Systematic review and meta-analysis of birth weight and PFNA exposures

We used a systematic review that included risk of bias and study sensitivity analysis to identify 34 studies examining changes in birth weight (BWT) in relation to PFNA biomarker measures (e.g., maternal serum/plasma or umbilical cord samples). We fit a random effects model of the overall pooled estimate and stratified estimates based on sample timing and overall study confidence. We conducted a meta-regression to further examine the impact of gestational age at biomarker sample timing. We detected a-32.9 g (95%CI:-47.0,-18.7) mean BWT deficit per each ln PFNA increase from 27 included studies. We did not detect evidence of publication bias (pE = 0.30) or between-study heterogeneity in the summary estimate (pQ = 0.05; I2 = 36%). The twelve high confi-dence studies yielded a smaller pooled effect estimate (beta =-28.0 g; 95%CI:-49.0,-6.9) than the ten medium (beta =-39.0 g; 95%CI:-61.8,-16.3) or four low (beta =-36.9 g; 95%CI:-82.9, 9.1) confidence studies. The stratum -specific results based on earlier pregnancy sampling periods in 11 studies showed smaller deficits (beta =-22.0 g; 95%CI:-40.1,-4.0) compared to 10 mid-and late-pregnancy (beta =-44.2 g; 95%CI:-64.8,-23.5) studies and six post-partum studies (beta =-42.9 g; 95%CI:-88.0, 2.2). Using estimates of the specific gestational week of sampling, the meta-regression showed results consistent with the categorical sample analysis, in that as gesta-tional age at sampling time increases across these studies, the summary effect estimate of a mean BWT deficit got larger. Overall, we detected mean BWT deficits for PFNA that were larger and more consistent across studies than previous PFAS meta-analyses. Compared to studies with later sampling, BWT deficits were smaller but remained sizeable for even the earliest sampling periods. Contrary to earlier meta-analyses for PFOA and PFOS, BWT deficits that were detected across all strata did not appear to be fully explained by potential bias due to preg-nancy hemodynamics from sampling timing differences.