Maternal Folic Acid Supplementation and Risk of Autism—Reply

Abstract

To the Editor: Dr Suren and colleagues reported on the decreased incidence of autistic disorder in children whose mothers received prenatal folic acid supplementation around the time of conception. The study expands on their previous report of an association between prenatal folic acid and severe childhood language delay, a key feature of autism spectrum disorders. Even though the epidemiological study design precludes a demonstration of causation, this study does suggest an association between folate metabolism and the development of autism spectrum disorders. Aberrant folatedependent metabolism and increased oxidative stress have been identified in autism spectrum disorders. Furthermore, cerebral folate receptor autoantibodies have been identified in up to three quarters of children with autism spectrum disorders. Treatment with folinic acid, a metabolically active form of folic acid, in children with autism spectrum disorders positive for folate receptor autoantibodies has led to significantly improved nonverbal communication, language, attention, and stereotypies. There is a dearth of research focusing on metabolic and immunological dysfunction in autism spectrum disorders and the neurobiological underpinnings of these disorders remain largely elusive. The combination of findings from clinical and epidemiological research should prompt heightened interest in and study of folate-related metabolic and immune processes in autism spectrum disorders.