Clinical Research: Maternal Multivitamin and B12 Supplementation – Incidence of Children with Autism Spectrum Disorder
Reviewed by: Alan Gaby, MD
Author: Raghavan R, et al
Reference: Maternal plasma folate, vitamin B12 levels and multivitamin supplementation during pregnancy and risk of autism spectrum disorder in the Boston Birth Cohort. Experimental Biology 2016 Meeting
Design: Prospective cohort study.
Participants: Low-income pregnant women living in Boston (n = 1,391).
Study Medication and Dosage: n/a
Primary Outcome Measure: Incidence of autism spectrum disorders (ASD) in the children.
Key Findings: Maternal multivitamin supplementation during pregnancy was associated with a significantly lower risk of ASD across all trimesters. However, high levels of maternal plasma folate (above 59 nmol/L; hazard ratio [HR] = 2.27; p = 0.007)) and vitamin B12 (above 600 pmol/L; HR = 3.01; p = 0.001) were associated with an increased risk of ASD. The greatest risk was in children of mothers who had high levels of both folate and vitamin B12 (HR = 17.6; p < 0.001).
Practice Implications: A superficial interpretation of this research might be that taking a multivitamin during pregnancy can prevent ASD, but that taking too much folic acid or vitamin B12 can increase the risk of developing ASD. This study was widely reported in the media and many reporters concluded that taking a lot of folic acid or vitamin B12 during pregnancy may be harmful. Neither the original study nor the media reports speculated on how much of these vitamins is too much.
The study described above was observational and therefore cannot prove causation. The likelihood is that the reported adverse associations are spurious and do not imply a deleterious effect of folic acid or vitamin B12. The presence of a high serum folate concentration in a person who is not taking large doses of folic acid is a marker for small-intestinal bacterial overgrowth (SIBO), because some organisms that colonize the small intestine are capable of synthesizing folates.i ii SIBO can cause deficiencies of many different nutrients, which could increase the risk of abnormal fetal brain development. Thus, high folate levels may be associated with an increased risk of ASD not because of any adverse effect of folate, but because of the association of high folate levels with SIBO. Similarly, an elevated vitamin B12 level is seen in people with liver disease,iii and even subtle liver dysfunction during pregnancy has the potential to cause adverse outcomes in the child.
Folic acid supplementation during pregnancy has clearly been shown to prevent neural tube defects. For women who have had a previous child with a neural tube defect, the Centers for Disease Control and Prevention (CDC) recommends a relatively large dose of folic acid (4,000 μg per day). Nothing about the present study should dissuade these women from following the CDC guidelines.
[i] Camilo E, et al. Folate synthesized by bacteria in the human upper small intestine is assimilated by the host. Gastroenterology 1996;110:991-998.
[ii] Shah HN, et al. Constipation in patients with thiamine deficiency after Roux-en-Y gastric bypass surgery. Digestion 2013;88:119-124.
[iii] Arendt JFB, Nexo E. Unexpected high plasma cobalamin: proposal for a diagnostic strategy. Clin Chem Lab Med 2013;51:489-496.