Results Summary
What was the research about?
Every year, about 16,000 newborns in the United States have seizures. A seizure is abnormal electrical activity in the brain. At least half of newborns who have seizures will have long-term health problems, such as epilepsy or an intellectual disability.
Medicines can treat seizures. But these medicines can have serious side effects and may harm children’s brain development. Questions remain about how long newborns can safely take these medicines.
In this study, the research team wanted to learn if stopping seizure medicines before newborns went home from the hospital would affect their health and their parents’ well-being. The team compared newborns who took medicines only in the hospital versus those who continued the medicines after they went home.
What were the results?
Of newborns in the study, 36 percent took medicines only in the hospital, and 64 percent took medicines in the hospital and at home. Among newborns who took medicines at home,
- 68 percent took phenobarbital
- 13 percent took levetiracetam
- 20 percent took more than one medicine
After two years, the two groups didn’t differ in
- Functional development, which included physical abilities, communication, skills like feeding and dressing, and social awareness
- Motor disability, or how well children could walk without stumbling or falling
- The risk of developing epilepsy
- Time newborns spent in the hospital
Further analyses by the research team found differences in parents’ well-being between the two groups. Parents of newborns who took medicines only in the hospital reported a lower impact of illness on the family. But they reported worse anxiety, depression, and resilience.
Who was in the study?
The study included 270 children who received care at nine hospitals across the United States. Of these, 63 percent were White, 12 percent were Black, 7 percent were Asian, 3 percent were more than one race, and 15 percent didn’t report a race; 54 percent were boys.
What did the research team do?
The research team enrolled children who were treated for seizures in the hospital as newborns and their parents. Doctors had worked with parents to choose if newborns took seizure medicines only in the hospital or also at home.
Parents completed surveys when children were 12, 18, and 24 months old. The research team reviewed health records to collect data about the newborns’ health and hospital stays.
Parents of newborns who had seizures and people from advocacy groups helped design and carry out the study.
What were the limits of the study?
The study looked at children’s health for two years; health differences could appear when children are older. Fewer infants developed epilepsy than expected, which made it hard to find differences in the risk of developing the illness.
Future research could follow children who had treatment for seizures as newborns for a longer time.
How can people use the results?
Doctors and parents can use these results when considering how to treat newborns with seizures.
Professional Abstract
Objective
To compare the effect of discontinuing versus maintaining treatment with antiseizure medications after hospital discharge on functional development among newborn infants with acute symptomatic seizures
Study Design
| Design Element | Description |
|---|---|
| Design | Observational: cohort study |
| Population | 270 infants less than 44 weeks postmenstrual age (the gestational age plus time elapsed since birth) with acute symptomatic neonatal seizures |
| Interventions/ Comparators |
|
| Outcomes |
Primary: functional development Secondary: diagnosis and timing of epilepsy; motor function; hospital length of stay; parent-reported outcomes of parent depression, anxiety, quality of life, posttraumatic stress, resilience, and impact of illness on family |
| Timeframe | 2-year follow-up for primary outcome |
This prospective cohort study compared the effect of short versus prolonged treatment duration of antiseizure medications on functional development, epilepsy, motor function, length of hospital stay, and parent-reported outcomes among infants hospitalized with acute symptomatic neonatal seizures.
Researchers used Neonatal Seizure Registry sites to recruit infants with acute symptomatic neonatal seizures and their parents. Prior to hospital discharge, hospital physicians worked with parents to decide either to discontinue or maintain treatment with antiseizure medications after discharge.
Parents completed surveys when children were 12, 18, and 24 months old. Researchers controlled for the influence of patient characteristics on the decision to discontinue or maintain antiseizure medication using propensity scores. Researchers extracted clinical data from medical records for propensity scores, which included seizure etiology, gestational age, treatment with therapeutic hypothermia, EEG severity on the first day of monitoring, number of days with seizures, and abnormalities in neurological exam at discharge.
The study included 270 children who were treated at nine hospitals across the United States. Of these, 63% were White, 12% were Black, 7% were Asian, 3% were more than one race, and 15% did not report a race; 54% were male.
