Acute Kidney Injury and Neurodevelopmental Outcomes in Extremely Premature Neonates: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Extremely low gestational age neonates are at risk of neurodevelopmental impairment (NDI). Limited data exist on the association between acute kidney injury (AKI) and NDI in this population. Objective: To describe neurodevelopmental outcomes in a cohort of extremely low gestational age neonates with AKI. Design, Setting, and Participants: This study is a secondary analysis of the Preterm Erythropoietin Neuroprotection Trial (PENUT), a phase 3 placebo-controlled randomized clinical trial of erythropoietin conducted from December 2013 to September 2016 in 30 neonatal intensive care units in the US. Participants were extremely premature neonates born at 24 to 27 weeks' gestation. Data were analyzed in February 2024. Exposure: AKI was the primary exposure. Key aspects of AKI were evaluated in this secondary analysis, including the stage of AKI, and timing (early defined as within the first 7 days after birth; late defined as after the first 7 days). Main Outcomes and Measures: The primary outcome for this secondary analysis was the composite outcome of death or moderate to severe NDI (moderate to severe cerebral palsy, Bayley Scales of Infant Development Third Edition [BSID-III] cognitive score <85, or BSID-III motor score <85) at 22 to 26 months' corrected gestational age. The secondary outcomes were the individual components of the composite outcome. Results: Of 941 enrolled neonates in PENUT, 660 had a follow-up visit with available BSID-III performed per protocol during the follow-up window of 22 to 26 months' corrected gestational age. Among the survivors, 256 neonates (39%) had AKI. Neonates with AKI had significantly lower mean (SD) GA (25.1 [1.1] weeks vs 25.7 [1.1] weeks), lower birth weight (755.3 [180.9] g vs 824.8 [189.4] g), were more likely to have an Apgar score of less than 5 at 5 minutes (24.1% vs 17.1%), and 57% were male. Those with AKI had higher odds of the composite outcome (adjusted odds ratio [AOR], 1.53; 95% CI, 1.07-2.18) and higher odds of cognitive BSID-III scores less than 85 (AOR, 1.94; 1.25-2.99). Neither the stage nor timing of AKI had an association with NDI. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, AKI in preterm infants was associated with poor neurodevelopmental outcomes at 22 to 26 months' corrected gestational age that was assessed by BSID-III scores. Trial Registration: ClinicalTrials.gov Identifier: NCT01378273.