Continued Anticonvulsants After Resolution of Neonatal Seizures: a Patient-centered Comparative Effectiveness Study

The purpose of this study is to examine whether the duration of treatment with phenobarbital has an impact on neurodevelopmental and epilepsy outcomes, as well as parent and family well-being, after neonatal seizures.

Study Overview

• Status: Completed
• Conditions: Neonatal Seizures
• Intervention / Treatment: Other: EEG; Other: Surveys

• Study Type: Observational
• Enrollment (Actual): 303

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
    • Stanford, California, United States, 94304
      • Stanford University
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • North Carolina
    • Durham, North Carolina, United States, 227710
      • Duke University
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Newborns with seizures who were admitted at one of the participating children's hospitals

Description

Inclusion Criteria:

• Neonates <44 weeks corrected age at seizure onset
• Seizures due to acute brain injury
• Parent(s) who are English or Spanish literate (with assistance of interpreter)

Exclusion Criteria:

• Neonates at risk for adverse outcome independent of seizures and underlying brain injury
• Neonates with mild, temporary causes for seizures
• Newborns with neonatal-onset epilepsy syndromes
• Neonates who do not survive the initial hospital admission
• Neonates will not be excluded based on race, ethnicity, gender or gestational age

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Outpatient Enrollees; This is a cohort of 150 subjects who were previously enrolled in the Neonatal Seizure Registry, a multi-center association of institutions across the United States, They were contacted to participate in the study after discharge from the Neonatal Intensive Care Unit (NICU) but prior to the prospective follow up. They were asked to take part in all prospective follow up surveys at 12, 18, & 24 months of age.	Other: Surveys; Regarding development, epilepsy, and family impact; Other Names: Former Neonatal Seizure Registry Subjects
NICU Enrollees; This is a cohort of 150 subjects who were enrolled in the study prior to discharge from the NICU. They were asked to complete surveys prior to discharge from the NICU, returned to the hospital for a 1 hour EEG to monitor brain activity between 2-4 months of age, & completed the follow surveys at 12, 18, & 24 months of age.	Other: EEG; Other: Surveys; Regarding development, epilepsy, and family impact; Other Names: Former Neonatal Seizure Registry Subjects

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
WIDEA Neurodevelopmental Outcome Score	The Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA FS) allowed us to compare the functional development between newborns who received short duration phenobarbital treatment and prolonged phenobarbital treatment. There were 50 questions with response options of 1(Never) to 4(all the time). WIDEA range was on a scale from 50-200 (At 24 months, the normal population mean score is 172±10).The higher the score the better the child's developmental function. Mean scores were calculated using data from any participant who completed surveys at 24 months.	24 months
Number of Participants With Post-neonatal Epilepsy	The diagnosis of epilepsy and the details of seizure types and frequencies were determined by telephone interview with the parent and corroborated by medical record review.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of Stay for the Neonatal Seizure Admission	Evaluation of medication exposure (dose and duration) during the admission as a predictor of the number of days the infant requires care (length of stay)	length of stay, measured in days, will be recorded during a chart review when the child is 12 months of age
Impact of Treatment Duration on Parent and Family Well-being	Surveys selected with the help of our Parent Partners were given at 12, 18, and 24 months to assess the impact of neonatal seizure treatment duration on parent and family quality of life and well-being. The 24 month data is presented, as they align with the primary outcome. The study team reviewed the HADS 24 month Anxiety and Depression Score range of possible scores from 0-21 (higher = more depressed/more anxious), the 24 month Transformed WHO Overall Quality of Life and General Health score range of scores 0-100 (higher=better quality of life), the 24 month Impact on Family Scale overall impact scale range from 15-60 (higher = more impact on family), the 24 month Post Traumatic Growth Inventory scale range from 0 -105 (higher = better/more growth), and the 24 month Impact of Events Scale-Revised scale range from 0 - 88 (higher score = worse impact).	24 months

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: Patient-Centered Outcomes Research Institute; Massachusetts General Hospital; Children's Hospital of Philadelphia; Beth Israel Deaconess Medical Center; Boston Children's Hospital; Duke University; Brigham and Women's Hospital; University of California, San Francisco; Stanford University; Children's Hospital Medical Center, Cincinnati; Children's National Research Institute
• Investigators: Principal Investigator: Renee A Shellhaas, MD, MS, University of Michigan

Publications and helpful links

General Publications

• Franck LS, Shellhaas RA, Lemmon M, Sturza J, Soul JS, Chang T, Wusthoff CJ, Chu CJ, Massey SL, Abend NS, Thomas C, Rogers EE, McCulloch CE, Grant K, Grossbauer L, Pawlowski K, Glass HC; Neonatal Seizure Registry study group. Associations between Infant and Parent Characteristics and Measures of Family Well-Being in Neonates with Seizures: A Cohort Study. J Pediatr. 2020 Jun;221:64-71.e4. doi: 10.1016/j.jpeds.2020.02.024.

Helpful Links

• PCORI website

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (Actual): March 24, 2020
• Study Completion (Actual): March 24, 2020

Study Registration Dates

• First Submitted: May 19, 2016
• First Submitted That Met QC Criteria: May 26, 2016
• First Posted (Estimate): June 2, 2016

Study Record Updates

• Last Update Posted (Actual): December 4, 2020
• Last Update Submitted That Met QC Criteria: November 20, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: EEG; neurodevelopment; Phenobarbital; family impact
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Seizures
• Other Study ID Numbers: HUM00114541; 1507-31187 (Other Identifier: PCORI project number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Will be posted on pcori.org