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INTRODUCTION: Environmental phenols are endocrine disrupting chemicals hypothesized to affect early life development. Previous research examining the effects of phenols on fetal growth has focused primarily on associations with measures of size at delivery. Few have included ultrasound measures to examine growth across pregnancy. OBJECTIVE: Investigate associations between prenatal exposure to phenols and ultrasound and delivery measures of fetal growth. METHODS: Using the LIFECODES Fetal Growth Study (n = 900), a case-cohort including 248 small-for-gestational-age, 240 large-for-gestational age, and 412 appropriate-for-gestational-age births, we estimated prenatal exposure to 12 phenols using three urine samples collected during pregnancy (median 10, 24, and 35 weeks gestation). We abstracted ultrasound and delivery measures of fetal growth from medical records. We estimated associations between pregnancy-average phenol biomarker concentrations and repeated ultrasound measures of fetal growth using linear mixed effects models and associations with birthweight using linear regression models. We also used logistic regression models to estimate associations with having a small- or large-for-gestational birth. RESULTS: We observed positive associations between 2,4-dichlorophenol, benzophenone-3, and triclosan (TCS) and multiple ultrasound measures of fetal growth. For example, TCS was associated with a 0.09 (95 % CI: 0.01, 0.18) higher estimated fetal weight z-score longitudinally across pregnancy. This effect size corresponds to a 21 g increase in estimated fetal weight at 30 weeks gestation. Associations with delivery measures of growth were attenuated, but TCS remained positively associated with birthweight z-scores (mean difference: 0.13, 95 % CI: 0.02, 0.25). Conversely, methylparaben was associated with higher odds of a small-for-gestational age birth (odds ratio: 1.45, 95 % CI: 1.06, 1.98). DISCUSSION: We observed associations between some biomarkers of phenol exposure and ultrasound measures of fetal growth, though associations at the time of delivery were attenuated. These findings are consistent with hypotheses that phenols have the potential to affect growth during the prenatal period.
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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.
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Desarrollo Fetal , Retardadores de Llama , Exposición Materna , Plastificantes , Humanos , Femenino , Desarrollo Fetal/efectos de los fármacos , Plastificantes/toxicidad , Embarazo , Exposición Materna/estadística & datos numéricos , Organofosfatos , Adulto , Peso al Nacer/efectos de los fármacos , Recién Nacido , Ésteres , Biomarcadores/orina , Estudios de Cohortes , MasculinoRESUMEN
INTRODUCTION: Prenatal exposure to non-persistent chemicals, including organophosphate pesticides, phthalates, and bisphenols, is associated with altered fetal and childhood growth. Few studies have examined these associations using longitudinal growth trajectories or considering exposure to chemical mixtures. METHODS: Among 777 participants from the Generation R Study, we used growth mixture models to identify weight and body mass index (BMI) trajectories using weight and height measures collected from the prenatal period to age 13. We measured exposure biomarkers for organophosphate pesticides, phthalates, and bisphenols in maternal urine at three timepoints during pregnancy. Multinomial logistic regression was used to estimate associations between averaged exposure biomarker concentrations and growth trajectories. We used quantile g-computation to estimate joint associations with growth trajectories. RESULTS: Phthalic acid (OR: 1.4, 95% CI: 1.01, 1.9) and bisphenol A (BPA; OR: 1.5, 95% CI: 1.0, 2.2) were associated with higher odds of a growth trajectory characterized by smaller prenatal and larger childhood weight relative to a referent trajectory of larger prenatal and average childhood weight. Biomarkers of organophosphate pesticides, individually and jointly, were associated with lower odds of a growth trajectory characterized by average prenatal and lower childhood weight. CONCLUSIONS: Exposure to phthalates and BPA was positively associated with a weight trajectory characterized by lower prenatal and higher childhood weight, while exposure to organophosphate pesticides was negatively associated with a trajectory of average prenatal and lower childhood weight. This study is consistent with the hypothesis that non-persistent chemical exposures disrupt growth trajectories from the prenatal period through childhood.
