Short-term outcomes of asphyxiated neonates depending on outborn versus inborn status

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. Objective: To compare in-hospital lethality, occurrence of seizures, and functional status at discharge in newborns with BA depending on postnatal transfer to another hospital within 24 hours of admission (outborn versus inborn). 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 modelling was performed to quantify the effect of being outborn on target outcomes. Setting: All admissions to German hospitals 2016 - 2021. Participants: Full term neonates with birth asphyxia (ICD-10 code: P21) admitted to a pediatric department on their first day of life. Exposures: Transfer to a pediatric department within 24 hours of admission to an external hospital (=outborn). Main outcomes: In-hospital death; secondary outcomes: seizures and pediatric complex chronic conditions category (PCCC) >= 2. Results: Of 11,703,800 pediatric cases, 25,914 fulfilled the inclusion criteria. Outborns had higher proportions of organ dysfunction, TH, organ replacement therapies, and neurological sequelae in spite of slightly lower proportions of maternal risk factors. 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, if infants were outborn compared to inborn. 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 inversed effects for PCCC >= 2 (0.81 (0.64 - 1.02)). Conclusion and relevance: This 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. Obstetrical units should be linked to a pediatric department to minimize risks of postnatal emergency transfer. Collaboration and coordination between centers should be improved to balance geographical coverage of different level care facilities.