Assessing the impact of per- and polyfluoroalkyl substances on pregnancy loss: An environmental-wide association study in Northwest China

Abstract

Background

Per- and polyfluoroalkyl substances (PFAS) are emerging environmental contaminants with potential metabolic and endocrine-disrupting properties that may affect women's reproductive health. However, their specific role in pregnancy loss remains relatively understudied.

Objectives

This study aimed to assess the association between exposure to multiple PFAS and the association with pregnancy loss (PL) in a population from Northwest China using an environment-wide association study (EWAS) approach.

Methods

A case-control study was conducted at a university-affiliated reproductive center, enrolling 348 women with a history of PL and 320 controls with at least one live birth and no history of pregnancy loss. Serum concentrations of ten PFAS were quantified using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) following a standardized extraction and purification protocol. Demographic and clinical data were collected via a structured questionnaire. An elastic net regression model (ENRM) was employed for variable selection, identifying PFASs to be included in the subsequent EWAS analysis. Associations between individual PFAS and PL were then evaluated using logistic regression, and EWAS was utilized to explore the overall associations between PFAS mixture exposure and PL, accounting for potential interactions and multicollinearity.

Results

The EWAS identified five PFASs—PFPeS, PFHxS, PFOA, PFOS, and PFNA—with significantly higher exposure odds in pregnancy loss cases versus live birth controls (adjusted ORs: 1.82 [1.31–2.62], 1.34 [1.19–1.51], 1.73 [1.46–2.07], 1.33 [1.14–1.56], and 1.73 [1.40–2.15], respectively). Subgroup analyses confirmed robust associations, with PFOA consistently linked to elevated exposure odds across demographic and clinical strata.

Conclusion

This study demonstrates a significant association between exposure to multiple PFAS, notably PFPeS, PFHxS, PFOA, PFOS, and PFNA, and an increased risk of pregnancy loss in a Northwest Chinese population. The particularly robust association observed with PFOA across diverse subgroups underscores its potential as a significant environmental risk factor for PL. These findings highlight the need for further research to elucidate the underlying mechanisms and to develop strategies for reducing PFAS exposure among women of reproductive age.