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

Clinical Snapshot

Key Findings

• P Value: Not specified in abstract

• Effect Size: Overall: no significant association; High-quality subgroups: -15.57 to -20.05 g reduction

• Primary Outcome: Birth weight change per ln-unit increase in 6:2 Cl-PFESA

• Nnt Or Sensitivity: Effect size of 15-20g reduction clinically modest but potentially significant at population level

• Confidence Interval: Sensitivity analysis: -24.74 to -6.40 g

Clinical Application

Limited by availability of 6:2 Cl-PFESA biomarker testing in routine clinical practice Relevant to Australian environmental health monitoring given industrial use of PFAS alternatives; may inform TGA chemical safety assessments and public health surveillance Pregnant women with potential occupational or environmental exposure to 6:2 Cl-PFESA

Abstract

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.

References

1. 1.Hu, X. F., Yang, X. H., Yuan, S., Chen, T., Luo, Z. Y., Wang, F. F., & Lu, C. (2026). Prenatal 6:2 Cl-PFESA exposure and birth weight: A systematic review and meta-analysis. Journal of Hazardous Materials, 142253. https://doi.org/10.1016/j.jhazmat.2026.142253