Sibling Analyses Attenuate Association Between Maternal Influenza and Offspring Neuropsychiatric Disorders

A JAMA Network Open cohort study examined maternal influenza during pregnancy and subsequent neuropsychiatric diagnoses in offspring using insurance data from South Korea and Japan. Researchers included children born in 2010–2017, with follow-up through December 2023. Exposure was a first recorded maternal influenza diagnosis during pregnancy; the primary outcome was the first postnatal diagnosis of any included neuropsychiatric disorder. Analyses used inverse probability weighting to adjust for measured confounding and comparisons of exposure-discordant siblings.

The South Korean cohort included 2,564,435 mother-child pairs, with 35,973 exposed to maternal influenza; the Japanese cohort included 181,681 pairs, with 11,198 exposed. Weighted population analyses found modest associations with offspring neuropsychiatric disorders in South Korea (adjusted hazard ratio [AHR], 1.09; 95% CI, 1.04–1.14) and Japan (AHR, 1.10; 95% CI, 1.02–1.19). Sibling-comparison analyses included 33,191 and 7,842 pairs, respectively, and found no statistically significant association in either cohort: AHR 0.98 (95% CI, 0.89–1.09) and 1.04 (95% CI, 0.88–1.22).

The attenuation in sibling analyses suggests shared familial factors may account for the population-level association, rather than establishing a causal effect of prenatal influenza. The observational design and reliance on recorded diagnoses warrant caution. Absolute risks and disorder-specific results were not provided in the supplied abstract, and the sibling estimates do not exclude modest effects.