Women With Lupus Have More Children With Autism

Alice Goodman

November 11, 2013

SAN DIEGO — Children born to women with lupus are at twice the risk for autism spectrum disorders as children born to women without a chronic inflammatory disease, according to a new study.

"Mothers with lupus should not be alarmed by our findings. The absolute risk of developing autism spectrum disorders still is relatively small," said lead author Evelyne Vinet, MD, from the McGill University Health Centre in Montreal.

The research implicates autoantibodies, such as N-methyl-D-aspartate receptor (NMDA) antibodies, in the pathogenesis of systemic lupus erythematosus. "Our findings should prompt further research on the role of NMDA receptor antibodies," she explained.

Dr. Vinet presented the results here at the American College of Rheumatology 2013 Annual Meeting.

Previous experimental studies have shown the antibodies are related to lupus, and that cytokines such as interleukin-6 alter fetal brain development and induce behavioral anomalies in offspring.

However, "no previous study has specifically addressed the risk of autism spectrum disorders in the offspring of mothers with lupus," Dr. Vinet explained. To assess that risk, the researchers used the largest cohort of offspring of mothers with lupus.

 
Mothers with lupus should not be alarmed by our findings. The absolute risk of developing autism spectrum disorders still is relatively small.
 

From the Offspring of Systemic Lupus Erythematosus Mothers Registry, they identified all women in Quebec who had at least 1 hospitalization for delivery after being diagnosed with lupus.

They found 509 women with lupus who gave birth to 719 children. These cases were matched for age and year of delivery with 5824 control mothers who gave birth to 8493 children.

Mean age of the mothers was about 30 years, and mean follow-up was about 9 years.

A diagnosis of autism was more common in children born to mothers with lupus than without (1.4% vs 0.6%). For children with autism, mean age at diagnosis was slightly younger in children born to mothers with lupus than without (3.8 vs 5.7 years).

Multivariate analysis revealed that children born to mothers with lupus were about twice as likely to develop autism as those born to mothers without lupus (hazard ratio, 2.31; 95% confidence interval, 1.03 - 5.16).

A subgroup analysis looked at in utero exposure to medication in 1925 children. None of the 18 children with autism had been exposed to antimalarials, antidepressants, or immunosuppressants. However, 1 child born to a mother with lupus was exposed to corticosteroids, and 1 child born to a mother without lupus was exposed to an anticonvulsant.

"Physicians should discuss these findings when counseling women with lupus who are considering getting pregnant, and ideally plan the pregnancy at a time of low disease activity, reviewing the safety of their medications," Dr. Vinet explained.

This research "supports other studies showing an increased risk for a child with autism in mothers with various autoimmune diseases," said Betty Diamond, MD, head of the Center for Autoimmune and Musculoskeletal Disorders at the Feinstein Institute for Medical Research in New York City, told Medscape Medical News.

"Our own studies show this for lupus as well. The presumption is that this is caused by maternal antibodies altering fetal brain development, but this requires further study," she explained.

"Our studies in lupus show that a subset of anti-DNA antibodies can bind a brain antigen and cause cognitive impairment. We believe that this might explain the increased incidence of learning disabilities that has been reported in the children of women with lupus. The exciting part of this is that decoy antigens may be a therapeutic strategy to protect to the brain," Dr. Diamond noted.

Dr. Vinet and Dr. Diamond have disclosed no relevant financial relationships.

ACR 2013 Annual Meeting: Abstract 2831. Presented October 30, 2013.

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