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BACKGROUND: Inflammation and oxidative stress are critical to pregnancy, but most human study has focused on downstream, non-causal indicators. Oxylipins are lipid mediators of inflammation and oxidative stress that act through many biological pathways. Our aim was to characterize predictors of circulating oxylipin concentrations based on maternal characteristics. METHODS: Our study was conducted among 901 singleton pregnancies in the LIFECODES Fetal Growth Study, a nested case-cohort with recruitment from 2007 to 2018. We measured a targeted panel of oxylipins in early pregnancy plasma and urine samples from several biosynthetic pathways, defined by the polyunsaturated fatty acid (PUFA) precursor and enzyme group. We evaluated levels across predictors, including characteristics of participants' pregnancy, socioeconomic determinants, and obstetric and medical history. RESULTS: Current pregnancy and sociodemographic characteristics were the most important predictors of circulating oxylipins concentrations. Plasma oxylipins were lower and urinary oxylipins higher for participants with a later gestational age at sampling (13-23 weeks), higher prepregnancy BMI (obesity class I, II, or III), Black or Hispanic race and ethnicity, and lower socioeconomic status (younger age, lower education, and uninsured). For example, compared to those with normal or underweight prepregnancy BMI, participants with class III prepregnancy obesity had 45-46% lower plasma epoxy-eicosatrienoic acids, the anti-inflammatory oxylipins produced from arachidonic acid (AA) by cytochrome P450, and had 81% higher urinary 15-series F2-isoprostanes, an indicator of oxidative stress produced from non-enzymatic AA oxidation. Similarly, in urine, Black participants had 92% higher prostaglandin E2 metabolite, a pro-inflammatory oxylipin, and 41% higher 5-series F2-isoprostane, an oxidative stress indicator. CONCLUSIONS: In this large pregnancy study, we found that circulating levels of oxylipins were different for participants of lower socioeconomic status or of a systematically marginalized racial and ethnic groups. Given associations differed along biosynthetic pathways, results provide insight into etiologic links between maternal predictors and inflammation and oxidative stress.
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F2-Isoprostanos , Oxilipinas , Embarazo , Femenino , Humanos , Lactante , Ácidos Grasos Insaturados , Isoprostanos , Inflamación , Obesidad , Ácido Araquidónico , Estrés OxidativoRESUMEN
BACKGROUND: Personal care products (PCPs) contain many different compounds and are a source of exposure to endocrine disrupting chemicals (EDCs), including phthalates and phenols. Early-life exposure to EDCs commonly found in PCPs has been linked to earlier onset of puberty. OBJECTIVE: To characterize the human and animal evidence on the association between puberty-related outcomes and exposure to PCPs and their chemical constituents and, if there is sufficient evidence, identify groups of chemicals and outcomes to support a systematic review for a class-based hazard or risk assessment. METHODS: We followed the OHAT systematic review framework to characterize the human and animal evidence on the association between puberty-related health outcomes and exposure to PCPs and their chemical constituents. RESULTS: Ninety-eight human and 299 animal studies that evaluated a total of 96 different chemicals were identified and mapped by key concepts including chemical class, data stream, and puberty-related health outcome. Among these studies, phthalates and phenols were the most well-studied chemical classes. Most of the phthalate and phenol studies examined secondary sex characteristics and changes in estradiol and testosterone levels. Studies evaluating PCP use and other chemical classes (e.g., parabens) had less data. CONCLUSIONS: This systematic evidence map identified and mapped the published research evaluating the association between exposure to PCPs and their chemical constituents and puberty-related health outcomes. The resulting interactive visualization allows researchers to make evidence-based decisions on the available research by enabling them to search, sort, and filter the literature base of puberty-related studies by key concepts. This map can be used by researchers and regulators to prioritize and target future research and funding to reduce uncertainties and address data gaps. It also provides information to inform a class-based hazard or risk assessment on the association between phthalate and phenol exposures and puberty-related health outcomes.
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Disruptores Endocrinos , Ácidos Ftálicos , Animales , Humanos , Exposición a Riesgos Ambientales , Fenol , Fenoles/toxicidad , Maduración SexualRESUMEN
BACKGROUND: Gestational phthalate and phenol exposure disrupts adipogenesis, contributing to obesity in mice. Whether gestational phthalate or phenol exposure is associated with infant body composition has not been investigated in humans. OBJECTIVE: We examined associations between biomarkers of phthalate and phenol exposure in midpregnancy and infant size and body composition at birth and at 5 months of age. METHODS: Analyses were conducted among 438 infants from the Healthy Start prospective pregnancy cohort. Sixteen phthalate and phenol biomarkers were quantified in spot urine samples collected at 24-28 wk of gestation. Infant outcomes measured at birth and at 5 months of age included size [weight (in grams)] and body composition [fat and lean masses (in grams); percentage fat mass]. Single- (linear) and multipollutant (quantile g-computation) models were used to estimate associations of phthalate and phenol biomarkers with infant outcomes at birth and at 5 months of age. Models were adjusted for sociodemographics, sample collection timing, and lifestyle factors and used to examine for effect modification by infant sex. RESULTS: In single-pollutant models, mono-benzyl phthalate and di-n-butyl phthalate were inversely associated with percentage fat mass [ß: -0.49 (95% CI: -0.91, -0.08) and -0.51 (95% CI: -1.02, 0.01), respectively] in male but not female infants at birth. Similar, but less precise, associations were observed at 5 months of age. In multipollutant models, a 1-quartile increase in the phthalate and phenol biomarker mixture was inversely associated with percentage fat mass at birth [-1.06 (95% CI: -2.21, 0.1)] and at 5 months of age [-2.14 (95% CI: -3.88, -0.39)] among males, but associations were null among females [0.48 (95% CI: -0.78, 1.75) and -0.64 (95% CI: -2.68, 1.41), respectively]. Similar associations were observed with infant weight. CONCLUSION: In this U.S.-based prospective cohort, gestational phthalate and phenol biomarkers were inversely associated with infant weight and fat mass, particularly in males. https://doi.org/10.1289/EHP12500.
