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BACKGROUND: Organophosphate esters (OPEs), used ubiquitously as flame retardants and plasticizers in consumer products, are suspected of having developmental toxicity. OBJECTIVES: Our study aimed to estimate associations between prenatal exposure to OPEs and fetal growth, including both ultrasound (head circumference, abdominal circumference, femur length, and estimated fetal weight) and delivery [birth weight z-score, small-for-gestational age (SGA), and large-for-gestational age (LGA)] measures of growth. METHODS: In the LIFECODES Fetal Growth Study (2008-2018), an enriched case--cohort of 900 babies born at the small and large ends of the growth spectrum, we quantified OPE biomarkers in three urine samples per pregnant participant and abstracted ultrasound and delivery measures of fetal growth from medical records. We estimated associations between pregnancy-averaged log-transformed OPE biomarkers and repeated ultrasound measures of fetal growth using linear mixed-effects models, and delivery measures of fetal growth using linear (birth weight) and logistic (SGA and LGA) regression models. RESULTS: Most OPE biomarkers were positively associated with at least one ultrasound measure of fetal growth, but associations with delivery measures were largely null. For example, an interquartile range (IQR; 1.31 ng=mL) increase in bis(2-chloroethyl) phosphate concentration was associated with larger z-scores in head circumference [mean difference (difference): 0.09; 95% confidence interval (CI): 0.01, 0.17], abdominal circumference (difference: 0.10; 95% CI: 0.02, 0.18), femur length (difference: 0.11; 95% CI: 0.03, 0.19), and estimated fetal weight (difference: 0.13; 95% CI: 0.04, 0.22) but not birth weight (difference: 0.04; 95% CI: -0.08, 0.17). At delivery, an IQR (1.00 ng=mL) increase in diphenyl phosphate (DPHP) concentration was associated with an SGA birth (odds ratio: 1.46; 95% CI: 1.10, 1.94). CONCLUSIONS: In a large prospective cohort, gestational OPE exposures were associated with larger fetal size during pregnancy, but associations at delivery were null. DPHP concentrations were associated with heightened risk of an SGA birth. These findings suggest that OPE exposure may affect fetal development. https://doi.org/10.1289/EHP14647, Introduction Organophosphate esters (OPEs) are high-production chemicals in widespread global use. (1) They are organic esters of phosphoric acid--containing alkyl chains or aryl groups, which may be halo-genated or nonhalogenated. [...]

BackgroundPhthalate exposures are ubiquitous during pregnancy and may contribute to racial and ethnic disparities in preterm birth.ObjectivesWe investigated race and ethnicity in the relationship between biomarkers of phthalate exposure and preterm birth by examining: a) how hypothetical reductions in racial and ethnic disparities in phthalate metabolites might reduce the probability of preterm birth; and b) exposure-response models stratified by race and ethnicity.MethodsWe pooled individual-level data on 6,045 pregnancies from 16 U.S. cohorts. We investigated covariate-adjusted differences in nine urinary phthalate metabolite concentrations by race and ethnicity [non-Hispanic White (White, 43%), non-Hispanic Black (Black, 13%), Hispanic/Latina (38%), and Asian/Pacific Islander (3%)]. Using g-computation, we estimated changes in the probability of preterm birth under hypothetical interventions to eliminate disparities in levels of urinary phthalate metabolites by proportionally lowering average concentrations in Black and Hispanic/Latina participants to be approximately equal to the averages in White participants. We also used race and ethnicity-stratified logistic regression to characterize associations between phthalate metabolites and preterm birth.ResultsIn comparison with concentrations among White participants, adjusted mean phthalate metabolite concentrations were consistently higher among Black and Hispanic/Latina participants by 23%-148% and 4%-94%, respectively. Asian/Pacific Islander participants had metabolite levels that were similar to those of White participants. Hypothetical interventions to reduce disparities in metabolite mixtures were associated with lower probabilities of preterm birth for Black [13% relative reduction; 95% confidence interval (CI): -34%, 8.6%] and Hispanic/Latina (9% relative reduction; 95% CI: -19%, 0.8%) participants. Odds ratios for preterm birth in association with phthalate metabolites demonstrated heterogeneity by race and ethnicity for two individual metabolites (mono-n-butyl and monoisobutyl phthalate), with positive associations that were larger in magnitude observed among Black or Hispanic/Latina participants.ConclusionsPhthalate metabolite concentrations differed substantially by race and ethnicity. Our results show hypothetical interventions to reduce population-level racial and ethnic disparities in biomarkers of phthalate exposure could potentially reduce the probability of preterm birth. https://doi.org/10.1289/EHP12831.

