Maternal Autoimmune Disease linked to ADHD in Children: JAMA Pediatrics

Several previous epidemiologic studies have found autoimmune diseases to be associated with mental disorders, with the largest evidence base being for associations with schizophrenia, bipolar disorder, depression, and an autism spectrum disorder. Multiple potential mechanisms have been proposed for the association between maternal autoimmune diseases and mental disorders. Overall, these mechanisms are thought to include shared genetic and environmental risk factors or direct effects of maternal autoantibodies or cytokines crossing the placenta and altering the fetal immune response, which in turns leads to changes in the central nervous system. However, much fewer studies have examined the associations with attention-deficit/hyperactivity disorder (ADHD), tic disorders, and obsessive-compulsive disorder. For this purpose, researchers of the University of Sydney, Australia, conducted a study to examine the association between maternal autoimmune disease and ADHD within a population-based cohort and combine results in a subsequent systematic review and meta-analysis.

It was a cohort study conducted of singleton children born at term gestation (37-41 weeks) in New South Wales, Australia, from July 1, 2000, to December 31, 2010, and followed up until the end of 2014. Researchers conducted a systematic review evaluating the articles from MEDLINE, Embase, and Web of Science databases to identify all studies published before November 20, 2019. They included a total of 12 610 children exposed to maternal autoimmune disease were propensity score-matched (1:4) to 50 440 unexposed children, for a total cohort of 63 050. They determined a child with ADHD if the child had

(1) an authorization or filled prescription for stimulant treatment for ADHD or

(2) a hospital diagnosis of ADHD.

The primary outcome assessed was a child ADHD identified from the stimulant authorization or prescription data and diagnoses in linked hospital admission records. They used multivariable Cox regression to assess the association between maternal autoimmune disease and ADHD adjusted for child sex. They assessed the data of 831 718 singleton, term infants born to 831 718 mothers from January 13 to April 20, 2020.

In this cohort, researchers found that any autoimmune disease was associated with ADHD in offspring (HR, 1.30), as was type 1 diabetes (HR, 2.23), psoriasis (HR, 1.66), and rheumatic fever or rheumatic carditis (HR, 1.75). In a systematic review of six studies (including this one), they found that any autoimmune disease (2 studies: HR, 1.20), type 1 diabetes (4 studies: HR, 1.53), hyperthyroidism (3 studies: HR, 1.15), and psoriasis (2 studies: HR, 1.31) were associated with ADHD.

The authors concluded, "In this cohort study, maternal autoimmune diseases were associated with increased ADHD among children. These findings suggest possible shared genetic vulnerability between autoimmune disease and ADHD or a potential role for maternal immune activation in the expression of neurodevelopmental disorders in children. Future studies measuring disease activity, modifiers, and medication use are required to better understand the mechanisms underlying this association".

For further information:

https://jamanetwork.com/journals/jamapediatrics/article-abstract/2775254