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Maternal hyperglycemia during pregnancy adversely affects maternal and child outcomes. While mechanisms are not fully understood, maternal circulating miRNAs may play a role. We examined whether continuous glucose levels and hyperglycemia subtypes (gestational diabetes, type 2 diabetes, and glucose intolerance) were associated with circulating miRNAs during late pregnancy. Seven miRNAs (hsa-miR-107, hsa-let-7b-5p, hsa-miR-126-3p, hsa-miR-181a-5p, hsa-miR-374a-5p, hsa-miR-382-5p, and hsa-miR-337-5p) were associated ( p  < 0.05) with either hyperglycemia or continuous glucose levels prior to multiple testing correction. These miRNAs target genes involved in pathways relevant to maternal and child health, including insulin signaling, placental development, energy balance, and appetite regulation.

Per- and polyfluoroalkyl substances (PFAS) are related to various adverse health outcomes, and food is a common source of PFAS exposure. Dietary sources of PFAS have not been adequately explored among U.S. pregnant individuals. We examined associations of dietary factors during pregnancy with PFAS concentrations in maternal plasma and human milk in the New Hampshire Birth Cohort Study. PFAS concentrations, including perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), and perfluorodecanoate (PFDA), were measured in maternal plasma collected at ∼28 gestational weeks and human milk collected at ∼6 postpartum weeks. Sociodemographic, lifestyle and reproductive factors were collected from prenatal questionnaires and diet from food frequency questionnaires at ∼28 gestational weeks. We used adaptive elastic net (AENET) to identify important dietary variables for PFAS concentrations. We used multivariable linear regression to assess associations of dietary variables selected by AENET models with PFAS concentrations. Models were adjusted for sociodemographic, lifestyle, and reproductive factors, as well as gestational week of blood sample collection (plasma PFAS), postpartum week of milk sample collection (milk PFAS), and enrollment year. A higher intake of fish/seafood, eggs, coffee, or white rice during pregnancy was associated with higher plasma or milk PFAS concentrations. For example, every 1 standard deviation (SD) servings/day increase in egg intake during pregnancy was associated with 4.4 % (95 % CI: 0.6, 8.4), 3.3 % (0.1, 6.7), and 10.3 % (5.6, 15.2) higher plasma PFOS, PFOA, and PFDA concentrations respectively. Similarly, every 1 SD servings/day increase in white rice intake during pregnancy was associated with 7.5 % (95 % CI: -0.2, 15.8) and 12.4 % (4.8, 20.5) greater milk PFOS and PFOA concentrations, respectively. Our study suggests that certain dietary factors during pregnancy may contribute to higher PFAS concentrations in maternal plasma and human milk, which could inform interventions to reduce PFAS exposure for both birthing people and offspring., 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 © 2024 Elsevier B.V. All rights reserved.)

Background: Growing evidence suggests that cardiovascular disease develops over the lifetime, often beginning in childhood. Metal exposures have been associated with cardiovascular disease and important risk factors, including dyslipidemia, but prior studies have largely focused on adult populations and single metal exposures., Objective: To investigate the individual and joint impacts of multiple metal exposures on lipid levels during childhood., Methods: This cross-sectional study included 291 4-year-old children from the Rhea Cohort Study in Heraklion, Greece. Seven metals (manganese, cobalt, selenium, molybdenum, cadmium, mercury, and lead) were measured in whole blood using inductively coupled plasma mass spectrometry. Serum lipid levels included total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol. To determine the joint and individual impacts of child metal exposures (log 2 -transformed) on lipid levels, Bayesian kernel machine regression (BKMR) was employed as the primary multi-pollutant approach. Potential effect modification by child sex and childhood environmental tobacco smoke exposure was also evaluated., Results: BKMR identified a positive association between the metal mixture and both total and LDL cholesterol. Of the seven metals examined, selenium (median 90.6 [IQR = 83.6, 96.5] µg/L) was assigned the highest posterior inclusion probability for both total and LDL cholesterol. A difference in LDL cholesterol of 8.22 mg/dL (95% CI = 1.85, 14.59) was observed when blood selenium was set to its 75th versus 25th percentile, holding all other metals at their median values. In stratified analyses, the positive association between selenium and LDL cholesterol was only observed among boys or among children exposed to environmental tobacco smoke during childhood., Impact Statement: Growing evidence indicates that cardiovascular events in adulthood are the consequence of the lifelong atherosclerotic process that begins in childhood. Therefore, public health interventions targeting childhood cardiovascular risk factors may have a particularly profound impact on reducing the burden of cardiovascular disease. Although growing evidence supports that both essential and nonessential metals contribute to cardiovascular disease and risk factors, such as dyslipidemia, prior studies have mainly focused on single metal exposures in adult populations. To address this research gap, the current study investigated the joint impacts of multiple metal exposures on lipid concentrations in early childhood., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Federal, state, tribal, or local entities in the United States issue fish consumption advisories (FCAs) as guidance for safer consumption of locally caught fish containing contaminants. Fish consumption advisories have been developed for commonly detected compounds such as mercury and polychlorinated biphenyls. The existing national guidance does not specifically address the unique challenges associated with bioaccumulation and consumption risk related to per- and polyfluoroalkyl substances (PFAS). As a result, several states have derived their own PFAS-related consumption guidelines, many of which focus on one frequently detected PFAS, known as perfluorooctane sulfonic acid (PFOS). However, there can be significant variation between tissue concentrations or trigger concentrations (TCs) of PFOS that support the individual state-issued FCAs. This variation in TCs can create challenges for risk assessors and risk communicators in their efforts to protect public health. The objective of this article is to review existing challenges, knowledge gaps, and needs related to issuing PFAS-related FCAs and to provide key considerations for the development of protective fish consumption guidance. The current state of the science and variability in FCA derivation, considerations for sampling and analytical methodologies, risk management, risk communication, and policy challenges are discussed. How to best address PFAS mixtures in the development of FCAs, in risk assessment, and establishment of effect thresholds remains a major challenge, as well as a source of uncertainty and scrutiny. This includes developments better elucidating toxicity factors, exposures to PFAS mixtures, community fish consumption behaviors, and evolving technology and analytical instrumentation, methods, and the associated detection limits. Given the evolving science and public interests informing PFAS-related FCAs, continued review and revision of FCA approaches and best practices are vital. Nonetheless, consistent, widely applicable, PFAS-specific approaches informing methods, critical concentration thresholds, and priority compounds may assist practitioners in PFAS-related FCA development and possibly reduce variability between states and jurisdictions. Integr Environ Assess Manag 2024;00:1-20. © 2024 SETAC., (© 2024 SETAC.)

Background: Prior studies suggest that prenatal per- and polyfluoroalkyl substances (PFAS) exposures are associated with shorter breastfeeding duration. Studies assessing PFAS mixtures and populations in North America are sparse., Methods: We quantified PFAS concentrations in maternal plasma collected during pregnancy in the New Hampshire Birth Cohort Study (2010-2017). Participants completed standardized breastfeeding surveys at regular intervals until weaning (n = 813). We estimated associations between mixtures of 5 PFAS and risk of stopping exclusive breastfeeding before 6 months or any breastfeeding before 12 months using probit Bayesian kernel machine regression. For individual PFAS, we calculated the relative risk and hazard ratio (HR) of stopping breastfeeding using modified Poisson regression and accelerated failure time models respectively., Results: PFAS mixtures were associated with stopping exclusive breastfeeding before 6 months, primarily driven by perfluorooctanoate (PFOA). We observed statistically significant trends in the association of perfluorohexane sulfonate (PFHxS), PFOA, and perfluorononanoate (PFNA) (p-trends≤0.02) with stopping exclusive breastfeeding. Participants in the highest PFOA quartile had a 28% higher risk of stopping exclusive breastfeeding before 6 months compared to those in the lowest quartile (95% Confidence Interval: 1.04, 1.56). Similar trends were observed for PFHxS and PFNA with exclusive breastfeeding (p-trends≤0.05). PFAS were not associated with stopping any breastfeeding before 12 months., Conclusions: In this cohort, we observed that participants with greater overall plasma PFAS concentrations had greater risk of stopping exclusive breastfeeding before 6 months and associations were driven largely by PFOA. These findings further support the growing literature indicating that PFAS may be associated with shorter duration of breastfeeding., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Purpose of Review: Triclosan is an endocrine-disrupting antimicrobial additive that is suspected of contributing to antibiotic resistance and altering the microbiome. In this scoping review, we summarize what is known about the association between triclosan exposure and the microbiome using evidence from in vivo and epidemiologic studies., Recent Findings: Our review includes 11 rodent studies, seven fish studies, and five human studies. Evidence from animal studies suggests that triclosan decreases the diversity of the microbiome, although only one epidemiologic study agreed. Most studies suggest that triclosan alters the microbial community beta diversity, but disagree on which taxa contributed to compositional differences. Taxa in the Bacteroidetes, Firmicutes, and Proteobacteria may be more influenced by triclosan than those in other phyla. Studies on triclosan and the microbiome were scarce and were inconclusive as to the effects of triclosan on the microbiome. Additional research is needed to clarify windows of heightened susceptibility of the microbiome to triclosan. We recommend guidelines for future microbiome research in environmental health to increase comparability across studies., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Research on the neurodevelopmental effects of metal(loid)s has focused mainly on outcomes assessed at one time point, even though brain development progresses over time. We investigated biomarkers of perinatal exposure to metals and changes in child behavior over time. We followed 268 participants from the prospective New Hampshire Birth Cohort Study between birth and age 5 years. We measured arsenic (As), copper (Cu), manganese (Mn), lead (Pb), selenium (Se), and zinc (Zn) in toenails from 6-week-old infants. The Behavioral Symptoms Index (BSI), externalizing, and internalizing symptoms were assessed using the Behavior Assessment System for Children, 2nd edition (BASC-2) at ages 3 and 5 years. Multivariable linear regression was used to estimate associations of metals with behavior change, calculated as the difference in symptom raw scores between 3 and 5 years, in addition to the associations for symptom scores at 3 and 5 years separately. Sex-specific associations were also explored using stratified models and a sex-metal interaction term. Adjusted associations of metals and change in behavior varied by exposure and outcome. Each 1 μg/g increase in ln toenail Cu was associated with improved behavior between 3 and 5 years [BSI: β = - 3.88 (95%CI: - 7.12, - 0.64); Externalizing problems: β = - 2.20 (95%CI: - 4.07, - 0.33)]. Increasing Zn was associated with increased externalizing behavior over time ( β = 3.42 (95%CI: 0.60, 6.25). Sex-stratified analyses suggested more pronounced associations among boys compared to girls. Perinatal exposure to metals may alter behavioral development between ages 3 and 5 years. Findings support the need for more research on associations between metals and neurodevelopment over longer time periods., Competing Interests: Competing interests The authors state they have no conflicts of interests.

