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. 2023 Jul:329:138644.
doi: 10.1016/j.chemosphere.2023.138644. Epub 2023 Apr 7.

Metals and per- and polyfluoroalkyl substances mixtures and birth outcomes in the New Hampshire Birth Cohort Study: Beyond single-class mixture approaches

Gyeyoon Yim  1 , Glen McGee  2 , Lisa Gallagher  3 , Emily Baker  4 , Brian P Jackson  5 , Antonia M Calafat  6 , Julianne Cook Botelho  6 , Diane Gilbert-Diamond  7 , Margaret R Karagas  3 , Megan E Romano  3 , Caitlin G Howe  3
Affiliations

Metals and per- and polyfluoroalkyl substances mixtures and birth outcomes in the New Hampshire Birth Cohort Study: Beyond single-class mixture approaches

Gyeyoon Yim et al. Chemosphere. 2023 Jul.

Abstract

We aimed to investigate the joint, class-specific, and individual impacts of (i) PFAS, (ii) toxic metals and metalloids (referred to collectively as "metals"), and (iii) essential elements on birth outcomes in a prospective pregnancy cohort using both established and recent mixture modeling approaches. Participants included 537 mother-child pairs from the New Hampshire Birth Cohort Study. Concentrations of 6 metals and 5 PFAS were measured in maternal toenail clippings and plasma, respectively. Birth weight, birth length, and head circumference at birth were abstracted from medical records. Joint, index-wise, and individual associations of the metals and PFAS concentrations with birth outcomes were evaluated using Bayesian Kernel Machine Regression (BKMR) and Bayesian Multiple Index Models (BMIM). After controlling for potential confounders, the metals-PFAS mixture was associated with a larger head circumference at birth, which was driven by manganese. When using BKMR, the difference in the head circumference z-score when changing manganese from its 25th to 75th percentiles while holding all other mixture components at their medians was 0.22 standard deviations (95% posterior credible interval [CI]: -0.02, 0.46). When using BMIM, the posterior mean of index weight estimates assigned to manganese for head circumference z-score was 0.72 (95% CI: 0, 0.99). Prenatal exposure to the metals-PFAS mixture was not associated with birth weight or birth length by either BKMR or BMIM. Using both traditional and new mixture modeling approaches, prenatal exposure to manganese was associated with a larger head circumference at birth after accounting for exposure to PFAS and multiple toxic and essential metals.

Keywords: Bayesian multiple index model (BMIM); Birth outcomes; Environmental mixtures; Essential elements; Per- and polyfluoroalkyl substances (PFAS); Toxic metals.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: National Institutes of Health, National Institute of Environmental Health Sciences, National Institute of General Medical Sciences, and United States Environmental Protection Agency. Dr. McGee reports financial support was provided by Natural Sciences and Engineering Research Council of Canada. Dr. Howe reports financial support was provided by National Institute of Environmental Health Sciences. Dr. Romano reports financial support was provided by National Institute of Environmental Health Sciences.

