Neonatal Seizures
Conditions
Keywords
Phenobarbital, EEG, family impact, neurodevelopment
Brief summary
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.
Interventions
OTHERSurveys
Regarding development, epilepsy, and family impact
OTHEREEG
Sponsors
University of California, San Francisco
Boston Children's Hospital
Children's Hospital of Philadelphia
Children's National Research Institute
Massachusetts General Hospital
Patient-Centered Outcomes Research Institute
Stanford University
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Duke University
Children's Hospital Medical Center, Cincinnati
University of Michigan
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
0 Weeks to 24 Months
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| WIDEA Neurodevelopmental Outcome Score | 24 months | 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. |
| Number of Participants With Post-neonatal Epilepsy | 24 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of Stay for the Neonatal Seizure Admission | length of stay, measured in days, will be recorded during a chart review when the child is 12 months of age | 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) |
| Impact of Treatment Duration on Parent and Family Well-being | 24 months | 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Outpatient Enrollees - Maintatin Anti-Seizure Medicine This is a cohort of subjects who were previously enrolled in the Neonatal Seizure Registry and had been discharged from the Neonatal Intensive Care Unit (NICU) on anti-seizure medicine. They were asked to take part in all prospective follow up surveys regarding development, epilepsy, and family impact at 12, 18, & 24 months of age. | 99 |
| Outpatient Enrollees - Discontinue Anti-Seizure Medicine This is a cohort of subjects who were previously enrolled in the Neonatal Seizure Registry and had been discharged from the Neonatal Intensive Care Unit (NICU) off anti-seizure medicine. They were asked to take part in all prospective follow up surveys regarding development, epilepsy, and family impact at 12, 18, & 24 months of age. | 55 |
| Inpatient Enrollees - Maintain Anti-Seizure Medicine This is a cohort of subjects who were enrolled in the study prior to discharge from the NICU and had been discharged on anti-seizure medicine. They were asked to return to the hospital for a 1 hour EEG to monitor brain activity between 2-4 months of age, and complete surveys regarding development, epilepsy, and family impact prior to discharge from the NICU and at 12, 18, & 24 months of age. | 95 |
| Inpatient Enrollees - Discontinue Anti-Seizure Medicine This is a cohort of subjects who were enrolled in the study prior to discharge from the NICU and had been discharged off anti-seizure medicine. They were asked to return to the hospital for a 1 hour EEG to monitor brain activity between 2-4 months of age, and complete surveys regarding development, epilepsy, and family impact prior to discharge from the NICU and at 12, 18, & 24 months of age. | 54 |
| Total | 303 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 3 | 0 |
| Overall Study | Lost to Follow-up | 8 | 2 | 6 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Outpatient Enrollees - Maintatin Anti-Seizure Medicine | Total | Inpatient Enrollees - Discontinue Anti-Seizure Medicine | Inpatient Enrollees - Maintain Anti-Seizure Medicine | Outpatient Enrollees - Discontinue Anti-Seizure Medicine |
|---|---|---|---|---|---|
| Age, Continuous | 23.89 Months STANDARD_DEVIATION 0.76 | 23.84 Months STANDARD_DEVIATION 0.72 | 23.97 Months STANDARD_DEVIATION 0.76 | 23.65 Months STANDARD_DEVIATION 0.56 | 23.94 Months STANDARD_DEVIATION 0.76 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 20 Participants | 6 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 36 Participants | 6 Participants | 7 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 10 Participants | 2 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 41 Participants | 11 Participants | 18 Participants | 5 Participants |
| Race (NIH/OMB) White | 69 Participants | 192 Participants | 28 Participants | 59 Participants | 36 Participants |
| Sex: Female, Male Female | 47 Participants | 133 Participants | 24 Participants | 36 Participants | 26 Participants |
| Sex: Female, Male Male | 52 Participants | 170 Participants | 30 Participants | 59 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 99 | 0 / 55 | 3 / 95 | 0 / 54 |
| other Total, other adverse events | 0 / 99 | 0 / 55 | 0 / 95 | 0 / 54 |
| serious Total, serious adverse events | 0 / 99 | 0 / 55 | 0 / 95 | 0 / 54 |
Outcome results
Primary
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.
