The effect of antenatal indomethacin on extremely preterm neonatal kidney function

Abstract

Introduction/Objective: Indomethacin is an effective tocolytic to prevent extremely preterm birth. Prior studies have associated antenatal indomethacin exposure with adverse preterm neonatal intestinal and neurological outcomes. Indomethacin is a nephrotoxic medication that may also affect preterm neonatal kidneys. We sought to evaluate the effect of antenatal indomethacin on extremely preterm neonatal kidney function and acute kidney injury (AKI) in the first week of age. Methods: A retrospective cohort study was conducted on neonates born < 29 weeks at a level III neonatal intensive care unit (NICU) from January 2018-April 2019. Serum creatinine (sCr) values and urine output (UOP) in the first seven days of age and the neonate’s peak serum creatinine within the first 30 days were evaluated. Neonatal AKI was defined by the modified neonatal Kidney Disease Improving Global Outcomes (KDIGO) definition including urine output. Results: 17 of the 55 neonates meeting criteria for this study were exposed to indomethacin. The average gestational age at birth was similar between study groups. Maternal preeclampsia was more common among women who did not receive indomethacin (p = 0.021). Indomethacin exposed neonates received more gentamicin (p = 0.024). Overall, staging of the neonatal AKI did not differ significantly between the study groups, regardless of how it was quantified (sCr or UOP) or the duration of time in which the injury developed (7 days or 30 days). Separate analysis of sCr and UOP in the first seven days also failed to show any statistically significant differences between the two groups. Conclusion: In this small cohort study of extremely preterm neonates, those born to mothers treated with indomethacin did not have an increased incidence of AKI compared to neonates born to unexposed mothers. Although no statistically significant differences in UOP or sCr were found, they deserve further evaluation in adequately powered prospective clinical trials. Future prospective studies with long-term follow-up utilizing advanced biomarkers are needed to determine how antenatal indomethacin affects extremely preterm neonatal kidney function in the NICU, during childhood, and as adults.