RESUMEN
BACKGROUND: Exposure during pregnancy to household air pollution caused by the burning of solid biomass fuel is associated with adverse health outcomes, including low birth weight. Whether the replacement of a biomass cookstove with a liquefied petroleum gas (LPG) cookstove would result in an increase in birth weight is unclear. METHODS: We performed a randomized, controlled trial involving pregnant women (18 to <35 years of age and at 9 to <20 weeks' gestation as confirmed on ultrasonography) in Guatemala, India, Peru, and Rwanda. The women were assigned in a 1:1 ratio to use a free LPG cookstove and fuel (intervention group) or to continue using a biomass cookstove (control group). Birth weight, one of four prespecified primary outcomes, was the primary outcome for this report; data for the other three outcomes are not yet available. Birth weight was measured within 24 hours after birth. In addition, 24-hour personal exposures to fine particulate matter (particles with a diameter of ≤2.5 µm [PM2.5]), black carbon, and carbon monoxide were measured at baseline and twice during pregnancy. RESULTS: A total of 3200 women underwent randomization; 1593 were assigned to the intervention group, and 1607 to the control group. Uptake of the intervention was nearly complete, with traditional biomass cookstoves being used at a median rate of less than 1 day per month. After randomization, the median 24-hour personal exposure to fine particulate matter was 23.9 µg per cubic meter in the intervention group and 70.7 µg per cubic meter in the control group. Among 3061 live births, a valid birth weight was available for 94.9% of the infants born to women in the intervention group and for 92.7% of infants born to those in the control group. The mean (±SD) birth weight was 2921±474.3 g in the intervention group and 2898±467.9 g in the control group, for an adjusted mean difference of 19.6 g (95% confidence interval, -10.1 to 49.2). CONCLUSIONS: The birth weight of infants did not differ significantly between those born to women who used LPG cookstoves and those born to women who used biomass cookstoves. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; HAPIN ClinicalTrials.gov number, NCT02944682.).
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Contaminación del Aire Interior , Peso al Nacer , Culinaria , Material Particulado , Petróleo , Femenino , Humanos , Embarazo , Contaminación del Aire Interior/efectos adversos , Contaminación del Aire Interior/análisis , Biomasa , Culinaria/métodos , Material Particulado/efectos adversos , Material Particulado/análisis , Petróleo/efectos adversos , Petróleo/análisis , Recién Nacido , Adolescente , Adulto Joven , AdultoRESUMEN
Acute myeloid leukemia (AML) is a rare malignancy representing 15-20% of all leukemia diagnoses among children. Maternal exposure to persistent organic pollutants is suggestive of increased risk for childhood AML based on existing evidence. We aimed to evaluate the relationship between persistent organic pollutants and childhood AML using newborn dried bloodspots (DBS) from the Michigan BioTrust for Health. We obtained data on AML cases diagnosed prior to 15 years of age (n = 130) and controls (n = 130) matched to cases on week of birth from the Michigan Department of Health and Human Services. We quantified levels of dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB), and polybrominated diphenyl ether congener 47 (BDE-47) in newborn DBS. We also evaluated other organochlorine pesticides, polychlorinated biphenyls, polybrominated biphenyl congener 153, and polybrominated diphenyl ethers, though these were not further evaluated as >60% of observations were above the limit of detection for these chemicals. To evaluate the association between each chemical and AML, we used multivariable conditional logistic regression. In our multivariable model of HCB adjusted for month of birth, maternal age at delivery, and area poverty, we observed no association with AML (Odds Ratio [OR] per interquartile range increase: 1.17, 95% CI: 0.80, 1.69). For p,p'-DDE, ORs were significantly lower for those exposed to the highest tertile of p,'p-DDE (≥0.29 pg/mL, OR: 0.32, 95% CI: 0.11, 0.95) compared to the first tertile (<0.09 pg/mL). We observed no statistically significant associations between HCB and BDE-47 and AML. We observed a reduced odds of exposure to p,'p-DDE and an increased, though imprecise, odds of exposure to HCB among AML cases compared to controls. Future studies would benefit from a larger sample of AML patients and pooling newborn DBS across multiple states to allow for additional variability in exposures and evaluation of AML subtypes, which may have differing etiology.
