Search

BackgroundPhthalates 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.MethodsIn 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.FindingsWe 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 log10 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).InterpretationIn 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.FundingNational Institutes of Health.

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.

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., Author(s): Kathryn A. Crawford [sup.1] [sup.2] , Lisa G. Gallagher [sup.2] , Emily R. Baker [sup.3] , Margaret R. Karagas [sup.2] , Megan E. Romano [sup.2] Author Affiliations: (1) grid.260002.6, [...]

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.

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. [ABSTRACT FROM AUTHOR]

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;20:1839–1858. © 2024 The Author(s). Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC). Key Points: Fish consumption advisories (FCAs) for per‐ and polyfluoroalkyl substances (PFAS) present unique scientific and public health policy challenges.The evolving information about PFAS toxicology and mixture effects presents a challenge for risk assessment and risk communication.Sampling for PFAS FCAs requires consideration of chemical, biological, and environmental features that can influence data quality.While FCAs are specific to the United States, these PFAS‐specific challenges are relevant for other forms of risk assessment, management, and communication. [ABSTRACT FROM AUTHOR]