High dose folic acid during pregnancy and the risk of autism; The birth order bias: A nested case-control study

Reprod Toxicol. 2019 Oct:89:173-177. doi: 10.1016/j.reprotox.2019.07.083. Epub 2019 Jul 31.

Abstract

Objective: To examine whether there is an association between the cumulative dose of folic acid (FA) purchased by mothers, and risk of autistic spectrum disorders (ASD) in their progeny.

Methods: We identified 2009 singletons who received an ASD diagnosis from a cohort of 480,526 children born in a large health organization in Israel from 2000 through 2013. ASD patients were individually matched to ASD-free children (n = 19,886). Median cumulative daily doses of supplemented FA during the 12-month period prior to the end of pregnancy (from dispensing records) were compared using conditional logistic regression models.

Results: Children with ASD were more likely to be first-born, and birth-order was significantly associated with FA use. In multivariable analysis, there were no statistically significant differences in the cumulative dose of FA between the groups.

Conclusion: Birth order effects need to be accounted for in analyses aiming to decipher the associations between gestational FA use and developmental outcomes.

Keywords: Autistic spectrum disorder; Birth order; Folate; Folic acid; Pregnancy.

MeSH terms

  • Autism Spectrum Disorder / chemically induced
  • Autism Spectrum Disorder / epidemiology*
  • Case-Control Studies
  • Child
  • Databases, Factual
  • Dose-Response Relationship, Drug
  • Female
  • Folic Acid / administration & dosage*
  • Folic Acid / adverse effects
  • Humans
  • Israel
  • Logistic Models
  • Male
  • Maternal Exposure / adverse effects*
  • Medical Records
  • Multivariate Analysis
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced
  • Prenatal Exposure Delayed Effects / epidemiology*

Substances

  • Folic Acid