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Contaminantes Ambientales , Éteres Difenilos Halogenados , Hidrocarburos Clorados , Leucemia Mieloide Aguda , Bifenilos Policlorados , Recién Nacido , Femenino , Humanos , Niño , Preescolar , Contaminantes Orgánicos Persistentes , Diclorodifenil Dicloroetileno , Hexaclorobenceno , Bifenilos Policlorados/análisis , Leucemia Mieloide Aguda/inducido químicamente , Leucemia Mieloide Aguda/epidemiologíaRESUMEN
Organophosphate (OP) insecticides are some of the most abundantly used insecticides, and prenatal exposures have been linked to adverse maternal and child health outcomes. Anogenital distance (AGD) has emerged as an early marker of androgen activity, and later reproductive outcomes, that is sensitive to alteration by environmental chemicals. Here, we examined associations between prenatal exposure to chlorpyrifos, an OP insecticide, with AGD. Pregnant farmworkers were enrolled in the Study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE; N = 104) between 2017 and 2019 in Northern Thailand. Concentrations of 3,5,6-trichloro-2-pyridinol (TCPy), a specific metabolite of chlorpyrifos, were measured in composited urine samples obtained from each trimester of pregnancy. AGD was measured at 12 months of age. Sex-specific adjusted linear regression models were used to examine associations between average and trimester-specific TCPy levels and AGD. In adjusted models for females and males, increasing TCPy was consistently associated with a modest, non-significant reduction in AGD. Across both strata of sex, associations were greatest in magnitude for trimester 3 (females: ß = -2.17, 95 % confidence interval (CI) = -4.99, 0.66; males: ß = -3.02, 95 % CI = -6.39, 0.35). In the SAWASDEE study, prenatal chlorpyrifos exposure was not strongly associated with AGD at 12 months of age.
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Cloropirifos , Insecticidas , Masculino , Embarazo , Niño , Humanos , Femenino , Cloropirifos/orina , Insecticidas/orina , Tailandia , Agricultores , Exposición a Riesgos Ambientales , Exposición MaternaRESUMEN
Per- and polyfluoroalkyl substances (PFAS) have been identified as environmental contributors to adverse birth outcomes. One potential mechanistic pathway could be through PFAS-related inflammation and cytokine production. Here, we examined associations between a PFAS mixture and inflammatory biomarkers during early and late pregnancy from participants enrolled in the Atlanta African American Maternal-Child Cohort (N = 425). Serum concentrations of multiple PFAS were detected in >90% samples at 8-14 weeks gestation. Serum concentrations of interferon-γ (IFN-γ), interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were measured at up to two time points (8-14 weeks and 24-30 weeks gestation). The effect of the PFAS mixture on each inflammatory biomarker was examined using quantile g-computation, Bayesian kernel machine regression (BKMR), Bayesian Weighted Sums (BWS), and weighted quantile sum (WQS) regression. Across all models, the PFAS mixture was associated with increased IFN-γ, IL-10, and TNF-α at both time points, with the strongest effects being observed at 24-30 weeks. Using quantile g-computation, increasing concentrations of a PFAS mixture were associated with a 29% (95% confidence interval = 18.0%, 40.7%) increase in TNF-α at 24-30 weeks. Similarly, using BWS, the PFAS mixture was associated with increased TNF-α at 24-30 weeks (summed effect = 0.29, 95% highest posterior density = 0.17, 0.41). The PFAS mixture was also positively associated with TNF-α at 24-30 weeks using BKMR [75th vs 50th percentile: 17.1% (95% credible interval = 7.7%, 27.4%)]. Meanwhile, PFOS was consistently the main drivers of overall mixture effect across four methods. Our findings indicated an increase in prenatal PFAS exposure is associated with an increase in multiple pro-inflammatory cytokines, potentially contributing to adverse pregnancy outcomes.
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Biomarcadores , Negro o Afroamericano , Fluorocarburos , Complicaciones del Embarazo , Efectos Tardíos de la Exposición Prenatal , Femenino , Humanos , Embarazo , Teorema de Bayes , Biomarcadores/sangre , Fluorocarburos/sangre , Interleucina-10 , Factor de Necrosis Tumoral alfa , Resultado del Embarazo , Complicaciones del Embarazo/sangre , Complicaciones del Embarazo/inmunología , Efectos Tardíos de la Exposición Prenatal/sangre , Efectos Tardíos de la Exposición Prenatal/inmunologíaRESUMEN
Prenatal exposure to single chemicals belonging to the per- and polyfluoroalkyl substances (PFAS) family is associated with biological perturbations in the mother, fetus, and placenta, plus adverse health outcomes. Despite our knowledge that humans are exposed to multiple PFAS, the potential joint effects of PFAS on the metabolome remain largely unknown. Here, we leveraged high-resolution metabolomics to identify metabolites and metabolic pathways perturbed by exposure to a PFAS mixture during pregnancy. Targeted assessment of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorooctanesulfonic acid (PFOS), and perfluorohexanesulfonic acid (PFHxS), along with untargeted metabolomics profiling, were conducted on nonfasting serum samples collected from pregnant African Americans at 6-17 weeks gestation. We estimated the overall mixture effect and partial effects using quantile g-computation and single-chemical effects using linear regression. All models were adjusted for maternal age, education, parity, early pregnancy body mass index, substance use, and gestational weeks at sample collection. Our analytic sample included 268 participants and was socioeconomically diverse, with the majority receiving public health insurance (78%). We observed 13.3% of the detected metabolic features were associated with the PFAS mixture (n = 1705, p < 0.05), which was more than any of the single PFAS chemicals. There was a consistent association with metabolic pathways indicative of systemic inflammation and oxidative stress (e.g., glutathione, histidine, leukotriene, linoleic acid, prostaglandins, and vitamins A, C, D, and E metabolism) across all metabolome-wide association studies. Twenty-six metabolites were validated against authenticated compounds and associated with the PFAS mixture (p < 0.05). Based on quantile g-computation weights, PFNA contributed the most to the overall mixture effect for γ-aminobutyric acid (GABA), tyrosine, and uracil. In one of the first studies of its kind, we demonstrate the feasibility and utility of using methods designed for exposure mixtures in conjunction with metabolomics to assess the potential joint effects of multiple PFAS chemicals on the human metabolome. We identified more pronounced metabolic perturbations associated with the PFAS mixture than for single PFAS chemicals. Taken together, our findings illustrate the potential for integrating environmental mixture analyses and high-throughput metabolomics to elucidate the molecular mechanisms underlying human health.
