Perfluoroalkyl Substances during Pregnancy and Offspring Weight and Adiposity at Birth: Examining Mediation by Maternal Fasting Glucose in the Healthy Start Study

Abstract

Background:Certain perfluoroalkyl and polyfluoroalkyl substances (PFAS) are widespread, persistent environmental contaminants. Prenatal PFAS exposure has been associated with lower birth weight; however, impacts on body composition and factors responsible for this association are unknown.Objectives:We aimed to estimate associations between maternal PFAS concentrations and offspring weight and adiposity at birth, and secondarily to estimate associations between PFAS concentrations and maternal glucose and lipids, and to evaluate the potential for these nutrients to mediate associations between PFAS and neonatal outcomes.Methods:Within the Healthy Start prospective cohort, concentrations of 11 PFAS, fasting glucose, and lipids were measured in maternal mid-pregnancy serum (n=628). Infant body composition was measured using air displacement plethysmography. Associations between PFAS and birth weight and adiposity, and between PFAS and maternal glucose and lipids, were estimated via linear regression. Associations were decomposed into direct and indirect effects.Results:Five PFAS were detectable in >50% of participants. Maternal perfluorooctanoate (PFOA) and perfluorononanoate (PFNA) concentrations were inversely associated with birth weight. Adiposity at birth was approximately 10% lower in the highest categories of PFOA, PFNA, and perfluorohexane sulfonate (PFHxS) compared to the lowest categories. PFOA, PFNA, perfluorodecanoate (PFDeA), and PFHxS were inversely associated with maternal glucose. Up to 11.6% of the effect of PFAS on neonatal adiposity was mediated by maternal glucose concentrations. Perfluorooctane sulfonate (PFOS) was not significantly associated with any outcomes studied.Conclusions:Follow-up of offspring will determine the potential long-term consequences of lower weight and adiposity at birth associated with prenatal PFAS exposure. https://doi.org/10.1289/EHP641

Maternal serum concentrations of perfluoroalkyl substances and birth size in British boys

“…Outside of the ALSPAC cohort, our weakly inverse or null results are consistent with those reported in other epidemiologic studies of PFAS and birth size. The PFAS concentrations in this study are generally similar to levels reported in previous studies (Apelberg et al, 2007b;Ashley-Martin et al, 2017;Chen et al, 2012;Fei et al, 2007;Hamm et al, 2010;Manzano-Salgado et al, 2017;Meng et al, 2018;Minatoya et al, 2017;Sagiv et al, 2018;Shoaff et al, 2018;Starling et al, 2017;Whitworth et al, 2012;Woods et al, 2017), though PFNA is lowest in the present study. Studies from Japan (n = 168) (Minatoya et al, 2017), the United States (Maryland) (n = 299) (Apelberg et al, 2007b), Denmark (n = 1,400) (Fei et al, 2007), and Taiwan (n = 429) (Chen et al, 2012) have found evidence of inverse associations of PFOA and PFOS with birth size.…”

“…Previous studies have examined the association of PFAS and birth size by infant sex, and most did not report differences by infant sex. Three studies found no interaction (Sagiv et al, 2018;Shoaff et al, 2018;Starling et al, 2017), while another study found interaction by sex only when examining dichotomous outcomes like low birth weight (Manzano-Salgado et al, 2017). Overall, the literature to date suggests PFAS may have little differential effect on fetal development by sex.…”

“…The epidemiological literature on prenatal PFAS exposure and birth size (birth weight, birth length, and head circumference) has been mixed, with some studies finding that higher concentrations are associated with reduced birth size (Apelberg et al, 2007b;Chen et al, 2012;Fei et al, 2007;Maisonet et al, 2012;Meng et al, 2018;Minatoya et al, 2017;Sagiv et al, 2018;Starling et al, 2017), while others observe largely null associations (Ashley-Martin et al, 2017;Hamm et al, 2010;Manzano-Salgado et al, 2017;Shoaff et al, 2018;Whitworth et al, 2012;Woods et al, 2017), with inconsistent results across PFAS chemicals. To date, studies of PFAS exposure and birth size have been conducted in American, Canadian, Danish, Norwegian, Spanish, Japanese, and Taiwanese populations.…”

Developmental Exposures to Perfluoroalkyl Substances (PFASs): An Update of Associated Health Outcomes

“…Additionally, the study reported inverse associations between maternal fasting glucose concentrations during pregnancy and PFASs, suggesting that reduced availability of maternal glucose reaching the fetus could be a potential mechanism linking PFAS exposure to reduced weight and adiposity at birth. [22]. In contrast, several studies did not find significant associations between PFASs and these birth outcomes [18, 19, 28, 29, 34].…”

Zebrafish as a Model for Toxicological Perturbation of Yolk and Nutrition in the Early Embryo

“…Though we are unable to probe the relationship between the human embryonic yolk and these parturition outcomes, the use of models such as the zebrafish may help to elucidate this relationship. Epidemiology studies have associated numerous environmental toxicants with reduced birth weight or size, including bisphenol A [81], phthalates [82], perfluorinated compounds [83, 84], and fine particulate matter [85]. However, the mechanisms underlying this relationship remain unknown.…”