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Fenol , Fenoles , Femenino , Embarazo , Humanos , Lactante , Masculino , Animales , Ratones , Estudios Prospectivos , Biomarcadores , Composición CorporalRESUMEN
This evaluation assessed the effectiveness of graphic-based (i.e., pictorial) report-back materials in communicating the presence of toxic metals in private well water and soil samples. It also explored associations between recommendations in the report-back materials and appropriate actions to protect health taken by a subset of participants in an environmental monitoring pilot study. Overall, 39 residents of Stokes County, North Carolina, participated in the Well Empowered pilot study, which included water and soil testing and analysis. All participants received materials explaining the extent to which toxic metals were present in their well water and soil. A subset of participants (n = 14) responded to a follow-up evaluation, which showed that many found at least one component of their test results "very easy to understand." The existence of a federal standard for comparison appeared to influence participant recall of results, which was more accurate for contaminants with a federal maximum contaminant level. Our evaluation results suggest that a simple pictorial format, in combination with more detailed supporting text, can be useful in highlighting results that require action.
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BACKGROUND: Pregnant persons are exposed ubiquitously to phthalates and increasingly to chemicals introduced to replace phthalates. In early pregnancy, exposure to these chemicals may disrupt fetal formation and development, manifesting adverse fetal growth. Previous studies examining the consequences of early pregnancy exposure relied on single spot urine measures and did not investigate replacement chemicals. OBJECTIVE: Characterize associations between urinary phthalate and replacement biomarkers in early pregnancy and fetal growth outcomes. METHODS: Analyses were conducted among 254 pregnancies in the Human Placenta and Phthalates Study, a prospective cohort with recruitment 2017-2020. Exposures were geometric mean concentrations of phthalate and replacement biomarkers quantified in two spot urine samples collected around 12- and 14-weeks of gestation. Outcomes were fetal ultrasound biometry (head and abdominal circumferences, femur length, estimated fetal weight) collected in each trimester and converted to z-scores. Adjusted linear mixed effects (single-pollutant) and quantile g-computation (mixture) models with participant-specific random effects estimated the difference, on average, in longitudinal fetal growth for a one-interquartile range (IQR) increase in individual (single-pollutant) or all (mixture) early pregnancy phthalate and replacement biomarkers. RESULTS: Mono carboxyisononyl phthalate and the sums of metabolites of di-n-butyl, di-iso-butyl, and di-2-ethylhexyl phthalate were inversely associated with fetal head and abdominal circumference z-scores. A one-IQR increase in the phthalate and replacement biomarker mixture was inversely associated with fetal head circumference (ß: -0.36 [95% confidence interval: -0.56, -0.15]) and abdominal circumference (-0.31 [-0.49, -0.12]) z-scores. This association was mainly driven by phthalate biomarkers. CONCLUSIONS: Urine concentrations of phthalate biomarkers, but not replacement biomarkers, in early pregnancy were associated with reductions in fetal growth. Though the clinical implications of these differences are unclear, reduced fetal growth contributes to excess morbidity and mortality across the lifecourse. Given widespread global exposure to phthalates, findings suggest a substantial population health burden resulting from early pregnancy phthalate exposure.
