Abstract

Importance: In neonates with birth asphyxia (BA) and hypoxic-ischemic encephalopathy, therapeutic hypothermia (TH), initiated within six hours, is the only safe and established neuroprotective measure to prevent secondary brain injury. Infants born outside of TH centers have delayed access to cooling. ObjectiveTo compare in-hospital mortality, occurrence of seizures, and functional status at discharge in newborns with BA depending on postnatal transfer for treatment to another hospital within 24 hours of admission (transferred (TN) versus non-transferred neonates (NTN)).Design: Nationwide retrospective cohort study from a comprehensive hospital dataset using codes of the International Classification of Diseases, 10th modification (ICD-10). Clinical and outcome information was retrieved from diagnostic and procedural codes. Hierarchical multilevel logistic regression modeling was performed to quantify the effect of being postnatally transferred on target outcomes.Setting: All discharges from German hospitals from 2016 to 2021.Participants: Full term neonates with birth asphyxia (ICD-10 code: P21) admitted to a pediatric department on their first day of life.Exposures: Postnatal transfer to a pediatric department within 24 hours of admission to an external hospital.Main outcomes: In-hospital death; secondary outcomes: seizures and pediatric complex chronic conditions category (PCCC) ≥ 2. ResultsOf 11,703,800 pediatric cases, 25,914 fulfilled the inclusion criteria. TNs had higher proportions of organ dysfunction, TH, organ replacement therapies, and neurological sequelae in spite of slightly lower proportions of maternal risk factors. In TNs, the adjusted odds ratios (OR) for death, seizures, and PCCC ≥ 2 were 4.08 ((95 % confidence interval 3.41 – 4.89), 2.99 (2.65 – 3.38), and 1.76 (1.52 – 2.05), respectively. A subgroup analysis among infants receiving TH (n = 3,283) found less pronounced adjusted ORs for death (1.67 (1.29 – 2.17)) and seizures (1.26 (1.07 – 1.48)) and inverse effects for PCCC ≥ 2 (0.81 (0.64 – 1.02)) in TNs.Conclusion and relevanceThis comprehensive nationwide study found increased odds for adverse outcomes in neonates with BA who were transferred to another facility within 24 hours of hospital admission. Closely linking obstetrical units to a pediatric department and balancing geographical coverage of different levels of care facilities might help to minimize risks for postnatal emergency transfer and optimize perinatal care.

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