Systematic Review and Meta-analysis of Birthweight and Perfluorononanoic Acid Exposures
Meta-analyses of per- and polyfluoroalkyl substances suggest that some reported birthweight deficits may be due to potential bias from pregnancy hemodynamics (e.g. increased plasma volume) related to biomarker sampling timing differences. We used a systematic review that included potential risk of bias and study sensitivity analysis to identify 34 studies examining changes in mean birthweight in relation to perfluorononanoic acid (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 detected a -32.9 g (95%CI: -47.0, -18.7) mean birthweight 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 confidence studies yielded a smaller pooled effect estimate (ß= -28.0 g; 95%CI: -49.0, -6.9) than the ten medium (ß= -39.0 g; 95%CI: -61.8, -16.3) or four low (ß= -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 (ß= -22.0 g; 95%CI: -40.1, -4.0) compared to 10 mid- and late-pregnancy (ß= -44.2 g; 95%CI: -64.8, -23.5) studies and six post-partum studies (ß= -42.9 g; 95%CI: -88.0, 2.2). Overall, we detected mean birthweight deficits for PFNA that were larger and more consistent across studies than previous per- and polyfluoroalkyl substances meta-analyses. Compared to studies with later sampling, birthweight deficits were smaller but remained sizeable for even the earliest sampling periods. Contrary to earlier meta-analyses for perfluorooctanoic acid and perfluorooctane sulfonate, birthweight deficits that were detected across all strata did not appear to be fully explained by potential bias due to pregnancy hemodynamics from sampling timing differences.
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