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Grand Rounds

Reduced Risk of Autism in Offspring Exposed to Folic Acid During Pregnancy

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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

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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

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