Background: Phthalates are synthetic chemicals widely used in consumer products and have been identified to contribute to preterm birth. Existing studies have methodological limitations and potential effects of di-2-ethylhexyl phthalate (DEHP) replacements are poorly characterised. Attributable fractions and costs have not been quantified, limiting the ability to weigh trade-offs involved in ongoing use. We aimed to leverage a large, diverse US cohort to study associations of phthalate metabolites with birthweight and gestational age, and estimate attributable adverse birth outcomes and associated costs., Methods: In this prospective analysis we used extant data in the US National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) Program from 1998 to 2022 to study associations of 20 phthalate metabolites with gestational age at birth, birthweight, birth length, and birthweight for gestational age z-scores. We also estimated attributable adverse birth outcomes and associated costs. Mother-child dyads were included in the study if there were one or more urinary phthalate measurements during the index pregnancy; data on child's gestational age and birthweight; and singleton delivery., Findings: We identified 5006 mother-child dyads from 13 cohorts in the ECHO Program. Phthalic acid, diisodecyl phthalate (DiDP), di-n-octyl phthalate (DnOP), and diisononyl phthalate (DiNP) were most strongly associated with gestational age, birth length, and birthweight, especially compared with DEHP or other metabolite groupings. Although DEHP was associated with preterm birth (odds ratio 1·45 [95% CI 1·05-2·01]), the risks per log 10 increase were higher for phthalic acid (2·71 [1·91-3·83]), DiNP (2·25 [1·67-3·00]), DiDP (1·69 [1·25-2·28]), and DnOP (2·90 [1·96-4·23]). We estimated 56 595 (sensitivity analyses 24 003-120 116) phthalate-attributable preterm birth cases in 2018 with associated costs of US$3·84 billion (sensitivity analysis 1·63- 8·14 billion)., Interpretation: In a large, diverse sample of US births, exposure to DEHP, DiDP, DiNP, and DnOP were associated with decreased gestational age and increased risk of preterm birth, suggesting substantial opportunities for prevention. This finding suggests the adverse consequences of substitution of DEHP with chemically similar phthalates and need to regulate chemicals with similar properties as a class., Funding: National Institutes of Health., Competing Interests: Declaration of interests LT acknowledges honoraria from Houghton Mifflin Harcourt, Audible, Paidos, and Kobunsha; travel support from the Endocrine Society, WHO, United Nations Environment Programme, Japan Environment and Health Ministries, and the American Academy of Pediatrics; and scientific advisory board activities for Beautycounter, IS-Global, and Footprint. MER acknowledges funding from the National Institute of General Medical Sciences, the National Institute of Environmental Health Sciences (NIEHS), and the New Hampshire Department of Environmental Services, as well as honoraria from the National Institutes of Health and UMass-Amherst, and advisory board relationships to the New England Graduate Women in Science and Engineering and Mill Run III Condo. AA acknowledges grant support from NIEHS. CN acknowledges the National Institute of Neurological Disorders and Stroke support. ESB acknowledges honoraria from the University of Rochester and SUNY-Downstate. All the authors have received funding from the NIH ECHO programme., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Synthetic chemicals are increasingly being recognized for potential independent contributions to preterm birth (PTB) and low birth weight (LBW). Bisphenols, parabens, and triclosan are consumer product chemicals that act via similar mechanisms including estrogen, androgen, and thyroid disruption and oxidative stress. Multiple cohort studies have endeavored to examine effects on birth outcomes, and systematic reviews have been limited due to measurement of 1-2 spot samples during pregnancy and limited diversity of populations., Objective: To study the effects of prenatal phenols and parabens on birth size and gestational age (GA) in 3,619 mother-infant pairs from 11 cohorts in the NIH Environmental influences on Child Health Outcomes program., Results: While many associations were modest and statistically imprecise, a 1-unit increase in log 10 pregnancy averaged concentration of benzophenone-3 and methylparaben were associated with decreases in birthweight, birthweight adjusted for gestational age and SGA. Increases in the odds of being SGA were 29% (95% CI: 5%, 58%) and 32% (95% CI: 3%, 70%), respectively. Bisphenol S in third trimester was also associated with SGA (OR 1.52, 95% CI 1.08, 2.13). Associations of benzophenone-3 and methylparaben with PTB and LBW were null. In addition, a 1-unit increase in log 10 pregnancy averaged concentration of 2,4-dichlorophenol was associated with 43% lower (95% CI: -67%, -2%) odds of low birthweight; the direction of effect was the same for the highly correlated 2,5-dichlorophenol, but with a smaller magnitude (-29%, 95% CI: -53%, 8%)., Discussion: In a large and diverse sample generally representative of the United States, benzophenone-3 and methylparaben were associated with lower birthweight as well as birthweight adjusted for gestational age and higher odds of SGA, while 2,4-dichlorophenol. These associations with smaller size at birth are concerning in light of the known consequences of intrauterine growth restriction for multiple important health outcomes emerging later in life., 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 © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Widespread exposure to organophosphate ester (OPE) flame retardants with potential reproductive toxicity raises concern regarding the impacts of gestational exposure on birth outcomes. Previous studies of prenatal OPE exposure and birth outcomes had limited sample sizes, with inconclusive results., Objectives: We conducted a collaborative analysis of associations between gestational OPE exposures and adverse birth outcomes and tested whether associations were modified by sex., Methods: We included 6,646 pregnant participants from 16 cohorts in the Environmental influences on Child Health Outcomes (ECHO) Program. Nine OPE biomarkers were quantified in maternal urine samples collected primarily during the second and third trimester and modeled as log 2 -transformed continuous, categorized (high/low/nondetect), or dichotomous (detect/nondetect) variables depending on detection frequency. We used covariate-adjusted linear, logistic, and multinomial regression with generalized estimating equations, accounting for cohort-level clustering, to estimate associations of OPE biomarkers with gestational length and birth weight outcomes. Secondarily, we assessed effect modification by sex., Results: Three OPE biomarkers [diphenyl phosphate (DPHP), a composite of dibutyl phosphate and di-isobutyl phosphate (DBUP/DIBP), and bis(1,3-dichloro-2-propyl) phosphate] were detected in > 85 % of participants. In adjusted models, DBUP/DIBP [odds ratio (OR) per doubling = 1.07 ; 95% confidence interval (CI): 1.02, 1.12] and bis(butoxyethyl) phosphate (OR for high vs. nondetect = 1.25 ; 95% CI: 1.06, 1.46), but not other OPE biomarkers, were associated with higher odds of preterm birth. We observed effect modification by sex for associations of DPHP and high bis(2-chloroethyl) phosphate with completed gestational weeks and odds of preterm birth, with adverse associations among females. In addition, newborns of mothers with detectable bis(1-chloro-2-propyl) phosphate, bis(2-methylphenyl) phosphate, and dipropyl phosphate had higher birth weight-for-gestational-age z -scores ( β for detect vs. nondetect = 0.04 - 0.07 ); other chemicals showed null associations., Discussion: In the largest study to date, we find gestational exposures to several OPEs are associated with earlier timing of birth, especially among female neonates, or with greater fetal growth. https://doi.org/10.1289/EHP13182.

Background: Per- and polyfluoroalkyl substances (PFAS) may disrupt mammary gland development and function; thereby inhibiting milk supply and breastfeeding duration. However, conclusions on the potential effects of PFAS and breastfeeding duration are limited by prior epidemiologic studies that inconsistently adjusted for past cumulative breastfeeding duration and by a lack of examination of the joint effects of PFAS mixtures., Methods: In Project Viva, a longitudinal cohort that enrolled pregnant participants from 1999 to 2002 in the greater Boston, MA area, we studied 1079 women who ever attempted to lactate. We investigated associations of plasma concentrations of select PFAS in early pregnancy (mean: 10.1 weeks gestation) with breastfeeding termination by 9 months, after which women typically cite self-weaning as the reason for terminating breastfeeding. We used Cox regression for single-PFAS models and quantile g-computation for mixture models, adjusting for sociodemographics, prior breastfeeding duration, and weeks of gestation at the time of blood draw., Results: We detected 6 PFAS [perfluorooctane sulfonate; perfluorooctanoate (PFOA); perfluorohexane sulfonate; perfluorononanoate; 2-(N-ethyl-perfluorooctane sulfonamido) acetate (EtFOSAA); 2-(N-methyl-perfluorooctane sulfonamide) acetate (MeFOSAA)] in >98 % of samples. Sixty percent of lactating women terminated breastfeeding by 9 months postpartum. Women with higher plasma concentrations of PFOA, EtFOSAA, and MeFOSAA had a greater hazard of terminating breastfeeding in the first 9 months postpartum [HR (95 % CI) per doubling concentration: 1.20 (1.04, 1.38) for PFOA; 1.10 (1.01, 1.20) for EtFOSAA; 1.18 (1.08, 1.30) for MeFOSAA]. In the quantile g-computation model, simultaneously increasing all PFAS in the mixture by one quartile was associated with 1.17 (95 % CI: 1.05, 1.31) greater hazard of terminating breastfeeding in the first 9 months., Conclusion: Our findings suggest that exposure to PFAS may be associated with reduced breastfeeding duration and draw further attention to environmental chemicals that may dysregulate human lactation., 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 © 2023 Elsevier B.V. All rights reserved.)

