Association of caffeine with renal and other short-term outcomes in neonates with hypoxic-ischaemic encephalopathy undergoing therapeutic hypothermia.

OBJECTIVE

To evaluate the association of caffeine with renal and other short-term clinical outcomes in neonates with moderate or severe hypoxic-ischaemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH).

STUDY

DESIGN

This retrospective cohort study included neonates born at ≥36 weeks gestational age with moderate or severe HIE treated with TH at our centre between January 2013 and December 2022. In 2019, there was a practice change to administer a single intravenous 20 mg/kg caffeine citrate dose for moderate/severe HIE, forming two cohorts (non-caffeine vs caffeine). The primary outcome was acute kidney injury (AKI), defined by modified Kidney Disease: Improving Global Outcomes criteria. Secondary outcomes included daily serum creatinine, blood-urea nitrogen (BUN), urine output, HIE-pattern lesion on brain-MRI, early EEG background grade, seizures, duration of mechanical ventilation, length of stay, tube-feeding at discharge and in-hospital mortality.

RESULTS

85 neonates met the inclusion criteria; 38 received caffeine, and 47 did not. AKI incidence was lower in the caffeine group (29% vs 47%), although not statistically significant (p=0.09). BUN levels and serum creatinine levels were significantly lower in the caffeine group on days 3-5 (p<0.05). MRI abnormalities consistent with HIE were more frequent in the caffeine group (60% vs 36%, p=0.028), particularly in infants with moderate HIE (p=0.004). EEG background profiles differed, with caffeine-exposed neonates displaying fewer severe (34% vs 65%) and more mild-to-moderate patterns. No significant differences were noted in other secondary outcomes.

CONCLUSION

Caffeine during TH lowered serum creatinine and BUN but did not significantly reduce AKI and was associated with higher rates of MRI lesions. Prospective, dose-controlled trials with pharmacokinetic monitoring and long-term neurodevelopmental follow-up are needed to clarify caffeine's renal benefits and neurological safety in neonatal HIE.