Longitudinal trajectories and determinants of plasma per- and polyfluoroalkyl substance (PFAS) levels from birth to early childhood and metabolomic associations: A pilot study in the Boston Birth Cohort.

Background: Per- and polyfluoroalkyl substances (PFAS) are a major public health concern worldwide due to their ubiquitous exposures, environmental persistence, maternal-to-fetal transfer, and multi-organ toxicity. This pilot study aimed to generate preliminary data to inform future studies to address data gaps in the field, including early life PFAS exposure levels, longitudinal changes, determinants, and associated metabolomic alterations in understudied Black and Hispanic children in the United States (U.S.).

Methods: This study leveraged existing biosamples and data in the Boston Birth Cohort and measured 12 legacy and emerging PFAS, including Me-PFOSA-AcOH, PFDA, PFDoA, PFHxS, PFNA, PFOA, PFOS, PFUnA, GenX, ADONA, 9Cl-PF3ONS, and PFHpS, in paired cord and early childhood plasma samples. Summary statistics and graphic plots were used to depict PFAS levels at the two time points and their longitudinal changes. Linear regression models were used to identify the early-life factors associated with cord and early childhood PFAS levels. Associations of cord PFAS with cord metabolites were explored using a metabolome-wide association approach and a targeted approach.

Results: This study included 39 children, of whom 25 (64%) were Black, 14 (36%) were Hispanic, and 15 (38%) were female. PFOA, PFOS, PFNA, and PFHpS were detectable in all cord and early childhood plasma samples, while GenX and ADONA were not detectable in any sample. Cord PFAS levels were weakly-to-moderately correlated with early childhood PFAS levels (r = -0.03 to 0.40). Several maternal and child factors, including gestational age, year at blood collection, and race/ethnicity, were associated with cord and early childhood PFAS levels. The metabolome-wide association study and the targeted study identified several cord metabolites that may have been affected by in utero PFAS exposure.

Conclusions: This pilot study found ubiquitous exposure to multiple PFAS in cord plasma (reflects in utero exposure) and in early childhood plasma (reflects both prenatal and postnatal exposure) among U.S. Black and Hispanic children. Metabolomic analysis suggests that in utero PFAS exposures may alter fetal metabolism. Future large-scale studies are needed to replicate the findings and further examine the associations of fetal PFAS exposure with long-term health outcomes and underlying metabolic pathways.