Anecdotal evidence suggests that pancreatic acinar metaplasia (PAM) and intestinal metaplasia (IM) overlap infrequently at the gastroesophageal junction/distal esophagus (GEJ/DE). The goal of this study was to evaluate the significance of PAM at GEJ/DE in relation to IM in patients with gastroesophageal reflux disease (GERD). Group 1 comprised 230 consecutive patients with GEJ/DE biopsies (80.6% with GERD symptoms). Group 2 comprised 151 patients with established GERD and GEJ/DE biopsies taken before Nissen fundoplication. Group 3 comprised 540 consecutive patients used for a follow-up study of PAM. PAM was present in 15.7%-15.9% and IM in 24.8%-31.1% of patients in groups 1 and 2, respectively. PAM-IM overlap was present in 2.2%-3.3%, respectively. Patients with PAM were, on average, 6-12 years younger than patients with IM, and were predominantly female (72.2%-75%), in contrast to patients with IM (47.3%-32%). In the unadjusted logistic regression model, patients with PAM were 69%-65% less likely to also have IM, as compared to patients without PAM. In the fully adjusted model, patients with PAM were 35%-61% less likely to also have IM, although the P-value was not significant. Follow-up analysis of patients with PAM from group 3 (n = 28) demonstrated the prevalence of IM and PAM in subsequent biopsies at 7.1% and 60.7%, respectively. No cases showed PAM-IM overlap on follow-up. The data suggests that PAM at the GEJ/DE is associated with protective effect against IM and thus could be useful as a marker of decreased susceptibility to IM., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Breastfeeding has significant health benefits for infants and birthing persons, including reduced risk of chronic disease. The American Academy of Pediatrics recommends exclusively breastfeeding infants for 6 months and recently extended its recommendation for continuing to breastfeed with supplementation of solid foods from one to two years. Studies consistently identify lower breastfeeding rates among US infants, with regional and demographic variability. We examined breastfeeding in birthing person-infant pairs among healthy, term pregnancies enrolled in the New Hampshire Birth Cohort Study between 2010 and 2017 (n = 1176)., Methods: Birthing persons 18-45 years old were enrolled during prenatal care visits at ~ 24-28 weeks gestation and have been followed since enrollment. Breastfeeding status was obtained from postpartum questionnaires. Birthing person and infant health and sociodemographic information was abstracted from medical records and prenatal and postpartum questionnaires. We evaluated the effects of birthing person age, education, relationship status, pre-pregnancy body mass index, gestational weight gain (GWG), smoking and parity, and infant sex, ponderal index, gestational age and delivery mode on breastfeeding initiation and duration using modified Poisson and multivariable linear regression., Results: Among healthy, term pregnancies, 96% of infants were breastfed at least once. Only 29% and 28% were exclusively breastfed at 6-months or received any breastmilk at 12-months, respectively. Higher birthing person age, education, and parity, being married, excessive GWG, and older gestational age at delivery were associated with better breastfeeding outcomes. Smoking, obesity, and cesarean delivery were negatively associated with breastfeeding outcomes., Conclusions: Given the public health importance of breastfeeding for infants and birthing persons, interventions are needed to support birthing persons to extend their breastfeeding duration., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We aimed to investigate the joint, class-specific, and individual impacts of (i) PFAS, (ii) toxic metals and metalloids (referred to collectively as "metals"), and (iii) essential elements on birth outcomes in a prospective pregnancy cohort using both established and recent mixture modeling approaches. Participants included 537 mother-child pairs from the New Hampshire Birth Cohort Study. Concentrations of 6 metals and 5 PFAS were measured in maternal toenail clippings and plasma, respectively. Birth weight, birth length, and head circumference at birth were abstracted from medical records. Joint, index-wise, and individual associations of the metals and PFAS concentrations with birth outcomes were evaluated using Bayesian Kernel Machine Regression (BKMR) and Bayesian Multiple Index Models (BMIM). After controlling for potential confounders, the metals-PFAS mixture was associated with a larger head circumference at birth, which was driven by manganese. When using BKMR, the difference in the head circumference z-score when changing manganese from its 25th to 75th percentiles while holding all other mixture components at their medians was 0.22 standard deviations (95% posterior credible interval [CI]: -0.02, 0.46). When using BMIM, the posterior mean of index weight estimates assigned to manganese for head circumference z-score was 0.72 (95% CI: 0, 0.99). Prenatal exposure to the metals-PFAS mixture was not associated with birth weight or birth length by either BKMR or BMIM. Using both traditional and new mixture modeling approaches, prenatal exposure to manganese was associated with a larger head circumference at birth after accounting for exposure to PFAS and multiple toxic and essential metals., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: National Institutes of Health, National Institute of Environmental Health Sciences, National Institute of General Medical Sciences, and United States Environmental Protection Agency. Dr. McGee reports financial support was provided by Natural Sciences and Engineering Research Council of Canada. Dr. Howe reports financial support was provided by National Institute of Environmental Health Sciences. Dr. Romano reports financial support was provided by National Institute of Environmental Health Sciences., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Gestational per- and polyfluoroalkyl substances (PFAS) exposure may be associated with adiposity and increased risk of obesity among children and adolescents. However, results from epidemiological studies evaluating these associations are inconsistent., Objectives: We estimated the associations of pregnancy PFAS concentrations with child body mass index (BMI) z -scores and risk of overweight/obesity in eight U.S. cohorts., Methods: We used data from 1,391 mother-child pairs who enrolled in eight Environmental influences on Child Health Outcomes (ECHO) cohorts (enrolled: 1999-2019). We quantified concentrations of seven PFAS in maternal plasma or serum in pregnancy. We measured child weight and height between the ages of 2 and 5 y and calculated age- and sex-specific BMI z -scores; 19.6% children had more than one BMI measurement. We estimated covariate-adjusted associations of individual PFAS and their mixture with child BMI z -scores and risk of overweight/obesity using linear mixed models, modified Poisson regression models, and Bayesian approaches for mixtures. We explored whether child sex modified these associations., Results: We observed a pattern of subtle positive associations of PFAS concentrations in pregnancy with BMI z -scores and risk of overweight/obesity. For instance, each doubling in perfluorohexane sulfonic acid concentrations was associated with higher BMI z -scores ( β = 0.07 ; 95% CI: 0.01, 0.12). Each doubling in perfluroundecanoic acid [ relative risk  ( RR ) = 1.10 ; 95% CI: 1.04, 1.16] and N -methyl perfluorooctane sulfonamido acetic acid ( RR = 1.06 ; 95% CI: 1.00, 1.12) was associated with increased risk of overweight/obesity, with some evidence of a monotonic dose-response relation. We observed weaker and more imprecise associations of the PFAS mixture with BMI or risk of overweight/obesity. Associations did not differ by child sex., Discussion: In eight U.S.-based prospective cohorts, gestational exposure to higher levels of PFAS were associated with slightly higher childhood BMI z -score and risk of overweight or obesity. Future studies should examine associations of gestational exposure to PFAS with adiposity and related cardiometabolic consequences in older children. https://doi.org/10.1289/EHP11545.

Per- and polyfluoroalkyl substances (PFAS), widely used in industrial and consumer products, are suspected metabolic disruptors. We examined the association between a PFAS mixture during pregnancy and postpartum weight retention in 482 participants from the New Hampshire Birth Cohort Study. PFAS concentrations, including perfluorohexane sulfonate, perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), and perfluorodecanoate, were quantified in maternal plasma collected at ~28 gestational weeks. Postpartum weight change was calculated as the difference between self-reported weight from a postpartum survey administered in 2020 and pre-pregnancy weight abstracted from medical records. Associations between PFAS and postpartum weight change were examined using Bayesian kernel machine regression and multivariable linear regression, adjusting for demographic, reproductive, dietary, and physical activity factors; gestational week of blood sample collection; and enrollment year. PFOS, PFOA, and PFNA were positively associated with postpartum weight retention, and associations were stronger among participants with a higher pre-pregnancy body mass index. A doubling of PFOS, PFOA, and PFNA concentrations was associated with a 1.76 kg (95%CI: 0.31, 3.22), 1.39 kg (-0.27, 3.04), and 1.04 kg (-0.19, 2.28) greater postpartum weight retention, respectively, among participants who had obesity/overweight prior to pregnancy. Prenatal PFAS exposure may be associated with increased postpartum weight retention.

Milk formation in the breast during breastfeeding is a complex hormonally regulated process, potentially sensitive to the effects of endocrine-disrupting chemical exposures. The environmental chemicals, per- and polyfluoroalkyl substances (PFAS) are known endocrine disruptors. PFAS exposure have been associated with insufficient mammary gland development in mice and reduced breastfeeding duration in humans. The aim of this review was to gather the epidemiological evidence on the association between PFAS exposure and breastfeeding duration. Using PubMed and Embase, we performed a systematic literature search (on 23 January 2023) to identify epidemiological studies examining the association between maternal PFAS exposure and breastfeeding duration. Animal studies, reviews, and non-English studies were excluded. The risk of bias was assessed using the risk of bias in non-randomized studies of exposures tool. Estimates describing the association between PFAS exposure and the duration of breastfeeding were identified, and the data were synthesized separately for each type of PFAS and for the duration of exclusive and total breastfeeding. Six studies with between 336 and 2374 participants each were identified. PFAS exposure was assessed in serum samples (five studies) or based on residential address (one study). Five out of six studies found shorter total duration of breastfeeding with higher PFAS exposure. The most consistent associations were seen for perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA). The finding of a potential causal association between PFAS exposure and breastfeeding duration is in agreement with findings from experimental studies.

