Associations of prenatal per- and polyfluoroalkyl substances exposure with glucose homeostasis and gestational diabetes mellitus: A systematic review and meta-analysis.

Per- and polyfluoroalkyl substances (PFAS) are recognized as ubiquitous "forever chemicals" with endocrine-disrupting properties. Prenatal exposure to PFAS has been implicated in the disruption of glucose homeostasis, potentially contributing to the development of gestational diabetes mellitus (GDM), thereby exerting a profound impact on both maternal and fetal health. However, the epidemiological evidence regarding this association remains inconsistent. We performed a systematic literature search in PubMed, Web of Science, Scopus for studies published before February 20, 2025. This meta-analysis synthesized data from 28 studies and indicates a significant correlation between prenatal PFAS exposure and the oral glucose tolerance test (OGTT), along with an elevated risk of developing GDM. Specifically, perfluorooctane sulfonate (PFOS) exhibited a weak but significant negative correlation with fasting blood glucose (FBG), while perfluorooctanoic acid (PFOA), PFOS, perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUnDA) were found to significantly elevate the levels of 1-h OGTT and 2-h OGTT, with perfluorodecanoic acid (PFDA) showing a significant positive association with 1-h OGTT. Furthermore, PFOA, PFNA, and PFDA were significantly associated with an increased risk of GDM when analyzed in ln-units. Additionally, we reviewed experimental studies (both murine and in vitro models) that elucidated the mechanisms through which PFAS exposure disrupts glucose homeostasis in various organs and tissues by impairing β-cell function and reduced insulin sensitivity. These findings provide data that can inform protective strategies for pregnant populations.