Prenatal per- and polyfluoroalkyl substances (PFAS) exposure in relation to preterm birth subtypes and size-for-gestational age in the LIFECODES cohort 2006-2008
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Background: Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic chemicals widely used in consumer and industrial products. Numerous studies have linked prenatal PFAS exposures to increased risks of adverse pregnancy outcomes such as preterm birth (PTB) and small-for-gestational age (SGA).However, limited evidence is available for the effects of PFAS on PTB subtypes and large-for-gestational age (LGA). Objective: To examine the associations of PFAS with PTB [overall, placental (pPTB), spontaneous (sPTB)], BW Z-score, and size-for-gestational age (SGA, LGA). Methods: Our nested case-control study included 128 preterm cases and 373 term controls from the LIFECODES cohort between 2006 and 2008 (n = 501). Plasma concentrations of nine PFAS were measured in early pregnancy samples. Logistic regression was used to assess individual PFAS-birth outcome associations, while Bayesian Kernel Machine Regression (BKMR) was used to evaluate the joint effects of all PFAS. Effect modification by fetal sex was examined, and stratified analyses were conducted to obtain fetal sex-specific estimates. Results: Compared to term births, the odds of pPTB were higher from an interquartile range increase in perfluorodecanoic acid (PFDA) (OR = 1.60, 95% CI: 1.00–2.56), perfluorononanoic acid (PFNA) (OR = 1.67, 95% CI: 1.06–2.61), and perfluoroundecanoic acid (PFUA) (OR = 1.77, 95% CI: 1.00–3.12), with stronger associations observed in women who delivered males. BKMR analysis identified PFNA as the most important PFAS responsible for pPTB (conditional PIP = 0.78), with increasing ORs at higher percentiles of PFAS mixture. For LGA, positive associations were observed with PFDA and perfluorooctanoic acid in females only, and with PFUA in males only. BKMR analysis showed increasing, but null effects of PFAS mixture on LGA. Conclusions: The effect of prenatal exposure to single and multiple PFAS on PTB and LGA depended on fetal sex. Future studies should strongly consider examining PTB subtypes and sex-specific effects of PFAS on pregnancy outcomes.
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- Authors
- Siwakoti, R. C., Cathey, A., Ferguson, K. K., Hao, W., Cantonwine, D. E., Mukherjee, B., McElrath, T. F., & Meeker, J. D.
- Affiliations
- University of Michigan (US)
- National Institutes of Health (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Meeker, John D.
- ORCID
- Venue
- Environmental Research
- Publisher
- Elsevier BV
- Published
- 2023-11
- Volume
- 237
- Issue
- Pt 2
- Pages
- 116967
- ISSN
- 0013-9351 (ISSN-L)
- PMC
- PMC10913455
- OpenAlex
- W4386157285
- Semantic Scholar
- fbf2bf41bc8526603d745169abc0a7ec83228369
- Cited by
- 32
- References
- 68
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 5
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 303 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Environmental Research (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (ZIA ES103321)
- National Institute of Environmental Health Sciences (R01ES031591)
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Health Professions › General Health Professions › Maternal and Neonatal Healthcare
- Keywords
- per- and polyfluoroalkyl substances, PFAS, preterm birth, spontaneous preterm birth, large for gestational age, small for gestational age, birth weight, perfluorooctanoic acid, perfluorodecanoic acid, perfluorononanoic acid, perfluoroundecanoic acid, fetal sex differences
- MeSH terms
- Bayes Theorem, Environmental Pollutants, Fatty Acids, Female, Fetal Growth Retardation, Fluorocarbons, Gestational Age, Humans, Infant, Newborn, Male, Placenta, Pregnancy, Vitamins, Case-Control Studies, Alkanesulfonic Acids, Polypyrimidine Tract-Binding Protein, Premature Birth
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