Background: Per- and polyfluoroalkyl substances (PFAS) are persistent and ubiquitous chemicals associated with risk of adverse birth outcomes. Results of previous studies have been inconsistent. Associations between PFAS and birth outcomes may be affected by psychosocial stress., Objectives: We estimated risk of adverse birth outcomes in relation to prenatal PFAS concentrations and evaluate whether maternal stress modifies those relationships., Methods: We included 3,339 participants from 11 prospective prenatal cohorts in the Environmental influences on the Child Health Outcomes (ECHO) program to estimate the associations of five PFAS and birth outcomes. We stratified by perceived stress scale scores to examine effect modification and used Bayesian Weighted Sums to estimate mixtures of PFAS., Results: We observed reduced birth size with increased concentrations of all PFAS. For a 1-unit higher log-normalized exposure to perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS), we observed lower birthweight-for-gestational-age z-scores of β = - 0.15 [95% confidence interval (CI): - 0.27 , - 0.03 ], β = - 0.14 (95% CI: - 0.28 , - 0.002 ), β = - 0.22 (95% CI: - 0.23 , - 0.10 ), β = - 0.06 (95% CI: - 0.18 , 0.06), and β = - 0.25 (95% CI: - 0.37 , - 0.14 ), respectively. We observed a lower odds ratio (OR) for large-for-gestational-age: OR PFNA = 0.56 (95% CI: 0.38, 0.83), OR PFDA = 0.52 (95% CI: 0.35, 0.77). For a 1-unit increase in log-normalized concentration of summed PFAS, we observed a lower birthweight-for-gestational-age z-score [ - 0.28 ; 95% highest posterior density (HPD): - 0.44 , - 0.14 ] and decreased odds of large-for-gestational-age ( OR = 0.49 ; 95% HPD: 0.29, 0.82). Perfluorodecanoic acid (PFDA) explained the highest percentage (40%) of the summed effect in both models. Associations were not modified by maternal perceived stress., Discussion: Our large, multi-cohort study of PFAS and adverse birth outcomes found a negative association between prenatal PFAS and birthweight-for-gestational-age, and the associations were not different in groups with high vs. low perceived stress. This study can help inform policy to reduce exposures in the environment and humans. https://doi.org/10.1289/EHP10723.

The COVID-19 pandemic-and its associated restrictions-have changed many behaviors that can influence environmental exposures including chemicals found in commercial products, packaging and those resulting from pollution. The pandemic also constitutes a stressful life event, leading to symptoms of acute traumatic stress. Data indicate that the combination of environmental exposure and psychological stress jointly contribute to adverse child health outcomes. Within the Environmental influences on Child Health Outcomes (ECHO)-wide Cohort, a national consortium initiated to understand the effects of environmental exposures on child health and development, our objective was to assess whether there were pandemic-related changes in behavior that may be associated with environmental exposures. A total of 1535 participants from nine cohorts completed a survey via RedCap from December 2020 through May 2021. The questionnaire identified behavioral changes associated with the COVID-19 pandemic in expected directions, providing evidence of construct validity. Behavior changes reported by at least a quarter of the respondents include eating less fast food and using fewer ultra-processed foods, hair products, and cosmetics. At least a quarter of respondents reported eating more home cooked meals and using more antibacterial soaps, liquid soaps, hand sanitizers, antibacterial and bleach cleaners. Most frequent predictors of behavior change included Hispanic ethnicity and older age (35 years and older). Respondents experiencing greater COVID-related stress altered their behaviors more than those not reporting stress. These findings highlight that behavior change associated with the pandemic, and pandemic-related psychological stress often co-occur. Thus, prevention strategies and campaigns that limit environmental exposures, support stress reduction, and facilitate behavioral change may lead to the largest health benefits in the context of a pandemic. Analyzing biomarker data in these participants will be helpful to determine if behavior changes reported associate with measured changes in exposure., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Herbstman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent endocrine-disrupting chemicals associated with long-term health outcomes. PFAS are transferred from maternal blood to human milk, an important exposure source for infants, and understanding of this transfer is evolving. We characterized concentrations of 10 PFAS in human milk ( n = 426) and compared milk-to-plasma concentrations of 9 PFAS among a subset of women with paired samples ( n = 294) from the New Hampshire Birth Cohort Study using liquid chromatography-isotope dilution tandem mass spectrometry. We examined the relationship between perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) in plasma versus milk and fit linear regression models to assess relationships between milk PFOA and PFOS and participant characteristics. The median plasma PFOA concentration was 0.94 ng/mL (interquartile range, IQR, 0.59-1.34) and that of PFOS was 2.60 ng/mL (IQR 1.80-3.90); the median milk PFOA concentration was 0.017 ng/mL (IQR 0.012-0.027) and that of PFOS was 0.024 ng/mL (IQR 0.016-0.036). PFOA and PFOS plasma and milk concentrations showed correlations of ρ = 0.83 and 0.77, respectively ( p < 0.001). Parity, previous lactation, week of milk collection, and body mass index were inversely associated with milk PFAS. We estimate that even among our general population cohort, some infants (∼6.5%) are exposed to amounts of PFAS via milk that may have long-term health impacts.

Human milk is rich in essential nutrients and immune-activating compounds but is also a source of toxicants including per- and polyfluoroalkyl substances (PFAS). Evidence suggests that immune-related effects of PFAS may, in part, be due to alterations of the microbiome. We aimed to identify the association between milk PFAS exposure and the infant gut microbiome., Methods: PFAS [perfluorooctane sulfonic acid (PFOS) and perfluorooctanoate (PFOA)] were quantified in milk from ~6 weeks postpartum using high-performance liquid chromatography with tandem mass spectrometry. A molar sum (ΣPFAS) was calculated. Caregivers collected infant stool samples at 6 weeks (n = 116) and/or 1 year postpartum (n = 119). Stool DNA underwent metagenomic sequencing. We estimated the association of PFAS with diversity and relative abundances of species with linear regression. Single- and multi-PFAS models adjusted for potential confounders in complete case analyses and with imputed missing covariate data for 6-week and 1-year microbiomes separately. We assessed sensitive populations with stratification., Results: PFOS and PFOA were detected in 94% and 83% of milk samples, respectively. PFOS was associated with increased diversity at 6 weeks among infants fed exclusively human milk [β = 0.24 per PFOS doubling, (95% CI = 0.03, 0.45), P = 0.03] and born to primiparous mothers [β = 0.37 (0.06, 0.67), P = 0.02]. Estimates were strongest in multi-PFAS models and among complete cases. ΣPFAS was associated with Bacteroides vulgatus relative abundance at 1 year [(β = -2.34% per doubling (-3.63, -1.05), FDR q = 0.099]., Conclusions: PFAS may increase infant gut microbiome diversity and alter the relative abundance of biologically relevant bacteria. Additional analyses may identify related health outcomes., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Background: Per- and polyfluoroalkyl substances (PFAS) are widespread pollutants and classified as potentially carcinogenic to humans. Although consumption of fish, seafood, and their byproducts is a known source of dietary PFAS exposure, little is known about the association between use of fish oil supplements and PFAS. Here, we examine associations between fish oil supplement use and serum PFAS concentrations., Methods: This analysis includes adults, ages 25 years of age and older, surveyed as part of the National Health and Nutrition Examinations Survey (NHANES). Outcomes include five serum PFAS compounds: perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulphonic acid (PFHxS) and perfluorodecanoic acid (PFDA). To determine the association between fish oil use and log-transformed PFAS concentrations, survey-weighted linear regression was used to estimate multivariate-adjusted ratios between supplement-users' and non-users' geometric mean serum PFAS concentrations., Results: No association was observed between fish oil use and PFAS. While results did not vary substantially by age, gender, study cycle, there was some indication of a potential inverse association in subgroups of interest. Specifically, an inverse association was observed between fish oil supplement use and PFOS levels in older adults, females, and in early calendar years; an inverse association was also observed between fish oil and PFNA in females and early calendar years., Conclusions: While fish oil users did not experience increased serum PFAS, there was an unexpected inverse association in some population subgroups. Further research will be needed to better understand whether this pattern reflects true differences, chance, or bias., 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 © 2022 Elsevier Inc. All rights reserved.)

Background: Skiers and snowboarders apply waxes and solvents to their equipment to enhance glide across the snow. Waxing results in exposures to per- and polyfluoroalkyl substances (PFAS) and particulate matter, which have been associated with adverse health effects among professional wax technicians in Scandinavia. However, little is known about exposure among people who participate at other levels of sport, including recreationally, in other regions., Objective: We sought to characterize wax-related exposures among US skiers and snowboarders who participate across numerous levels of sport to expand scientific understanding of environmental health risks among this population., Methods: We used an anonymous electronic survey to evaluate wax-related exposures among US cross-country and downhill skiers and snowboarders. Specifically, we assessed (Fang et al., 2020): duration of time involved with each sport in any role (Freberg et al., 2013), intensity of wax-related exposures based on time spent in waxing areas, wax use, and wax type (Rogowski et al., 2007), frequency of fluorinated wax application, and (Freberg et al., 2010) use of exposure interventions., Results: Participants tended to be long-term winter sports enthusiasts (e.g., median downhill skiing duration: 31 years). Nearly all (92%) participants personally applied some wax to their skis/snowboards and most applied waxes containing PFAS (67%) and solvents (62%). Ski professionals waxed the most pairs of skis with fluorinated waxes annually (median (IQR): 20 (1, 100)), though individuals participating recreationally also applied fluorinated waxes regularly. Exposure interventions were not widely used., Significance: Waxing activities may pose significant risk of exposure to PFAS and other environmental contaminants among the US ski and snowboard community. Efforts are needed to reduce these exposures through changes to wax use patterns and broader adoption of exposure reduction strategies., 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 © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent, potential metabolic disruptors of concern for infants. Mothers participating in the New Hampshire Birth Cohort Study (NHBCS) provided a plasma sample during pregnancy to measure concentrations of seven PFAS, and infant weight and length were abstracted from well-child visits between birth and 12 months. Sex-specific growth patterns of child body mass index (BMI) were fit using a growth mixture model (GMM) and the relative risk ratios (RRR) and 95% Confidence Intervals (95% CI) for the association of maternal plasma PFAS with BMI growth patterns during infancy were estimated by using multinomial logistic model for the group probabilities in the GMM. Four growth patterns were identified: Group 1) a steep increase in BMI during the first 6 months, then a leveling off; Group 2) a gradual increase in BMI across the year; Group 3) a steep increase in BMI during months 1-3, then stable BMI; and Group 4) a gradual increase in BMI with plateau around 3 months (reference group). For boys, higher maternal pregnancy perfluorooctanoate concentrations were associated with a 60% decreased chance of being in group 3 as compared to group 4, after adjusting for potential confounding variables (RRR = 0.4; 95% CI: 0.1, 0.9). For girls, higher maternal perfluorooctane sulfonate (PFOS) concentrations during pregnancy were associated with a higher likelihood of following the growth pattern of groups 2 (RRR = 2.5; 95% CI: 1.0, 6.1) and 3 (RRR = 2.8; 95% CI: 1.0, 7.6) as compared to group 4, adjusting for potential confounding variables. In this cohort, sex-specific associations of maternal plasma PFAS concentrations during pregnancy with growth patterns during the first year of life were observed, with greater BMI growth observed among infant girls born to mothers with higher pregnancy concentrations of PFOS., 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 © 2022 Elsevier Inc. All rights reserved.)

