Sibling analysis weakens link between flu in pregnancy and children’s psychiatric diagnoses

A large South Korean and Japanese study found a modest population-level association between maternal influenza and later neuropsychiatric diagnoses, but no significant link when siblings were compared.

A large binational study from South Korea and Japan suggests that influenza during pregnancy may be associated with a small increase in neuropsychiatric diagnoses in children at the population level, but that the link weakens when brothers and sisters are compared within the same family. The research, published in JAMA Network Open and led by Jaehyun Kong of Kyung Hee University College of Medicine in Seoul, examined whether maternal influenza was followed by later psychiatric or developmental conditions in offspring.

Using health insurance records, the investigators analysed more than 2.5 million mother-child pairs in South Korea and 181,681 in Japan. They followed children born between January 2010 and December 2017 through the end of 2023, looking for diagnoses that included attention-deficit/hyperactivity disorder, autism spectrum disorder, obsessive-compulsive disorder, intellectual disability and severe neuropsychiatric disorders. In the overall cohort, maternal influenza was linked with about a 9% higher risk of any neuropsychiatric disorder in South Korea and a 10% higher risk in Japan.

That signal disappeared in sibling-comparison analyses, however, with no statistically significant association seen once family-shared factors were taken into account. The authors said this raises the possibility that genetics, household environment or other familial characteristics may explain at least part of the relationship seen in the broader population. They also noted limits to the work, including the chance of influenza misclassification, residual confounding and the possibility that shorter follow-up missed disorders that emerge later in life.

The findings fit with earlier evidence that has been mixed and methodologically uneven. A systematic review of the field, published previously in the same scientific literature, concluded that existing studies on maternal influenza and offspring neuropsychiatric health are inconsistent and not strong enough to establish a clear causal relationship. Against that backdrop, the new binational study adds weight to the view that any apparent risk may be modest and partly driven by family-level factors rather than infection alone.