Background: Prenatal exposure to perfluoroalkyl substances (PFAS) has been previously associated with preeclampsia, although findings are mixed with respect to the direction and magnitude of effect. To our knowledge, no studies have examined associations between PFAS and preeclampsia subtypes, which may have distinct etiologies. Objective: We examined associations between PFAS, any preeclampsia diagnosis, and early- and late-onset preeclampsia. In addition, we estimated associations between PFAS and the angiogenic biomarkers soluble fms-like tyrosine kinase-1 (sFLT-1) and placental growth factor (PlGF), which provide an estimate of pro- and anti-angiogenic activity within the placenta. Methods: This case-control study (n = 75 cases, n = 75 controls) was sampled from the LIFECODES birth cohort. Nine legacy PFAS were quantified in maternal plasma from early pregnancy (median =10 wk) and angiogenic biomarkers were quantified in maternal plasma from four study visits (median = 10, 18, 26, and 35 wk). Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of the association between an interquartile range (IQR)-increase in PFAS and preeclampsia outcomes. Linear regression was used to estimate associations between an IQR-increase in PFAS and concentrations of angiogenic biomarkers. Results: Both perfluorodecanoic acid (OR= 1.64, 95% CI: 1.08, 2.47) and perfluorooctanesulfonic acid (OR= 1.60, 95% CI: 1.06, 2.43) were associated with higher odds of late-onset preeclampsia. Associations tended to be below the null for early-onset preeclampsia, although findings were imprecise. Few associations were noted between PFAS and angiogenic biomarkers. Discussion: Maternal PFAS concentrations were associated with higher odds of late-onset preeclampsia. Heterogeneity of preeclampsia should be considered in future studies because populations may have different distributions of disease subtypes. https://doi.org/10.1289/EHP9091, Introduction Perfluoroalkyl substances (PFAS) are a set of synthetic chemicals that are used widely in commercial products and manufacturing (ITRC 2020a). These compounds are characterized by a perfluoroalkyl chain and [...]

Background: Humans are exposed to mixtures of toxicants that can impact several biological pathways. We investigated the associations between multiple classes of toxicants and an extensive panel of biomarkers indicative of lipid metabolism, inflammation, oxidative stress, and angiogenesis. Methods: We conducted a cross-sectional study of 173 participants (median 26 wk gestation) from the LIFECODES birth cohort. We measured exposure analytes of multiple toxicant classes [metals, phthalates, phenols, and polycyclic aromatic hydrocarbons (PAHs)] in urine samples. We also measured endogenous biomarkers (eicosanoids, cytokines, angiogenic markers, and oxidative stress markers) in either plasma or urine. We estimated pair-wise associations between exposure analytes and endogenous biomarkers using multiple linear regression after adjusting for covariates. We used adaptive elastic net regression, hierarchical Bayesian kernel machine regression, and sparse-group LASSO regression to evaluate toxicant mixtures associated with individual endogenous biomarkers. Results: After false-discovery adjustment (q Discussion: This study characterizes cross-sectional endogenous biomarker signatures associated with individual and mixtures of prenatal toxicant exposures. These results can help inform the prioritization of specific pairs or clusters of endogenous biomarkers and exposure analytes for investigating health outcomes. https://doi.org/10.1289/EHP7396, Introduction Observational studies are leveraging increasingly high-dimensional data sets, both in terms of data collected on exogenous environmental toxicants and endogenous biomarkers. Historically, studies have characterized single-pollutant associations between individual [...]