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Contaminantes Ambientales , Ácidos Ftálicos , Embarazo , Femenino , Humanos , Estudios Prospectivos , Ácidos Ftálicos/toxicidad , Ácidos Ftálicos/metabolismo , Desarrollo Fetal , Placenta/metabolismo , Contaminantes Ambientales/toxicidad , Biomarcadores , Exposición a Riesgos AmbientalesRESUMEN
Excessive gestational weight gain contributes to adverse maternal and neonatal outcomes. Environmental exposures such as phthalates may lead to metabolic dysregulation, and studies suggest possible associations between maternal phthalate exposure and altered gestational weight gain. We assessed the association between nine maternal phthalate metabolites and measures of total gestational weight gain (pre-pregnancy to median 35.1 weeks of gestation) in a case-control study nested within LIFECODES (N = 379), a prospective birth cohort from Boston, Massachusetts (2006-2008). Our primary outcome was total gestational weight gain z score, a measure independent of gestational age that can provide a less biased estimate of this association. Our secondary outcomes were total gestational weight gain, rate of gestational weight gain, and adequacy ratio. The results were stratified by pre-pregnancy body mass index category. We found that concentrations of mono-(3-carboxypropyl) phthalate (MCPP) and mono-n-butyl phthalate (MBP) were positively associated with total gestational weight gain z scores among participants with obesity: adjusted mean difference (95% Confidence Interval [CI]) = 0.242 (0.030 - 0.455) and 0.105 (-0.002 - 0.212) corresponding to an excess weight gain of 1.81 kg and 0.77 kg at 35 weeks of gestation per interquartile range-increase in MCPP and MBP, respectively. Also, among participants with obesity, MBP demonstrated a potential non-linear relationship with gestational weight gain in cubic spline models. These findings suggest that phthalates may be related to higher gestational weight gain, specifically, among individuals with pre-pregnancy obesity. Future research should investigate whether pregnant people with obesity represent a subpopulation with sensitivity to phthalate exposures.
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Contaminantes Ambientales , Ganancia de Peso Gestacional , Ácidos Ftálicos , Embarazo , Recién Nacido , Femenino , Humanos , Exposición Materna/efectos adversos , Estudios Prospectivos , Cohorte de Nacimiento , Estudios de Casos y Controles , Ácidos Ftálicos/efectos adversos , Aumento de Peso , Obesidad/epidemiología , Peso al NacerRESUMEN
BACKGROUND: Babies born large-for-gestational age have an increased risk of adverse health outcomes, including birth injuries, childhood obesity, and cardiometabolic disorders. However, little work has been done to characterize patterns of fetal growth among large-for-gestational age births, which may further elucidate high- and low-risk subgroups. OBJECTIVE: This study aimed to identify subgroups of large-for-gestational age births based on trajectories of fetal growth derived from prenatal ultrasound measurements and explore differences in sociodemographic, pregnancy, and birth outcome characteristics across subgroups. STUDY DESIGN: This study identified and described trajectories of fetal growth among large-for-gestational age births (n=235) in the LIFECODES Fetal Growth Study. Ultrasound measurements of fetal growth in middle to late pregnancy were abstracted from health records. Group-based multi-trajectory modeling was applied to measurements of head circumference, abdominal circumference, and femur length z-scores to identify multivariate trajectories of fetal growth. Moreover, sociodemographic variables, pregnancy characteristics, and birth outcomes based on trajectory membership were summarized. RESULTS: This study identified 4 multivariate trajectories of fetal growth among large-for-gestational age births: catch-up growth (n=28), proportional abdominal circumference-to-femur length growth (n=67), disproportional abdominal circumference-to-femur length growth (n=96), and consistently large (n=44). Fetuses in the "catch-up growth" group exhibited small relative sizes in midpregnancy (ie, below average head circumference, abdominal circumference, and femur length z-scores) and large relative sizes in late pregnancy. Growth among these births was driven by increases in relative abdominal circumference and head circumference sizes. Participants who delivered births assigned to this group were less likely to have normal glucose control (40% vs 65%-75%) and more likely to have pregestational diabetes mellitus (36% vs 10%-17%) than other large-for-gestational age subgroups. In addition, the babies in this trajectory group were more likely to have macrosomia (86% vs 67%-73%) and to be admitted to the neonatal intensive care unit (32% vs 14%-21%) than other large-for-gestational age subgroups. In contrast, babies in the "consistently large" group had the largest relative size for all growth parameters throughout gestation and experienced a lower risk of adverse birth outcomes than other large-for-gestational age subgroups. CONCLUSION: This study characterized several trajectories of fetal growth among large-for-gestational age births, which were related to different pregnancy characteristics and the distribution of adverse birth outcomes. Although the number of individuals within some trajectories was small, a subgroup that exhibited a catch-up growth phenotype during gestation was identified, which may be uniquely associated with exposure to pregestational diabetes mellitus and a higher risk of admission to the neonatal intensive care unit. These results have highlighted that the risk of adverse outcomes may not be evenly distributed across all large-for-gestational age births.
