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Chock VY, Cho SH, Frymoyer A. Aminophylline for renal protection in neonatal hypoxic-ischemic encephalopathy in the era of therapeutic hypothermia. Pediatr Res. 2020 Jun 5. pii: 10.1038/s41390-020-0999.

Background: Neonates with hypoxic-ischemic encephalopathy (HIE) frequently develop acute kidney injury (AKI). Aminophylline has been shown to reduce severe renal dysfunction in neonates after perinatal asphyxia. However, the effect of aminophylline on renal function in neonates undergoing hypothermia has not been studied.

Methods: A single-center, retrospective chart review of neonates cooled for moderate/severe HIE who received aminophylline for AKI was conducted to assess changes in urine output (UOP) and serum creatinine (SCr). Comparisons were also made to control neonates matched for hours of life who were cooled but unexposed to aminophylline.

Results: Sixteen neonates cooled for HIE received aminophylline starting at 25 ± 14 h of life. Within 12 h of starting aminophylline, UOP increased by 2.6 ± 1.9 mL/kg/h. SCr declined by 0.4 ± 0.2 mg/dL in survivors over the first 4 days. When compared to control neonates, UOP increase was greater in the aminophylline group (p < 0.001). SCr declined in survivors in both groups, although baseline SCr was higher in the aminophylline group.

Conclusions: Aminophylline use in neonates with HIE undergoing hypothermia was associated with an increase in UOP and a decline in SCr. A randomized trial will be needed to establish a potential renal protective role of aminophylline.

Impact: The renal protective effect of aminophylline in neonates with HIE has not yet been studied in the context of therapeutic hypothermia.Aminophylline exposure in neonates cooled for HIE was associated with increased UOP and a similar decline in SCr when compared to control infants unexposed to aminophylline.Improved renal function after receiving aminophylline in this observational cohort study suggests the need for future randomized trials to establish the potential benefit of aminophylline in the HIE population undergoing hypothermia.

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