Background: In addition to its well-established role in maintaining skeletal health, vitamin D has essential regulatory functions in female reproductive and pregnancy outcomes. Phthalates and bisphenol A (BPA) are endocrine disruptors, and previous research has suggested that these chemical agents may disrupt circulating levels of total 25(OH)D in adults. Objectives: We investigated the relationships between repeated measures of urinary phthalate metabolites and BPA and circulating total 25(OH)D in a prospective cohort of pregnant women. Methods: The present study population includes participants (n = 477) in a nested case-control study of preterm birth drawn from a prospective birth cohort of pregnant women at Brigham and Women's Hospital in Boston, Massachusetts. Urine and blood samples were collected for biomarker measurements at median 10 wk and 26 wk of gestation. Results: In repeated measures analysis, we observed that an interquartile range (IQR) increase in urinary mono-3- carboxypropyl phthalate (MCPP) was associated with a 4.48% decrease [95% confidence interval (CI): -7.37, -1.58] in total 25(OH)D. We also detected inverse associations for metabolites of di(2-ethylhexyl) phthalate (DEHP) [percent difference (%[DELTA]) = -2.83 to -2.16]. For BPA, we observed a nonsignificant inverse association with total 25(OH)D in the overall population. Our sensitivity analysis revealed that the associations for some metabolites (e.g., MEHP) varied by race/ethnicity, which may reflect potential differences in susceptibility. In agreement with findings from repeated measures analysis, we reported that DEHP metabolites and BPA were significantly associated with an approximate 20% increase in the odds of vitamin D deficiency ([less than or equal to] 20ng/mL) [odds ratio (95% CI): 1.19 (1.06, 1.35) for molar sum of DEHP metabolites and 1.22 (1.01, 1.47) for BPA] at median 10 wk and 26 wk, respectively. Conclusions: Our results provide suggestive evidence of the potential for environmental exposure to phthalates and/or BPA to disrupt circulating vitamin D levels in pregnancy. https://doi.org/10.1289/EHP1178, Introduction Vitamin D is a prohormone that plays an integral role in the regulation of bone metabolism and calcium and phosphorous absorption (Holick 2007; Norman 2008). The major source of [...]

Background: Preeclampsia represents a major cause of maternal mortality and morbidity worldwide. Although it is known that the placenta plays a central role in development of preeclampsia, investigation into the contribution of environmental toxicants to the risk of preeclampsia has been sparse. Objectives: In the present study we examined the relationship between longitudinally measured urinary BPA and phthalate metabolite concentrations during gestation and preeclampsia. Methods: A nested case-control study of preterm birth was performed in 2011 from women enrolled in a prospective birth cohort study at Brigham and Women's Hospital in Boston. There were 50 cases of preeclampsia as part of this study. Urine samples were analyzed for concentrations of BPA and nine phthalate metabolites several times during pregnancy. Adjusted Cox proportional hazard models were used to calculate hazard ratios of preeclampsia in association with an interquartile range increase in BPA and phthalate concentrations and were weighted to reflect results generalizable to the base population. RESULTS: Adjusted hazard ratios indicated that an interquartile range increase of urinary concentrations of BPA (1.53; 95% CI: 1.04, 2.25) and MEP (monoethyl phthalate) (1.72; 95% CI: 1.28, 2.30) at 10 weeks gestation was associated with onset of preeclampsia, whereas significantly elevated hazard ratios were found across gestation for all DEHP [di(2-ethylhexyl) phthalate] metabolites. These relationships differed based on infant sex. CONCLUSIONS: Urinary concentrations of BPA and several phthalate metabolites were significantly associated with increased risk of preeclampsia. If validated, these results indicate an environmental contribution of endocrine-disrupting chemicals to preeclampsia and suggest a modifiable means to reduce the mortality and morbidity associated with this condition. http://dx.doi.org/10.1289/EHP188, Introduction Preeclampsia (PE) is characterized by new-onset or worsening hypertension and significant proteinuria after 20 weeks of gestation and still represents a major cause of preterm birth and maternal mortality/morbidity [...]