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Negro o Afroamericano , Contaminantes Ambientales , Fluorocarburos , Embarazo , Efectos Tardíos de la Exposición Prenatal , Femenino , Humanos , Embarazo/metabolismo , Ácidos Alcanesulfónicos , Contaminantes Ambientales/toxicidad , Feto/metabolismo , Fluorocarburos/toxicidad , Placenta/metabolismo , Georgia , MetabolómicaRESUMEN
BACKGROUND: Consumer products are common sources of exposure for phthalates and bisphenol A (BPA), which disrupt the endocrine system. Psychosocial stressors have been shown to amplify the toxic effects of endocrine disruptors but, information is limited among African Americans (AAs), who experience the highest rates of adverse pregnancy outcomes and are often exposed to the highest levels of chemical and non-chemical stressors. We examined the association between an exposure mixture of phthalate metabolites, BPA, and psychosocial stressors with gestational age at delivery and birthweight for gestational age z-scores in pregnant AA women. STUDY DESIGN: Participants were enrolled in the Atlanta African American Maternal-Child Cohort (N = 247). Concentrations of eight phthalate metabolites and BPA were measured in urine samples collected at up to two timepoints during pregnancy (8-14 weeks gestation and 20-32 weeks gestation) and were averaged. Psychosocial stressors were measured using self-reported, validated questionnaires that assessed experiences of discrimination, gendered racial stress, depression, and anxiety. Linear regression was used to estimate individual associations between stress exposures (chemical and psychosocial) and birth outcomes. We leveraged quantile g-computation was used to examine joint effects of chemical and stress exposures on gestational age at delivery (in weeks) and birthweight for gestational age z-scores. RESULTS: A simultaneous increase in all phthalate metabolites and BPA was associated with a moderate reduction in birthweight z-scores (mean change per quartile increase = -0.22, 95% CI = -0.45, 0.0). The association between our exposure mixture and birthweight z-scores became stronger when including psychosocial stressors as additional exposures (mean change per quantile increase = -0.35, 95% CI = -0.61, -0.08). Overall, we found null associations between exposure to chemical and non-chemical stressors with gestational age at delivery. CONCLUSIONS: In a prospective cohort of AA mother-newborn dyads, we observed that increased prenatal exposure to phthalates, BPA, and psychosocial stressors were associated with adverse pregnancy outcomes.
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Compuestos de Bencidrilo , Peso al Nacer , Negro o Afroamericano , Exposición a Riesgos Ambientales , Ácidos Ftálicos , Estrés Psicológico , Femenino , Humanos , Recién Nacido , Embarazo , Compuestos de Bencidrilo/efectos adversos , Compuestos de Bencidrilo/metabolismo , Compuestos de Bencidrilo/farmacología , Compuestos de Bencidrilo/orina , Peso al Nacer/efectos de los fármacos , Negro o Afroamericano/psicología , Contaminantes Ambientales/efectos adversos , Contaminantes Ambientales/metabolismo , Contaminantes Ambientales/farmacología , Contaminantes Ambientales/orina , Ácidos Ftálicos/efectos adversos , Ácidos Ftálicos/metabolismo , Ácidos Ftálicos/farmacología , Ácidos Ftálicos/orina , Resultado del Embarazo/etnología , Estudios Prospectivos , Estrés Psicológico/etnología , Georgia , Efectos Tardíos de la Exposición Prenatal/etnología , Exposición a Riesgos Ambientales/efectos adversos , Edad GestacionalRESUMEN
BACKGROUND: An industrial accident led to the widespread contamination of polybrominated biphenyl (PBB), a flame retardant, into the food system in Michigan in the 1970's. PBB continues to be detected in Michiganders' blood some forty years later. It is necessary to understand the elimination rate and half-life of PBB because it may provide clues on how to hasten the elimination of it from the human body. METHODS: Serum samples were taken from young adult and adult participants of the Michigan PBB registry from 1974 to 2019. A single compartment model was assumed for the elimination rate for PBB-153 in young adults and adults (≥16 years). Generalized linear mixed models were used to estimate the average elimination rate of PBB-153 and allowed for a random intercept and slope for the time between measurements. Models were adjusted for age at exposure, body mass index (BMI) at initial measurement, and smoking. Models were also stratified by demographic characteristics. RESULTS: In total, 1974 participants contributed 4768 samples over a forty-year span. The median initial PBB-153 level was 1.542 parts per billion (ppb) (Range: 0.001-1442.48 ppb). The adjusted median participant-specific half-life for PBB-153 was 12.23 years. The half-life of PBB-153 was lengthened by higher initial PBB level (â¼1.5 years), younger age at exposure (â¼5.4 years), higher BMI (â¼1.0 years), and increased gravidity (â¼7.3 years). Additionally, the half-life of PBB-153 was shortened by smoking status (â¼-2.8 years) and breastfeeding (â¼-3.5 years). CONCLUSIONS: Consistent with previous studies, PBB-153 has been demonstrated to have a long half-life in the human body and may be modified by some demographic characteristics. These updated estimates of half-life will further support evaluation of health effects associated with PBB exposure. Investigations into mechanisms to accelerate elimination and reduce body burdens of PBB-153, especially those related to body weight, are needed.
