Children With Congenital Zika Syndrome Face 34-Fold Higher Risk of Epilepsy Hospitalizations: JAMA
Brazil: A major population-based study from Brazil, published in JAMA Pediatrics, offers important clarity on the long-debated question of whether prenatal exposure to the Zika virus (ZIKV) increases the risk of epilepsy during early childhood.
The research, led by João Guilherme G. Tedde and colleagues from the Oswaldo Cruz Foundation, indicates that epilepsy-related hospitalization is significantly elevated only in children born with congenital Zika syndrome (CZS). In contrast, those exposed to the virus in utero but who did not develop CZS did not show increased risk.
The investigators analyzed health outcomes for more than 10.8 million singleton children born in Brazil between January 2015 and November 2018. All infants included had a gestational age of 22 weeks or more. The team examined whether maternal notification of ZIKV infection during pregnancy—either resulting in CZS or not—was associated with hospital admissions for epilepsy in the first four years of life.
The study assessed the time from birth to a child’s first epilepsy-related hospitalization. Using a cause-specific Cox regression model, researchers calculated hazard ratios after adjusting for key maternal and perinatal factors, including education, self-reported race and ethnicity, maternal age, year of birth, and adequacy of antenatal care. All-cause mortality was also considered a competing event.
The key findings of the study were as follows:
- A total of 2,780 children (0.03%) were diagnosed with CZS, while 8,361 children (0.08%) were exposed to ZIKV during pregnancy without developing CZS.
- Children with CZS had a markedly higher risk of epilepsy-related hospitalization, with an adjusted hazard ratio (aHR) of 34.22.
- The risk of epilepsy hospitalization varied by age, peaking between 7–18 months with an aHR of 44.58.
- Elevated risks were also observed during 0–6 months (aHR 33.72) and 19–48 months (aHR 20.62).
- This increased susceptibility was seen regardless of head size, affecting microcephalic, normocephalic, and macrocephalic children with CZS alike.
- Children exposed to ZIKV prenatally without developing CZS did not show an increased risk of epilepsy-related hospitalization compared with unexposed peers (aHR 0.66).
- The findings indicate that ZIKV exposure alone is unlikely to lead to epilepsy severe enough to require hospitalization in early childhood.
The authors emphasize that these robust findings, drawn from one of the world’s largest Zika-related cohorts, reinforce the need for continued surveillance and specialized neurological care for children with CZS. At the same time, the results offer reassurance for families of ZIKV-exposed but clinically unaffected infants.
"Overall, the study highlights that while congenital Zika syndrome carries a markedly elevated risk of early-life epilepsy requiring hospital care, prenatal Zika exposure without CZS does not appear to increase epilepsy risk during the first four years of life," the authors concluded.
Reference:
Tedde JGG, Cerqueira-Silva T, Carroll O, et al. Prenatal Exposure to Zika Virus and Risk of Epilepsy-Related Hospitalization During Early Childhood. JAMA Pediatr. Published online December 01, 2025. doi:10.1001/jamapediatrics.2025.4935
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