Purpose of Review: Per- and polyfluoroalkyl substances (PFAS) are a diverse class of persistent, fluorinated surfactants used widely in industrial and commercial applications with known adverse health effects. Seafood consumption is thought to be an underappreciated source of PFAS exposure in the general population. This review synthesizes the current understanding of PFAS occurrence in shellfish, a term used to describe animals such as mollusk bivalves, certain gastropods (snails), cephalopods (e.g., octopuses and squid), and crustaceans, and highlights scientific gaps relative to bioaccumulation and the protection of shellfish consumers., Recent Findings: A range of sampling methodologies are used across studies, and the suite of PFAS surveyed across studies is highly variable. Concentrations of PFAS observed in shellfish vary by geographic location, shellfish species, habitat, and across PFAS compounds, and studies informing estimates of bioaccumulation of PFAS in shellfish are extremely limited at this time. This review identifies several important opportunities for researchers to standardize PFAS sampling techniques, sample preparation, and analytical methodologies to allow for better comparison of PFAS analytes both within and across future studies. Increasing the range of geographic locations where samples are collected is also a critical priority to support a greater knowledge of worldwide PFAS contamination. When put into the context of risk to consumer, concentrations of PFAS, especially PFOS, found in shellfish collected from sites containing aqueous film-forming foam (AFFF) and industrial contamination may present risks to frequent consumers. Further research is needed to protect shellfish consumers and to inform shellfish advisories and health protective policies., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose of Review: Toxic metal exposures have been associated with cardiovascular disease in adults and growing evidence suggests metal exposures also adversely affect cardiovascular phenotypes in childhood and adolescence. However, to our knowledge, the influence of perinatal metals exposure, particularly metal mixtures, in relation to cardiovascular-related outcomes have not been comprehensively reviewed., Recent Findings: We summarized 17 contemporary studies (2017-2021) that investigated the impact of perinatal metal exposures on measures of cardiovascular health in children. Accumulating evidence supports a potential adverse impact of perinatal Pb exposure on BP in children. Fewer recent studies have focused on perinatal As, Hg, and Cd; thus, the cardiovascular impacts of these metals are less clear. Studies of metal mixtures demonstrate that interactions between metals may be complex and have identified numerous understudied elements and essential metals, including Mo, Co, Ni, Se, Zn, and Mn, which may influence cardiovascular risk. A key question that remains is whether perinatal metals exposure influences cardiovascular health into adulthood. Comparisons across studies remain challenging due to several factors, including differences in the timing of exposure/outcome assessments and exposure biomarkers, as well as variability in exposure levels and mixture compositions across populations. Future studies longitudinally investigating trajectories of cardiovascular outcomes could help determine the influence of perinatal metals exposure on long-term effects of clinical relevance in later life and whether interventions, which reduce metals exposures during this key developmental window, could alter disease development., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Drawing upon extant data from existing pediatric cohorts and new follow-up of a diverse set of pediatric cohorts from across the United States, the Environmental influences on Child Health Outcomes (ECHO) Program creates the opportunity for novel and innovative investigations of many previously inaccessible scientific questions in the area of child health. We describe how the large sample size, diversity of participants, emphasis on team science, and infrastructure for improving research methodology make the ECHO Program a major research resource for improving our understanding of early life determinants of childhood health and well-being. Pediatric researchers leverage the unique features of the ECHO Program to address research questions with the potential to yield far-reaching and long-term impacts on child health. IMPACT: The ECHO Program unites pediatric cohorts from across the United States, allowing for investigations of compelling research questions that were previously infeasible due to limited sample sizes or lack of participant diversity. The focus of the ECHO Program on team science, solution-oriented research, and methodological innovation propels novel scientific investigations that are responsive to the needs of a wide range of stakeholders. Features of the ECHO program's infrastructure poise its investigators to rapidly launch research endeavors that are responsive to time-sensitive and critical needs within the realm of pediatric research., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Silicone wristbands act as passive environmental samplers capable of detecting and measuring concentrations of a variety of chemicals. They offer a noninvasive method to collect complex exposure data in large-scale epidemiological studies. We evaluated the inter-method reliability of silicone wristbands and urinary biomarkers in the New Hampshire Birth Cohort Study. A subset of study participants (n = 96) provided a urine sample and wore a silicone wristband for 7 days at approximately 12 gestational weeks. Women were instructed to wear the wristbands during all their normal activities. Concentrations of urinary compounds and metabolites in the urine and parent compounds in wristbands were compared. High detection rates were observed for triphenyl phosphate (76.0%) and benzophenone (78.1%) in wristbands, although the distribution of corresponding urinary concentrations of chemicals did not differ according to whether chemicals were detected or not detected in wristbands. While detected among only 8.3% of wristbands, median urinary triclosan concentrations were higher among those with triclosan detected in wristbands (9.04 ng/mL) than without (0.16 ng/mL). For most chemicals slight to fair agreement was observed across exposure assessment methods, potentially due to low rates of detection in the wristbands for chemicals where observed urinary concentrations were relatively low as compared to background concentrations in the general population. Our findings support the growing body of research in support of deploying silicone wristbands as an important exposure assessment tool., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kim Anderson, an author of this research, discloses a financial interest in MyExposome, Inc., which is marketing products related to the research being reported. The terms of this arrangement have been reviewed and approved by OSU in accordance with its policy on research conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Melamine, melamine derivatives, and aromatic amines are nitrogen-containing compounds with known toxicity and widespread commercial uses. Nevertheless, biomonitoring of these chemicals is lacking, particularly during pregnancy, a period of increased susceptibility to adverse health effects., Objectives: We aimed to measure melamine, melamine derivatives, and aromatic amine exposure in pregnant women across the United States (U.S.) and evaluate associations with participant and urine sample collection characteristics., Methods: We measured 43 analytes, representing 45 chemicals (i.e., melamine, three melamine derivatives, and 41 aromatic amines), in urine from pregnant women in nine diverse ECHO cohorts during 2008-2020 (N = 171). To assess relations with participant and urine sample collection characteristics, we used generalized estimating equations to estimate prevalence ratios (PRs) for analytes dichotomized at the detection limit, % differences (%Δ) for continuous analytes, and 95% confidence intervals. Multivariable models included age, race/ethnicity, marital status, urinary cotinine, and year of sample collection., Results: Twelve chemicals were detected in >60% of samples, with near ubiquitous detection of cyanuric acid, melamine, aniline, 4,4'-methylenedianiline, and a composite of o-toluidine and m-toluidine (99-100%). In multivariable adjusted models, most chemicals were associated with higher exposures among Hispanic and non-Hispanic Black participants. For example, concentrations of 3,4-dichloroaniline were higher among Hispanic (%Δ: +149, 95% CI: +17, +431) and non-Hispanic Black (%Δ: +136, 95% CI: +35, +311) women compared with non-Hispanic White women. We observed similar results for ammelide, o-/m-toluidine, 4,4'-methylenedianiline, and 4-chloroaniline. Most chemicals were positively associated with urinary cotinine, with strongest associations observed for o-/m-toluidine (%Δ: +23; 95% CI: +16, +31) and 3,4-dichloroaniline (%Δ: +25; 95% CI: +17, +33). Some chemicals exhibited annual trends (e.g., %Δ in melamine per year: -11; 95% CI: -19, -1) or time of day, seasonal, and geographic variability., Discussion: Exposure to melamine, cyanuric acid, and some aromatic amines was ubiquitous in this first investigation of these analytes in pregnant women. Future research should expand biomonitoring, identify sources of exposure disparities by race/ethnicity, and evaluate potential adverse health effects., 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 © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Arsenic exposure during pregnancy may increase the risk for intellectual deficits in children, but limited data exist from prospective epidemiologic studies, particularly at low arsenic exposure levels. We investigated the association between prenatal maternal urinary arsenic concentrations and childhood cognitive abilities in the Health Outcomes and Measures of the Environment (HOME) Study. We used anion exchange chromatography coupled with inductively coupled plasma mass spectrometry detection to measure arsenic species content in pregnant women's urine. The summation of inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) refers to ∑As. We assessed children's cognitive function (n = 260) longitudinally at 1-, 2-, and 3-years using Bayley Scales of Infant and Toddler Development, at 5 years using Wechsler Preschool and Primary Scale of Intelligence, and at 8 years using Wechsler Intelligence Scale for Children. We observed a modest decrease in mental development index and full-scale intelligence quotient at ages 3 and 5 years with each doubling of ∑As with estimated score (ß) differences and 95% confidence interval (CI) of -1.8 from -4.1 to 0.5 and -2.5 from -5.1 to 0.0, respectively. This trend was stronger and reached statistical significance among children whose mothers had lower iAs methylation capacity and low urinary arsenobetaine concentrations. Our findings suggest that arsenic exposure levels relevant to the general US population may affect children's cognitive abilities., 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 © 2022 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Prenatal chemical exposures can influence maternal and child health; however, few industrial chemicals are routinely biomonitored. We assessed an extensive panel of contemporary and emerging chemicals in 171 pregnant women across the United States (U.S.) and Puerto Rico in the Environmental influences on Child Health Outcomes (ECHO) Program. We simultaneously measured urinary concentrations of 89 analytes (103 total chemicals representing 73 parent compounds) in nine chemical groups: bactericides, benzophenones, bisphenols, fungicides and herbicides, insecticides, organophosphate esters (OPEs), parabens, phthalates/alternative plasticizers, and polycyclic aromatic hydrocarbons (PAHs). We estimated associations of creatinine-adjusted concentrations with sociodemographic and specimen characteristics. Among our diverse prenatal population (60% non-Hispanic Black or Hispanic), we detected 73 of 89 analytes in ≥1 participant and 36 in >50% of participants. Five analytes not currently included in the U.S. biomonitoring were detected in ≥90% of samples: benzophenone-1, thiamethoxam, mono-2-(propyl-6-carboxy-hexyl) phthalate, monocarboxy isooctyl phthalate, and monohydroxy-iso-decyl phthalate. Many analyte concentrations were higher among women of Hispanic ethnicity compared to those of non-Hispanic White women. Concentrations of certain chemicals decreased with the calendar year, whereas concentrations of their replacements increased. Our largest study to date identified widespread exposures to prevalent and understudied chemicals in a diverse sample of pregnant women in the U.S.

