Quantifying PFAS-Omics Burden Scores for Nontargeted Analysis Using Multidimensional Item Response Theory: An Exploratory Analysis of Novel and Legacy PFAS in Cord Blood

Fetal development is a vulnerable period for exposure to per- and polyfluoroalkyl substances (PFAS). However, certified analytical standards do not exist for many PFAS, limiting our ability to quantify overall exposure burden to PFAS as a chemical class. PFAS-focused nontargeted analysis (NTA) enables detection of PFAS for which chemical standards may not exist. The overall objectives of this study were to provide a more comprehensive picture of PFAS exposure in cord blood, develop cumulative exposure burden scores for the PFAS detected, and evaluate differences in the infant's PFAS burden score with respect to mother's parity. We measured PFAS using targeted and NTA methods in cord blood samples collected between 2003 and 2006 in the HOME Study (Cincinnati, Ohio). Using NTA, we putatively identified 42 PFAS in cord blood, 4 of which were also detected in targeted analysis. We summarized an infant's overall prenatal exposure burden to PFAS using item response theory methods. We constructed two scores, one based on PFAS concentrations from targeted analysis ("PFAS exposure burden scores"), and one based on relative abundance from NTA ("PFAS-omics scores"). As expected, infants with multiparous mothers had significantly lower PFAS exposure burden scores than those with nulliparous mothers, but these disparities were not present when comparing their PFAS-omics scores. Our results show that infants are exposed to a wide range of PFAS, including perfluorinated chemicals, polyfluorinated chemicals, and fluorotelomers, before birth. Further, PFAS-focused NTA can help estimate total exposure to PFAS. Lastly, reported disparities in PFAS exposure burden across parity may depend on the panel of assessed PFAS and their half-lives.