Early-Life Exposure to Per- and Poly-Fluorinated Alkyl Substances and Growth, Adiposity, and Puberty in Children: A Systematic Review

Abstract

Per- or polyfluoroalkyl substances (PFAS), a family of synthetic polyfluorinated compounds, are widely used in consumer products. Ubiquitous exposures to PFAS, in consideration of their persistence, bioaccumulation potential, and toxicities have led to concerns regarding possible harmful effects during critical periods of development in early-life and long-term consequences on health. The potential effects of PFAS depend on various factors including the type of PFAS and the timing and level of exposure. We performed a systematic review of the epidemiologic literature to assess the effects of early-life PFAS exposure on prenatal and postnatal growth, adiposity, and puberty in children and adolescents. For birth size, most studies indicated that prenatal PFAS exposure, in particular long-chain PFAS, may impair fetal growth, albeit some reports of null associations with maternal PFAS. For growth within 2 years of age, prenatal PFAS exposure showed no associations with height and either null or negative associations with weight. However, postnatal PFAS exposures were inversely related to height and weight at 2 years in a cross-sectional study. For postnatal adiposity, prenatal PFAS may mostly have negative associations with body mass index in the first 2 years of life, but positive relationships with adiposity in childhood and adolescence, although some studies showed null associations. For puberty, the evidence for associations between early-life PFAS exposure and pubertal development or sex hormone levels were limited and inconclusive. From experimental studies, plausible mechanisms through which PFAS may affect early-life growth and puberty include PFAS-induced activation of peroxisome proliferator-activated receptor, alterations of thyroid or steroid hormone synthesis and metabolism, and their weak estrogenic or anti-androgenic properties. Although the published literature suggests possible effects of PFAS exposures on early-life growth, adiposity, and puberty, current human evidence is limited in establishing PFAS-induced effects on early-life physical development. Further investigation is warranted to clarify PFAS-induced effects on growth and physical development in consideration of the critical time-window of exposure, concomitant exposure to chemical mixtures including various PFAS types, and possible non-monotonic dose-response relationship for growth and adiposity trajectories.

New insights on the effects of endocrine-disrupting chemicals on children

“… 44 These results need to be confirmed because the role of these compounds as complex mixtures remains largely unknown. 45 …”

Prenatal Exposure to Per- and Polyfluoroalkyl Substances and Child Growth Trajectories in the First Two Years

“…For other types of PFAS and other growth measures besides weight, the evidence was very limited and more inconclusive as reviewed by Lee et al. ( Lee et al. 2021 ).…”

“…PFAS can transfer across the placenta during pregnancy (Eryasa et al 2019;Wang et al 2019), making them a potential threat to fetuses during the most sensitive early stages of life. Previous epidemiological studies have suggested that prenatal PFAS exposures, mainly PFOS and PFOA, may be associated with decreased birth weight (Chen et al 2021;Gyllenhammar et al 2018;Lee et al 2021;Liew et al 2018;Maisonet et al 2012;Marks et al 2019;Meng et al 2018;Starling et al 2017) and increased risk of childhood overweight or adiposity (Braun et al 2016;Chen et al 2017Chen et al , 2019Gyllenhammar et al 2018;Lee et al 2021;Maisonet et al 2012;Starling et al 2019). However, several inconsistent results have also been reported, such as inverse or null associations for childhood growth (Andersen et al 2013;Barry et al 2014;Shoaff et al 2018).…”

“…However, several inconsistent results have also been reported, such as inverse or null associations for childhood growth (Andersen et al 2013;Barry et al 2014;Shoaff et al 2018). For other types of PFAS and other growth measures besides weight, the evidence was very limited and more inconclusive as reviewed by Lee et al (Lee et al 2021). Taken together, prenatal PFAS exposures may show mixed and conflicting associations with human growth at different developmental stages, raising concerns over their long-term health influence.…”

“…Growth processes during the first 2 y of life, when the greatest variations in rates of weight gain usually occur, deserve more attention (Ong et al 2000;Pryor et al 2011). In addition, prior studies have almost exclusively used static anthropometric measures, which lack information on the dynamic growth processes (Braun et al 2016;Gyllenhammar et al 2018;Kashino et al 2020;Lee et al 2021). The heterogeneity in earlylife growth calls for finer modeling of these variations into several typical trajectories instead of an average growth pattern (Herle et al 2020).…”