Maternal Influenza Infection During Pregnancy and Risk of Attention-Deficit/Hyperactivity Disorder in Offspring
Han-Ping Wu1, Vincent Chin-Hung Chen2, YiLung Chen3
1Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan.
Objective:
Maternal infections during pregnancy have been implicated in neurodevelopmental disorders in offspring, but evidence regarding influenza infection and antiviral treatments remains limited. This study examined the associations between maternal influenza infection and prenatal oseltamivir exposure with attention-deficit/hyperactivity disorder (ADHD) in offspring.
Method:
A nationwide population-based birth cohort study was conducted in Taiwan comprising 2,231,264 mother-child dyads born between 2004 and 2015. Maternal influenza infection during pregnancy was identified from medical records and categorized by trimester. ADHD in offspring was ascertained using ICD-9-CM and ICD-10-CM codes. Cox proportional hazards models and sibling comparison analyses were employed to estimate adjusted hazard ratios (aHRs) and 95% CIs, adjusting for maternal characteristics, comorbidities, and child-specific characteristics.
Results:
During follow-up, 116,080 (5.2%) mothers were diagnosed with influenza during pregnancy. ADHD was diagnosed in 102,717 children in the unexposed group (4.86%) and 6,620 children in the exposed group (5.36%). In the partially adjusted model, any trimester of maternal influenza exposure showed a small but statistically significant association with ADHD in offspring (aHR 1.04, 95% CI 1.02-1.06). In the sibling comparison analysis, which accounts for shared familial and genetic factors, this association was no longer significant (aHR 1.02, 95% CI 0.96-1.08). Prenatal exposure to oseltamivir among influenza-infected mothers was not significantly associated with an increased risk of ADHD in offspring in the sibling comparison model (aHR 0.46, 95% CI 0.08-2.67).
Conclusion:
Initial analyses suggested a very small though statistically significant association between maternal influenza infection during pregnancy and ADHD in offspring; however, sibling comparison analysis revealed no significant risk, pointing to familial confounding. Additionally, prenatal oseltamivir exposure may not increase ADHD risk, supporting the safety of antiviral management during pregnancy.
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