Systematic review and meta-analysis of birth weight and prenatal exposure to perfluoroundecanoic acid

BACKGROUND: Due to transplacental exposure to perfluoroundecanoic acid (PFUnDA), there is a need to evaluate potential developmental effects in humans. We examined the association between PFUnDA exposure and birth weight (BW) using systematic review methodology. METHODS: We used a random effects model with inverse-variance weighting to meta-analyze associations between PFUnDA exposure biomarkers and changes in BW. We report a pooled estimate and stratified estimates based on factors including study confidence and timing of sample collection. RESULTS: We detected a pooled mean BW deficit (β) of 15.3 g (95%CI: -23.4, -7.1) per ln(ng/mL) PFUnDA increase in our primary analysis of 28 studies. We observed deficits in 5 low (β = -26.3 g, 95%CI: -56.5, 3.8), 14 medium (β = -16.5 g, 95%CI: -26.8, -6.1), and 9 high confidence studies (β = -10.3 g, 95%CI: -24.8, 4.1). The magnitude of the pooled BW deficit varied across sample timing categories, with the largest average deficit in eight studies with postpartum samples (β = -21.0 g, 95%CI: -43.8, 1.8) and the smallest among eight studies with early pregnancy samples (β = -6.8 g, 95%CI: -21.5, 7.9). CONCLUSIONS: We observed lower BW associated with higher PFUnDA exposure. Although confidence intervals overlapped across strata, we detected smaller BW deficits in higher quality studies and larger deficits among studies that collected samples in late pregnancy or postpartum. These trends may be partly explained by bias from pregnancy hemodynamics. Future studies conducted in populations with serial pregnancy PFUnDA measures would facilitate data interpretation and address some methodological challenges.