Maternal Exposure to Per- and Polyfluoroalkyl Substances and Offspring Chromosomal Abnormalities: The Japan Environment and Children's Study

Environ Health Perspect. 2024 Sep;132(9):97004. doi: 10.1289/EHP13617. Epub 2024 Sep 11.

Abstract

Background: Although recent in vitro experimental results have raised the question of whether maternal exposure to per- and polyfluoroalkyl substances (PFAS) may be a potential environmental risk factor for chromosomal abnormalities, epidemiological studies investigating these associations are lacking.

Objectives: This study examined whether prenatal PFAS exposure is associated with a higher prevalence of chromosomal abnormalities among offspring.

Methods: We used data from the Japan Environment and Children's Study, a nationwide birth cohort study, and employed logistic regression models to examine the associations between maternal plasma PFAS concentrations in the first trimester and the diagnosis of chromosomal abnormalities in all births (artificial abortions, miscarriages, stillbirths, and live births) up to 2 years of age. In addition, we examined associations with mixtures of PFAS using multipollutant models.

Results: The final sample consisted of 24,724 births with singleton pregnancies, of which 44 confirmed cases of chromosomal abnormalities were identified (prevalence: 17.8/10,000 births). When examined individually, exposure to perfluorononanoic acid (PFNA) and perfluorooctane sulfonic acid (PFOS) showed positive associations with any chromosomal abnormalities with age-adjusted odds ratios of 1.81 (95% CI: 1.26, 2.61) and 2.08 (95% CI: 1.41, 3.07) per doubling in concentration, respectively. These associations remained significant after Bonferroni correction, although they did not reach the adjusted significance threshold in certain sensitivity analyses. Furthermore, the doubling in all PFAS included as a mixture was associated with chromosomal abnormalities, indicating an age-adjusted odds ratio of 2.25 (95% CI: 1.34, 3.80), with PFOS as the predominant contributor, followed by PFNA, perfluoroundecanoic acid (PFUnA), and perfluorooctanoic acid (PFOA).

Discussion: The study findings suggested a potential association between maternal exposure to PFAS, particularly PFOS, and chromosomal abnormalities in offspring. However, the results should be interpreted cautiously, because selection bias arising from the recruitment of women in early pregnancy may explain the associations. https://doi.org/10.1289/EHP13617.

MeSH terms

  • Adult
  • Alkanesulfonic Acids* / blood
  • Alkanesulfonic Acids* / toxicity
  • Birth Cohort
  • Caprylates / blood
  • Caprylates / toxicity
  • Child, Preschool
  • Chromosome Aberrations* / chemically induced
  • Chromosome Aberrations* / statistics & numerical data
  • Cohort Studies
  • Environmental Pollutants / blood
  • Environmental Pollutants / toxicity
  • Female
  • Fluorocarbons* / blood
  • Fluorocarbons* / toxicity
  • Humans
  • Infant
  • Infant, Newborn
  • Japan / epidemiology
  • Male
  • Maternal Exposure* / adverse effects
  • Maternal Exposure* / statistics & numerical data
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced
  • Prenatal Exposure Delayed Effects / epidemiology

Substances

  • Fluorocarbons
  • Alkanesulfonic Acids
  • perfluorooctane sulfonic acid
  • Environmental Pollutants
  • Caprylates