Association between maternal influenza vaccination and neurodevelopmental disorders in childhood: a longitudinal, population-based linked cohort study

Objective: To assess the association between in utero exposure to seasonal inactivated influenza vaccine (IIV) and the risk of a diagnosis of a neurodevelopmental disorder in early childhood. Design: Retrospective cohort study. Setting: Population-based birth registry linked with health administrative databases in Western Australia (WA). Participants: Singleton, liveborn children born between 1 April 2012 and 1 July 2016 in WA. Exposure: Receipt of seasonal IIV during pregnancy obtained from a state-wide antenatal vaccination database. Main outcome measures: Clinical diagnosis of a neurodevelopmental disorder was recorded from hospital inpatient and emergency department records. We used Cox proportional hazard regression, weighted by the inverse-probability of treatment (vaccination), to estimate the hazard ratio (HR) of neurodevelopmental disorders associated with in utero exposure to seasonal IIV. Results: The study included 140 514 children of whom, 15 663 (11.2%) were exposed to seasonal IIV in utero. The prevalence of neurodevelopmental disorders was 5.4%, including mental or behavioural (0.4%), neurological (5.1%), seizure (2.2%) and sleep disorders (2.7%). Maternal IIV was not associated with increased risk of neurodevelopmental disorders (HR 1.00; 95% CI 0.91 to 1.08). Children exposed in the first trimester had a lower risk of seizure disorders (adjusted HR [aHR] 0.73; 95% CI 0.54 to 0.998), and preterm children exposed any time during pregnancy had a lower risk of sleep disorders (aHR 0.63; 95% CI 0.41 to 0.98). Conclusions: We did not observe increased risk of neurodevelopmental disorders following in utero exposure to seasonal IIV. Although we observed some evidence for lower risk of seizure and sleep disorders, additional studies are required to confirm.