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Contaminantes Ambientales , Bifenilos Polibrominados , Femenino , Adulto Joven , Humanos , Preescolar , Michigan , Índice de Masa CorporalRESUMEN
BACKGROUND: Polybrominated biphenyls (PBBs), a class of endocrine disrupting chemicals, were the main chemicals present in one of the largest industrial accidents in the United States. We investigated the association between serum PBB-153 levels and autoimmune disorders among members of the Michigan PBB Registry. METHODS: Eight hundred and ninety-five members of the registry had both a serum PBB-153 measurement and had completed one or more questionnaires about autoimmune disorders. Autoimmune disorders were examined collectively and within specific organ systems. Sex-stratified unadjusted and adjusted log-binomial models were used to examine the association between tertiles of serum PBB-153 levels and autoimmune disorders. Models were adjusted by lifestage at exposure (in utero, childhood, adulthood), smoking history (never, past, current), and total serum lipid levels (continuous). We utilized cubic spline models to investigate non-linearity between serum PBB-153 levels and the prevalence of autoimmune disorders. RESULTS: Approximately 12.9% and 20.7% of male and female participants reported having one or more autoimmune disorders, respectively. After adjustment for potential confounders, we observed no association between PBB-153 tertiles and the composite classification of 'any autoimmune disorder' in either sex. We observed some evidence for an association between serum PBB-153 levels and rheumatoid arthritis in males and females; however, this was not statistically significant in females. We also observed some evidence for an association between serum PBB-153 levels and neurological- and thyroid-related autoimmune disorders in females, but again this was not statistically significant. Additionally, we identified dose-response curves for serum PBB-153 levels and the prevalence of autoimmune disorders that differed by lifestage of exposure and sex. CONCLUSIONS: We observed some evidence that increasing serum PBB-153 levels were associated with three specified autoimmune disorders. Studies focusing on these three autoimmune disorders and the potential non-linear trend differences by lifestage of exposure warrant further investigation.
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Enfermedades Autoinmunes , Bifenilos Polibrominados , Femenino , Humanos , Masculino , Adulto , Niño , Michigan/epidemiología , Prevalencia , Enfermedades Autoinmunes/inducido químicamente , Enfermedades Autoinmunes/epidemiología , Sistema de RegistrosRESUMEN
BACKGROUND: Exposure to organophosphate (OP) pesticides during pregnancy has been linked to deficiencies of neurobehavioral development in childhood; however, the molecular mechanisms underlying this association remain elusive. The placenta plays a crucial role in protecting the fetus from environmental insults and safeguarding proper fetal development including neurodevelopment. The aim of our study is to evaluate changes in the placental transcriptome associated with prenatal OP exposure. METHODS: Pregnant farm workers from two agricultural districts in northern Thailand were recruited for the Study of Asian Women and Offspring's Development and Environmental Exposures (SAWASDEE) from 2017 to 2019. For 254 participants, we measured maternal urinary concentrations of six nonspecific dialkyl phosphates (DAP) metabolites in early, middle, and late pregnancy. In parallel, we profiled the term placental transcriptome from the same participants using RNA-Sequencing and performed Weighted Gene co-expression Network Analysis (WGCNA). Generalized linear regression modeling was used to examine associations of urinary OP metabolites and placental co-expression module eigenvalues. RESULTS: We identified 21 gene co-expression modules in the placenta. From the six DAP metabolites assayed, diethylphosphate (DEP) and diethylthiophosphate (DETP) were detected in more than 70% of the urine samples. Significant associations between DEP at multiple time points and two specific placental gene modules were observed. The 'black' module, enriched in genes involved in epithelial-to-mesenchymal transition (EMT) and hypoxia, was negatively associated with DEP in early (p = 0.034), and late pregnancies (p = 0.016). The 'lightgreen' module, enriched in genes involved in myogenesis and EMT, was negatively associated with DEP in late pregnancy (p = 0.010). We observed 2 hub genes (CELSR1 and PYCR1) of the 'black' module to be negatively associated with DEP in early and late pregnancies. CONCLUSIONS: Our results suggest that prenatal OP exposure may disrupt placental gene networks in a time-dependent manner. Such transcriptomic effects may lead to down-stream changes in placental function that ultimately affect the developing fetus.