Figures

Figure 1.
Figure 1.. Spearman correlation plot between metal or per- and polyfluoroalkyl substances (PFAS) pairs in the New Hampshire Birth Cohort Study (n=537)
In the upper right-hand corner, the strength and direction of each correlation is depicted as circles, with blue color indicating positive correlation and red color representing negative correlation. Darker and bigger circles suggest stronger correlations. In the lower left-hand corner, Spearman correlation coefficient estimates are shown. Correlation coefficients that were statistically significant (P<0.1) are only illustrated here. Abbreviations: As, arsenic; Cu, cooper; Hg, mercury; Mn, manganese; Pb, lead; PFDA, perfluorodecanoic acid; PFHxS, perfluorohexane sulfonic acid; PFNA, perfluorononanoic acid; PFOA, perfluorooctanoic acid; PFOS, perfluorooctane sulfonic acid; Se, selenium.
Figure 2.
Figure 2.. Joint and individual associations of exposure to metals and per- and polyfluoroalkyl substances (PFAS) with head circumference z-score by Bayesian kernel machine regression (BKMR) in the New Hampshire Birth Cohort Study (n=537)
a. Joint associations (95% CI) of the metals-PFAS mixture and head circumference when all the mixtures are at particular percentiles compared with their medians b. Univariate exposure-response functions (95% CIs) between individual metal or PFAS and head circumference, while holding others at their median values c. Bivariate exposure-response functions for each metal or PFAS congener when another metal or PFAS congener is fixed at 10th, 50th, or 90th percentile, while holding the others at their median values All models were adjusted for maternal age, education attainment level, parity, smoking status, fish and seafood consumption during pregnancy, pre-pregnancy body mass index (BMI), blood draw gestational age, and delivery mode. Abbreviations: As, arsenic; CI, credible interval; Cu, cooper; Hg, mercury; Mn, manganese; Pb, lead; PFDA, perfluorodecanoic acid; PFHxS, perfluorohexane sulfonic acid; PFNA, perfluorononanoic acid; PFOA, perfluorooctanoic acid; PFOS, perfluorooctane sulfonic acid; Se, selenium.
Figure 2.
Figure 2.. Joint and individual associations of exposure to metals and per- and polyfluoroalkyl substances (PFAS) with head circumference z-score by Bayesian kernel machine regression (BKMR) in the New Hampshire Birth Cohort Study (n=537)
a. Joint associations (95% CI) of the metals-PFAS mixture and head circumference when all the mixtures are at particular percentiles compared with their medians b. Univariate exposure-response functions (95% CIs) between individual metal or PFAS and head circumference, while holding others at their median values c. Bivariate exposure-response functions for each metal or PFAS congener when another metal or PFAS congener is fixed at 10th, 50th, or 90th percentile, while holding the others at their median values All models were adjusted for maternal age, education attainment level, parity, smoking status, fish and seafood consumption during pregnancy, pre-pregnancy body mass index (BMI), blood draw gestational age, and delivery mode. Abbreviations: As, arsenic; CI, credible interval; Cu, cooper; Hg, mercury; Mn, manganese; Pb, lead; PFDA, perfluorodecanoic acid; PFHxS, perfluorohexane sulfonic acid; PFNA, perfluorononanoic acid; PFOA, perfluorooctanoic acid; PFOS, perfluorooctane sulfonic acid; Se, selenium.
Figure 2.
Figure 2.. Joint and individual associations of exposure to metals and per- and polyfluoroalkyl substances (PFAS) with head circumference z-score by Bayesian kernel machine regression (BKMR) in the New Hampshire Birth Cohort Study (n=537)
a. Joint associations (95% CI) of the metals-PFAS mixture and head circumference when all the mixtures are at particular percentiles compared with their medians b. Univariate exposure-response functions (95% CIs) between individual metal or PFAS and head circumference, while holding others at their median values c. Bivariate exposure-response functions for each metal or PFAS congener when another metal or PFAS congener is fixed at 10th, 50th, or 90th percentile, while holding the others at their median values All models were adjusted for maternal age, education attainment level, parity, smoking status, fish and seafood consumption during pregnancy, pre-pregnancy body mass index (BMI), blood draw gestational age, and delivery mode. Abbreviations: As, arsenic; CI, credible interval; Cu, cooper; Hg, mercury; Mn, manganese; Pb, lead; PFDA, perfluorodecanoic acid; PFHxS, perfluorohexane sulfonic acid; PFNA, perfluorononanoic acid; PFOA, perfluorooctanoic acid; PFOS, perfluorooctane sulfonic acid; Se, selenium.
