Prenatal 6:2 Cl-PFESA exposure and birth weight: A systematic review and meta-analysis

Most existing systematic reviews and meta-analyses on PFAS have focused on legacy compounds, yet with less attention on PFAS alternatives and mixtures. Chlorinated polyfluorinated ether sulfonic acids (Cl-PFESAs) have been introduced as PFOS alternatives. Among these, 6:2 Cl-PFESA has accumulated persistent environmental residues and has recently emerged as a significant health concern. We aim to evaluate the association between prenatal 6:2 Cl-PFESA exposure and birth weight using a meta-analysis. A systematic review identified 12 studies reporting birth weight in relation to 6:2 Cl-PFESA biomarker measures, including maternal serum and umbilical cord samples. Risk of bias and study sensitivity were assessed, and overall effects were estimated by random-effects model. Stratified analyses were conducted by study confidence, sample size, and exposure level. The overall pooled estimate showed no statistically significant association between 6:2 Cl-PFESA exposure and birth weight. However, subgroup analyses revealed a consistent reduction in birth weight per ln-unit increase in 6:2 Cl-PFESA in studies with large sample sizes (β = -20.05 g; 95% CI: -33.13, -6.97), high methodological confidence (β = -16.74 g; 95% CI: -26.42, -7.06), or higher exposure levels (β = -16.15 g; 95% CI: -25.43, -6.87), all showing low between-study heterogeneity. Sensitivity analysis excluding the study contributing most to heterogeneity indicated a 15.57 g decrease in birth weight per ln ng/mL increase in 6:2 Cl-PFESA (95% CI: -24.74, -6.40). Although current evidence suggests that prenatal 6:2 Cl-PFESA exposure may adversely affect fetal growth, well-designed prospective studies with standardized exposure assessments are needed to confirm this potential risk.