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Insecticidas , Plaguicidas , Efectos Tardíos de la Exposición Prenatal , Femenino , Embarazo , Humanos , Redes Reguladoras de Genes , Plaguicidas/orina , Organofosfatos/orina , Exposición Materna , Placenta/metabolismo , Compuestos Organofosforados/orina , Insecticidas/orina , Exposición a Riesgos Ambientales , FosfatosRESUMEN
INTRODUCTION: Children's overweight and obesity are global public health problems, children with obesity have grater obesity risk as adults, thus leading to develop cardiometabolic diseases. Previous studies have found positive and significant associations between the exposure to phthalates and body mass index and body composition. OBJECTIVE: To evaluate the modification of the association by sex between DEHP exposure during pregnancy and the percentage of body fat in a cohort of Mexican schoolchildren. MATERIAL AND METHODS: The sample was comprised by children which had previously participated in a POSGRAD longitudinal study. A subsample of 190 mother-children binomials were included. Mothers' DEHP concentrations and its metabolites had been measured in the second trimester of pregnancy: Mono-2-ethylhexyl phthalate (MEHP), Mono-2-ethyl-5-carboxypentyl phthalate (MECPP), Mono-2-ethyl-5-hidroxyhexyl phthalate (MEHHP), and Mono-2-ethyl-5-oxohexyl phthalate (MEOHP). The children's adipose mass was measured at age 8, 9, and 10. Longitudinal data were analyzed using the mixed effects linear regression model, with intercept and random slope, adjusted by important confounders and stratified by sex. RESULTS: We found a differentiated effect by sex, the exposure to DEHP during pregnancy significantly increases the adipose mass in boys. The average increase was 0.058% (p = 0.02) for every 1% variation in MECPP; 0.047% (p = 0.04) in MEHHP; 0.051% (p = 0.03) in MEOHP, and 0.066% (p = 0.007) in MECPP. CONCLUSIONS: The results suggest an effect differentiated by sex; with boys being the main ones affected by the prenatal exposure to phthalates. However, we cannot rule out effects in girls.
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Tejido Adiposo/fisiopatología , Dietilhexil Ftalato/efectos adversos , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Factores Sexuales , Adulto , Estudios de Cohortes , Dietilhexil Ftalato/metabolismo , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Femenino , Humanos , Estudios Longitudinales , México/epidemiología , Embarazo , Efectos Tardíos de la Exposición Prenatal/epidemiologíaRESUMEN
INTRODUCTION: Organophosphate (OP) insecticides, including chlorpyrifos, have been linked with numerous harmful health effects on maternal and child health. Limited data are available on the biological mechanisms and endogenous pathways underlying the toxicity of chlorpyrifos exposures on pregnancy and birth outcomes. In this study, we measured a urinary chlorpyrifos metabolite and used high-resolution metabolomics (HRM) to identify biological perturbations associated with chlorpyrifos exposure among pregnant women in Thailand, who are disparately exposed to high levels of OP insecticides. METHODS: This study included 50 participants from the Study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE). We used liquid chromatography-high resolution mass spectrometry to conduct metabolic profiling on first trimester serum samples collected from participants to evaluate metabolic perturbations in relation to chlorpyrifos exposures. We measured 3,5,6-trichloro-2-pyridinol (TCPy), a specific metabolite of chlorpyrifos and chlorpyrifos-methyl, in first trimester urine samples to assess the levels of exposures. Following an untargeted metabolome-wide association study workflow, we used generalized linear models, pathway enrichment analyses, and chemical annotation to identify significant metabolites and pathways associated with urinary TCPy levels. RESULTS: In the 50 SAWASDEE participants, the median urinary TCPy level was 4.36 µg TCPy/g creatinine. In total, 691 unique metabolic features were found significantly associated with TCPy levels (p < 0.05) after controlling for confounding factors. Pathway analysis of metabolic features associated with TCPy indicated perturbations in 24 metabolic pathways, most closely linked to the production of reactive oxygen species and cellular damage. These pathways include tryptophan metabolism, fatty acid oxidation and peroxisome metabolism, cytochromes P450 metabolism, glutathione metabolism, and vitamin B3 metabolism. We confirmed the chemical identities of 25 metabolites associated with TCPy levels, including glutathione, cystine, arachidic acid, itaconate, and nicotinamide adenine dinucleotide. DISCUSSION: The metabolic perturbations associated with TCPy levels were related to oxidative stress, cellular damage and repair, and systemic inflammation, which could ultimately contribute to health outcomes, including neurodevelopmental deficits in the child. These findings support the future development of sensitive biomarkers to investigate the metabolic underpinnings related to pesticide exposure during pregnancy and to understand its link to adverse outcomes in children.
