Maternal autoimmunity associated with ADHD in children

JAMA Pediatrics: Association of Maternal Autoimmune Disease With Attention-Deficit/Hyperactivity Disorder in Children

The biology of autoimmunity during pregnancy can have numerous consequences for the health of both mother and offspring; these include such conditions as childhood tics and OCD, autism, congenital heart block; infertility, miscarriage and preterm birth; placental abruption, numerous consequences of antithyroid antibodies, etc. Now, an original investigation just published in JAMA Pediatrics adds to the evidence associating maternal autoimmune disorders and subsequent ADHD in their children. The authors state:

There is growing evidence that immune-related cells and proteins play a role in brain development and function7 and that maternal immune activation, including infection, autoimmune disease, and chronic inflammation during pregnancy, increases the risk of neurodevelopmental disorders among children.8-10 Maternal autoantibodies and proinflammatory cytokines are hypothesized to cross the placenta and alter fetal brain development. Potential mechanisms include epigenetic modulation of neurodevelopmental genes,11 activation of microglia (the innate immune cells of the brain), and modification of synapse formation and function.12

The authors examined data for 63,050 whose mother's had various autoimmune diagnoses. This original paper included both their own study and a meta-analysis of earlier studies. This yielded a correlation between maternal autoimmunity and ADHD in their offspring.

Any maternal autoimmune disease increases ADHD risk

Both their study results and the meta-analysis confirmed the association.

In this cohort, any autoimmune disease was associated with ADHD in offspring (HR, 1.30; 95% CI 1.15-1.46), as was 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). Five studies (including the present study) were included in the meta-analysis. Any autoimmune disease (2 studies: HR, 1.20; 95% CI, 1.03-1.38), type 1 diabetes (4 studies: HR, 1.53; 95% CI, 1.27-1.85), hyperthyroidism (3 studies: HR, 1.15; 95% CI, 1.06-1.26), and psoriasis (2 studies: HR, 1.31; 95% CI, 1.10-1.56) were associated with ADHD.

Type 1 diabetes, formerly virtually unknown in adults, now accounts for more than half the new cases of autoimmune diabetes. Taking into consideration LADA (latent autoimmune diabetes of adults) that precedes the onset of diabetes would likely greatly expand the numbers. Autoimmune thyroiditis is a common diagnosis; including individuals who have predictive antibodies prior to qualifying for fully developed Hashimoto's disease (autoimmune thyroiditis) vastly increases the numbers.

Consistent with earlier research associated with other brain-based conditions

The authors note the consistency of their findings with previous research including association with additional brain-based diagnoses in offspring:

Our results were consistent with previous research reporting an association between autoimmune disease and impaired mental health, particularly depression and psychosis,29-31 and between maternal autoimmune disease and child neurodevelopmental disorders, including autism spectrum disorder,14obsessive compulsive disorder, and tics or Tourette syndrome.32 Results were also consistent with the general hypothesis that adverse maternal immune function during pregnancy alters fetal neurodevelopment via direct action of cytokines and autoantibodies, epigenetic modulation, or microglia activation. The observed association may also be a product of shared genetic vulnerability between autoimmune diseases and ADHD. Attention-deficit/hyperactivity disorder is highly heritable,33 and population-based cohort studies have reported associations between allergic and autoimmune diseases and ADHD within individuals.17,34

An editorial in the same volume of JAMA Pediatrics states:

...there is a growing body of evidence for associations between both the overall category and some specific autoimmune diseases and ADHD.

The authors conclude:

In this cohort study, maternal autoimmune disease was associated with increased risk of ADHD among offspring. Our study provides justification for future studies that examine the effect of maternal autoimmune diseases, including biomarkers, condition severity, and management in pregnancy and in the periconception period, on neurodevelopmental disorders in children. It also highlights the importance of high-quality multidisciplinary care for women with autoimmune diseases and their children. Health care professionals should discuss reproductive goals with women who have autoimmune disease,and clinicians should encourage planning pregnancies when the disease is stable and well managed.36,37 Children of women with autoimmune disease may benefit from additional follow-up and support for developmental issues. The causes of neurodevelopmental disorders are complex and multifactorial; however, our study suggests maternal autoimmunity may represent one avenue for further investigation.