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Obesidad Infantil , Complicaciones del Embarazo , Niño , Humanos , Femenino , Embarazo , Edad Gestacional , Peso al Nacer , Ultrasonografía Prenatal/métodos , Desarrollo Fetal , Macrosomía Fetal/epidemiologíaRESUMEN
BACKGROUND: Reductions in fetal growth are associated with adverse outcomes at birth and later in life. However, identifying fetuses with pathologically small growth remains challenging. Definitions of small-for-gestational age are often used as a proxy to identify those experiencing pathologic growth (ie, fetal growth restriction). However, this approach is subject to limitation as most newborns labeled small-for-gestational age are constitutionally, not pathologically, small. Incorporating repeated ultrasound measures to examine fetal growth trajectories may help distinguish pathologic deviations in growth from normal variability, beyond a simple definition of small-for-gestational age. OBJECTIVE: This study aimed to characterize phenotypes of growth using ultrasound trajectories of fetal growth among small-for-gestational-age births. STUDY DESIGN: This study identified and described trajectories of fetal growth among small-for-gestational-age births (<10th percentile weight for gestational age; n=245) in the LIFECODES Fetal Growth Study using univariate and multivariate trajectory modeling approaches. Available ultrasound measures of fetal growth (estimated fetal weight, head circumference, abdominal circumference, and femur length) from health records were abstracted. First, univariate group-based trajectory modeling was used to define trajectories of estimated fetal weight z scores during gestation. Second, group-based multi-trajectory modeling was used to identify trajectories based on concurrent measures of head circumference, abdominal circumference, and femur length z scores. Last, how these trajectories were related to patient demographics, pregnancy characteristics, and birth outcomes compared with those observed among appropriate-for-gestational-age controls was described. RESULTS: Of note, 3 univariate trajectories of estimated fetal weight and 4 multivariate trajectories of fetal growth among small-for-gestational-age births were identified. In our univariate approach, infants with the smallest estimated fetal weight trajectory throughout pregnancy had poorer outcomes, including the highest risk of neonatal intensive care unit admission. The remaining univariate trajectory groups did not have an elevated risk of adverse birth outcomes relative to appropriate-for-gestational-age controls. In our multivariate approach, 2 groups at increased or moderately increased risk of neonatal intensive care unit admission were identified, including infants that remained extremely small for all parameters throughout pregnancy and those who had disproportionately smaller femur length and abdominal circumference compared with head circumference. The remaining multivariate trajectory groups did not have an elevated risk of adverse birth outcome relative to appropriate-for-gestational-age controls. CONCLUSION: Latent class group-based trajectory modeling applied to ultrasound measures of fetal growth may help distinguish pathologic vs constitutional growth profiles among newborns born small-for-gestational age. Although trajectories cannot be fully characterized until delivery, limiting the direct clinical application of these methods, they may still contribute to the development of approaches for separating growth restriction from constitutional smallness.
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Retardo del Crecimiento Fetal , Enfermedades del Recién Nacido , Embarazo , Humanos , Femenino , Recién Nacido , Retardo del Crecimiento Fetal/diagnóstico por imagen , Peso Fetal , Desarrollo Fetal , Recién Nacido Pequeño para la Edad Gestacional , Edad Gestacional , Ultrasonografía Prenatal , Peso al NacerRESUMEN
BACKGROUND: Prenatal phthalate exposure has been associated with lower birth weight but also higher weight in childhood. Few studies have examined weight or adiposity from birth to childhood and thus cannot assess growth trajectories associated with exposure. OBJECTIVE: We assessed associations between maternal phthalate exposures in pregnancy and child weight and adiposity measured prenatally through childhood (3-6 years of age). METHODS: Within The Infant Development and the Environment Study (TIDES), a prospective pregnancy cohort, we analyzed a panel of phthalate metabolites in urine collected at two visits from early and late gestation (N=780). We estimated average phthalate metabolite associations with child weight z-scores from â¼20wk gestation (estimated by ultrasound), birth, and 1, 3, 4, and 6 years of age using linear mixed-effects (LME) models. We also modeled associations with adiposity z-scores from birth (weight for length) and 1, 3, 4, and 6 years of age [body mass index (BMI)] using LME models. RESULTS: For weight, we observed inverse associations between several phthalate metabolites and birth weight z-scores, but no associations were observed with postnatal weight z-scores in LME models. Regarding adiposity, we observed inverse associations between phthalate metabolites and weight-for-length z-scores at birth, but positive associations were observed with BMI z-scores at 3-4 years of age in LME models. For example, mono-ethyl phthalate was associated with a 0.17-unit decrease in birth weight-for-length z-score [95% confidence interval (CI): -0.29, -0.05] and a 0.18-unit increase in 4-years-of-age BMI z-score (95% CI: 0.04, 0.32). DISCUSSION: We observed associations between prenatal exposure to phthalates and lower weight at birth but not at childhood follow-up visits. However, for adiposity, we observed an interesting pattern of association with low adiposity at delivery as well as high adiposity at 3-4 years of age. Although it is not clear from our results whether these associations occur within the same children, such a pattern of adiposity in early life has been linked to cardiometabolic disease in adulthood and deserves special attention as an outcome in the study of prenatal exposures in the developmental origins of health and disease. https://doi.org/10.1289/EHP10077.
