Birth weight in relation to maternal and neonatal biomarker concentration of perfluorooctane sulfonic acid: a meta-analysis and meta-regression from a systematic review.

backgroundPerfluorooctane sulfonic acid (PFOS) is a legacy chemical, that while banned in some countries, is still found in various environmental media and in nearly all humans given its long half-life.

objectiveWe examined mean birth weight (BW) differences in relation to PFOS exposure biomarkers using systematic review methods.

methodsWe fit a random effects model to obtain the overall pooled effect and for stratified analyses examining biomarker sample type and timing, study confidence, scaling factors, and country of study origin. We also conducted a meta-regression to assess the impact of gestational age and other factors on the overall pooled effect.

resultsWe found a 30-gram BW deficit (β = -30.3 g; 95%CI: -41.6, -18.9) with each ln-unit PFOS increase based on 53 studies identified in the systematic literature review. We detected BW deficits across all study confidence levels (β range: -27 to -37 g per ln-unit increase) with the largest deficit in the medium confidence grouping (β = -36.6 g; 95%CI: -56.3, -16.8). We did not see evidence of a gradient of BW deficits across biomarker sample timing (β range: -24 to -39 g per ln-unit increase), but the smallest deficit in our primary analyses was detected for the 18 early sample timing studies (β = -23.6 g; 95%CI: -38.7, -8.6). Robust deficits were also seen across various subgroups including by geographical region of study origin (e.g., Asian studies), more restrictive early biomarker sample collection, and post-partum samples (β range: -16.9 to -30.6 g). For meta-regression analyses, none of the investigated factors explained significant heterogeneity across studies. IMPACT: We detected a statistically significant BW deficit of 30 grams per each ln-unit PFOS increase across all 53 studies in our meta-analysis; results were comparable in magnitude across study confidence, sample timing, and other strata. Unlike previous meta-analyses based on fewer studies, our results suggest that pregnancy hemodynamics do not fully explain the overall association. Characterization of the potential risk of developmental effects related to PFOS and other legacy chemicals will have important risk assessment and risk management ramifications in the future.