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Background: Humans are typically exposed to mixtures of environmental endocrine-disrupting chemicals simultaneously, but most studies have considered only a single chemical or a class of similar chemicals., Objectives: We examined the association of exposure to mixtures of 7 chemicals, including 2 phenols [bisphenol A (BPA) and bisphenol S (BPS)], 2 parabens [methylparaben (MeP) and propyl paraben (PrP)], and 3 phthalate metabolites [Mono-benzyl phthalate (MBzP), mono-isobutyl phthalate (MiBP), mono (carboxyoctyl) phthalate (MCOP)] with sex steroid hormones., Methods: A total of 1179 children aged 6-19 years who had complete data on both 7 chemicals and sex steroid hormones of estradiol (E 2 ), total testosterone (TT), and sex hormone-binding globulin (SHBG) were analyzed from the U.S. National Health and Nutrition Examination Survey 2013-2016. Free androgen index (FAI) calculated by TT/SHBG, and the ratio of TT to E 2 (TT/E 2 ) were also estimated. Puberty was defined if TT ≥ 50 ng/dL in boys, E 2 ≥ 20 pg/mL in girls; otherwise prepuberty was defined. Linear regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were performed to estimate the associations of individual chemical or chemical mixtures with sex hormones., Results: The linear regression showed that 2 phenols, 2 parabens, and 3 phthalate metabolites were generally negatively associated with E 2 , TT, FAI, and TT/E 2 , while positively with SHBG. Moreover, these associations were more pronounced among pubertal than prepubertal children. The aforementioned associations were confirmed when further applying WQS and BKMR, and the 3 phthalates metabolites were identified to be the most heavily weighing chemicals., Conclusions: Exposure to phenols, parabens, and phthalates, either individuals or as a mixture, was negatively associated with E 2 , TT, FAI and TT/E 2 , while positively with SHBG. Those associations were stronger among pubertal children., Competing Interests: Declaration of competing interest The authors declare no actual or potential conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Background: Per- and polyfluoroalkyl substances (PFAS) are believed to impair early neurodevelopment and disrupt thyroid hormone (TH) levels. However, there are limited epidemiological data on the neurodevelopmental effects in infancy of prenatal PFAS exposure and the potential mediating effects of TH., Objectives: To evaluate potential associations between prenatal PFAS exposure and early neurodevelopmental deficiencies, and assess mediator effects of TH., Methods: From 2010 to 2013, 274 mother-infant pairs were recruited to the Laizhou Wan Birth Cohort in China. Ten PFAS and five TH were measured in cord serum. Developmental quotient (DQ) from 5 domains (adaptive, social, language, gross and fine motor) was assessed using Gesell Developmental Schedules for each child at 1 year of age. The associations between PFAS and DQs were evaluated using multivariable linear regressions. TH-mediated effects of PFAS on DQs were calculated by mediation analyses., Results: Among our study population, PFAS exposures were common and associated with DQ decrement in infants. For each 10-fold increase in PFBS concentrations, gross motor and adaptive DQ decreased by 8.56 (95%CI: -15.15, -1.97) and 5.87 (95%CI: -8.07, -3.67) points, respectively. TSH mediated 12.90% of the association of PFBS with gross motor DQ and FT4 explained 19.63% of the association of PFBS with adaptive DQ. The negative association was also found between PFHxS exposure and gross motor DQ (β = 8.14, 95%CI: -15.39, -0.98)., Conclusions: PFBS and PFHxS were negatively associated with early neurodevelopment, especially consistent in gross motor domain. The associations were partly explained by TSH and FT4., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Pregnant women are ubiquitously exposed to per- and polyfluoroalkyl substances (PFAS). Prenatal exposure to PFAS has been associated with lower birth weight but also with excess adiposity and higher weight in childhood. These mixed findings warrant investigation of the relationship between PFAS and dynamic offspring growth., Objectives: To investigate the association between prenatal PFAS exposure and early-life growth trajectories during the first 2 y., Methods: Pregnant women ( n = 3,426 ) were recruited from 2013 to 2016 from the Shanghai Birth Cohort (SBC) Study, and their children were followed up from birth to 2 y of age. Seven PFAS congeners were quantified in pregnant women's serum during the first trimester. Our study population was restricted to 1,350 children who had five repeated measurements for at least one anthropometric measure. Four anthropometric measures, including weight, length/height, weight-for-length, and head circumference, were evaluated at birth, 42 d, 6 months, 12 months, and 24 months, and standardized into z -scores using the World Health Organization reference. Trajectories of each measure were classified into five groups using group-based trajectory modeling. Multinomial logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) for trajectory groups according to log 2 -transformed PFAS concentrations, and the moderate-stable group was selected as the reference group for all measures., Results: Higher prenatal exposure to PFAS was associated with elevated odds for the low-rising weight-for-age z -score (WAZ) trajectory, and the high-rising length-for-age z -score (LAZ) trajectory. Meanwhile, PFAS levels were associated with decreased odds for the low-rising and high-rising weight-for-length z -score (WLZ) trajectories. In addition, the associations of PFAS with growth trajectory groups differed by sex, where males had greater odds for the low-rising and low-stable WAZ trajectories and for the high-stable and low-rising WLZ trajectories. In contrast, inverse associations were consistently observed with trajectories of the high-stable, low-stable, and low-rising head-circumference-for-age z -score (HCZ) in relation to most individual PFAS congeners. PFAS mixtures analysis further confirmed the above findings., Discussion: Trajectory analysis approach provided insight into the complex associations between PFAS exposure and offspring growth. Future studies are warranted to confirm the present findings with trajectory modeling strategies and understand the clinical significance of these trajectory groups. https://doi.org/10.1289/EHP9875.

