Prenatal phthalate exposures and autism spectrum disorder symptoms in low-risk children

Neurotoxicol Teratol. 2021 Jan-Feb;83:106947. doi: 10.1016/ Epub 2021 Jan 5.


Background: Prenatal exposure to environmental chemicals has been associated with Autism Spectrum Disorder (ASD) symptoms in some, but not all, studies, but most research has not accounted for other childhood behavior problems.

Objectives: To evaluate the specific associations of prenatal phthalate exposures with ASD symptoms in children (ages 3-6) accounting for other behavior problems, and to assess sex differences in these associations.

Methods: We measured phthalate metabolites in prenatal urine samples. Mothers completed the Social Responsiveness Scale-2nd edition (SRS-2) to assess child ASD symptoms and the Child Behavior Checklist (CBCL) to assess general behavior problems. We assessed associations of the sum of di-(2-ethylhexyl) phthalate metabolites, monobutyl phthalate, mono-isobutyl phthalate, and monoethyl phthalate (mEP) with ASD symptoms, adjusting for other behavior problems, using linear regression models (n=77).

Results: Most associations were null, and the sample size limited power to detect associations, particularly in the stratified analyses. After adjusting for internalizing and externalizing problems from the CBCL, ASD symptoms increased for each doubling of prenatal mEP concentration among boys only.

Conclusions: Further investigation of maternal prenatal urinary phthalate metabolite concentrations and ASD symptoms while adjusting for other behavioral problems is warranted.

Keywords: Autism Spectrum disorder; Broad autism phenotype; Child behavior checklist; Endocrine disruptors; Phthalates; Social responsiveness scale–2nd edition.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autism Spectrum Disorder / etiology*
  • Child
  • Child Behavior Disorders / etiology
  • Child, Preschool
  • Cohort Studies
  • Endocrine Disruptors / administration & dosage
  • Endocrine Disruptors / toxicity*
  • Endocrine Disruptors / urine
  • Female
  • Humans
  • Linear Models
  • Male
  • Michigan
  • Phthalic Acids / administration & dosage
  • Phthalic Acids / toxicity*
  • Phthalic Acids / urine
  • Pregnancy
  • Prenatal Exposure Delayed Effects / etiology*
  • Prenatal Exposure Delayed Effects / urine
  • Risk Factors
  • Young Adult


  • Endocrine Disruptors
  • Phthalic Acids