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PFAS exposure during pregnancy: Implications for placental health and functioning

Sadia Khan¹, Marion Ouidir¹, Nicolas Lemaitre²

¹University Grenoble Alpes, Inserm U-1209, CNRS-UMR-5309, Environmental Epidemiology Applied to Reproduction and Respiratory Health Team, Institute for Advanced Biosciences, 38000, Grenoble, France.

Environment International

|February 22, 2025

Insights

Prenatal exposure to poly- and perfluoroalkyl substances (PFAS) impacts placental function and fetal-maternal exchange. This study found associations between specific PFAS and altered placental parameters, suggesting broad physiological effects.

Area of Science:

Environmental Health
Reproductive Toxicology
Per- and Polyfluoroalkyl Substances (PFAS) Research

Background:

Animal studies suggest prenatal exposure to poly- and perfluoroalkyl substances (PFAS) negatively affects placental structure and function.
Human studies on the association between prenatal PFAS exposure and placental outcomes are limited.

Purpose of the Study:

To investigate the effects of individual and mixed PFAS exposures on placental function in pregnant women.
To assess the relationship between serum PFAS levels and placental parameters related to fetal-maternal exchange.

Main Methods:

Quantified 13 PFAS in serum from 367 pregnant women at median 19.3 gestational weeks.
Assessed placental weight at delivery and examined placental tissues for vascular perfusion and aging markers.
Utilized linear, logistic regressions, and mixture modeling (cluster analysis, BKMR) to analyze PFAS associations with placental parameters.

Main Results:

Perfluorohexanoic acid (PFHxA) and perfluoroheptanoic acid (PFHpA) were linked to increased syncytial knots and reduced intervillous spaces.
Perfluorotridecanoic acid (PFTrDA) associated with increased syncytial knots, while 6:2 diPAP associated with reduced capillary density.
Higher overall PFAS exposure correlated with lower average placental weight.

Conclusions:

Maternal serum PFAS levels during pregnancy are associated with placental parameters crucial for fetal-maternal exchange.
These findings highlight the potential for broad physiological impacts of PFAS on pregnancy outcomes.

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Abstract

Background:

Animal studies have linked prenatal poly- and perfluoroalkyl substances (PFAS) exposures with impaired placental structure and function. In humans, only few studies have investigated such associations.

Objective:

We studied whether PFAS, individually and as a mixture, affected placental function.

Methods:

In 367 pregnant women, we quantified 13 PFAS in serum collected at 19.3 gestational weeks (median). Placental weight was recorded at delivery. Histological examination of placental tissues allowed estimation of vascular perfusion (percentage of villi with syncytial knots, capillary density, intervillous space) and placental aging (fibrin deposition, calcification). Associations between PFAS and each of these parameters were assessed using adjusted linear, logistic regressions and mixture modeling through cluster analysis and Bayesian kernel machine regression (BKMR).

Results:

PFHxPA quantification (yes versus no) was associated with an increase in the percentages of villi with syncytial knots (β = 6.0% [95% CI: 1.1; 11]) and reduced intervillous spaces (β = 4.7% [95% CI: 0.1; 9.3]). A similar pattern was observed with PFHpA. Isolated associations were observed between PFTrDA and percentages of villi with syncytial knots (β = 8.6% [95% CI: 2.2; 15]) and 6:2diPAP and capillary density (β = -17% [95% CI: -30; -4.6]). Cluster analysis suggested that women in the moderate-to-higher PFAS exposure group had on average lower placental weight (β= -30 g [95% CI: -56; -4.3]), compared to those in the lower exposure group.

Conclusions:

Pregnancy PFAS levels were associated with placental parameters of fetal-maternal exchange, highlighting their broad physiological impacts.

Keywords:

Angiogenesis Endocrine disruptors Fetal maternal exchanges Histology Mixture Per- and Polyfluoroalkyl Substances Placental Vascularization

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