Children born to women who develop diabetes either before or during their pregnancy could be at risk for developing attention-deficit/hyperactivity disorder, data from a large multinational cohort study appear to show.
Considering more than 4.5 million mother-child pairs, it was found that children whose mothers had diabetes around the time of their pregnancy were 16% more likely to have ADHD diagnosed than were those whose mothers did not.
An increased risk was seen regardless of the type of diabetes, and regardless of whether or not the diabetes was present before or appeared during the pregnancy.
“We found a small increased risk of ADHD in children born to mothers with diabetes, including pregestational diabetes and gestational diabetes,”, reported at the annual meeting of the European Association for the Study of Diabetes.
Dr. Cesta, a postdoctoral researcher in the Centre for Pharmacoepidemiology at the Karolinska Institutet in Stockholm noted that the effect sizes seen were lower than had been reported previously.
“This may be because we adjusted for a large number of covariates, including maternal ADHD and psychiatric disorders,” Dr. Cesta said.
ADHD and diabetes
“Previous studies have reported an increase in the risk of ADHD in children born to mothers with diabetes,” explained Dr. Cesta.
However, “these studies have been limited by the use of self-reported data, small sample sizes, lack of adjustment for important confounders, and they’re often limited to [White] populations,” she added. “There’s a lot of heterogeneity between these studies,” she said.
To try to iron out the differences seen in the prior studies, Dr. Cesta and associates looked at data from several databases based in Hong Kong (Clinical Data Analysis and Reporting System), four Nordic countries (Population Health Registers for Finland, Iceland, Norway, and Sweden), and Taiwan (National Health Insurance Database).
To create the matched mother-child pairs, the databases were searched to find women who had children born between 2001 and 2018, and who had follow-up data available up to 2020 on not only their diabetes status and child’s ADHD status, but also other parameters, such as other maternal diagnoses, maternal medications, and a host of sociodemographic factors.
More than 24 potentially confounding or covariates were considered in the analysis, which used Cox proportional hazard regression modeling and propensity score analysis to calculate hazard ratios with 95% confidence intervals.
“We looked at whether [mothers] had a diagnosis of ADHD themselves, or other psychiatric disorders, because there is high heritability for these disorders,” Dr. Cesta said, indicating that all bases had endeavored to be covered.
Results showed some differences in the prevalence of diabetes and ADHD between the three cohorts used in the analysis. The prevalence of any maternal diabetes ranged from 8.8% in the Hong Kong cohort to 3.3% in the Taiwan cohort, with a prevalence of 6.8% for the Nordic cohort.
Rates of pregestational diabetes were lowest in the Taiwan and Hong Kong cohorts, at 0.2% and 0.5%, respectively, and 2.2% in the Nordic cohort. Gestational diabetes rates were a respective 3.1%, 7.8%, and 4.6%.
The highest rate of ADHD in children was seen in the Taiwan cohort, at 9.6%, followed by 4.2% for the Hong Kong cohort, and 2.6% for the Nordic cohort.
The hazard ratio for having childhood ADHD was 1.16 when comparing any maternal diabetes to no maternal diabetes, 1.40 comparing mothers with and without pregestational diabetes, and a respective 1.36 and 1.37 comparing those with and without type 1 diabetes, and those with and without type 2 diabetes.
The HR for childhood ADHD comparing mothers with and without gestational diabetes was 1.13.
“Within the analysis for gestational diabetes, we had enough numbers to look at siblings that are discordant for maternal gestational diabetes,” Dr. Cesta said. Essentially “we’re comparing two siblings from the same mother, one that was exposed to gestational diabetes, one that wasn’t,” she explained.
Interestingly there was no association between ADHD and maternal gestational diabetes in the sibling analysis (HR, 1.0).
“When it comes to gestational diabetes, the evidence from our sibling analysis indicate that the association may actually be confounded by shared genetics and environmental factors,” said Dr. Cesta.
“So, future studies should explore the role of specific genetic factors in glycemic control during pregnancy and the relationship between maternal diabetes and ADHD.”