HEPATITIS E vaccine safety in pregnancy appears reassuring, with no detected rise in fetal loss in outbreak settings.
Hepatitis E Vaccine Safety in Pregnancy
New real-world evidence is helping address a major safety gap around hepatitis E vaccine use in pregnancy, a population at disproportionate risk from hepatitis E virus infection. The comment highlights data from a large study conducted in an internally displaced persons camp in South Sudan, where hepatitis E vaccination during pregnancy was not associated with a statistically significant increase in fetal loss.
Hepatitis E virus, particularly genotype 1, can cause severe outcomes in pregnancy, including fulminant hepatic failure, miscarriage, and maternal death. Yet pregnant women are often excluded from initial vaccine trials, leaving clinicians and policymakers with limited safety evidence when outbreaks occur in high-risk settings.
Fetal Loss Risk Was Not Increased
Among pregnant women vaccinated during pregnancy, the cumulative risk of fetal loss was 7.2%, compared with 6.1% among unvaccinated women. The risk ratio was 1.2, with a 95% confidence interval of 0.7 to 1.9, meaning the analysis did not detect a statistically significant increase in fetal loss.
Findings remained consistent in analyses focused on first trimester exposure, the most sensitive period for fetal development, as well as analyses of vaccination before pregnancy. Sensitivity analyses using different assumptions and more restricted data also did not change the overall conclusion.
Translational evidence from rabbit models has suggested that HEV239 vaccination before or during pregnancy may protect against adverse pregnancy outcomes. However, the comment emphasizes that animal data can support, but not replace, clinical evidence.
Evidence Supports Outbreak Decision Making
The findings carry practical importance for outbreak response, particularly in fragile, conflict affected, and vulnerable settings where hepatitis E virus circulation is documented and access to care may be limited. Safety data from more than 2,000 women vaccinated during pregnancy may help reduce uncertainty when considering whether pregnant women should be included in vaccination strategies.
Several limitations remain. Pregnancy status and vaccination dates were partly self reported, with documentary confirmation available for only 57–65% of participants. Very early miscarriages may have been missed, which could bias findings toward no effect. Unmeasured confounding also cannot be fully excluded, despite matching methods and supportive bias indicator analyses.
Overall, the evidence is reassuring but not definitive. Additional prospective studies across diverse pregnant populations are needed to confirm hepatitis E vaccine safety, assess longer term outcomes, and evaluate practical questions around schedule, effectiveness, logistics, and community acceptance during outbreaks.
Reference
Zhang F et al. Safety of hepatitis E vaccine in pregnancy. Virol J. 2026;23:130.
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