Pregnancy Per- and Polyfluoroalkyl Substance Concentrations and Postpartum Health in Project Viva: A Prospective Cohort

Abstract

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Context</jats:title> <jats:p>Per- and polyfluoroalkyl substances (PFAS) are environmental chemicals linked to weight gain and type 2 diabetes.</jats:p> </jats:sec> <jats:sec> <jats:title>Objective</jats:title> <jats:p>We examined the extent to which PFAS plasma concentrations during pregnancy were associated with postpartum anthropometry and biomarkers.</jats:p> </jats:sec> <jats:sec> <jats:title>Design, Patients, Measures</jats:title> <jats:p>We studied women recruited between 1999-2002 in the Project Viva prospective cohort with pregnancy plasma concentrations of PFAS, including perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and 2-(N-ethyl-perfluorooctane sulfonamide) acetic acid (EtFOSAA). Three-year postpartum anthropometry measurements were available from 786-801 women, blood pressure from 761 women, and blood biomarkers from 450-454 women. We used multivariable regression to evaluate the association of log2-transformed PFAS with postpartum anthropometry, blood pressure, and blood biomarkers (leptin, adiponectin, sex hormone binding globulin [SHBG], hemoglobin A1c [HbA1c], interleukin-6 [IL-6], C-reactive protein [CRP]), adjusting for age, pre-pregnancy BMI, marital status, race/ethnicity, education, income, smoking, parity, and breastfeeding history.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Pregnancy concentrations of certain PFAS were associated with greater adiposity (e.g., 0.4 cm [95%CI: -0.1, 0.9] greater waist circumference per doubling in EtFOSAA; 0.2 cm [95%CI: -0.1, 0.5] greater mid-upper arm circumference per doubling in PFOA; 1.2 mm [95%CI: 0.1, 2.2] thicker sum of subscapular and triceps skinfolds per doubling in PFOS) and higher systolic blood pressure (e.g., 1.2 mm Hg [95%CI: 0.3, 2.2] per doubling in PFOS) at three years postpartum. Higher EtFOSAA concentrations were also associated with 10.8% higher IL-6 (95%CI: 3.3, 18.9) and 6.1% lower SHBG (95%CI: 0.7, 11.2) per doubling.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Pregnancy concentrations of EtFOSAA, PFOS, and PFOA were associated with adverse postpartum cardiometabolic markers.</jats:p> </jats:sec>

Protracted Impairment of Maternal Metabolic Health in Mouse Dams Following Pregnancy Exposure to a Mixture of Low Dose Endocrine-Disrupting Chemicals, a Pilot Study

“…Pregnancy is an understudied window of vulnerability for later-life maternal health [1,84], as the metabolic demands necessary for supporting fetal development may enhance maternal metabolic disease risk [2,3,85,86]. Recent epidemiological studies have shown an increased prevalence of life-long maternal metabolic alterations following gestational EDC exposures [23][24][25], yet few rodent models have explored the role of pregnancy per se by directly comparing non-pregnant and pregnant female mice, nor have they examined exposure to EDC mixtures, a phenomenon consistent with the human environment. The present pilot study examined the potential for protracted maternal metabolic toxicity following gestational EDC exposures, singly and in the mixture.…”

“…TCDD was found to upregulate genes in inflammatory pathways in adipose tissue both in vitro and in vivo [102], and numerous other EDCs have been observed to alter the differentiation of adipocytes and expression of adipokines [24,[101][102][103]. Furthermore, in epidemiological studies, exposures during pregnancy to phthalates and per and polyfluoroalkyl substances, such as PFOA, have been associated with elevated long-term maternal weight gain, despite weight gain in pregnancy [23,24]. While such findings are notable, it is possible that a much greater risk is conferred given that women are exposed to multiple EDCs during pregnancy, and the effect of such mixtures on long-term maternal adiposity remains to be investigated [6][7][8][9]31].…”

“…Following pregnancy, women undergo a metabolic reset to return to the physiological state experienced prior to pregnancy adaptations, the persistence of these pregnancy-specific changes in maternal metabolic physiology increases the risk of later-life maternal metabolic disease [21,22]. Furthermore, epidemiological studies have found per and poly-fluoroalkyl substances and phthalates exposure during pregnancy to be associated with increased postpartum maternal adiposity [23,24]. Pregnancy phthalate exposures have also been found in an epidemiological study to be associated with postpartum maternal elevated plasma glucose, insulin resistance, and adverse lipid changes, i.e., lower HDL and higher triglyceride levels [25].…”

Exposome and foetoplacental vascular dysfunction in gestational diabetes mellitus

“…Arsenic (As), Mercury (Hg), Lead (Pb), Copper (Cu), and other heavy metals are found either as contaminants or as natural components in the environment (Huang et al, 2011;Marshall et al, 2007). It is also known that environmental contamination with per-and polyfluoroakyl substances (PFAS) generated in industrial activity is a reality (Al Amin et al, 2020;Birru et al, 2021;Mitro et al, 2020;Xu et al, 2020). Exposure to these environmental factors has been shown to lead to health complications in adults, in which pregnant women are a high-risk group (Gómez-Roig et al, 2021;Liu et al, 2021;Rolland et al, 2020;Soomro et al, 2019).…”

Endocrine disruption by PFAS: A major concern associated with legacy and replacement substances

“…In this respect, there is a growing interest in assessing chemicals that can interfere with hormonal function -a specific class of substances known as endocrine disruptors (EDs) -and their impact on human health (16). Accumulating evidence suggests that PFAS can also act as endocrine disrupting molecules, exerting proestrogenic (17) or anti-androgenic effects (18), as well as antagonistic activities at the level of thyroid hormone signalling both in vitro an in vivo (18,19), thus raising additional concerns, especially for the most vulnerable categories such as pregnant women, children, newborns and the elderly (20)(21)(22)(23)(24). In light of this problematic aspect, in this review we aim to summarize the current knowledge on PFAS as endocrinedisrupting agents in humans, focusing on legacy substances as well as short-chain substitutes.…”