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Cloropirifos , Insecticidas , Plaguicidas , Biomarcadores/orina , Niño , Creatinina , Cistina/metabolismo , Citocromos/metabolismo , Agricultores , Ácidos Grasos , Femenino , Glutatión/metabolismo , Humanos , Insecticidas/toxicidad , Metaboloma , NAD/metabolismo , Niacinamida , Compuestos Organofosforados/toxicidad , Plaguicidas/orina , Embarazo , Primer Trimestre del Embarazo , Especies Reactivas de Oxígeno , Tailandia , Triptófano/metabolismoRESUMEN
Little is known about temporal trends of pregnant women's exposures to environmental phenols and parabens. We quantified four phenols [bisphenol A (BPA), bisphenol F, bisphenol S, and triclosan), four parabens [butyl paraben, ethyl paraben (ETPB), methyl paraben (MEPB), and propyl paraben (PRPB)], and triclocarban in 760 urine samples collected during 2007-2014 from 218 California pregnant women participating in a high-familial risk autism spectrum disorder cohort. We applied multiple regression to compute least square geometric means of urinary concentrations and computed average annual percent changes. We compared our urinary concentrations with those of other study populations to examine geographic variations in pregnant women's exposure to these target compounds. Urinary concentrations of BPA, MEPB, ETPB, and PRPB in this study population decreased over the study period [percent change per year (95% confidence interval): -5.7% (-8.2%, -3.2%); -13.0% (-18.1%, -7.7%); -5.5% (-11.0%, 0.3%); and -13.3% (-18.3%, -8.1%), respectively] and were consistently lower than those in pregnant women in other U.S. regions during the same study period. In recent years, certain phenols and parabens with known adverse health effects are being regulated or replaced with alternatives, which explains decreased body burdens observed in this study population. Either the national regulations or the advocacy campaigns in California may have influenced exposures or consumer product choices.
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Trastorno del Espectro Autista , Parabenos , Carbanilidas , Exposición a Riesgos Ambientales/análisis , Femenino , Humanos , Parabenos/análisis , Fenol , Fenoles , Embarazo , Mujeres EmbarazadasRESUMEN
Urinary concentrations of phenols, parabens, and triclocarban have been extensively used as biomarkers of exposure. However, because these compounds are quickly metabolized and excreted in urine, characterizing participants' long-term average exposure from a few spot samples is challenging. To examine the variability of urinary concentrations of these compounds during pregnancy, we quantified four phenols, four parabens, and triclocarban in 357 first morning voids (FMVs) and 203 pooled samples collected during the second and third trimesters of 173 pregnancies. We computed intraclass correlation coefficients (ICCs) by the sample type (FMV and pool) across two trimesters and by the number of composite samples in pools, ranging from 2 to 4, within the same trimester. Among the three compounds detected in more than 50% of the samples, the ICCs across two trimesters were higher in pools (0.29-0.68) than in FMVs (0.17-0.52) and the highest ICC within the same trimester was observed when pooling either two or three composites. Methyl paraben and propyl paraben primarily exposed via cosmetic use had approximately 2-3 times higher ICCs than bisphenol A primarily exposed via diet. Our findings support that within-subject pooling of biospecimens can increase the reproducibility of pregnant women's exposure to these compounds and thus could potentially minimize exposure misclassification.
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Carbanilidas , Parabenos , Biomarcadores , Femenino , Humanos , Fenoles , Embarazo , Reproducibilidad de los ResultadosRESUMEN
Biomonitoring is a commonly used tool for exposure assessment of organic environmental chemicals with urine and blood samples being the most commonly used matrices. However, for children's studies, blood samples are often difficult to obtain. Dried blood spots (DBS) represent a potential matrix for blood collection in children that may be used for biomonitoring. DBS are typically collected at birth to screen for several congenital disorders and diseases; many of the states that are required to collect DBS archive these spots for years. If the archived DBS can be accessed by environmental health researchers, they potentially could be analyzed to retrospectively assess exposure in these children. Furthermore, DBS can be collected prospectively in the field from children ranging in age from newborn to school-aged with little concern from parents and minimal risk to the child. Here, we review studies that have evaluated the measurement of organic environmental toxicants in both archived and prospectively collected DBS, and where available, the validation procedures that have been performed to ensure these measurements are comparable to traditional biomonitoring measurements. Among studies thus far, the amount of validation has varied considerably with no studies systematically evaluating all parameters from field collection, shipping and storage contamination and stability to laboratory analysis feasibility. These validation studies are requisite to ensure reliability of the measurement and comparability to more traditional matrices. Thus, we offer some recommendations for validation studies and other considerations before DBS should be adopted as a routine matrix for biomonitoring.
