Prenatal Exposure to Per- and Polyfluoroalkyl Substances and Facial Features at 5 Years of Age: A Study from the Danish National Birth Cohort

BACKGROUND: Per-and polyfluoroalkyl substances (PFAS) are widespread persistent pollutants. Evidence regarding neurodevelopmental effects of PFAS have been mixed. The relation between PFAS exposure and anatomical markers that have been suggested to correlate with fetal brain development have not been studied. OBJECTIVES: We investigated the association between prenatal PFAS exposures and three craniofacial features in children measured at 5 years of age. METHODS: Measures of palpebral fissure length (PFL), philtrum groove, and upper-lip thickness were generated from standardized digital facial pho-tographs from 656 children in the Danish National Birth Cohort. PFL was classified into two groups (shorter; normal), and the philtrum (grooved; smooth; normal) and upper-lip (thick; thin; normal) measures into three groups each. Six PFAS were measured in maternal plasma (median = 8 gesta-tional wk). Multinomial logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for each facial feature using the normal group as the reference according to log ₂-PFAS concentration (in nanograms per milliliter) or PFAS tertiles, adjusting for potential con-founders, including maternal alcohol intake and smoking. Stratified analyses by maternal alcohol intake or child’s sex were performed. RESULTS: Prenatal exposure to each PFAS was associated with elevated odds for a shorter PFL, with the strongest association observed for perfluoro-decanoic acid (PFDA; per doubling OR = 2:02; 95% CI: 1.11, 3.70). Some nonlinear associations were found for philtrum measures: the second tertile of PFDA and perfluorononanoic acid were associated with grooved philtrum, whereas the second tertile of perfluoroheptane sulfonate with smooth philtrum. The associations between PFAS exposure and a shorter PFL were stronger among mothers who consumed alcohol in the first trimester, some sex-specific associations were noted for philtrum and upper-lip measures. DISCUSSION: Prenatal PFAS exposures might influence fetal craniofacial development. A larger study is needed to replicate the potential modifying effects observed for alcohol exposure and to clarify whether associations of craniofacial markers observed reflect specific neurologic deficits.