BACKGROUND AND PURPOSE: 

• Data on whether maternal vitamin supplements may reduce the risk for autism spectrum disorder (ASD) in offspring are inconclusive  
• Levine et al. (JAMA Psychiatry, 2017) sought to determine whether the use of folic acid and multivitamin supplements during pregnancy are associated with a decreased risk of autism in offspring 

METHODS: 

• Case-control cohort study  
• 1/3 of all children born in Israel between 2003 – 2007 derived from a national database and followed to 2015 
• Comparison of rates were made between the following two cohorts 
  • Children diagnosed with ASD  
  • Controls using a random sample from the cohort  
• Primary outcome was association between maternal multivitamin supplementation and risk of ASD in offspring  
  • In Israel, folic acid supplementation is recommended but food is not fortified  
• Vitamin supplements were classified as folic acid (B9) and multivitamin supplements (Anatomical Therapeutic Chemical A11 codes vitamins A, B, C, and D) 
  • Coding system cannot discriminate multivitamins with and without folic acid  
• Risks were adjusted for confounders and quantified by relative risk (RR) 

RESULTS: 

• Data were collected from 45,300 children (22,090 girls and 23 210 boys) 
  • Mean [SD] age was 10.0 [1.4] years at the end of follow-up 
  • 572 (1.3%) received a diagnosis of ASD 
• Maternal exposure to folic acid and/or multivitamin supplements compared with no exposure
  • Before pregnancy:  Was associated with a lower likelihood of ASD in offspring 
    • (RR, 0.39; 95% CI, 0.30-0.50; P < .001)  
  • During pregnancy:  Was associated with a lower likelihood of ASD in offspring 
    • (RR, 0.27; 95% CI, 0.22-0.33; P < .001)  
• When analyzing folic acid separately, maternal exposure was associated with a lower likelihood of ASD   
  • Folic acid before pregnancy (RR, 0.56; 95% CI, 0.42-0.74; P = .001) 
  • Folic acid during pregnancy (RR, 0.32; 95% CI, 0.26-0.41; P < .001) 
• When analyzing multivitamin supplements separately, maternal exposure was associated with a lower likelihood of ASD  
  • Multivitamin supplements before pregnancy (RR, 0.36; 95% CI, 0.24-0.52; P < .001) 
  • Multivitamin supplements during pregnancy (RR, 0.35; 95% CI, 0.28-0.44; P < .001) 
• Similar results in male and female offspring 

CONCLUSION: 

• The authors recognize limitations 
  • Cannot account for all confounders 
  • Study had limited sample size and they could not perform sibling control analyses  
  • Causality cannot be inferred from an association study  
• Maternal exposure to folic acid and/or multivitamin supplements was associated with a lower likelihood of ASD in the offspring 

Learn More – Primary Sources:  

Association of Maternal Use of Folic Acid and Multivitamin Supplements in the Periods Before and During Pregnancy With the Risk of Autism Spectrum Disorder in Offspring

Related ObG Topics:

(Cochrane 2016) Vitamin D During Pregnancy and Adverse Pregnancy Outcomes

Do Multivitamins Reduce Risk for Adverse Birth Outcomes?

Do Maternal Multivitamin Supplements Decrease Risk for Autism in Offspring?

NTDs and Pregnancy – Folic Acid Recommendations