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Contaminantes Ambientales , Ácidos Ftálicos , Efectos Tardíos de la Exposición Prenatal , Adiposidad , Adulto , Peso al Nacer , Niño , Exposición a Riesgos Ambientales , Contaminantes Ambientales/metabolismo , Contaminantes Ambientales/toxicidad , Femenino , Humanos , Lactante , Recién Nacido , Obesidad , Ácidos Ftálicos/orina , Embarazo , Efectos Tardíos de la Exposición Prenatal/epidemiología , Estudios ProspectivosRESUMEN
BACKGROUND: Prenatal phthalate exposure has been linked to reductions in fetal growth in animal and laboratory studies, but epidemiologic evidence is equivocal. OBJECTIVE: Examine the association between prenatal phthalate metabolite mixtures and fetal growth and evaluate whether that association is modified by fetal sex or omega-3 intake during pregnancy. METHODS: Analyses included 604 singleton pregnancies from TIDES, a prospective pregnancy cohort with spot urine samples and questionnaires collected in each trimester. Pregnancy-averaged phthalate exposure estimates were calculated as the geometric means of specific-gravity corrected phthalate metabolites. Fetal growth outcomes included birthweight and length, and ultrasound-derived size and velocity of estimated fetal weight, femur length, abdominal and head circumferences in the second and third trimesters. We used a novel application of quantile g-computation to estimate the joint association between pregnancy-averaged phthalate exposure and fetal growth, and to examine effect modification of that association by infant sex or omega-3 intake during pregnancy. RESULTS: There were few statistically significant differences in birth size and fetal growth by exposure. A one-quartile increase in the phthalate mixture was modestly associated with reduced birthweight(ß [95% confidence interval)]: -54.6 [-128.9, 19.7] grams; p = 0.15) and length (-0.2 [-0.6, 0.2] centimeters; p = 0.40). A one-quartile increase in the phthalate mixture was associated with reduced birth length in males (-0.5 [-1.0, 0.0] centimeters) but not for females (0.1 [-0.2, 0.3] centimeters); interaction p = 0.05. The phthalate metabolite mixture was inversely associated with ultrasound-derived fetal growth among those with adequate omega-3 intake. For example, a one-quartile increase in the phthalate mixture was associated with reduced abdominal circumference in the third trimesters in those with adequate omega-3 intake (-3.3 [-6.8, 0.1] millimeters) but not those with inadequate omega-3 intake (1.8 [-0.8, 4.5] millimeters); interaction p = 0.01. CONCLUSION: Prenatal phthalate exposure was not significantly associated with fetal growth outcomes, with some exceptions for certain subgroups.
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Exposición Materna , Ácidos Ftálicos , Peso al Nacer , Desarrollo Infantil , Femenino , Desarrollo Fetal , Humanos , Masculino , Exposición Materna/efectos adversos , Ácidos Ftálicos/toxicidad , Ácidos Ftálicos/orina , Embarazo , Estudios ProspectivosRESUMEN
Per- and polyfluoroalkyl substances (PFAS) accumulation and elimination in both wildlife and humans is largely attributed to PFAS interactions with proteins, including but not limited to organic anion transporters (OATs), fatty acid binding proteins (FABPs), and serum proteins such as albumin. In wildlife, changes in the biotic and abiotic environment (e.g. salinity, temperature, reproductive stage, and health status) often lead to dynamic and responsive physiological changes that alter the prevalence and location of many proteins, including PFAS-related proteins. Therefore, we hypothesize that if key PFAS-related proteins are impacted as a result of environmentally induced as well as biologically programmed physiological changes (e.g. reproduction), then PFAS that associate with those proteins will also be impacted. Changes in tissue distribution across tissues of PFAS due to these dynamics may have implications for wildlife studies where these chemicals are measured in biological matrices (e.g., serum, feathers, eggs). For example, failure to account for factors contributing to PFAS variability in a tissue may result in exposure misclassification as measured concentrations may not reflect average exposure levels. The goal of this review is to share general information with the PFAS research community on what biotic and abiotic changes might be important to consider when designing and interpreting a biomonitoring or an ecotoxicity based wildlife study. This review will also draw on parallels from the epidemiological discipline to improve study design in wildlife research. Overall, understanding these connections between biotic and abiotic environments, dynamic protein levels, PFAS levels measured in wildlife, and epidemiology serves to strengthen study design and study interpretation and thus strengthen conclusions derived from wildlife studies for years to come.
