Perfluoroalkyl Substances and Birth Outcomes: A Pool Analysis in the Danish National Birth Cohort

Abstract

BACKGROUND: Perfluoroalkyl substances (PFASs) are widespread persistent organic pollutants. Animal studies indicated that in-utero PFAS exposure may affect fetal growth, but human studies findings are inconclusive. Few human studies evaluated adverse birth outcomes primarily due to small sample size. METHODS: We conducted a pooled analysis using data of 3,535 mothers and infant pairs from three sub-samples originating from the Danish National Birth Cohort (DNBC), with 1398, 545, and 1592 mutually exclusive births respectively. All sub-samples have first trimester maternal plasma concentrations of PFOS and PFOA, and 4 additional PFAS (PFHxS, PFNA, PFHpS and PFDA) were available in sub-sample 2 and 3. PFAS measures were analyzed as continuous variables after natural-log (LN) transformation or categorized into tertiles. We estimated changes in birth weight (grams) or gestational age (days), odds ratios (OR) and 95% confidence intervals (CI) for infants born preterm (< 37 gestational week) or low birth weight (< 2500 gram). Potential confounders were included, and sampling weights of each sub-sample were accounted in statistical analyses. RESULTS: We estimated that each LN-ng/ml increase in PFOS, PFOA and PFHpS was associated with a 64g, 51g or 55g decrease in average birth weight. Several PFASs (PFOS, PFNA, and PFHpS) were also associated with a small decrease in gestational age at delivery. Moreover, we estimated elevated ORs for PFOS and PFHpS and low birth weight and preterm. For instance, OR for low birth weight and preterm were 1.7 (95% CI 0.9, 3.2) and 2.0 (95% CI 1.2, 3.2) respectively comparing the highest to the lowest exposure tertile. CONCLUSION: Our pooled analyses demonstrated that several prenatal PFASs are inversely associated with birth weight and gestational age, and prenatal PFOS and PFHpS exposure may affect the risks of being born low birth weight and preterm. Our findings strengthen the evidence that in-utero PFAS exposures may affect fetal growth.