Time frame: 24 months
Population: Participants analyzed reflect the number of participants who completed the 24 month follow-up survey. Also one participant did not have data for epilepsy diagnosis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Outpatient Enrollees - Maintain Anti-Seizure Medicine | Number of Participants With Post-neonatal Epilepsy | 14 Participants |
| Outpatient Enrollees - Discontinue Anti-Seizure Medicine | Number of Participants With Post-neonatal Epilepsy | 2 Participants |
| Inpatient Enrollees - Maintain Anti-Seizure Medicine | Number of Participants With Post-neonatal Epilepsy | 11 Participants |
| Inpatient Enrollees - Discontinue Anti-Seizure Medicine | Number of Participants With Post-neonatal Epilepsy | 10 Participants |
Primary
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.
Time frame: 24 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Outpatient Enrollees - Maintain Anti-Seizure Medicine | WIDEA Neurodevelopmental Outcome Score | 149.04 score on a scale | Standard Deviation 34.55 |
| Outpatient Enrollees - Discontinue Anti-Seizure Medicine | WIDEA Neurodevelopmental Outcome Score | 162.46 score on a scale | Standard Deviation 25.94 |
| Inpatient Enrollees - Maintain Anti-Seizure Medicine | WIDEA Neurodevelopmental Outcome Score | 148.80 score on a scale | Standard Deviation 33.52 |
| Inpatient Enrollees - Discontinue Anti-Seizure Medicine | WIDEA Neurodevelopmental Outcome Score | 151.89 score on a scale | Standard Deviation 33.24 |
Secondary
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).
Time frame: 24 months
Population: Not all subjects completed every survey question, therefore some rows have different participants for the various outcome measures.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Outpatient Enrollees - Maintain Anti-Seizure Medicine | Impact of Treatment Duration on Parent and Family Well-being | 24 month HADS Depression Score | 3.44 score on a scale | Standard Deviation 3.01 |
| Outpatient Enrollees - Maintain Anti-Seizure Medicine | Impact of Treatment Duration on Parent and Family Well-being | 24 month HADS Anxiety Score | 6.15 score on a scale | Standard Deviation 4.2 |
| Outpatient Enrollees - Maintain Anti-Seizure Medicine | Impact of Treatment Duration on Parent and Family Well-being | 24 month Transformed WHO Overall Quality of Life Score | 76.09 score on a scale | Standard Deviation 18.14 |
| Outpatient Enrollees - Maintain Anti-Seizure Medicine | Impact of Treatment Duration on Parent and Family Well-being | 24 month Impact on Family Scale overall impact scale, 24 mo | 28.78 score on a scale | Standard Deviation 10.41 |
| Outpatient Enrollees - Maintain Anti-Seizure Medicine | Impact of Treatment Duration on Parent and Family Well-being | 24 month Post Traumatic Growth Inventory | 59.5 score on a scale | Standard Deviation 25.1 |
| Outpatient Enrollees - Maintain Anti-Seizure Medicine | Impact of Treatment Duration on Parent and Family Well-being | 24 month Impact of Events Scale | 15.1 score on a scale | Standard Deviation 15 |
| Outpatient Enrollees - Discontinue Anti-Seizure Medicine | Impact of Treatment Duration on Parent and Family Well-being | 24 month Impact of Events Scale | 14.7 score on a scale | Standard Deviation 13.6 |
| Outpatient Enrollees - Discontinue Anti-Seizure Medicine | Impact of Treatment Duration on Parent and Family Well-being | 24 month Impact on Family Scale overall impact scale, 24 mo | 25.50 score on a scale | Standard Deviation 9.26 |
| Outpatient Enrollees - Discontinue Anti-Seizure Medicine | Impact of Treatment Duration on Parent and Family Well-being | 24 month HADS Depression Score | 2.92 score on a scale | Standard Deviation 2.61 |
| Outpatient Enrollees - Discontinue Anti-Seizure Medicine | Impact of Treatment Duration on Parent and Family Well-being | 24 month Transformed WHO Overall Quality of Life Score | 78.00 score on a scale | Standard Deviation 16.67 |
