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. 2023 Aug 15;231(Pt 2):116215.
doi: 10.1016/j.envres.2023.116215. Epub 2023 May 22.

Prenatal exposures to per- and polyfluoroalkyl substances and epigenetic aging in umbilical cord blood: The Healthy Start study

Sierra S Niemiec  1 , Katerina Kechris  2 , Jack Pattee  2 , Ivana V Yang  3 , John L Adgate  4 , Antonia M Calafat  5 , Dana Dabelea  6 , Anne P Starling  7
Affiliations

Prenatal exposures to per- and polyfluoroalkyl substances and epigenetic aging in umbilical cord blood: The Healthy Start study

Sierra S Niemiec et al. Environ Res. .

Abstract

Background: Per- and polyfluoroalkyl substances (PFAS) are ubiquitous, environmentally persistent chemicals, and prenatal exposures have been associated with adverse child health outcomes. Prenatal PFAS exposure may lead to epigenetic age acceleration (EAA), defined as the discrepancy between an individual's chronologic and epigenetic or biological age.

Objectives: We estimated associations of maternal serum PFAS concentrations with EAA in umbilical cord blood DNA methylation using linear regression, and a multivariable exposure-response function of the PFAS mixture using Bayesian kernel machine regression.

Methods: Five PFAS were quantified in maternal serum (median: 27 weeks of gestation) among 577 mother-infant dyads from a prospective cohort. Cord blood DNA methylation data were assessed with the Illumina HumanMethylation450 array. EAA was calculated as the residuals from regressing gestational age on epigenetic age, calculated using a cord-blood specific epigenetic clock. Linear regression tested for associations between each maternal PFAS concentration with EAA. Bayesian kernel machine regression with hierarchical selection estimated an exposure-response function for the PFAS mixture.

Results: In single pollutant models we observed an inverse relationship between perfluorodecanoate (PFDA) and EAA (-0.148 weeks per log-unit increase, 95% CI: -0.283, -0.013). Mixture analysis with hierarchical selection between perfluoroalkyl carboxylates and sulfonates indicated the carboxylates had the highest group posterior inclusion probability (PIP), or relative importance. Within this group, PFDA had the highest conditional PIP. Univariate predictor-response functions indicated PFDA and perfluorononanoate were inversely associated with EAA, while perfluorohexane sulfonate had a positive association with EAA.

Conclusions: Maternal mid-pregnancy serum concentrations of PFDA were negatively associated with EAA in cord blood, suggesting a pathway by which prenatal PFAS exposures may affect infant development. No significant associations were observed with other PFAS. Mixture models suggested opposite directions of association between perfluoroalkyl sulfonates and carboxylates. Future studies are needed to determine the importance of neonatal EAA for later child health outcomes.

Keywords: Epigenetic aging; Mixtures analysis; Per- and polyfluoroalkyl substances (PFAS); Perfluoroalkyl carboxylates; Perfluoroalkyl sulfonates; Prenatal exposures.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1.
Figure 1.
Overall effect (95% credible interval) of the PFAS mixture on EAA, estimated by Bayesian kernel machine regression. Estimates present the difference in the response (EAA) when all the PFAS are fixed at a specific quantile, as compared to when all the exposures are fixed at their median value. h(Z) can be interpreted as the relationship between the PFAS mixture and EAA. The model implemented hierarchical selection between carboxylates (PFDA, PFNA, PFOA) and sulfonates (PFHxS, PFOS) and was adjusted for infant sex, gestational age at time of PFAS measurement, and maternal parity, educational levels, and race/ethnicity. Abbreviations: PFDA, perfluorodecanoate; PFHxS, perfluorohexane sulfonate; PFNA, perfluorononanoate; PFOA, perfluorooctanoate; PFOS, perfluorooctane sulfonate
Figure 2.
Figure 2.
Univariate exposure–response function (95% credible interval) between PFAS serum concentrations and EAA while fixing the concentrations of other PFAS at median values, estimated by Bayesian kernel machine regression. h(Z) can be interpreted as the relationship between chemicals and EAA. Model adjusted for infant sex, gestational age at time of PFAS measurement, and maternal parity, educational levels, and race/ethnicity. Abbreviations: PFDA, perfluorodecanoate; PFHxS, perfluorohexane sulfonate; PFNA, perfluorononanoate; PFOA, perfluorooctanoate; PFOS, perfluorooctane sulfonate
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