Maternal diabetes and risk of attention-deficit/hyperactivity disorder in offspring in a multinational cohort of 3.6 million mother-child pairs

Adrienne Y. L. Chan, Le Gao, Miyuki Hsing-Chun Hsieh, Lars J. Kjerpeseth, Raquel Avelar, Tobias Banaschewski, Amy Hai Yan Chan, David Coghill, Jacqueline M. Cohen, Mika Gissler, Jeff Harrison, Patrick Ip, Øystein Karlstad, Wallis C. Y. Lau, Maarit K. Leinonen, Wing Cheong Leung, Tzu-Chi Liao, Johan Reutfors, Shih-Chieh Shao, Emily SimonoffKathryn Choon Beng Tan, Katja Taxis, Andrew Tomlin, Carolyn E. Cesta, Edward Chia-Cheng Lai, Helga Zoega, Kenneth K. C. Man, Ian C. K. Wong

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Previous studies report an association between maternal diabetes mellitus (MDM) and attention-deficit/hyperactivity disorder (ADHD), often overlooking unmeasured confounders such as shared genetics and environmental factors. We therefore conducted a multinational cohort study with linked mother-child pairs data in Hong Kong, New Zealand, Taiwan, Finland, Iceland, Norway and Sweden to evaluate associations between different MDM (any MDM, gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (PGDM)) and ADHD using Cox proportional hazards regression. We included over 3.6 million mother-child pairs between 2001 and 2014 with follow-up until 2020. Children who were born to mothers with any type of diabetes during pregnancy had a higher risk of ADHD than unexposed children (pooled hazard ratio (HR) = 1.16, 95% confidence interval (CI) = 1.08-1.24). Higher risks of ADHD were also observed for both GDM (pooled HR = 1.10, 95% CI = 1.04-1.17) and PGDM (pooled HR = 1.39, 95% CI = 1.25-1.55). However, siblings with discordant exposure to GDM in pregnancy had similar risks of ADHD (pooled HR = 1.05, 95% CI = 0.94-1.17), suggesting potential confounding by unmeasured, shared familial factors. Our findings indicate that there is a small-to-moderate association between MDM and ADHD, whereas the association between GDM and ADHD is unlikely to be causal. This finding contrast with previous studies, which reported substantially higher risk estimates, and underscores the need to reevaluate the precise roles of hyperglycemia and genetic factors in the relationship between MDM and ADHD.
Original languageEnglish
Pages (from-to)1416-1423
Number of pages8
JournalNature medicine
Issue number5
Early online date8 Apr 2024
Publication statusPublished - May 2024

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