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 ( ASD s). We aimed to systematically review the risk of ASD s 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 ASD s versus control mothers. Another case–control study showed a statistically significant 8‐fold increase in autoimmune disorders, including RA , in mothers of offspring with ASD s compared to controls. Forty‐six percent of offspring with ASD s 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 ASD s 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 ASD s in children born to mothers with RA compared to children born to mothers without RA , although data are limited.