Background: Metabolomics is a promising method to investigate physiological effects of chemical exposures during pregnancy, with the potential to clarify toxicological mechanisms, suggest sensitive endpoints, and identify novel biomarkers of exposures., Objective: Investigate the influence of chemical exposures on the maternal plasma metabolome during pregnancy., Methods: Data were obtained from participants (n = 177) in the New Hampshire Birth Cohort Study, a prospective pregnancy cohort. Chemical exposures were assessed via silicone wristbands worn for one week at ~13 gestational weeks. Metabolomic features were assessed in plasma samples obtained at ~24-28 gestational weeks via the Biocrates AbsoluteIDQ® p180 kit and nuclear magnetic resonance (NMR) spectroscopy. Associations between chemical exposures and plasma metabolomics were investigated using multivariate modeling., Results: Chemical exposures predicted 11 (of 226) and 23 (of 125) metabolomic features in Biocrates and NMR, respectively. The joint chemical exposures did not significantly predict pathway enrichment, though some individual chemicals were associated with certain amino acids and related metabolic pathways. For example, N,N-diethyl-m-toluamide was associated with the amino acids glycine, L-glutamic acid, L-asparagine, and L-aspartic acid and enrichment of the ammonia recycling pathway., Significance: This study contributes evidence to the potential effects of chemical exposures during pregnancy upon the endogenous maternal plasma metabolome., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Since the National Institute of Environmental Health Sciences (NIEHS) declared conducting combined exposure research as a priority area, literature on chemical mixtures has grown dramatically. However, a systematic evaluation of the current literature investigating the impacts of metal mixtures on cardiovascular disease (CVD) risk factors and outcomes has thus far not been performed. This scoping review aims to summarize published epidemiology literature on the cardiotoxicity of exposure to multiple metals. We performed systematic searches of MEDLINE (PubMed), Scopus, and Web of Science to identify peer-reviewed studies employing statistical mixture analysis methods to evaluate the impact of metal mixtures on CVD risk factors and outcomes among nonoccupationally exposed populations. The search was limited to papers published on or after 1998, when the first dedicated funding for mixtures research was granted by NIEHS, through 1 October 2021. Twenty-nine original research studies were identified for review. A notable increase in relevant mixtures publications was observed starting in 2019. The majority of eligible studies were conducted in the United States ( n = 10) and China ( n = 9). Sample sizes ranged from 127 to 10,818. Many of the included studies were cross-sectional in design. Four primary focus areas included: (i) blood pressure and/or diagnosis of hypertension ( n = 15), (ii) risk of preeclampsia ( n = 3), (iii) dyslipidemia and/or serum lipid markers ( n = 5), and (iv) CVD outcomes, including stroke incidence or coronary heart disease ( n = 8). The most frequently investigated metals included cadmium, lead, arsenic, and cobalt, which were typically measured in blood ( n = 15). The most commonly utilized multipollutant analysis approaches were Bayesian kernel machine regression (BKMR), weighted quantile sum regression (WQSR), and principal component analysis (PCA). To our knowledge, this is the first scoping review to assess exposure to metal mixtures in relation to CVD risk factors and outcomes. Recommendations for future studies evaluating the associations of exposure to metal mixtures with risk of CVDs and related risk factors include extending environmental mixtures epidemiologic studies to populations with wider metals exposure ranges, including other CVD risk factors or outcomes outside hypertension or dyslipidemia, using repeated measurement of metals to detect windows of susceptibility, and further examining the impacts of potential effect modifiers and confounding factors, such as fish and seafood intake.

Purpose of Review: Our comparative analysis sought to understand the factors which drive differences in fish consumption advisories across the USA - including exposure scenarios (acute and chronic health risk, non-cancer and cancer health endpoints), toxicity values (reference dose, cancer slope factor, acute tolerance level), and meal size and bodyweight assumptions., Recent Findings: Fish consumption provides essential nutrients but also results in exposure to contaminants such as PCBs and methylmercury. To protect consumers from the risks of fish contaminants, fish consumption advisories are established, most often by state jurisdictions, to estimate the amount of a certain fish species a person could consume throughout their lifetime without harm. However, inconsistencies in advisories across the USA confuse consumers and undermine the public health goals of fish advisory programs. To date, no rigorous comparison of state and national fish consumption advisories has been reported. Our work identifies discrepancies in key assumptions used to derive risk-based advisories between US states, reflecting differences in the interpretation of toxicity science. We also address the implications for these differences by reviewing advisories issued by contiguous states bordering two waterbodies: Lake Michigan and the Lower Mississippi River. Our findings highlight the importance of regional collaboration when issuing advisories, so that consumers of self-caught fish are equipped with clear knowledge to make decisions to protect their health.

Introduction: Gestational exposure to chemical mixtures, which is prevalent among pregnant women, may be associated with adverse childhood neurodevelopment. However, few studies have examined relations between gestational chemical mixture exposure and children's cognitive abilities., Methods: In a cohort of 253 pregnant women and their children from Cincinnati, OH (enrolled 2003-2006), we quantified biomarker concentrations of 43 metals, phthalates, phenols, polybrominated diphenyl ethers, organophosphate and organochlorine pesticides, polychlorinated biphenyls, perfluoroalkyl substances, and environmental tobacco smoke in blood or urine. Using k-means clustering and principal component (PC) analysis, we characterized chemical mixtures among pregnant women. We assessed children's cognitive abilities using the Wechsler Preschool and Primary Scale of Intelligence-III and Wechsler Intelligence Scale for Children-IV at ages 5 and 8 years, respectively. We estimated covariate-adjusted differences in children's cognitive ability scores ]=cross clusters, and with increasing PC scores and individual biomarker concentrations., Results: Geometric mean biomarker concentrations were generally highest, intermediate, and lowest among women in clusters 1, 2, and 3, respectively. Children born to women in clusters 1 and 2 had 5.1 (95% CI: 9.4,-0.8) and 2.0 (95% CI: 5.5, 1,4) lower performance IQ scores compared to children in cluster 3, respectively. PC scores and individual chemical biomarker concentrations were not associated with cognitive abilities., Conclusions: In this cohort, combined prenatal exposure to phenols, certain phthalates, pesticides, and perfluoroalkyl substances was inversely associated with children's cognition, but some individual chemical biomarker concentrations were not. Additional studies should determine if the aggregate impact of these chemicals on cognition is different from their individual effects., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Occupational exposure to agrochemicals, some of which are known or suspected carcinogens, is a major health hazard for subsistence agricultural workers and their families. These impacts are more prevalent in low-and-middle income countries (LMIC) due to weak regulations, lack of awareness of the risks of contamination, predominant use of handheld backpack style spraying equipment, general lack of personal protective equipment (PPE), and low literacy about proper agrochemical application techniques. Reducing exposure to agrochemicals was identified as a paramount concern by rural Hondurans working with a community-engaged research initiative. Fluorescent tracer dyes have been described as a means of visualizing and quantifying dermal exposure to agricultural chemicals, and exposure models adapted for LMIC have been developed previously. Tracer dyes have also been used in educational simulations to promote pesticide safety. However, studies evaluating the effectiveness of these educational dye interventions in reducing future exposure have been lacking., Aim: To evaluate whether observing one's own chemical contamination after applying agrochemicals changed the amount of occupational dermal exposure during a subsequent chemical application., Methods: We employed a multi-modal community intervention in a rural village in Honduras that incorporated chemical safety education and use of a fluorescent tracer dye during pesticide application on two consecutive occasions, and compared dermal exposure between the intervention group (previous dye experience and safety education, n = 6) and the control group (safety education only, n = 7)., Results: Mean total visual score (TVS) of the tracer dye, which accounts for both extent and intensity of whole-body contamination, was lower among those who had previously experienced the dye intervention (mean TVS = 41.3) than among participants who were dye-naïve (mean TVS = 78.4), with a difference between means of -37.10 (95% CI [-66.26, -7.95], p = 0.02). Stratifying by body part, contamination was significantly lower for the anterior left lower extremity and bilateral feet for the dye-experienced group vs. dye-naïve, with most other segments showing a trend toward decreased contamination as well., Conclusion: Participants who had previously experienced the dye intervention were significantly less contaminated than the dye-naïve control group during a subsequent spraying event. The findings of this small pilot study suggest that a multi-modal, community-based approach that utilizes fluorescence-augmented contamination for individualized learning (FACIL) may be effective in reducing dermal exposure to carcinogenic agrochemicals among subsistence farmers in Honduras and other LMIC., (Copyright © 2021 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Purpose of Review: The exposome is a recently coined concept that comprises the totality of nongenetic factors that affect human health. It is recognized as a major conceptual advancement in environmental epidemiology, and there is increased demand for technologies that capture the spatial, temporal, and chemical variability of exposures across individuals (i.e., "exposomic sensors"). We review a selection of these tools, highlighting their strengths and limitations with regard to epidemiological research., Recent Findings: Wearable passive samplers are emerging as promising exposomic sensors for individuals. In conjunction with targeted and untargeted assays, these sensors enable the measurement of complex multipollutant mixtures, which can include both known and previously unknown environmental contaminants. Because of their minimally burdensome and noninvasive nature, they are deployable among sensitive populations, such as seniors, pregnant women, and children. The integration of exposomic data captured by these sensors with other omic data (e.g., transcriptomic and metabolomic) presents exciting opportunities for investigating disease risk factors. For example, the linkage of exposomic sensor data with other omic data may indicate perturbation by multipollutant mixtures at multiple physiological levels, which would strengthen evidence of their effects and potentially indicate targets for interventions. However, there remain considerable theoretical and methodological challenges that must be overcome to realize the potential promise of omic integration. Through continued investment and improvement in exposomic sensor technologies, it may be possible to refine their application and reduce their outstanding limitations to advance the fields of exposure science and epidemiology.

