Link between maternal diabetes and child ADHD may not be causal

While children of mothers with diabetes and more likely to develop ADHD, a new global analysis co-led by UCL and University of Hong Kong researchers suggests the relationship is likely not causal.

The authors of the new Nature Medicine study, using data from over 3.6 million mother-baby pairs across three continents, say the link is likely due to genetic and familial factors that are shared between people with diabetes and ADHD.

Globally, approximately 16% of women have high blood sugar levels during pregnancy, and the prevalence of diabetes during pregnancy has been on the rise owing to factors like obesity and older maternal age. This can negatively affect the baby’s brain and nervous system development. ADHD is one of the most common neurodevelopmental disorders in children, and can increase the risk of emotional problems, self-harm, substance misuse, educational underachievement, exclusion from school, and difficulties in employment and relationships.

The impact of maternal diabetes on the risk of ADHD in children has been a subject of debate because of inconsistent findings in previous studies.

This extensive study, which included over 3.6 million mother-child pairs in Hong Kong, Taiwan, New Zealand, Finland, Iceland, Norway and Sweden, from 2001 to 2014 with follow-up until 2020, yielded crucial observations regarding the association between maternal diabetes during pregnancy and the risk of ADHD. The research team first found that children born to mothers with any type of diabetes, whether before or during pregnancy, had a slightly higher risk of ADHD compared to unexposed children, with a hazard ratio of 1.16, meaning that children born to mother with diabetes are 16% more likely than other children to have ADHD.

The study further identified elevated risks of ADHD for both gestational diabetes (diabetes during pregnancy) and pregestational diabetes (diabetes before pregnancy). The hazard ratio for gestational diabetes was 1.10, indicating a modestly increased risk, whereas the hazard ratio for pregestational diabetes was 1.39, suggesting a more substantial association.

However, an intriguing finding emerged when the research team compared the risk of ADHD between siblings with different exposure to gestational diabetes and found no significant difference. This unexpected result indicates that the previously identified risk of ADHD when children were exposed to gestational diabetes during pregnancy is likely due to shared genetic and familial factors, rather than gestational diabetes itself. These findings challenge the conclusions of previous studies that suggested maternal diabetes during or before pregnancy could heighten the risk of ADHD in children.

Co-lead author Professor Ian C.K. Wong (UCL School of Pharmacy and University of Hong Kong) said: "In contrast to previous studies, which hypothesised that maternal diabetes during pregnancy could significantly increase the risk of ADHD, our study found only a modest association between maternal diabetes and ADHD in children after considering the intricate interplay of various influential factors. Notably, sibling comparisons showed this association is likely influenced by shared genetic and familial factors, particularly in the case of gestational diabetes.

"This implies that women who are planning pregnancy should look at their holistic risk profile rather than focusing solely on gestational diabetes.

"Moving forward, it is crucial for future research to investigate the specific roles of genetic factors and proper blood sugar control during different stages of embryonic brain development in humans."

Co-lead author Dr Kenneth Man (UCL School of Pharmacy and University of Hong Kong) added: "Children born to mothers with a history of diabetes may be more likely to develop ADHD not because of the diabetes specifically, but because of factors that influence both conditions, such as maternal depression or other mental health conditions. Expectant mothers with diabetes may not need to worry specifically about diabetes influencing their child’s risk of ADHD, but should still follow the advice of health professionals to take care of their overall health."

Chris Lane

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