Time to response and predictors of seizure response to phenobarbitone therapy among neonates admitted with hypoxic-ischemic encephalopathy at Nekemte Comprehensive Specialized Hospital, Ethiopia

Background

Hypoxic-ischemic encephalopathy is a brain injury that occurs in newborns when there is not enough blood flow to the brain. Recent studies have raised concerns about how well phenobarbitone works for treating seizures in newborns, as it may not effectively control seizures with the initial loading and repeated doses.

Objective

This study evaluated the time to respond and predictors of seizure response to phenobarbitone therapy among neonates admitted with hypoxic-ischemic encephalopathy.

Methods and Materials

A retrospective cohort study was conducted at Nekemte Comprehensive Specialized Hospital, using randomly selected medical records of 284 neonates who were treated between January 2020 and December 31, 2023. The study included neonates diagnosed with perinatal asphyxia stage II and III hypoxic-ischemic encephalopathy, who were treated with nasogastric phenobarbitone. The treatment included an initial loading dose of 20 mg/kg and two repeated doses of 10 mg/kg. Survival analysis was conducted. Predictor variables with a p-value ≤ 0.25 in bivariate Cox regression were included in the multivariable Cox regression analysis. Adjusted Hazard Ratios with 95 % confidence intervals were computed, and a p-value < 0.05 was considered statistically significant.

Results

Out of the 284 neonates, 210 (73.9 %) responded to the phenobarbitone treatment. The incidence rate of response was 27.73 per 1000 person-hours of observation, with a median time to response of 29 h (IQR 26.5–32 h). Low birth weight (AHR = 0.59; 95 %CI 0.58, 0.98), subtle seizure type (AHR: 2.35; 95 % CI 1.09, 5.08), severe hypothermia (AHR = 0.23; 95 % CI 0.052, 0.26), and seizure frequency of twice or more (AHR = 0.436, 95 % CI 0.31, 0.61) were identified as predictors of seizure response.

Conclusion and recommendations

The overall incidence rate of response was low. Having a history of twice or more frequency of seizure insult, severe hypothermia and low birth weight decreased the response rate while subtle types of seizure increased the likelihood of response to phenobarbitone therapy. Electroencephalogram-confirmed seizure treatment and combined management with therapeutic hypothermia for high-risk newborns need to be started for better response and reduced response time. Further controlled studies utilizing both clinical and neuroimaging for definitive outcome measurement are recommended.