Acute kidney injury in early preterm neonates with severe birth asphyxia: Incidence, predictors and role of caffeine initiation timing

Background Acute kidney injury (AKI) is a serious complication in early preterm neonates with severe birth asphyxia, yet its incidence and predictors in this specific population remain incompletely characterised. The effect of caffeine initiation timing on AKI outcomes has not been prospectively examined. Methods This prospective observational cohort study enrolled 112 neonates of 28–32 weeks gestational age with severe birth asphyxia admitted to a level III neonatal intensive care unit (NICU) in South India (February–August 2025). AKI was defined by neonatal KDIGO (nKDIGO) criteria. Neonates were categorised according to early (≤6 h) or delayed (>6 h) caffeine initiation; delayed initiation was primarily associated with outborn status and haemodynamic instability at admission. Independent predictors of AKI were identified by multivariate logistic regression with bootstrap confidence intervals. Results AKI was diagnosed in 48 of 112 neonates (42.9%; 95% CI 34.1–52.1%). Stage 1 disease predominated (47.9% of AKI cases), with onset in the first 48 h in the majority. On multivariate analysis, early caffeine initiation was independently associated with reduced odds of AKI (aOR 0.22; 95% CI 0.11–0.43; p < 0.001), and cumulative fluid balance at 48 h was associated with increased odds (aOR 6.30 per SD [21.8 ml/kg]; 95% CI 4.27–13.05; p < 0.001). AKI incidence was 24.1% in the early caffeine group versus 60.3% in the delayed group ( p < 0.001), with an observed difference in AKI incidence of 36.2%. In-hospital mortality was higher in the AKI group (10.4% vs 0%; p = 0.013). Conclusions AKI occurred in 42.9% of early preterm neonates with severe birth asphyxia. Early caffeine initiation (≤6 h) was associated with reduced AKI incidence. Positive fluid balance at 48 h was an independent predictor. These findings suggest early caffeine initiation as a potentially modifiable factor associated with reduced AKI risk and identify fluid balance as a clinically relevant early marker in this high-risk population.