Children of women with autoimmune diseases may be at increased risk of attention-deficit/hyperactivity disorder (ADHD), a new study suggests. Researchers examined data on 12,767 full-term singleton infants whose mothers had any autoimmune disease, as well as a propensity score-matched control group of 50,440 babies whose mothers had no history of autoimmune disease. A total of 1,094 male children (3.4%) and 332 female children (1.1%) were diagnosed with ADHD during follow-up, with the majority diagnosed before their eighth birthday. Overall, children whose mothers had one of 35 different autoimmune diseases were significantly more likely to develop ADHD (hazard ratio 1.30) compared to the control group. Certain individual maternal autoimmune diseases were associated with even higher risk, including type 1 diabetes (HR 2.23), psoriasis (HR 1.66), and rheumatic fever or rheumatic carditis (HR 1.75) according to the report in JAMA Pediatrics. "ADHD, like other neurodevelopmental disorders, has a significant genetic component, but there is increasing evidence that environmental factors with an inflammatory response, such as maternal autoimmune disease, can increase expression of neurodevelopmental disorders," said lead study author Timothy Nielsen of the University of Sydney in Australia. Previous research has found associations between maternal inflammation and neurodevelopmental outcomes both in humans and in animal models, Nielsen said by email. He and his colleagues hypothesized that autoimmune-related inflammation might alter brain development by directly causing inflammation via chemical signaling, changing the expression of genes, or by activating microglia in the unborn child's brain. "These changes may lead directly to ADHD symptoms or may make the child more vulnerable to other environmental factors later in life," Nielsen said. Researchers performed a meta-analysis of data from the current study as well as from five previous studies of the connection between maternal autoimmune disease and offspring ADHD. In the meta-analysis, any maternal autoimmune disease was associated with an increased risk of ADHD in children (HR 1.20). The meta-analysis also found an increased risk of ADHD in kids when mothers had type 1 diabetes (HR 1.53), hyperthyroidism (HR 1.15), and psoriasis (HR 1.31). One limitation of the study is the lack of outpatient or primary care records for identifying maternal autoimmune disease; hospital records used in the analysis may underestimate the prevalence of these conditions because patients don't always require hospitalization. Other limitations of the analysis include the reliance on stimulant prescriptions to identify children with ADHD, as well as the lack of data on symptom severity or comorbidities among those with ADHD," the authors note. "It is also important not to alarm mothers with autoimmune disease and to remember that despite the large increased relative risk of ADHD, previous studies have shown that the absolute risk among mothers with autoimmune disease is low," said Dr. Soren Dalsgaard, a professor of psychiatric epidemiology at Aarhus University, in Denmark, who authored a commentary accompanying the study. Clinicians should be more aware that several immune-related disorders are strongly associated with ADHD, an awareness that might help lead to earlier diagnosis and treatment of ADHD in children, Dr. Dalsgaard said by email. "However, maternal autoimmune diseases explain only a small fraction of all cases with ADHD," Dr. Dalsgaard said. —Lisa Rapaport Source