BACKGROUND: Preterm birth (PTB), a leading cause of infant mortality and morbidity, has a complex etiology with a multitude of interacting causes and risk factors. The role of environmental contaminants, particularly bisphenol A (BPA), is understudied with regard to PTB. OBJECTIVES: In the present study we examined the relationship between longitudinally measured BPA exposure during gestation and PTB. METHODS: A nested case-control study was performed from women enrolled in a prospective birth cohort study at Brigham and Women's Hospital in Boston, Massachusetts, during 2006-2008. Urine samples were analyzed for BPA concentrations at a minimum of three time points during pregnancy on 130 cases of PTB and 352 randomly assigned controls. Clinical classifications of PTB were defined as 'spontaneous,' which was preceded by spontaneous preterm labor or preterm premature rupture of membranes, or 'placental,' which was preceded by preeclampsia or intrauterine growth restriction. RESULTS: Geometric mean concentrations of BPA did not differ significantly between cases and controls. In adjusted models, urinary BPA averaged across pregnancy was not significantly associated with PTB. When examining clinical classifications of PTB, urinary BPA late in pregnancy was significantly associated with increased odds of delivering a spontaneous PTB. After stratification on infant's sex, averaged BPA exposure during pregnancy was associated with significantly increased odds of being delivered preterm among females, but not males. CONCLUSIONS: These results provide little evidence of a relationship between BPA and prematurity, though further research may be warranted given the generalizability of participant recruitment from a tertiary teaching hospital, limited sample size, and significant associations among females and within the clinical subcategories of PTB. http://dx.doi.org/10.1289/ehp.1408126, Introduction Preterm birth (PTB), defined as delivery before 37 weeks completed gestation, is a leading cause of infant mortality and significant precursor to future morbidity. Overall rates of PTB in [...]

BACKGROUND: Previous studies suggest that blood lead levels are positively associated with attention deficit/hyperactivity disorder (ADHD) and ADHD-symptoms in children. However, the associations between lead exposure and ADHD subtypes are inconsistent and understudied. OBJECTIVE: The objective of this study was to explore the association of low-level concurrent lead exposure with subtypes of ADHD symptoms in 578 Mexican children 6-13 years of age. METHODS: We measured concurrent blood lead levels using inductively coupled plasma mass spectrometry (ICPMS). We administered the Conners' Rating Scales-Revised (CRS-R) to mothers to evaluate their children's ADHD symptoms. We used imputation to fill missing values in blood lead levels and used segmented regression models adjusted for relevant covariates to model the nonlinear relationship between blood lead and ADHD symptoms. RESULTS: Mean ± SD blood lead levels were 3.4 ± 2.9 µg/dL. In adjusted models, a 1-µg/dL increase in blood lead was positively associated with Hyperactivity and Restless-Impulsivity scores on the CRS-R scale and Hyperactivity-Impulsivity scores on the CRS-R scale of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, but only in children with blood lead level ≤ 5 µg/dL. Blood lead was not associated with Inattentive symptoms or overall ADHD behavior. CONCLUSIONS: In this population of Mexican children, current blood lead level among children with low exposure (≤ 5 µg/dL) was positively associated with hyperactive/impulsive behaviors, but not with inattentiveness. These results add to the existing evidence of lead-associated neurodevelopmental deficits at low levels of exposure. CITATION: Huang S, Hu H, Sánchez BN, Peterson KE, Ettinger AS, Lamadrid-Figueroa H, Schnaas L, Mercado-García A, Wright RO, Basu N, Cantonwine DE, Hernández-Avila M, Téllez-Rojo MM. 2016. Childhood blood lead levels and symptoms of attention deficit hyperactivity disorder (ADHD): a cross-sectional study of Mexican children. Environ Health Perspect 124:868-874; http://dx.doi.org/10.1289/ehp.1510067 [ABSTRACT FROM AUTHOR]