| Outpatient Enrollees - Discontinue Anti-Seizure Medicine | Impact of Treatment Duration on Parent and Family Well-being | 24 month HADS Anxiety Score | 5.30 score on a scale | Standard Deviation 3.81 |
| Outpatient Enrollees - Discontinue Anti-Seizure Medicine | Impact of Treatment Duration on Parent and Family Well-being | 24 month Post Traumatic Growth Inventory | 61.9 score on a scale | Standard Deviation 25.3 |
| Inpatient Enrollees - Maintain Anti-Seizure Medicine | Impact of Treatment Duration on Parent and Family Well-being | 24 month HADS Anxiety Score | 5.83 score on a scale | Standard Deviation 3.79 |
| Inpatient Enrollees - Maintain Anti-Seizure Medicine | Impact of Treatment Duration on Parent and Family Well-being | 24 month Transformed WHO Overall Quality of Life Score | 76.67 score on a scale | Standard Deviation 17.75 |
| Inpatient Enrollees - Maintain Anti-Seizure Medicine | Impact of Treatment Duration on Parent and Family Well-being | 24 month Impact on Family Scale overall impact scale, 24 mo | 28.30 score on a scale | Standard Deviation 10.31 |
| Inpatient Enrollees - Maintain Anti-Seizure Medicine | Impact of Treatment Duration on Parent and Family Well-being | 24 month Impact of Events Scale | 13.8 score on a scale | Standard Deviation 13.9 |
| Inpatient Enrollees - Maintain Anti-Seizure Medicine | Impact of Treatment Duration on Parent and Family Well-being | 24 month Post Traumatic Growth Inventory | 61.7 score on a scale | Standard Deviation 27 |
| Inpatient Enrollees - Maintain Anti-Seizure Medicine | Impact of Treatment Duration on Parent and Family Well-being | 24 month HADS Depression Score | 3.17 score on a scale | Standard Deviation 2.97 |
| Inpatient Enrollees - Discontinue Anti-Seizure Medicine | Impact of Treatment Duration on Parent and Family Well-being | 24 month Post Traumatic Growth Inventory | 62.7 score on a scale | Standard Deviation 25 |
| Inpatient Enrollees - Discontinue Anti-Seizure Medicine | Impact of Treatment Duration on Parent and Family Well-being | 24 month Impact of Events Scale | 16.3 score on a scale | Standard Deviation 15 |
| Inpatient Enrollees - Discontinue Anti-Seizure Medicine | Impact of Treatment Duration on Parent and Family Well-being | 24 month HADS Anxiety Score | 6.84 score on a scale | Standard Deviation 4.89 |
| Inpatient Enrollees - Discontinue Anti-Seizure Medicine | Impact of Treatment Duration on Parent and Family Well-being | 24 month Impact on Family Scale overall impact scale, 24 mo | 28.88 score on a scale | Standard Deviation 11.42 |
| Inpatient Enrollees - Discontinue Anti-Seizure Medicine | Impact of Treatment Duration on Parent and Family Well-being | 24 month HADS Depression Score | 3.72 score on a scale | Standard Deviation 4.04 |
| Inpatient Enrollees - Discontinue Anti-Seizure Medicine | Impact of Treatment Duration on Parent and Family Well-being | 24 month Transformed WHO Overall Quality of Life Score | 75.32 score on a scale | Standard Deviation 20.97 |
Secondary
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)
Time frame: length of stay, measured in days, will be recorded during a chart review when the child is 12 months of age
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Outpatient Enrollees - Maintain Anti-Seizure Medicine | Length of Stay for the Neonatal Seizure Admission | 15 number of days |
| Outpatient Enrollees - Discontinue Anti-Seizure Medicine | Length of Stay for the Neonatal Seizure Admission | 11 number of days |
| Inpatient Enrollees - Maintain Anti-Seizure Medicine | Length of Stay for the Neonatal Seizure Admission | 17 number of days |
| Inpatient Enrollees - Discontinue Anti-Seizure Medicine | Length of Stay for the Neonatal Seizure Admission | 15 number of days |