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Monitoreo Biológico , Compuestos Orgánicos , Niño , Pruebas con Sangre Seca , Exposición a Riesgos Ambientales/análisis , Humanos , Recién Nacido , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
Exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with adverse health outcomes, especially when exposure occurs within sensitive time windows such as the pre- and post-natal periods and early childhood. However, few studies have focused on PFAS exposure distribution and predictors in pregnant women, especially among African American women. We quantified serum concentrations of the four most common PFAS collected in all 453 participants and an additional 10 PFAS in 356 participants who were pregnant African American women enrolled from 2014 to 2018 in Atlanta, Georgia, and investigated the sociodemographic predictors of exposure. Additional home environment and behavior predictors were also examined in 130 participants. Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) were detected in >95% of the samples with PFOS having the highest concentrations (geometric mean (GM) 2.03 ng/mL). N-Methyl perfluorooctane sulfonamido acetic acid (NMeFOSAA), perfluoropentanoic acid (PFPeA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) were found in 40-50% of the samples, whereas the detection frequencies for the other six PFAS were below 15%. When compared to National Health and Nutrition Examination Survey (NHANES) participants matching sex, race, and age with this study, our results showed similar concentrations of most PFAS, but higher concentrations of PFHxS (GM 0.99 ng/mL in this study; 0.63 and 0.4 ng/mL in NHANES, 2014-2015 and 2016-2017 cycles). A decline in concentrations over the study period was found for most PFAS but not PFPeA. In adjusted models, education, sampling year, parity, BMI, tobacco and marijuana use, age of house, drinking water source, and cosmetic use were significantly associated with serum PFAS concentrations. Our study reports the first PFAS exposure data among pregnant African American women in the Atlanta area, Georgia. The identified predictors will facilitate the setting of research priorities and enable development of exposure mitigation strategies.
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Ácidos Alcanesulfónicos , Contaminantes Ambientales , Fluorocarburos , Negro o Afroamericano , Preescolar , Femenino , Georgia , Humanos , Encuestas Nutricionales , Embarazo , Mujeres EmbarazadasRESUMEN
Vitamin D has been linked to various physiological functions in pregnant women and their fetuses. Previous studies have suggested that some per- and polyfluoroalkyl substances (PFAS) may alter serum vitamin D concentrations. However, no study has investigated the relationship between PFAS and vitamin D in pregnant women. This study aims to evaluate the associations of serum PFAS with serum total and free 25-hydroxyvitamin D (25(OH)D) during pregnancy in a cohort of African American women in Atlanta, GA. Blood samples from 442 participants were collected in early pregnancy (8-14 weeks of gestation) for PFAS and 25(OH)D measurements, and additional samples were collected in late pregnancy (24-30 weeks) for the second 25(OH)D measurements. We fit multivariable linear regressions and weighted quantile sum (WQS) regressions to estimate the associations of individual PFAS and their mixtures with 25(OH)D concentrations. We found mostly positive associations of total 25(OH)D with PFHxS (perfluorohexane sulfonic acid), PFOS (perfluorooctane sulfonic acid), PFDA (perfluorodecanoic acid), and NMeFOSAA (N-methyl perfluorooctane sulfonamido acetic acid), and negative associations with PFPeA (perfluoropentanoic acid). For free 25(OH)D, positive associations were observed with PFHxS, PFOS, PFOA (perfluorooctanoic acid), and PFDA, and a negative association with PFPeA among the women with male fetuses in the models using 25(OH)D measured in late pregnancy. In mixture models, a quartile increase in WQS index was associated with 2.88 ng/mL (95%CI 1.14-4.59) and 5.68 ng/mL (95%CI 3.31-8.04) increases in total 25(OH)D measured in the early and late pregnancy, respectively. NMeFOSAA, PFDA, and PFOS contributed the most to the overall effects among the eight PFAS. No association was found between free 25(OH)D and the PFAS mixture. These results suggest that PFAS may affect vitamin D biomarker concentrations in pregnant African American women, and some of the associations were modified by fetal sex.
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Ácidos Alcanesulfónicos , Contaminantes Ambientales , Fluorocarburos , Negro o Afroamericano , Biomarcadores , Femenino , Fluorocarburos/toxicidad , Humanos , Masculino , Embarazo , Vitamina DRESUMEN
BACKGROUND: We assessed the relationships between prenatal pyrethroid pesticide exposure and autism spectrum disorders (ASD) or non-typical development (non-TD) at 3 years. METHODS: Participants were mother-child pairs (n = 201) in the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) cohort. Because familial recurrence risk is high, MARBLES enrolls pregnant women with a family history of ASD. Children from these pregnancies were clinically assessed at 3 years of age and classified into 3 outcome categories: ASD, typically developing (TD), or non-TD (neither TD or ASD). Repeated maternal second and third trimester urine samples were analyzed for pyrethroid metabolite 3-phenoxybenzoic acid (3-PBA). Multinomial logistic regression was used to obtain relative risk ratios (RRR) linking 3-PBA concentrations averaged across each trimester and over pregnancy with child's outcome: ASD or non-TD vs. TD. Models were adjusted for specific gravity, maternal pre-pregnancy BMI, prenatal vitamin use, birth year, home-ownership, and pregnancy concentrations of TCPy (3,5,6-trichloro-2-pyridinol, a metabolite of chlorpyrifos). RESULTS: The median specific gravity corrected 3-PBA concentration of all samples was 1.46 ng/mL. Greater second trimester 3-PBA concentrations were associated with a relative risk ratio (RRR) for ASD of (RRR: 1.50 (95% CI 0.89 to 2.51), p = 0.12). There were no differences between non-TD and TD. CONCLUSIONS: This study found no evidence for differences in 3-PBA comparing non-TD with TD. A modestly elevated RRR was found comparing second trimester urinary 3-PBA concentrations for ASD versus TD; however, the confidence interval was wide and hence, these findings cannot be considered definitive.