Birth weight is a key consequence of environmental exposures and metabolic alterations and can influence lifelong health. While a number of methods have been used to examine associations of trace element (including essential nutrients and toxic metals) concentrations or metabolite concentrations with a health outcome, birth weight, studies evaluating how the coexistence of these factors impacts birth weight are extremely limited. Here, we present a novel algorithm NETwork Clusters (NET-C), to improve the prediction of outcome by considering the interactions of features in the network and then apply this method to predict birth weight by jointly modelling trace element and cord blood metabolite data. Specifically, by using trace element and/or metabolite subnetworks as groups, we apply group lasso to estimate birth weight. We conducted statistical simulation studies to examine how both sample size and correlations between grouped features and the outcome affect prediction performance. We showed that in terms of prediction error, our proposed method outperformed other methods such as (a) group lasso with groups defined by hierarchical clustering, (b) random forest regression and (c) neural networks. We applied our method to data ascertained as part of the New Hampshire Birth Cohort Study on trace elements, metabolites and birth outcomes, adjusting for other covariates such as maternal body mass index (BMI) and enrollment age. Our proposed method can be applied to a variety of similarly structured high-dimensional datasets to predict health outcomes., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent chemicals commonly used in the production of household and consumer goods. While exposure to PFAS has been associated with greater adiposity in children and adults, less is known about associations with gestational weight gain (GWG)., Methods: We quantified using mass spectrometry perfluorooctanoate (PFOA), perfluorooctanesulfonate (PFOS), perfluorohexanesulfanoate (PFHxS) and perfluorononanoate (PFNA) in maternal serum from 18 ± 5 weeks' gestation (mean ± standard deviation (std)) in a prospective pregnancy and birth cohort (2003-2006, Cincinnati, Ohio) (n = 277). After abstracting weight data from medical records, we calculated GWG from 16 ± 2 weeks' gestation (mean ± std) to the measured weight at the last visit or at delivery, rate of weight gain in the 2nd and 3rd trimesters (GWR), and total weight gain z-scores standardized for gestational age at delivery and pre-pregnancy BMI. We investigated covariate-adjusted associations between individual PFAS using multivariable linear regression; we assessed potential effect measure modification (EMM) by overweight/obese status (pre-pregnancy BMI<25 kg/m 2 v. ≥25 kg/m 2 ). Using weighted quantile sum regression, we assessed the combined influence of these four PFAS on GWG and GWR., Results: Each doubling in serum concentrations of PFOA, PFOS, and PFNA was associated with a small increase in GWG (range 0.5-0.8 lbs) and GWR (range 0.03-0.05 lbs/week) among all women. The association of PFNA with GWG was stronger among women with BMI≥25 kg/m 2 (β = 2.6 lbs; 95% CI:-0.8, 6.0) than those with BMI<25 kg/m 2 (β = -1.0 lbs; 95% CI:-3.8, 1.8; p-EMM = 0.10). We observed associations close to the null between PFAS and z-scores and between the PFAS exposure index (a combined summary measure) and the outcomes., Conclusion: Although there were consistent small increases in gestational weight gain with increasing PFOA, PFOS, and PFNA serum concentrations in this cohort, the associations were imprecise. Additional investigation of the association of PFAS with GWG in other cohorts would be informative and could consider pre-pregnancy BMI as a potential modifier., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Purpose of Review: The purpose of this review is to describe epidemiologic and toxicological literature investigating how endocrine-disrupting chemicals (EDCs) affect mammary gland development and function, thereby impacting lactation duration., Recent Findings: Perfluoroalkyl and polyfluoroalkyl substances appear to reduce breastfeeding duration through impaired mammary gland development, lactogenesis, and suppressed endocrine signaling. Halogenated aromatic hydrocarbons have differing associations with lactation duration, likely because of the variety of signaling pathways that they affect, pointing to the importance of complex mixtures in epidemiologic studies. Although epidemiologic literature suggests that pesticides and fungicides decrease or have no effect on lactation duration, toxicology literature suggests enhanced mammary gland development through estrogenic and/or antiandrogenic pathways. Toxicological studies suggest that phthalates may affect mammary gland development via estrogenic pathways but no association with lactation duration has been observed. Bisphenol A was associated with decreased duration of breastfeeding, likely through direct and indirect action on estrogenic pathways., Summary: EDCs play a role in mammary gland development, function, and lactogenesis, which can affect breastfeeding duration. Further research should explore direct mechanisms of EDCs on lactation, the significance of toxicant mixtures, and transgenerational effects of EDCs on lactation.

Objective: The primary aim of this study was to evaluate if maternal age at birth of last child is associated with leukocyte telomere length in a nationally representative population of perimenopausal and postmenopausal women., Methods: We conducted a cross-sectional analysis of 1,232 women from the National Health and Nutrition Examination Survey to examine maternal age at last birth and telomere length, surveyed between 1999 and 2002. We included perimenopausal and postmenopausal women age 40 years and older. Maternal age at last live birth was self-reported, and leukocyte telomere length was measured using quantitative polymerase chain reaction. We calculated least-squares geometric mean telomere length across categories of maternal age adjusted for age, race/ethnicity, number of live births, survey cycle, and history of hysterectomy or oophorectomy. P trend < 0.05 was considered statistically significant. For hypothesis-generation, we explored modification by reproductive and sociodemographic factors., Results: Maternal age at last birth was positively associated with telomere length: the multivariable-adjusted least-squares geometric mean leukocyte telomere length across categories of age at last birth (<25, 25-29, 30-34, 35-39, ≥40 y) was 0.90, 0.93, 0.93, 0.95, and 0.96, respectively (P trend = 0.04). There was suggestive evidence this association may be restricted to those women with one or two live births or women who reported ever using oral contraceptives (P interaction <0.10 for both)., Conclusions: Later maternal age was associated with longer telomere length in a nationally representative population of women. These data provide new insight into the biological relationship between reproductive history and long-term health. : Video Summary:http://links.lww.com/MENO/A662.

Silicone wristbands can assess multipollutant exposures in a non-invasive and minimally burdensome manner, which may be suitable for use among pregnant women. We investigated silicone wristbands as passive environmental samplers in the New Hampshire Birth Cohort Study, a prospective pregnancy cohort. We used wristbands to assess exposure to a broad range of organic chemicals, identified multipollutant exposure profiles using self-organizing maps (SOMs), and assessed temporal consistency and determinants of exposures during pregnancy. Participants ( n = 255) wore wristbands for 1 week at 12 gestational weeks. Of 1,530 chemicals assayed, 199 were detected in at least one wristband and 16 were detected in >60% of wristbands. A median of 23 (range: 12,37) chemicals were detected in each wristband, and chemicals in commerce and personal care products were most frequently detected. A subset of participants ( n =20) wore a second wristband at 24 gestational weeks, and concentrations of frequently detected chemicals were moderately correlated between time points (median intraclass correlation: 0.22; range: 0.00,0.69). Women with higher educational attainment had fewer chemicals detected in their wristbands and the total number of chemicals detected varied seasonally. Triphenyl phosphate concentrations were positively associated with nail polish use, and benzophenone concentrations were highest in summer. No clear associations were observed with other a priori relations, including certain behaviors, season, and socioeconomic factors. SOM analyses revealed 12 profiles, ranging from 2 to 149 participants, captured multipollutant exposure profiles observed in this cohort. The most common profile ( n = 149) indicated that 58% of participants experienced relatively low exposures to frequently detected chemicals. Less common ( n ≥ 10) and rare ( n < 10) profiles were characterized by low to moderate exposures to most chemicals and very high and/or very low exposure to a subset of chemicals. Certain covariates varied across SOM profile membership; for example, relative to women in the most common profile who had low exposures to most chemicals, women in the profile with elevated exposure to galaxolide and benzyl benzoate were younger, more likely to be single, and more likely to report nail polish use. Our study illustrates the utility of silicone wristbands for measurement of multipollutant exposures in sensitive populations, including pregnant women., (Copyright © 2020 Doherty, Pearce, Anderson, Karagas and Romano.)