Parents of children who experienced neonatal seizures and representatives from advocacy groups helped with all phases of the study including design, study implementation, and results interpretation.
Results
Of the children in the study, 36% discontinued treatment with antiseizure medications prior to hospital discharge, and 64% maintained treatment with medications after discharge. Among infants who maintained treatment with medications, 68% took phenobarbital alone, 13% took levetiracetam alone, and 20% took more than one medication.
After 24 months, with adjustment for propensity to maintain antiseizure medications upon hospital discharge, the two treatment duration groups did not differ significantly in functional development, risk of post-neonatal epilepsy, motor disability, hospital length of stay, or any parent-reported outcomes.
In multivariate analyses, some parent-reported outcomes differed. Compared with parents whose infants maintained treatment with antiseizure medications after discharge, parents of infants who discontinued treatment with medications reported a lower impact of the illness on the family but worse anxiety, depression, and resilience.
Limitations
Researchers followed the infants until age two. Longer follow-up may be able to detect differences in outcomes in older children. Fewer infants developed epilepsy than researchers anticipated, which reduced the precision of the estimated differences in the risk of developing epilepsy.
Conclusions and Relevance
In this study, among infants with acute symptomatic neonatal seizures, discontinuing treatment with antiseizure medications prior to hospital discharge was not associated with risk of impaired functional development or epilepsy at age two.
Future Research Needs
Future research could compare the effect of short versus prolonged treatment duration with antiseizure medications on health and functional development at school age among infants with acute symptomatic neonatal seizures.
Final Research Report
View this project's final research report.
Journal Citations
Article Highlight: Every year, about 16,000 newborns in the United States have seizures. Medications can treat seizures but can also have serious side effects and may harm children’s brain development. This PCORI-funded study compared functional development outcomes of 270 newborns who developed seizures due to acute brain injury in the first days to weeks after birth and were treated with antiseizure medication (ASM) prior to hospital discharge and those who continued ASM after hospital discharge. Reporting in JAMA Neurology, the study found that after two years, children in both groups did not differ significantly in their functional development and risk of epilepsy. These results support discontinuation of ASM prior to hospital discharge for most newborns with acute symptomatic neonatal seizures.
Results of This Project
Related Journal Citations
Peer-Review Summary
Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.
The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments.
Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following:
- The reviewers asked the researchers to clarify their process for balancing patient characteristics across the two treatment groups in order to test a causal hypothesis in this observational study. The researchers calculated patient scores using participant characteristics that were associated with the chosen treatment approach, but the reviewers asked for assurances that the propensity score calculations were accurate, as this would affect the validity of the results. The researchers responded by describing several methods they used to calculate propensity score, all of which gave similar results. They also included a new table and figure showing how patient characteristics matched between the two treatment groups once propensity score adjustments were made.
- The reviewers questioned why the researchers focused the second study aim on length of hospital stay instead of medication side effects or other clinical outcomes. The researchers explained that they were interested in assessing whether hospital discharge for the infant patients could happen sooner if antiseizure medications are withdrawn sooner. The researchers hoped that if they demonstrated shorter hospital stays related to medication discontinuation, they would encourage clinical teams to try to safely discontinue antiseizure medication sooner.
- The reviewers challenged comments in the report linking phenobarbital use in infants to sedation and feeding problems as well as developmental delays, stating that some of these assertions have been challenged in the past. The researchers clarified their statements regarding sedation and feeding problems associated with any antiseizure medications, noting that their concerns specifically relate to prolonged phenobarbital use in infancy but not adequate dosage of phenobarbital to prevent seizures.
Conflict of Interest Disclosures
Project Information
Patient / Caregiver Partners
- Elizabeth Hill, MD, University of Michigan Dept of Pediatrics (lead Parent Partner)
- Jennifer Guerriero, Boston Children's Hospital Lisa Grossbauer, Children's Hospital of Philadelphia
- Dana Annis, Children’s National Medical Center
- Meg Spodick, Massachusetts General Hospital
- Gwen Ma, Stanford University, Hand to Hold.org (contact: Kelli Kelly) CaseyBarnes.org (contact: Marty Barnes)
Other Stakeholder Partners
No information provided by awardee