomaly, intrauterine growth restriction, prenatal indomethacin exposure, or missing data), with 301 infants included in final analysis. 132 (44%) received indomethacin during their NICU course. Infants exposed to indomethacin had lower gestational ages (26.4±1.9 weeks vs. 29.1±1.9, P<0.0001) and birth weights (921.8±226.7 g vs. 1244.5±214.7, P<0.0001) compared to non-exposed infants. Exposed infants had an increased incidence of hypertension compared to non-exposed (6% vs. 2%). After adjusting for confounders, this was not statistically significant (P=0.12). Conclusions: In VLBW infants, indomethacin is not independently associated with increased rates of hypertension at discharge. Infants receiving indomethacin tended to be those already at highest risk for long-term renal impairment given lower gestational age and birth weight, and increased illness severity. More judicious use of indomethacin and further studies of long-term renal functionare warranted in this vulnerable population.