Maternal Autoimmune Diseases Up Risk of Mental Illness in Children

Heidi Splete

May 03, 2022

Mental disorders were significantly more likely in children whose mothers had one of five common autoimmune diseases, a new study found.

Previous research has linked both maternal and paternal autoimmune diseases and specific mental disorders, such as attention-deficit/hyperactivity disorder (ADHD), but most of these studies focused on specific conditions in relatively small populations. The new study included data on more than 2 million births, making it one of the largest efforts to date to examine the association, according to the researchers, whose findings were published in JAMA Network Open.

Previous evidence of the possible association between certain maternal autoimmune diseases and mental disorders in offspring has been "scattered and limited," which "hampered an overall understanding" of the link, Fei Li, MD, the corresponding author of the study, told Medscape Medical News.

Li, of Shanghai Jiao Tong University School of Medicine, in China, and her colleagues reviewed data from a Danish registry cohort of singleton births with up to 38 years of follow-up. They explored associations between a range of maternal autoimmune diseases diagnosed before childbirth and the risks of mental disorders in children in early childhood through young adulthood.

The study population included 2,254,234 births and 38,916,359 person-years. Data on mental health were collected from the Psychiatric Central Research Register and the country's National Patient Register. The median age of the children at the time of assessment was 16.7 years; approximately half were male.

A total of 50,863 children (2.26%) were born to mothers who had been diagnosed with autoimmune diseases before childbirth. During the follow-up period, 5460 children of mothers with autoimmune diseases and 303,092 children of mothers without autoimmune diseases were diagnosed with a mental disorder (10.73% vs 13.76%), according to the researchers.

The risk of being diagnosed with a mental disorder was significantly higher among children of mothers with any autoimmune disease (hazard ratio [HR], 1.16), with an incidence of 9.38 vs 7.91 per 1000 person-years, the researchers report.

Should be: The increased risk persisted when the results were classified by organ system, including connective tissue (HR, 1.24), endocrine (HR, 1.19), gastrointestinal (HR, 1.11), blood (HR, 1.10), nervous (HR, 1.17), and skin (HR, 1.19).

The five autoimmune diseases in mothers that were most commonly associated mental health disorders in children were type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and psoriasis vulgaris.

The greatest risk for children of mothers with any autoimmune disease was observed for organic conditions such as delirium (HR, 1.54), followed by obsessive-compulsive disorder (HR, 1.42), schizophrenia (HR, 1.35), and mood problems (HR, 1.12).

Children of mothers with any autoimmune disorder also had a significantly increased risk of autism (HR, 1.21), intellectual disability (HR, 1.19), and ADHD (HR, 1.19).

The results add to evidence that activation of the maternal immune system may drive changes in the brain and behavioral problems, which has been observed in animal studies, the researchers write.

Potential underlying mechanisms in need of more exploration include genetic risk factors, maternal transmission of autoantibodies to the fetus during pregnancy, and the increased risk of obstetric complications, such as preterm birth, for women with autoimmune disorders that could affect mental development in children, they add.

The study findings were limited by several factors, including the lack of data on potential exacerbation of autoimmune disease activity during pregnancy and its effect on the fetus, the researchers note. Other limitations included potential detection bias, lack of data on mental disorders in adulthood, and potential changes in diagnostic criteria over the long study period.

The results were strengthened by the use of a population-based registry, the large sample size, and ability to consider a range of confounders, the researchers say.

"This study could help acquire a comprehensive compilation of the associations between maternal autoimmune disorders diagnosed before childbirth and offspring's mental disorders from childhood through early adulthood," Li told Medscape Medical News.

For clinicians, Li said, the findings suggest that the offspring of mothers with autoimmune diseases may benefit from long-term surveillance for mental health disorders.

"Further studies should provide more evidence on the detailed associations of specific maternal autoimmune diseases with a full spectrum of mental disorders in offspring, and more research on underlying mechanisms is needed as well," she said.

Pay Early Attention

M. Susan Jay, MD, an adjunct professor of pediatrics at the Medical College of Wisconsin, Milwaukee, said previous efforts to examine the association between maternal autoimmunity were hampered by study design, small samples, and self-report of disease history ― problems the new research avoids.

The large patient population allowed for detailed subgroup analysis of different conditions and outcomes. Another advantage was the availability of sociodemographic and clinical information, which allowed for the elimination of confounding factors, said Jay, who was not involved in the research.

"It would be prudent to follow children of mothers with autoimmune disorders before or during pregnancy for mental health issues, and if identified clinically, to offer psychological and developmental behavioral support options," Jay added.

The authors have reported no relevant financial relationships.

JAMA Netw Open. April 15, 2022. Full text

Heidi Splete is a freelance medical journalist with 20 years of experience.

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