Folate in maternal rheumatoid arthritis-filial autism spectrum disorder continuum

Rheumatoid Arthritis (RA) is an inflammatory autoimmune disease that affects women three times more than men. Epidemiological studies found that the incidence of Autism Spectrum Disorder (ASD), a neurological and developmental disorder, in children born to mothers suffering from RA is higher compared with the control population. Considering that the pathogenesis of ASD could be traced back to pregnancy and in uterine conditions, and the evidence of reduced folate levels in the brain of ASD-affected children, we aimed to study the role of folate, as an important nutritional factor during pregnancy, in associating maternal RA to ASD development in the offspring. Folate balance during RA could be influenced twice, initially during the immune activation associated with disease onset, and later during the treatment with anti-folate drugs, with a potential consequence of folate deficiency. Maternal folate deficiency during pregnancy could increase homocysteine levels, oxidative stress, and global DNA hypomethylation, all known risk factors in ASD pathogenesis. These effects could be intensified by genetic polymorphisms in the folate system, which were also found as genetic risk factors for both RA and ASD. The available evidence suggests that folate level as an important factor during RA, pregnancy and ASD could have pathological and therapeutical significance and should be carefully monitored and investigated in the RA-pregnancy-ASD axis.