Becky McCall

September 22, 2016

MUNICH — Risk of attention-deficit/hyperactivity disorder (ADHD) may be increased in children of mothers who used medication for gestational diabetes or type 2 diabetes for more than 2 months during pregnancy, new research shows.

"Our data show that children exposed to their mothers' gestational diabetes or type 2 diabetes that required antidiabetic medication during pregnancy were found to be at greater risk of ADHD than children" who were not exposed to antidiabetic medications, reported Anny Xiang, PhD, Kaiser Permanente Southern California (KPSC), Pasadena, at the recent European Association for the Study of Diabetes (EASD) 2016 Annual Meeting.

"The magnitude of association seems to increase with increasing duration of…use," she added. "In children whose mothers took antidiabetic medication for over 60 days, after multivariate adjustment, we found a 23% increased incidence of ADHD (hazard ratio [HR], 1.23; P = .06)."

Comoderator of the session, Alexandra Kautzky-Willer, MD, professor of gender medicine at the Medical University of Vienna, Austria, commented on the findings, bearing in mind that 85% of the pregnant women in the study were on insulin treatment.

"These results are interesting, but we cannot say that insulin has a negative effect on offspring. It would be good to know about the hyperglycemic states of patients, which were not actually discussed but might be related to the outcomes."

Dr Kautzky-Willer emphasized that it was an important study due to the lack of work in this field currently and because insulin treatment is very common in pregnant women with type 2 diabetes. However, she stressed, "We cannot conclude that medication is dangerous at the moment."

Fellow moderator Adam Tabak, MD, PhD, from University College, London, United Kingdom, agreed. These are "interesting hypothesis-generating data, but I wouldn't rush to any conclusions at this stage. We need more phenotypically defined details of the population and to catch the unmeasured confounders," he stated.

Knowledge Gap: Gestational Diabetes, Type 2 Diabetes, and ADHD

Maternal type 2 diabetes and gestational diabetes are associated with increased risks of perinatal morbidities as well as obesity and metabolic disorders in the child, but the relationship between gestational diabetes and neurobehavioral disorders is not well studied, noted Dr Xiang.

This large, retrospective, population-based study aimed to assess the association of maternal type 2 diabetes or gestational diabetes with the risk of ADHD in the offspring, she added.

Information was extracted from electronic medical records on singleton pregnancies from 1995 to 2009 held by KPSC where delivery occurred between 18 and 44 gestational weeks.

Children with a diagnosis of autism were excluded, as were mothers with type 1 diabetes or polycystic ovarian syndrome, to focus specifically on type 2 diabetes and gestational diabetes, explained Dr Xiang.

Participant children were followed until the date of diagnosis of ADHD, last date of KPSC membership, death, or until December 31, 2014.

Children exposed to type 2 diabetes or gestational diabetes were stratified according to maternal age and ethnicity, and they were matched with children not exposed to maternal diabetes.

Of those children eligible for inclusion, 20,481 were exposed to gestational diabetes, 3407 were exposed to type 2 diabetes, and 110,905 were not exposed to diabetes.

Duration of Antidiabetic Medication Use Associated With ADHD

Outcomes were the development of ADHD and the age at diagnosis, with adjustments made for maternal age at delivery, household income, education, mother's history of ADHD, and gender, as well as potential confounders including preeclampsia/eclampsia, gestational weeks at delivery, birth weight, and birth defects.

The incidence of ADHD was similar in all groups: 4.1% in those not exposed to maternal diabetes, 3.9% in children of mothers with type 2 diabetes, and 3.8% in those exposed to gestational diabetes.

But Dr Xiang went on to explain that in children whose mothers were treated with antidiabetic medication (n = 7479), there was a small but significant increased risk of ADHD (HR, 1.20, adjusted to 1.16; P = .03), compared with children from mothers with diabetes [gestational or type 2 diabetes] who did not take any medication at all during pregnancy.

Among women with type 2 diabetes, 47% used medication during pregnancy, while 29% of those with gestational diabetes received pharmacologic treatment.

Results were then further stratified by duration of antidiabetic medication use into 1 to 29 days, 30 to 59 days, and 60 days or more, and a duration-dependent relationship with ADHD incidence was identified.

"The trend was significant both with and without adjustment for covariates, with a 23% increased incidence of ADHD in children whose mothers took antidiabetic medication for over 60 days."

The associations of ADHD with antidiabetic medication use for less than 60 days did not reach significance.

Dr Xiang acknowledged, however, that the study has limitations and stressed that more research is needed.

"We wonder if the increased duration [of use] might be a surrogate for the severity of diabetes during pregnancy and that this might be the surrogate for the increasing risk of ADHD," she observed, noting that this might be an avenue for future work.

And moderator Dr Tabak stressed that the limitations of the study should be taken seriously. "Some unmeasured confounders could be behind these findings…because these women could be socioeconomically very different."

Drs Xiang, Kautzky-Willer, and Tabak have declared no relevant financial relationships.

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European Association for the Study of Diabetes (EASD) 2016 Annual Meeting; September 16, 2016; Munich, Germany. Abstract 244.


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