Risk of Autism Spectrum Disorders in Children Born to Mothers With Rheumatoid Arthritis: A Systematic Literature Review

Objective: There is recent evidence to suggest that in utero exposure to maternal antibodies and cytokines is an important risk factor for autism spectrum disorders (ASDs). We aimed to systematically review the risk of ASDs in children born to mothers with rheumatoid arthritis (RA) compared to children born to mothers without RA. Methods: We conducted a systematic review of original articles using the electronic databases PubMed, Embase, and Web of Science. Results: Our literature search yielded a total of 70 articles. Of the potentially relevant studies retrieved, 67 were excluded for lack of relevance and/or because they did not report original data. Three studies were included in the final analysis. A case–control study found no difference in the prevalence of RA in mothers of children with ASDs versus control mothers. Another case–control study showed a statistically significant 8-fold increase in autoimmune disorders, including RA, in mothers of offspring with ASDs compared to controls. Forty-six percent of offspring with ASDs had a first-degree relative with RA, compared to 26% of controls. And in a population-based cohort study, investigators observed an increased risk of ASDs in children with a maternal history of RA compared to children born to unaffected mothers. These studies had methodologic limitations: none controlled for medication exposures, only 1 controlled for obstetric complications and considered the timing of RA diagnosis in relation to pregnancy, and all but 1 used a case–control study design. Conclusion: Observational studies suggest a potentially increased risk of ASDs in children born to mothers with RA compared to children born to mothers without RA, although data are limited.