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

Abstract

To assess the association between <i>in utero</i> exposure to seasonal inactivated influenza vaccine (IIV) and the risk of a diagnosis of a neurodevelopmental disorder in early childhood. Retrospective cohort study. Population-based birth registry linked with health administrative databases in Western Australia (WA). Singleton, liveborn children born between 1 April 2012 and 1 July 2016 in WA. Receipt of seasonal IIV during pregnancy obtained from a state-wide antenatal vaccination database. 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 <i>in utero</i> exposure to seasonal IIV. The study included 140 514 children of whom, 15 663 (11.2%) were exposed to seasonal IIV <i>in utero</i>. 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). We did not observe increased risk of neurodevelopmental disorders following <i>in utero</i> exposure to seasonal IIV. Although we observed some evidence for lower risk of seizure and sleep disorders, additional studies are required to confirm.