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Ácidos Alcanesulfónicos , Fluorocarburos , Ácidos Alcanesulfónicos/toxicidad , Animales , Animales Salvajes , Monitoreo Biológico , Fluorocarburos/análisis , Fluorocarburos/toxicidad , Humanos , ReproducciónRESUMEN
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.
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Fluorocarburos , Preeclampsia , Biomarcadores , Estudios de Casos y Controles , Femenino , Humanos , Factor de Crecimiento Placentario , Preeclampsia/epidemiología , Embarazo , Receptor 1 de Factores de Crecimiento Endotelial VascularRESUMEN
BACKGROUND: Exposure to consumer product chemicals during pregnancy may increase susceptibility to pregnancy disorders by influencing maternal inflammation. However, effects on specific inflammatory pathways have not been well characterized. Oxylipins are a diverse class of lipids that act as important mediators and biomarkers of several biological pathways that regulate inflammation. Adverse pregnancy outcomes have been associated with circulating oxylipin levels in pregnancy. In this study, we aimed to determine the longitudinal associations between plasma oxylipins and urinary biomarkers of three classes of consumer product chemicals among pregnant women. METHODS: Data come from a study of 90 pregnant women nested within the LIFECODES cohort. Maternal plasma and urine were collected at three prenatal visits. Plasma was analyzed for 61 oxylipins, which were grouped according to biosynthetic pathways that we defined by upstream: 1) fatty acid precursor, including linoleic, arachidonic, docosahexaenoic, or eicosapentaenoic acid; and 2) enzyme pathway, including cyclooxygenase (COX), lipoxygenase (LOX), or cytochrome P450 (CYP). Urine was analyzed for 12 phenol, 12 phthalate, and 9 organophosphate ester (OPE) biomarkers. Linear mixed effect models were used for single-pollutant analyses. We implemented a novel extension of quantile g-computation for longitudinal data to examine the joint effect of class-specific chemical mixtures on individual plasma oxylipin concentrations. RESULTS: We found that urinary biomarkers of consumer product chemicals were positively associated with pro-inflammatory oxylipins from several biosynthetic pathways. Importantly, these associations depended upon the chemical class of exposure biomarker. We estimated positive associations between urinary phenol biomarkers and oxylipins produced from arachidonic acid by LOX enzymes, including several important pro-inflammatory hydroxyeicosatetraenoic acids (HETEs). On average, mean concentrations of oxylipin produced from the arachidonic acid/LOX pathway were 48%-71% higher per quartile increase in the phenol biomarker mixture. For example, a simultaneous quartile increase in all urinary phenols was associated with 53% higher (95% confidence interval [CI]: 11%, 111%) concentrations of 12-HETE. The positive associations among phenols were primarily driven by methyl paraben, 2,5-dichlorophenol, and triclosan. Additionally, we observed that phthalate and OPE metabolites were associated with higher concentrations of oxylipins produced from linoleic acid by CYP enzymes, including the pro-inflammatory dihydroxy-octadecenoic acids (DiHOMEs). Associations among DiHOME oxylipins were driven by metabolites of benzylbutyl and di-isodecyl phthalate, and by the metabolite of tris(1,3-dichloro-2-propyl) phosphate among OPEs. We also observed inverse associations between phthalate and OPE metabolites and oxylipins produced from other pathways; however, adjusting for a plasma indicator of dietary fatty acid intake attenuated those results. CONCLUSIONS: Our findings support the hypothesis that consumer product chemicals may have diverse impacts on inflammation processes in pregnancy. Certain pro-inflammatory oxylipins were generally higher among participants with higher urinary chemical biomarker concentrations. Associations varied by class of chemical and by the biosynthetic pathway of oxylipin production, indicating potential specificity in the inflammatory effects of these environmental chemicals during pregnancy that warrant investigation in larger studies.
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Oxilipinas , Mujeres Embarazadas , Estudios de Cohortes , Femenino , Humanos , Fenoles , Embarazo , Resultado del EmbarazoRESUMEN
BACKGROUND: The ubiquitous metals cadmium and lead are immunotoxic, but little is known about their relations to cytomegalovirus (CMV), a widespread herpesvirus. Although CMV infections are mostly asymptomatic, congenital infections are a leading cause of birth defects. In otherwise healthy individuals, there is also some evidence linking subclinical reactivations to accelerated age-related declines in immune function and chronic disease. METHODS: Our objective was to evaluate associations of blood cadmium and lead biomarkers with CMV infection in a representative sample of the United States population. In seropositive individuals, we also examined associations with CMV-specific immunoglobulin G (IgG) antibody levels and suspected CMV recurrences. Using cross-sectional data from the 1999-2004 National Health and Nutrition Examination Surveys, we fit multivariable survey-weighted regression models accounting for potential confounding by sociodemographic and lifestyle factors and stratifying by age group to allow for heterogeneity. CMV recurrences were defined according to (1) the presence of either CMV-specific immunoglobulin M in sera or CMV viral DNA in urine, and (2) high CMV-specific IgG avidity. RESULTS: We observed null associations for blood cadmium. Increasing blood lead quartiles were related to CMV seropositivity and higher CMV IgG levels (both P trend < 0.01), but not CMV recurrence, only among individuals who were 20-29 years of age. CONCLUSION: Blood cadmium levels do not appear to be related to immunological markers of CMV infections. The possibility that lead exposures increase the risk of CMV infection and impair immune control of the virus in young adults was suggested. Prospective studies are needed to confirm.
