Renal Effects of Aminophylline in Cooled Neonates with Hypoxic-Ischemic Encephalopathy

This study aimed to evaluate the renal effects and safety of adjunct aminophylline therapy in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH).

This retrospective cohort study included neonates ≥36 weeks and >2,000 g diagnosed with HIE and treated with TH between May 2018 and January 2025. Infants were classified into two groups: those receiving TH alone (TH group) and those given a single intravenous 8 mg/kg dose of aminophylline at the initiation of cooling (TH + A group). Demographic, perinatal, and laboratory characteristics were collected, and serial serum creatinine (sCr) measurements at 24, 48, 72, and 96 hours were analyzed to compare renal and clinical outcomes.

A total of 297 infants were included (TH: 210; TH + A: 87). Baseline demographic and clinical characteristics were similar between the groups. While sCr values at each fixed time point did not significantly differ, repeated-measures analysis demonstrated a significantly steeper decline in sCr over time in the TH + A group (p < 0.001). Convulsions were more frequent in the TH + A group (23.0 vs. 10.5%, p = 0.005), whereas mortality and other major clinical outcomes were comparable.

Aminophylline administration at the start of TH was associated with a steeper decline in serum creatinine, suggesting a potential renoprotective effect in neonates with HIE. However, the higher frequency of convulsions emphasizes the need for careful neurological monitoring. Further studies are needed to clarify optimal dosing and the balance between potential renal benefits and neurological risks.

· Aminophylline did not change creatinine at fixed time points in cooled HIE.. · A steeper creatinine decline with aminophylline suggests a more favorable pattern of renal recovery.. · Convulsions were more frequent with aminophylline, requiring close monitoring..