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BackgroundSynthetic 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.ObjectiveTo 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.ResultsWhile many associations were modest and statistically imprecise, a 1-unit increase in log10 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 log10 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%).DiscussionIn 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.

BackgroundWidespread 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.ObjectivesWe conducted a collaborative analysis of associations between gestational OPE exposures and adverse birth outcomes and tested whether associations were modified by sex.MethodsWe 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 log2-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.ResultsThree 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.DiscussionIn 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.

BackgroundGestational 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.ObjectivesWe 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.MethodsWe 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.ResultsWe 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.DiscussionIn 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.

BackgroundPer- 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.ObjectivesWe estimated risk of adverse birth outcomes in relation to prenatal PFAS concentrations and evaluate whether maternal stress modifies those relationships.MethodsWe 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.ResultsWe 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: ORPFNA=0.56 (95% CI: 0.38, 0.83), ORPFDA=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.DiscussionOur 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.

BackgroundMelamine, 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.ObjectivesWe 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.MethodsWe 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.ResultsTwelve 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.DiscussionExposure 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.

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.

Following publication of the original article [1], the author reported that, because of a programming error, incorrect sentences and incorrect Table 3 has been published. The correct sentences and Table 3 are shown below.

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 풵-scores; 19.6% children had more than one BMI measurement. We estimated covariate-adjusted associations of individual PFAS and their mixture with child BMI 풵-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 풵-scores and risk of overweight/obesity. For instance, each doubling in perfluorohexane sulfonic acid concentrations was associated with higher BMI 풵-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 푁-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 풵-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. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To describe ethics consultations at a single institution that has a mandatory ethics consultation policy. PATIENTS AND METHODS: We retrospectively reviewed the medical records of all adult patients who [...]

This article is being retracted at the request of the authors because of inadvertent errors in the statistical code that resulted in the exclusion of 12 gestational diabetes mellitus cases [...]

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) reduce blood concentrations of thyroid hormones in laboratory animals, but it is unclear whether PBDEs disrupt thyroid hormones in pregnant women or newborn infants. OBJECTIVES: We investigated the relationship between maternal PBDE levels and thyroid hormone concentrations in maternal and cord sera. Methods: we used data from the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort of 389 pregnant women in Cincinnati, Ohio, who were enrolled from 2003 through 2006 and delivered singleton infants. Maternal serum PBDE concentrations were measured at enrollment (16 ± 3 weeks of gestation). Thyroid hormone concentrations were measured in maternal serum at enrollment (n = 187) and in cord serum samples (n = 256). RESULTS: Median maternal serum concentrations of BDEs 28 and 47 were 1.0 and 19.1 ng/g lipid, respectively. A 10-fold increase in BDEs 28 and 47 concentrations was associated with a 0.85-µg/dL [95% confidence interval (CI): 0.05, 1.64] and 0.82-µg/dL (95% CI: 0.12, 1.51) increase in maternal total thyroxine concentrations ([TT.sub.4]), respectively. Both congeners were also positively associated with maternal free thyroxine ([FT.sub.4]). We also observed positive associations between BDE-47 and maternal total and free triiodothyronine ([TT.sub.4] and [FT.sub.3]). A 10-fold increase in BDE-28 was associated with elevated [FT.sub.3] concentrations (β = 0.14 µg/mL; 95% CI: 0.02, 0.26). In contrast, maternal PBDE levels were not associated with thyroid hormone concentrations in cord serum. CONCLUSIONS: These findings suggest that maternal PBDE exposure, particularly BDEs 28 and 47, are associated with maternal concentrations of [T.sub.4] and [T.sub.3] during pregnancy. http://dx.doi.org/10.1289/ehp.1408996, Introduction Polybrominated diphenyl ethers (PBDEs), synthetic flame retardants, have been used in the manufacture of consumer products, including furniture foam, carpet padding, and electronics. Because they are semivolatile and are [...]

BACKGROUND: Environmental cadmium (Cd) exposure is associated with type 2 diabetes. However, the association of Cd and gestational diabetes mellitus (GDM) is unknown. OBJECTIVES: We examined the association between body burden of Cd and GDM risk. METHODS: we used 140 GDM cases and 481 randomly selected noncase subcohort members from the Omega Study to conduct a case-cohort study. Creatinine (Cr)-corrected Cd in early pregnancy urine (U-Cd) was measured by inductively coupled plasma mass spectrometry. Tertiles (< 0.29; 0.29-0.42; [greater than or equal to] 0.43 [micro]g/g Cr) were defined using the subcohort's U-Cd distribution. GDM was diagnosed using the 2004 American Diabetes Association guidelines. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression. RESULTS: GDM cases had higher geometric mean U-Cd (0.39 [micro]g/g Cr; 95% CI: 0.37, 0.41) than noncases (0.31 [micro]g/g Cr; 95% CI: 0.29, 0.33). Odds ratios for GDM increased with increasing U-Cd tertile (OR = 1.64; 95% CI: 0.88, 3.05 for middle vs. low tertile; OR = 2.07; 95% CI: 1.15, 3.73 for high vs. low tertile; p-trend = 0.015). Overweight/obesity (body mass index [greater than or equal to] 25 kg/[m.sup.2]) did not modify the association between U-Cd and GDM (p = 0.26). CONCLUSIONS: Our findings suggest that body burden of Cd increases risk of GDM in a dose-dependent manner. Improved understanding of environmental factors influencing GDM may facilitate early identification of women at high risk of GDM. http://dx.doi.org/10.1289/ehp.1408282, Introduction Gestational diabetes mellitus (GDM), a pregnancy-related glucose intolerance disorder, complicates up to 14% of pregnancies each year in the United States [American Diabetes Association (ADA) 2004]. GDM increases the [...]

Abstract Background Many studies of adults with acute and chronic solvent exposure have shown adverse effects on cognition, behavior and mood. No prior study has investigated the long-term impact of prenatal and early childhood exposure to the solvent tetrachloroethylene (PCE) on the affinity for risky behaviors, defined as smoking, drinking or drug use as a teen or adult. Objectives This retrospective cohort study examined whether early life exposure to PCE-contaminated drinking water influenced the occurrence of cigarette smoking, alcohol consumption, and drug use among adults from Cape Cod, Massachusetts. Methods Eight hundred and thirty-one subjects with prenatal and early childhood PCE exposure and 547 unexposed subjects were studied. Participants completed questionnaires to gather information on risky behaviors as a teenager and young adult, demographic characteristics, other sources of solvent exposure, and residences from birth through 1990. PCE exposure was estimated using the U.S. EPA's water distribution system modeling software (EPANET) that was modified to incorporate a leaching and transport model to estimate PCE exposures from pipe linings. Results Individuals who were highly exposed to PCE-contaminated drinking water during gestation and early childhood experienced 50-60% increases in the risk of using two or more major illicit drugs as a teenager or as an adult (Relative Risk (RR) for teen use = 1.6, 95% CI: 1.2-2.2; and RR for adult use = 1.5, 95% CI: 1.2-1.9). Specific drugs for which increased risks were observed included crack/cocaine, psychedelics/hallucinogens, club/designer drugs, Ritalin without a prescription, and heroin (RRs:1.4-2.1). Thirty to 60% increases in the risk of certain smoking and drinking behaviors were also seen among highly exposed subjects. Conclusions The results of this study suggest that risky behaviors, particularly drug use, are more frequent among adults with high PCE exposure levels during gestation and early childhood. These findings should be confirmed in follow-up investigations of other exposed populations.