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Trastorno del Espectro Autista , Plaguicidas , Piretrinas , Trastorno del Espectro Autista/inducido químicamente , Trastorno del Espectro Autista/epidemiología , Carbonato de Calcio , Niño , Estudios de Cohortes , Femenino , Humanos , Plaguicidas/toxicidad , Embarazo , Piretrinas/toxicidadRESUMEN
BACKGROUND: The objective of this study was to identify conditional relationships between multiple metal biomarkers that predict systolic and diastolic blood pressure in the non-institutionalized United States adult population below the age of 60. METHODS: We used inorganic exposure biomarker data and blood pressure data from three cycles (1999-2004) of the National Health and Nutrition Examination Survey (NHANES) to construct regression trees for blood pressure among adults ages 20-60 (adjusted for age, sex, body mass index, race, and smoking status) to identify predictors of systolic (SBP) and diastolic blood pressure (DBP). We also considered relationships among non-Hispanic black, Mexican-American, and white adults separately. RESULTS: The following metal exposure biomarkers were conditionally predictive of SBP and/or DBP in the full sample: antimony (Sb), barium (Ba), cadmium (Cd), cesium (Cs), lead (Pb), tungsten (W) and molybdenum (Mo). The highest average SBP (> 120 mmHg) was observed among those with low Sb (≤ 0.21 µg/dL) high Cd (> 0.22 µg/g creatinine) and high Pb (> 2.55 µg/dL) biomarkers. Those with the highest average DBP had high urinary W levels (> 0.10 µg/g creatinine) in combination with either urinary Sb > 0.17 µg/g creatinine or those with urinary Sb ≤ 0.17 µg/g creatinine, but with high blood Pb levels (> 1.35 µg/dL). Predictors differed by ethnicity, with Cd as the main predictor of SBP among non-Hispanic black adults, and Pb not selected by the algorithm as a predictor of SBP among non-Hispanic white adults. CONCLUSIONS: Combinations of metal biomarkers have different apparent relationships with blood pressure. Additional research in toxicological experimental models and in epidemiological studies is warranted to evaluate the suggested possible toxicological interactions between Sb, Cd, and Pb; and between W, Sb, and Pb; for cardiovascular (e.g., blood pressure) health. We also think future epidemiological research on inorganic exposure sets in relation to health outcomes like blood pressure might benefit from stratification by race and ethnicity.
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Presión Sanguínea , Metales Pesados/sangre , Metales Pesados/orina , Adulto , Monitoreo Biológico , Biomarcadores/sangre , Biomarcadores/orina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Estados Unidos , Adulto JovenRESUMEN
Household air pollution (HAP) from biomass stoves is a leading risk factor for cardiopulmonary outcomes; however, its toxicity pathways and relationship with inflammation markers are poorly understood. Among 180 adult women in rural Peru, we examined the cross-sectional exposure-response relationship between biomass HAP and markers of inflammation in blood using baseline measurements from a randomized trial. We measured markers of inflammation (CRP, IL-6, IL-10, IL-1ß, and TNF-α) with dried blood spots, 48-h kitchen area concentrations and personal exposures to fine particulate matter (PM2.5 ), black carbon (BC), and carbon monoxide (CO), and 48-h kitchen concentrations of nitrogen dioxide (NO2 ) in a subset of 97 participants. We conducted an exposure-response analysis between quintiles of HAP levels and markers of inflammation. Markers of inflammation were more strongly associated with kitchen area concentrations of BC than PM2.5 . As expected, kitchen area BC concentrations were positively associated with TNF-α (pro-inflammatory) concentrations and negatively associated with IL-10, an anti-inflammatory marker, controlling for confounders in single- and multi-pollutant models. However, contrary to expectations, kitchen area BC and NO2 concentrations were negatively associated with IL-1ß, a pro-inflammatory marker. No associations were identified for IL-6 or CRP, or for any marker in relation to personal exposures.
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Contaminación del Aire Interior/estadística & datos numéricos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Adulto , Biomarcadores/sangre , Femenino , Humanos , Inflamación/sangre , PerúRESUMEN
Infections with enteric pathogens impose a heavy disease burden, especially among young children in low-income countries. Recent findings from randomized controlled trials of water, sanitation, and hygiene interventions have raised questions about current methods for assessing environmental exposure to enteric pathogens. Approaches for estimating sources and doses of exposure suffer from a number of shortcomings, including reliance on imperfect indicators of fecal contamination instead of actual pathogens and estimating exposure indirectly from imprecise measurements of pathogens in the environment and human interaction therewith. These shortcomings limit the potential for effective surveillance of exposures, identification of important sources and modes of transmission, and evaluation of the effectiveness of interventions. In this review, we summarize current and emerging approaches used to characterize enteric pathogen hazards in different environmental media as well as human interaction with those media (external measures of exposure), and review methods that measure human infection with enteric pathogens as a proxy for past exposure (internal measures of exposure). We draw from lessons learned in other areas of environmental health to highlight how external and internal measures of exposure can be used to more comprehensively assess exposure. We conclude by recommending strategies for advancing enteric pathogen exposure assessments.