Maternal influenza vaccination during pregnancy and risk of autism spectrum disorder in the offspring

Background: Vaccination has been proposed as a potential risk factor for autism spectrum disorder (ASD), contributing to public hesitancy and mistrust toward immunization. Influenza vaccination during pregnancy is considered safe and effective in preventing serious maternal complications and adverse birth outcomes associated with influenza infection. However, limited research exists regarding the long-term impact of maternal influenza vaccination on offspring neurodevelopment. Methods: We conducted a retrospective cohort study of all singleton-live births among members of Clalit Health Services (CHS), Israel's largest healthcare provider, between January 2016 and December 2020, with follow-up through May 2024. Offspring with developmental disorders of known genetic etiology were excluded. Maternal influenza vaccination during pregnancy (exposure) and offspring ASD diagnosis (outcome) were identified via CHS electronic medical records. The association between exposure and outcome was assessed using Cox proportional hazards models, adjusting for sociodemographic, maternal, and gestational covariates. Results: Of 153,321 children included in the analysis, 39,361 (25.7%) were exposed to maternal influenza vaccination during pregnancy. The cumulative incidence of ASD was 3.6% for offspring of vaccinated mothers and 2.9% for offspring of unvaccinated mothers resulting in a modestly increased hazard ratio (HR) of ASD associated with influenza vaccination during pregnancy (HR = 1.22, 95% CI: 1.14–1.31). However, this association was no longer evident after adjustment for sociodemographic and clinical covariates (aHR = 0.97, 95% CI: 0.91–1.05). Conclusion: Maternal influenza vaccination during pregnancy was not associated with an increased risk of ASD in offspring. These results provide valuable confirmation of similar findings from earlier studies, thus further support the long-term safety of maternal influenza vaccination as a preventive healthcare measure.