Objectives To assess variability in continuation of antiseizure medication (ASM) at discharge and to evaluate if continuation of ASM at discharge is associated with death or disability among infants with hypoxic-ischaemic encephalopathy (HIE) and seizures.
Design Retrospective study of infants enrolled in three National Institute of Child Health and Human Development Neonatal Research Network Trials of therapeutic hypothermia.
Setting 22 US centres.
Patients Infants with HIE who survived to discharge and had clinical or electrographic seizures treated with ASM.
Exposures ASM continued or discontinued at discharge.
Outcomes Death or moderate-to-severe disability at 18–22 months, using trial definitions. Multivariable logistic regression evaluated the association between continuation of ASM at discharge and the primary outcome, adjusting for severity of HIE, hypothermia trial treatment arm, use of electroencephalogram, discharge on gavage feeds, Apgar Score at 5 min, birth year and centre.
Results Of 302 infants included, 61% were continued on ASMs at discharge (range 13%–100% among 22 centres). Electroencephalogram use occurred in 92% of the cohort. Infants with severe HIE comprised 24% and 22% of those discharged with and without ASM, respectively. The risk of death or moderate-to-severe disability was greater for infants continued on ASM at discharge, compared with those infants discharged without ASM (44% vs 28%, adjusted OR 2.14; 95% CI 1.13 to 4.05).
Conclusions In infants with HIE and seizures, continuation of ASM at discharge varies substantially among centres and may be associated with a higher risk of death or disability at 18–22 months of age.
- Intensive Care Units, Neonatal
- Infant Development
Data availability statement
Data are available upon reasonable request. Details on data sharing are available at: https://neonatal.rti.org/index.cfm?fuseaction=DataRequest.Home.
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Collaborators Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.
Contributors ES made substantial contributions to the manuscript including conception and design, analysis and interpretation of the data, and drafting of the manuscript. SS made substantial contributions to the manuscript including acquisition of data, analysis and interpretation of the data, and critical revision of the manuscript for important intellectual content and obtaining funding. SAM and AD made substantial contributions to the manuscript including statistical analysis, analysis and interpretation of the data, as well as critical revision of the manuscript for important intellectual content. SH, LFC and IA-C (deceased) made substantial contributions to the manuscript including analysis and interpretation of data, critical revision of the manuscript for important intellectual content, and supervision of the project. CJW, AD, KVM, NM and AL made substantial contributions to the manuscript including analysis and interpretation of the data, as well as critical revision of the manuscript for important intellectual content. RMP made substantial contributions to the manuscript including conception and design, analysis and interpretation of data, critical revision of the manuscript for important intellectual content, obtaining funding and supervision of the project. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
Funding The National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Center for Research Resources (NCRR), and the National Center for Advancing Translational Sciences (NCATS) provided grant support for the Neonatal Research Network’s Induced Hypothermia, Late Hypothermia, and Optimizing Cooling trials through the following cooperative agreements and awards: U10 HD27904, U10 HD21364, U10 HD68284, U10 HD27853, UL1 TR77, U10 HD40492, UL1 TR1117, U10 HD27851, UL1 TR454, U10 HD27856, UL1 TR6, U10 HD21373, U10 HD68278, U10 HD36790, U10 HD27880, UL1 TR93, U10 HD53119, M01 RR54, U10 HD34216, M01 RR32, U10 HD68270, U10 HD40461, U10 HD53109, UL1 TR442, U10 HD21397, M01 RR16587, U10 HD53089, UL1 TR41, U10 HD68244, U10 HD68263, UL1 TR42, U10 HD40689, U10 HD53124, U10 HD21385, U10 HD27871, UL1 TR142.
Disclaimer While NICHD staff had input into the study design, conduct, analysis, and manuscript drafting, the comments and views of the authors do not necessarily represent the views of NICHD, the National Institutes of Health, the Department of Health and Human Services, or the US Government.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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