Prenatal Exposure to Nonpersistent Chemical Mixtures and Fetal Growth: A Population-Based Study

Environ Health Perspect. 2021 Nov;129(11):117008. doi: 10.1289/EHP9178. Epub 2021 Nov 24.


Background: Prenatal exposure to mixtures of nonpersistent chemicals is universal. Most studies examining these chemicals in association with fetal growth have been restricted to single exposure models, ignoring their potentially cumulative impact.

Objective: We aimed to assess the association between prenatal exposure to a mixture of phthalates, bisphenols, and organophosphate (OP) pesticides and fetal measures of head circumference, femur length, and weight.

Methods: Within the Generation R Study, a population-based cohort in Netherlands (n=776), urinary concentrations of 11 phthalate metabolites, 3 bisphenols, and 5 dialkylphosphate (DAP) metabolites were measured at <18, 18-25, and >25 weeks of gestation and averaged. Ultrasound measures of head circumference, femur length, and estimated fetal weight (EFW) were taken at 18-25 and >25 weeks of gestation, and measurements of head circumference, length, and weight were performed at delivery. We estimated the difference in each fetal measurement per quartile increase in all exposures within the mixture with quantile g-computation.

Results: The average EFW at 18-25 wk and >25wk was 369 and 1,626g, respectively, and the average birth weight was 3,451g. Higher exposure was associated with smaller fetal and newborn growth parameters in a nonlinear fashion. At 18-25 wk, fetuses in the second, third, and fourth quartiles of exposure (Q2-Q4) had 26g [95% confidence intervals (CI):-38, -13], 35g (95% CI: -55, -15), and 27g (95% CI: -54, 1) lower EFW compared with those in the first quartile (Q1). A similar dose-response pattern was observed at >25wk, but all effect sizes were smaller, and no association was observed comparing Q4 to Q1. At birth, we observed no differences in weight between Q1-Q2 or Q1-Q3. However, fetuses in Q4 had 91g (95% CI: -258, 76) lower birth weight in comparison with those in Q1. Results observed at 18-25 and >25wk were similar for femur length; however, no differences were observed at birth. No associations were observed for head circumference.

Discussion: Higher exposure to a mixture of phthalates, bisphenols, and OP pesticides was associated with lower EFW in the midpregnancy period. In late pregnancy, these differences were similar but less pronounced. At birth, the only associations observed appeared when comparing individuals from Q1 and Q4. This finding suggests that even low levels of exposure may be sufficient to influence growth in early pregnancy, whereas higher levels may be necessary to affect birth weight. Joint exposure to nonpersistent chemicals may adversely impact fetal growth, and because these exposures are widespread, this impact could be substantial.

Publication types

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

MeSH terms

  • Birth Weight
  • Female
  • Fetal Development
  • Humans
  • Infant, Newborn
  • Maternal Exposure
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Prospective Studies
  • Ultrasonography, Prenatal