Study IDs Puzzling Risk Factor for ADHD

Kids whose mothers had an autoimmune disease were more likely to develop attention-deficit/hyperactivity disorder (ADHD), according to results of a cohort study and meta-analysis.

Mothers with an autoimmune disease were 30% more likely to have a child with ADHD (hazard ratio 1.30, 95% CI 1.15-1.46), reported Timothy Nielsen, MPH, of the University of Sydney in Australia, and colleagues.

Type 1 diabetes (HR 2.23, 95% CI 1.66-3.00), psoriasis (HR 1.66, 95% CI 1.02-2.70), and rheumatic fever or rheumatic carditis (HR 1.75, 95% CI 1.06-2.89) were all associated with increased risk of ADHD in offspring, researchers reported in JAMA Pediatrics.

Results of the group’s present study and meta-analysis showed that maternal type 1 diabetes had the strongest association with ADHD. The researchers stated that the relationship with ADHD may be related to several potential mechanisms, such as shared genetic factors, or non-immune aspects of type 1 diabetes like glycemic control.

“Our study provides justification for future studies that examine the effect of maternal autoimmune diseases… on neurodevelopmental disorders in children,” Nielsen and colleagues wrote in the study. “It also highlights the importance of high quality multidisciplinary care for women with autoimmune diseases and their children.”

In an accompanying editorial, Søren Dalsgaard, MD, PhD, of Aarhus University in Denmark, wrote that this study adds important data to the field’s understanding of ADHD’s relation to specific autoimmune diseases.

Dalsgaard said that there were potential mechanisms outlined in this article, such as shared genetic or environmental factors between autoimmune illness and ADHD, or the “direct effects of maternal autoantibodies or cytokines crossing the placenta and altering the fetal immune response.” But he added that these explanations need further investigation.

“Neither this hybrid article by Nielsen et al nor the previously published epidemiologic studies give any clear answers as to which mechanisms may explain the association between autoimmune diseases and ADHD,” Dalsgaard stated. “Still, there is a growing body of evidence for associations between both the overall category and some specific autoimmune diseases and ADHD.”

Autoimmune diseases affect 3%-9% of the world’s population, disproportionately affecting reproductive-age women. Nielsen and colleagues suggested that a shared genetic weakness in both ADHD and maternal immune diseases or maternal immune activation could potentially play a role in neurodevelopmental disorders in children.

Nielsen and colleagues conducted a systematic review of the literature published before November 2019, along with analysis of a dataset from New South Wales, Australia, covering all singleton live births that took place from 2000 to 2014. In particular, the group looked for hospitalizations for both mother and child up to 2012, and matched birth data to children’s pharmaceutical information to determine ADHD treatment. Children in the study were followed until 2014.

Kids who had an ADHD hospital diagnosis or pharmaceutical treatment before they reached 3 years old were excluded from the analysis.

The researchers assessed nearly 832,000 babies, with around 12,000 born to mothers with an autoimmune disorder. Babies in the autoimmune illness cohort were matched to a control group of around 50,000 infants, for a population of about 63,000 infants. Around 1,100 male children and 330 female children were diagnosed with ADHD.

Mothers in the study were an average of 29 years old. Those with an autoimmune disease were more likely to have a mental health disorder compared to mothers who did not.

Overall, children born to mothers with an autoimmune disease were more likely to have an ADHD diagnosis. Findings did not differ in male versus female children.

In an analysis of mothers who were diagnosed with an autoimmune disease up to six months after birth, all maternal autoimmune diseases and type 1 diabetes remained associated with ADHD in children.

In a systematic review of six studies (including this one), the researchers found that any autoimmune illness (HR 1.20, 95% CI 1.03-1.38), type 1 diabetes (HR 1.53, 95% CI 1.27-1.85), hyperthyroidism (HR 1.15, 95% CI 1.06-1.26), and psoriasis (HR 1.31, 95% CI 1.10-1.56) were all associated with ADHD.

Nielsen’s group acknowledged that mothers with an autoimmune disorder recorded in this study were likely undercounted, as they did not include patients who received care for autoimmune illnesses in primary care or outpatient settings. They also did not include any data about medications mothers took during pregnancy or disease severity, which may have influenced their results.