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Epidemiology and Population Health

Prenatal exposure to per- and polyfluoroalkyl substances and early childhood adiposity and cardiometabolic health in the Healthy Start study

International Journal of Obesity volume 48, pages 276–283 (2024)Cite this article

Subjects

Abstract

Background/Objectives

Observational and experimental studies have suggested that prenatal exposure to per- and polyfluoroalkyl substances (PFAS) can increase childhood adiposity and cardiometabolic disruption. However, most previous studies have used weight-based measures that cannot distinguish between fat mass and lean mass. We evaluated associations of prenatal PFAS exposure with precisely measured body composition and cardiometabolic biomarkers in early childhood.

Subjects

373 eligible mother-infant pairs in the Healthy Start longitudinal cohort.

Methods

We used multiple linear regression and Bayesian kernel machine regression models to estimate associations between five PFAS in maternal mid-pregnancy serum, and early childhood adiposity via air displacement plethysmography. Secondary outcomes included body mass index, waist circumference, and fasting serum lipids, glucose, insulin and adipokines. Models were adjusted for potential confounders and effect modification by child sex was evaluated.

Results

The median age of children at assessment was 4.6 years. Prenatal concentration of perfluorooctanoate (PFOA) was positively associated with percent fat mass (0.89% per log2-unit increase, 95% CI: 0.15, 1.64), while perfluorononanoate (PFNA) was positively associated with fat mass index and body mass index. Cardiometabolic markers in blood were generally not associated with prenatal PFAS in this population. Mixture models confirmed the importance of PFNA and PFOA in predicting percent fat mass, while PFNA was most important for fat mass index, body mass index, and waist circumference. There were no significant effects of the five PFAS as a mixture, potentially due to opposing effects of different PFAS.

Conclusions

Our results agree with previous studies showing that prenatal serum concentrations of certain PFAS are positively associated with early childhood adiposity. Notably, associations were stronger for measures incorporating precisely measured fat mass compared to measures of body size or weight. Early life increases in adiposity may precede the development of adverse cardiometabolic health outcomes in children exposed to PFAS during gestation.

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Fig. 1: Directed acyclic graph representing hypothesized causal relationships between variables.

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Data availability

The dataset analyzed in the current study may not be posted publicly in accordance with the original participant informed consent document. However, de-identified data may be requested from the parent Healthy Start study with an approved data use agreement through the LEAD Center at the University of Colorado Anschutz Medical Campus. The statistical code used to generate the results is available upon request from the corresponding author.

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Funding

This work was supported by grants from the National Institute of Environmental Health Sciences (R01ES022934), the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK076648), and the National Institutes of Health Office of the Director (UH3OD023248). Funders had no involvement in the data collection, analysis, or interpretation of results, and were not involved in the writing of the article or the decision to submit the article for publication.

Author information

Authors and Affiliations

  1. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Anne P. Starling

  2. Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Anne P. Starling, Chloe Friedman, Deborah H. Glueck, Lizan D. Bloemsma & Dana Dabelea

  3. Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Anne P. Starling, Chloe Friedman & Dana Dabelea

  4. Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Kristen E. Boyle, Deborah H. Glueck & Dana Dabelea

  5. Department of Environmental and Occupational Health, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    John L. Adgate & William B. Allshouse

  6. Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA

    Antonia M. Calafat

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Contributions

APS, JLA, KEB, and DD conceived of the study. APS designed and conducted the statistical analyses and wrote the first draft of the manuscript. CF and LDB contributed to the definition of the early childhood outcomes and provided critical feedback on the manuscript. DHG and WBA provided subject-matter expertise and critical feedback on the manuscript. AMC oversaw the quantification of PFAS in maternal serum and provided critical feedback on the manuscript. All authors read and approved the final version of the manuscript prior to submission.

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Correspondence to Anne P. Starling.

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Starling, A.P., Friedman, C., Boyle, K.E. et al. Prenatal exposure to per- and polyfluoroalkyl substances and early childhood adiposity and cardiometabolic health in the Healthy Start study. Int J Obes 48, 276–283 (2024). https://doi.org/10.1038/s41366-023-01420-3

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