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.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study was funded by the Stiftung Universitaetsmedizin Essen

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

An existing routine data set from the Federal Statics Office of Germany available at the research data center Duesseldorf was used. No ethics approvement was necessary according to German law. All results were checked by the Federal Data Protection Officer.

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Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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Data Availability

Data produced in this study cannot be provided upon request because the original data have to remain at the research data center. Any qualified researcher can file a request to access the data set at the site.

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