Enteral feeding timing and clinical outcomes in neonates with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia: a retrospective cohort study highlighting the challenge of confounding by indication.

Objective: To analyze real-world feeding decisions in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH), assess potential confounding by indication, and clarify how this bias may affect the interpretation of the association between feeding timing and clinical outcomes. Methods: We conducted a single-center retrospective cohort study involving 94 consecutive neonates with moderate to severe HIE who received standardized TH at the Children's Hospital of Chongqing Medical University from March 2024 to March 2025. These neonates were assigned to either the early enteral feeding (EEF) group (initiated during TH/rewarming, Results: The DEF group had significantly higher rates of invasive ventilation (28.3% vs. 6.3%), hemodynamic support (82.6% vs. 29.2%), and peripherally inserted central catheter (PICC) placement (50.0% vs. 14.6%) (all Conclusions: Confounding by indication may have contributed to the observed associations between early feeding and outcomes in prior studies. In clinically stable neonates with moderate HIE, early enteral feeding (≤20 mL/kg/day, with gradual advancement <20 mL/kg/day) was associated with shorter parenteral nutrition duration and reduced hospitalization costs. However, these findings should be interpreted with caution given the potential for residual confounding, and future prospective studies are needed for confirmation.