Background: Perfluoroalkyl substances (PFASs) are persistent and bio-accumulative compounds that have been recognized as important immune hazards by animal studies. However, epidemiological studies regarding the impact on infant infections were inconsistent., Objectives: We investigated the associations between prenatal exposure to PFASs and acute infectious diseases including common cold, bronchitis/pneumonia, and diarrhea in early childhood., Methods: Participating 235 mother-infant pairs were recruited from the Laizhou Wan (Bay) birth cohort (LWBC), a prospective study in Shandong, China between September 2010 and 2013. Ten selected PFASs congeners including PFOA, PFOS, PFNA, PFDA, PFUA, PFDoA, PFHxS, PFBS, PFHpA, and PFOSA were measured from maternal serum by HPLC-MS/MS. Detailed information on parent-reported frequency of acute infectious diseases was collected from questionnaires at 1-year follow-up, which was confirmed by the medical records. Logistic and Poisson regression models were used on binary health outcomes (yes/no) and the number of episodes of outcomes, which were reported as odds ratio (OR) and incidence rate-ratio (IRR), respectively., Results: The risk of diarrhea increased by 4.99 (95% CI = 1.86, 13.39) per log-unit increase in PFOA. The frequencies of diarrhea increased by 97%-116% for each 10-fold increase in PFOA, PFNA, and PFDA. Moreover, when stratified by exclusively breastfeeding duration (at least 4 months or not), the adverse effects of PFASs exposures on diarrhea were more pronounced among the breastfed infants. There were no associations between prenatal PFASs exposure and common cold or bronchitis/pneumonia., Conclusions: Exposure to PFASs was associated with increased risks of diarrhea during the first year of life, and these effects were stronger among the breastfed infants. Due to the small sample size, our results should be interpreted with caution and additional studies on larger populations are needed to confirm our findings., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Although maternal perfluoroalkyl and polyfluroalkyl substances (PFASs) were associated with adverse birth outcomes, much less is known about their impact on infant growth during early infancy., Objectives: We investigated the association between maternal PFASs exposure and infant growth during the first 12 months of life., Methods: Participating 2395 pregnancies were recruited from Shanghai Birth Cohort between 2013 and 2016. Ten PFASs were quantified from maternal plasma collected during early pregnancy (median, 15 gestational weeks). We measured infant length, weight, and head circumference at birth, 42 days, 6 months, and 12 months. Linear mixed regression model was used to estimate the associations between PFAS concentrations and repeated measurements of infant growth. Effect modification by infant sex was estimated., Results: Elevated perfluoroheptanoic acid (PFHpA) concentration was negatively associated with infant length-for-age Z score (LAZ) (β = -0.06, 95% confidence interval (CI): -0.11, -0.01) during the first year. Adverse associations were also observed for perfluorobutane sulfonate (PFBS) and weight-for-length Z score (WFL) (β = -0.02, 95% CI: -0.04, -0.00) and BMI-for-age Z score (BAZ) (β = -0.02, 95% CI: -0.04, -0.00). However, perfluorododecanoic acid (PFDoA) was positively associated with WFL (β = 0.03, 95% CI: 0.00, 0.06) and BAZ (β = 0.03, 95% CI: 0.00, 0.06). The adverse association of PFHpA and LAZ was more pronounced among males (β = -0.06; 95% CI: -0.11, -0.00) than females (β = 0.06; 95% CI: 0.01, 0.12)., Conclusions: In our study, negative associations were found for maternal PFHpA exposure and infant LAZ, PFBS and WFL and BAZ. Meanwhile, maternal PFDoA exposure was positively related with WFL and BAZ. The adverse association of maternal PFHpA exposure and infant LAZ was more pronounced among males. The results should be interpreted with caution, further prospective cohort studies with longitudinal and detailed measures are warranted to confirm these findings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)