Background: Organophosphate esters (OPEs)-used as flame retardants and plasticizers-are associated with adverse pregnancy outcomes such as reduced fecundity and live births and increased preterm delivery. OPEs may interfere with growth and metabolism via endocrine-disruption, but few studies have investigated endocrine-related outcomes. The objective of this pilot study (n = 56 mother-infant pairs) was to evaluate associations of OPEs with gestational weight gain (GWG), gestational age at delivery, infant anthropometry, and infant feeding behaviors., Methods: We quantified OPE metabolites (bis-2-chloroethyl phosphate [BCEP], bis (1,3-dichloro-2-propyl) phosphate [BDCPP], diphenyl phosphate [DPHP]) in pooled maternal spot urine collected throughout pregnancy (~ 12, 28, and 35 weeks' gestation). We obtained maternal sociodemographic characteristics from questionnaires administered at enrollment and perinatal characteristics from medical record abstraction. Trained research assistants measured infant weight, length, head and abdominal circumferences, and skinfold thicknesses at birth and 6 weeks postpartum. Mothers reported infant feeding behavior via the Baby Eating Behavior Questionnaire (BEBQ). Using multiple linear regression, we assessed associations of log 2 -transformed maternal urinary OPE metabolites with GWG, gestational age at delivery, infant anthropometry at birth, weekly growth rate, and BEBQ scores at 6 weeks postpartum. We used linear mixed effects (LME) models to analyze overall infant anthropometry during the first 6 weeks of life. Additionally, we considered effect modification by infant sex., Results: We observed weak positive associations between all OPE metabolites and GWG. In LME models, BDCPP was associated with increased infant length (β = 0.44 cm, 95%CI = 0.01, 0.87) and weight in males (β = 0.14 kg, 95%CI = 0.03, 0.24). BDCPP was also associated with increased food responsiveness (β = 0.23, 95%CI = 0.06, 0.40). DPHP was inversely associated with infant abdominal circumference (β = - 0.50 cm, 95%CI = - 0.86, - 0.14) and female weight (β = - 0.19 kg, 95%CI = - 0.36, - 0.02), but positively associated with weekly growth in iliac skinfold thickness (β = 0.10 mm/wk., 95%CI = 0.02, 0.19). Further, DPHP was weakly associated with increased feeding speed. BCEP was associated with greater infant thigh skinfold thickness (β = 0.34 mm, 95%CI = 0.16, 0.52) and subscapular skinfold thickness in males (β = 0.14 mm, 95%CI = 0.002, 0.28)., Conclusions: Collectively, these findings suggest that select OPEs may affect infant anthropometry and feeding behavior, with the most compelling evidence for BDCPP and DPHP.

Background: Behavioral effects of prenatal exposure to mixtures of essential and toxic metals are incompletely understood., Methods: We investigated neurodevelopmental effects of prenatal metal exposures in the New Hampshire Birth Cohort Study, a prospective birth cohort. We measured metals (As, Cu, Mn, Pb, Se, Zn) in maternal prenatal and postnatal toenails and infant toenails, reflecting exposures during periconception and early pregnancy, mid pregnancy, and late pregnancy and early neonatal life, respectively. Mothers completed the Social Responsiveness Scale, 2nd ed. (SRS-2) and the Behavior Assessment System for Children, 2nd ed. (BASC-2) to assess their child's neurobehavior at 3 years. We used mean field variational Bayes for lagged kernel machine regression to investigate associations of toenail metal concentrations with SRS-2 Total Scores and BASC-2 composite scores (SRS-2: n = 371; BASC-2: n = 318)., Results: Infant toenail Mn was associated with poorer performance on multiple BASC-2 composite scores. Maternal postnatal toenail As was associated with worse scores on the BASC-2 Internalizing Problems and Behavioral Symptoms Index. Associations with Mn were generally stronger in males, and associations with As were generally stronger in females. Other metals, including Pb, were weakly or inconsistently associated with BASC-2 outcomes, and there were no strong associations of individual metals and SRS-2 Total Scores. We observed suggestive evidence of interaction between As and Se for SRS-2 Total Scores and BASC-2 Adaptive Skills, though overall evidence of interactions between metals was weak., Conclusion: Our results support the hypothesis that exposure to Mn and As in mid to late pregnancy may be neurodevelopmentally harmful., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report. The specific aims of the study were supported by P01ES022832 from National Institute of Environmental Health Sciences, RD83544201 from United States Environmental Protection Agency, and P20GM104416 from National Institute of General Medical Sciences. The Trace Element Analysis Facility is supported in part by P42ES007373 from National Institute of Environmental Health Sciences and by 5P30CA023108-37 from National Cancer Institute. B.T.D. was supported by R25CA134286 from National Cancer Institute. Use of the data may be possible under certain conditions by contacting the New Hampshire Birth Cohort Study Principal Investigator: Margaret Karagas, PhD, (margaret.r.karagas@dartmouth.edu)., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Background: Per- and polyfluoroalkyl substances (PFAS) are ubiquitous. Previous studies have found associations between PFAS and thyroid hormones in maternal and cord sera, but the results are inconsistent. To further address this research question, we used mixture modeling to assess the associations with individual PFAS, interactions among PFAS chemicals, and the overall mixture., Methods: We collected data through the Health Outcomes and Measures of the Environment (HOME) Study, a prospective cohort study that between 2003 and 2006 enrolled 468 pregnant women and their children in the greater Cincinnati, Ohio region. We assessed the associations of maternal serum PFAS concentrations measured during pregnancy with maternal (n = 185) and cord (n = 256) sera thyroid stimulating hormone (TSH), total thyroxine (TT 4 ), total triiodothyronine (TT 3 ), free thyroxine (FT 4 ), and free triiodothyronine (FT 3 ) using two mixture modeling approaches (Bayesian kernel machine regression (BKMR) and quantile g-computation) and multivariable linear regression. Additional models considered thyroid autoantibodies, other non-PFAS chemicals, and iodine deficiency as potential confounders or effect measure modifiers., Results: PFAS, considered individually or as mixtures, were generally not associated with any thyroid hormones. A doubling of perfluorooctanesulfonic acid (PFOS) had a positive association with cord serum TSH in BKMR models but the 95% Credible Interval included the null (β = 0.09; 95% CrI: -0.08, 0.27). Using BKMR and multivariable models, we found that among children born to mothers with higher thyroid peroxidase antibody (TPOAb), perfluorooctanoic acid (PFOA), PFOS, and perfluorohexanesulfonic acid (PFHxS) were associated with decreased cord FT 4 suggesting modification by maternal TPOAb status., Conclusions: These findings suggest that maternal serum PFAS concentrations measured in the second trimester of pregnancy are not strongly associated with thyroid hormones in maternal and cord sera. Further analyses using robust mixture models in other cohorts are required to corroborate these findings., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Maternal thyroid function during pregnancy may influence offspring thyroid function, though relations between maternal and child thyroid function are incompletely understood. We sought to characterize relations between maternal, cord and child thyroid hormone concentrations in a population of mother-child pairs with largely normal thyroid function., Methods: In a prospective birth cohort, we measured thyroid hormone concentrations in 203 mothers at 16 gestational weeks, 273 newborns and 159 children at 3 years among participants in the Health Outcomes and Measures of the Environment (HOME) Study. We used multivariable linear regression to estimate associations of maternal thyroid hormones during pregnancy with cord serum thyroid hormones and also estimated associations of maternal and cord thyroid hormones with child thyroid-stimulating hormone (TSH)., Results: Each doubling of maternal TSH was associated with a 16.4% increase of newborn TSH (95% CI: 3.9%, 30.5%), and each doubling of newborn TSH concentrations was associated with a 10.4% increase in child TSH concentrations at 3 years (95% CI: 0.1%, 21.7%). An interquartile range increase in cord FT4 concentrations was associated with an 11.7% decrease in child TSH concentrations at 3 years (95% CI: -20.2%, -2.3%)., Conclusions: We observed relationships between maternal, newborn and child thyroid hormone concentrations in the HOME Study. Our study contributes to understandings of interindividual variability in thyroid function among mother-child pairs, which may inform future efforts to identify risk factors for thyroid disorders or thyroid-related health outcomes., (© 2020 John Wiley & Sons Ltd.)

Epidemiologic studies suggest that prenatal urinary bisphenol A (BPA) concentrations are associated with childhood behavior problems, but there is limited research on prenatal paraben concentrations. In rodent offspring, preconception maternal BPA exposure caused behavioral problems and paraben exposure impacted sperm quality. However, the effects of parental preconception and prenatal BPA and paraben exposure on children's neurodevelopment are unknown., Methods: The Environment and Reproductive Health (EARTH) Study is a prospective cohort of couples from a fertility clinic at Massachusetts General Hospital. The Centers for Disease Control and Prevention (CDC) quantified BPA, butylparaben, ethylparaben, methylparaben, and propylparaben concentrations in multiple urine samples collected before conception and during pregnancy. From the eligible parents (N = 220), we enrolled 158 children between 2 and 9 years of age. The parents completed the Behavior-Assessment-System-for-Children-2 (BASC-2). We estimated covariate-adjusted associations of average parental preconception and prenatal ln-transformed urinary BPA and sum of paraben concentrations (∑paraben) with BASC-2 scores using linear regression with generalized estimating equations., Results: Median urinary BPA and Σparaben concentrations were 1.2 and 189 μg/L in mothers preconception and 1.7 and 25 μg/L in fathers preconception, respectively. Among all children, parental BPA and ∑paraben concentrations were not associated with BASC-2 behavioral symptoms index, internalizing, or externalizing problems scores. Point estimates ranged from -1.5 to 1.4 with wide 95% confidence intervals that included the null value., Conclusion: In this fertility clinic cohort, parental preconception and maternal prenatal BPA and paraben concentrations were not associated with problem behaviors among children. However, our small sample sizes reduced the precision of our results., Competing Interests: Sponsorships or competing interests that may be relevant to content are disclosed at the end of the article. J.M.B. was financially compensated for serving as an expert witness for plaintiffs in litigation related to tobacco smoke exposures and served as a paid consultant to Quest Diagnostics. The other authors have no conflicts to report., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of Environmental Epidemiology. All rights reserved.)