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BACKGROUND: Exposure to some toxic metals, such as lead and cadmium, has been associated with increased oxidative stress. However less is known about other metals and metal mixtures, especially in pregnant women who are a vulnerable population. METHODS: To study the relationship between exposure to trace metals and oxidative stress, we analyzed a panel of 17 metals and two oxidative stress biomarkers (8-isoprostane and 8-hydroxydeoxyguanosine [8-OHdG]) in urine samples collected at ~26 weeks gestation from pregnant women in Boston (nâ¯=â¯380). We used linear regression models to calculate percent differences and 95% confidence intervals (CI) in oxidative stress markers for an interquartile range (IQR) increase in each urinary metal with adjustment for other metals. In addition, we applied principal components analysis (PCA) and Bayesian kernel machine regression (BKMR), to examine cumulative effects (within correlated groups of exposures as well as overall) and interactions. RESULTS: We estimated 109% (95% CI: 47, 198) higher 8-isoprostane and 71% (95% CI: 45, 102) higher 8-OHdG with an IQR increase in urinary selenium (Se). We also estimated higher 8-isoprostane (47%, 95% CI: 20.5, 79.4) and 8-OHdG (15.3%, 95% CI: 5.09, 26.5) in association with urinary copper (Cu). In our PCA, we observed higher 8-isoprostane levels in association with the "essential" PC (highly loaded by Cu, Se, and Zinc). In BKMR analyses, we also estimated higher levels of both oxidative stress biomarkers with increasing Se and Cu as well as increasing levels of both oxidative stress biomarkers in association with cumulative concentrations of urinary trace metals. CONCLUSION: We observed higher 8-isoprostane and 8-OHdG levels in association with urinary trace metals and elements, particularly Se and Cu, in linear models and using mixtures approaches. Additionally, increasing cumulative exposure to urinary trace metals was associated with higher levels of both oxidative stress biomarkers. The beneficial effects of these compounds should be carefully questioned.
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Contaminantes Ambientales/metabolismo , Exposición Materna/estadística & datos numéricos , Metales/metabolismo , Estrés Oxidativo/fisiología , Teorema de Bayes , Biomarcadores/orina , Boston , Femenino , Humanos , Recién Nacido , EmbarazoRESUMEN
BACKGROUND: Exposures to toxic metals and deficiencies in essential metals disrupt placentation and may contribute to preeclampsia. However, effects of exposure to combinations of metals remain unknown. OBJECTIVE: We investigated the relationship between urinary trace metals, circulating angiogenic biomarkers, and preeclampsia using the LIFECODES birth cohort. METHODS: Urine samples collected during pregnancy were analyzed for 17 trace metals and plasma samples were analyzed for soluble fms-like tyrosine-1 (sFlt-1) and placental growth factor (PlGF). Cox proportional hazard models were used to estimate the hazard ratios (HR) of preeclampsia associated with urinary trace metals. Linear regression models were used to estimate the relationship between urinary trace metals and angiogenic biomarkers. Principal components analysis (PCA) was used to identify groups of metals and interactions between principal components (PCs) loaded by toxic and essential metals were examined. RESULTS: In single-contaminant models, several toxic and essential metals were associated with lower PlGF and higher sFlt-1/PlGF ratio. Detection of urinary chromium was associated with preeclampsia: HR (95% Confidence Interval [CI]) = 3.48 (1.02, 11.8) and an IQR-increase in urinary selenium was associated with reduced risk of preeclampsia (HR: 0.28, 95% CI: 0.08, 0.94). Using PCA, 3 PCs were identified, characterized by essential metals (PC1), toxic metals (PC2), and seafood-associated metals (PC3). PC1 and PC2 were associated with lower PlGF levels, but not preeclampsia risk in the overall cohort. CONCLUSIONS: Trace urinary metals may be associated with adverse profiles of angiogenic biomarkers and preeclampsia.