Prenatal Exposure to Zika Virus and Risk of Epilepsy-Related Hospitalization During Early Childhood
João Guilherme G Tedde1,2, Thiago Cerqueira-Silva3,4, Orlagh Carroll3
1Center for Data and Knowledge Integration for Health, Oswaldo Cruz Foundation, Salvador, Brazil.
Insights
Congenital Zika syndrome (CZS) significantly increases epilepsy risk in children. However, Zika virus (ZIKV) exposure during pregnancy without CZS did not elevate epilepsy hospitalization rates in this Brazilian study.
Area of Science:
- Pediatric Neurology
- Infectious Diseases
- Epidemiology
Background:
- Epilepsy is a significant concern in children with congenital Zika syndrome (CZS).
- The epilepsy risk for children exposed in utero to Zika virus (ZIKV) without developing CZS remains unclear compared to unexposed children.
Purpose of the Study:
- To compare the risk of epilepsy-related hospitalizations in the first four years of life.
- To assess risk among children exposed to ZIKV in utero (with and without CZS) versus unexposed children.
Main Methods:
- Population-based cohort study in Brazil (January 2015 - November 2018).
- Included live-born singleton children with 22+ weeks gestation.
- Analyzed epilepsy-related hospitalizations using Cox regression, adjusting for confounders.
Main Results:
- CZS was strongly associated with increased epilepsy hospitalization risk (aHR, 34.22).
- Risk peaked between 7-18 months of age.
- ZIKV exposure without CZS showed no increased epilepsy risk compared to unexposed children (aHR, 0.66).
Conclusions:
- CZS is linked to a substantially elevated risk of epilepsy-related hospitalizations in early childhood.
- In utero ZIKV exposure without CZS does not appear to increase epilepsy risk.
Importance:
Epilepsy is a major clinical concern in children with congenital Zika syndrome (CZS). However, whether in utero exposure to Zika virus (ZIKV) without development of CZS is associated with increased epilepsy risk compared with unexposed children remains unclear.
Objective:
To compare the risk of epilepsy-related hospitalizations during the first 4 years of life among children exposed to ZIKV during pregnancy (with and without CZS) vs an unexposed group.
Design, Setting, And Participants:
This was a population-based cohort study conducted in Brazil among live-born singleton children with 22 or more weeks' gestation born from January 2015 to November 2018. Data analysis was conducted from December 2024 to March 2025.
Exposure:
In utero exposure to ZIKV by maternal notification during pregnancy.
Main Outcomes And Measures:
The primary outcome was the time from birth to the first epilepsy-related hospitalization. Hazard ratios (HRs) and 95% CIs were estimated using a cause-specific Cox regression model, adjusting for maternal education level, maternal self-reported race and ethnicity, maternal age, year of child birth, and adequacy of the number of antenatal appointments. All-cause deaths were also considered as competing events.
Results:
Among 10 828 887 children (5 275 628 [48.7%] female; mean [SD] gestational age, 38.5 [2.0] weeks), 2780 (0.03%) had CZS and 8361 (0.08%) were exposed to ZIKV during pregnancy without developing CZS. After adjusting for confounders, CZS was associated with an increased risk of epilepsy-related hospital admission (adjusted HR [aHR], 34.22 [95% CI, 29.16-40.16]). Age-specific aHRs peaked at age 7 to 18 months (aHR [95% CI], 33.72 [24.70-46.04] for 0-6 months, 44.58 [35.89-55.36] for 7-18 months, and 20.62 [14.31-29.72] for 19-48 months). Children with CZS who were microcephalic, normocephalic, or macrocephalic showed similar associations with epilepsy-related admissions. Children exposed to ZIKV without CZS did not show increased risk compared with unexposed peers (aHR, 0.66 [95% CI, 0.34-1.27]).
Conclusions And Relevance:
In this population-based cohort study, CZS was associated with elevated risk of epilepsy-related hospitalization in early childhood in Brazil. In contrast, children exposed to ZIKV during pregnancy without CZS did not appear to have higher risk of epilepsy-related admission compared with unexposed children.
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