Correlation of perfluoroalkyl and polyfluoroalkyl substance levels during pregnancy with gestational diabetes mellitus: a systematic review and meta-analysis

Background: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a major class of contaminants in recent years. Pregnant women are more susceptible to the influence of these compounds, which could heighten the risk of developing gestational diabetes mellitus (GDM). This study aims to conduct an updated systematic review and meta-analysis to determine the correlation between PFAS exposure during pregnancy and the risk of developing GDM and delve into their dose-response relationship. Methods: Pubmed, EMBASE, Web of Science, and Cochrane Library databases were searched. Data were statistically analyzed using Stata 15.0. Fixed-effects (FEM) or random-effects (REM) models were used to combine STD mean difference (SMD) or odds ratio (OR) and 95% confidence intervals (CIs) according to heterogeneity. Dose-response meta-analyses were performed when applicable. Results: A total of 12 papers were included in this study. Meta-analysis results indicated significantly higher levels of PFOA, PFBS, and PFUnDA in GDM patients compared to healthy pregnant women. Pregnant women exposed to high levels of PFOA and PFBS had a significantly increased risk of developing GDM, with ORs of 1.513 and 1.436, respectively. Dose-response analyses indicated that for each 1 ng/ml increase in PFOA and PFBS exposure, the risk of GDM increased by 0.3% and 11.7%, respectively. In contrast, no significant associations were observed between high exposure to other PFAS compounds, such as PFNA, PFHxS, and PFOS, and the development of GDM. Subgroup analyses suggested that PFOA, PFBS, and PFOS levels were higher in GDM patients from China compared to those from Western countries. The differences in PFOA and PFOS levels between GDM and normal pregnant women were more pronounced during late pregnancy. Conclusion: Exposure to PFOA, PFBS, and PFUnDA during pregnancy is associated with an increased risk of GDM. Given the elevated risk, particularly in the Chinese population, it is crucial to reduce exposure to these substances, especially from the preconception period onward.