Figure 3.
Figure 3.. Joint and index-wise associations of exposure to metals and per- and polyfluoroalkyl substances (PFAS) with head circumference z-score by Bayesian multiple index models (BMIM) in the New Hampshire Birth Cohort Study (n=537)
a. Overall exposure-response function (M= 1; L1 = 11) with 95% CIs b. Index-wise exposure-response function (95% CIs) while holding the other indices at their posterior means c. Index-wise two-way interactions (95% CIs) when another index is fixed at 10th, 50th, or 90th percentile, while holding the other indices at their posterior means Index-wise interactions are centered estimates. PFAS group includes PHFxS, PFOS, PFOA, PFNA, and PFDA; toxic metal group includes As, Hg, and Pb; and essential element group includes Cu, Mn, and Se. All models were adjusted for maternal age, education attainment level, parity, smoking status, fish and seafood consumption during pregnancy, pre-pregnancy body mass index (BMI), blood draw gestational age, and delivery mode. Abbreviations: As, arsenic; CI, credible interval; Cu, cooper; Hg, mercury; Mn, manganese; Pb, lead; PFDA, perfluorodecanoic acid; PFHxS, perfluorohexane sulfonic acid; PFNA, perfluorononanoic acid; PFOA, perfluorooctanoic acid; PFOS, perfluorooctane sulfonic acid; Se, selenium.
Figure 3.
Figure 3.. Joint and index-wise associations of exposure to metals and per- and polyfluoroalkyl substances (PFAS) with head circumference z-score by Bayesian multiple index models (BMIM) in the New Hampshire Birth Cohort Study (n=537)
a. Overall exposure-response function (M= 1; L1 = 11) with 95% CIs b. Index-wise exposure-response function (95% CIs) while holding the other indices at their posterior means c. Index-wise two-way interactions (95% CIs) when another index is fixed at 10th, 50th, or 90th percentile, while holding the other indices at their posterior means Index-wise interactions are centered estimates. PFAS group includes PHFxS, PFOS, PFOA, PFNA, and PFDA; toxic metal group includes As, Hg, and Pb; and essential element group includes Cu, Mn, and Se. All models were adjusted for maternal age, education attainment level, parity, smoking status, fish and seafood consumption during pregnancy, pre-pregnancy body mass index (BMI), blood draw gestational age, and delivery mode. Abbreviations: As, arsenic; CI, credible interval; Cu, cooper; Hg, mercury; Mn, manganese; Pb, lead; PFDA, perfluorodecanoic acid; PFHxS, perfluorohexane sulfonic acid; PFNA, perfluorononanoic acid; PFOA, perfluorooctanoic acid; PFOS, perfluorooctane sulfonic acid; Se, selenium.
Figure 3.
Figure 3.. Joint and index-wise associations of exposure to metals and per- and polyfluoroalkyl substances (PFAS) with head circumference z-score by Bayesian multiple index models (BMIM) in the New Hampshire Birth Cohort Study (n=537)
a. Overall exposure-response function (M= 1; L1 = 11) with 95% CIs b. Index-wise exposure-response function (95% CIs) while holding the other indices at their posterior means c. Index-wise two-way interactions (95% CIs) when another index is fixed at 10th, 50th, or 90th percentile, while holding the other indices at their posterior means Index-wise interactions are centered estimates. PFAS group includes PHFxS, PFOS, PFOA, PFNA, and PFDA; toxic metal group includes As, Hg, and Pb; and essential element group includes Cu, Mn, and Se. All models were adjusted for maternal age, education attainment level, parity, smoking status, fish and seafood consumption during pregnancy, pre-pregnancy body mass index (BMI), blood draw gestational age, and delivery mode. Abbreviations: As, arsenic; CI, credible interval; Cu, cooper; Hg, mercury; Mn, manganese; Pb, lead; PFDA, perfluorodecanoic acid; PFHxS, perfluorohexane sulfonic acid; PFNA, perfluorononanoic acid; PFOA, perfluorooctanoic acid; PFOS, perfluorooctane sulfonic acid; Se, selenium.
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