Prenatal Exposure to Chemical Mixtures and Inhibition among Adolescents.
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ABSTRACT:
SUBMITTER: Oppenheimer AV
PROVIDER: S-EPMC8619850 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Working memory is the ability to keep information in one's mind and mentally manipulate it. Decrements in working memory play a key role in many behavioral and psychiatric disorders, therefore identifying modifiable environmental risk factors for such decrements is important for mitigating these disorders. There is some evidence that prenatal exposure to individual chemicals may adversely impact working memory among children, but few studies have explored the association of co-exposure to multiple chemicals with this outcome in adolescence, a time when working memory skills undergo substantial development. We investigated the association of organochlorines (DDE, HCB, PCBs) and metals (lead, manganese) measured in cord serum and cord blood, respectively, with working memory measured with the Wide Range Assessment of Memory and Learning, 2nd Edition among 373 adolescents living near a Superfund site in New Bedford, Massachusetts. We used Bayesian Kernel Machine Regression (BKMR) and linear regression analyses and assessed effect modification by sex and prenatal social disadvantage. In BKMR models, we observed an adverse joint association of the chemical mixture with Verbal, but not Symbolic, Working Memory. In co-exposure and covariate-adjusted linear regression models, a twofold increase in cord blood manganese was associated with lower working memory scaled scores, with a stronger association with Verbal Working Memory (difference = -0.75; 95% CI: -1.29, -0.20 points) compared to Symbolic Working Memory (difference = -0.44; 95% CI: -1.00, 0.12 points). There was little evidence of effect modification by sex and some evidence associating organochlorine pesticides with poorer working memory scores among those with greater prenatal social disadvantage. This study provided evidence of an adverse joint association of a chemical mixture with a verbal working memory task among adolescents, as well as an adverse association of prenatal manganese exposure with working memory.
| S-EPMC8760169 | biostudies-literature
Project description:Cognitive flexibility, the ability to smoothly adapt to changing circumstances, is a skill that is vital to higher-level executive functions such as problem-solving, planning, and reasoning. As it undergoes substantial development during adolescence, decrements in cognitive flexibility may not become apparent until this time. There is evidence that prenatal exposure to individual chemicals may adversely impact executive functions in children, but few studies have explored the association of co-exposure to multiple chemicals with cognitive flexibility specifically among adolescents. We investigated this association among a diverse group of adolescents living near a Superfund site in New Bedford, Massachusetts. Specifically, using Bayesian kernel machine regression (BKMR) and multivariable regression analyses, we investigated the association of biomarkers of prenatal exposure to organochlorines (DDE, HCB, PCBs) and metals (lead, manganese) with cognitive flexibility, measured with four subtests of the Delis-Kaplan Executive Function System. In BKMR models, we observed adverse joint associations of the chemical mixture with two of the four cognitive flexibility subtests. In covariate-adjusted linear regression models, a two-fold increase in cord blood Mn was associated with poorer performance on two of the subtests: Trail-Making (scaled score difference = -0.60; 95% CI: -1.16, -0.05 points) and Color-Word Interference (scaled score difference = -0.53; 95% CI: -1.08, 0.01 points). These adverse Mn-cognitive flexibility associations were supported by the results of the BKMR. There was little evidence of effect modification by sex and some evidence of effect modification by a measure of social disadvantage, particularly for the associations between HCB and cognitive flexibility. This study is among the first to provide evidence of an adverse association of prenatal exposure to a chemical mixture with cognitive flexibility in adolescence.
| S-EPMC8708222 | biostudies-literature
Project description:BackgroundPrenatal exposure to mixtures of nonpersistent chemicals is universal. Most studies examining these chemicals in association with fetal growth have been restricted to single exposure models, ignoring their potentially cumulative impact.ObjectiveWe aimed to assess the association between prenatal exposure to a mixture of phthalates, bisphenols, and organophosphate (OP) pesticides and fetal measures of head circumference, femur length, and weight.MethodsWithin the Generation R Study, a population-based cohort in Netherlands (n=776), urinary concentrations of 11 phthalate metabolites, 3 bisphenols, and 5 dialkylphosphate (DAP) metabolites were measured at <18, 18-25, and >25 weeks of gestation and averaged. Ultrasound measures of head circumference, femur length, and estimated fetal weight (EFW) were taken at 18-25 and >25 weeks of gestation, and measurements of head circumference, length, and weight were performed at delivery. We estimated the difference in each fetal measurement per quartile increase in all exposures within the mixture with quantile g-computation.ResultsThe average EFW at 18-25 wk and >25wk was 369 and 1,626g, respectively, and the average birth weight was 3,451g. Higher exposure was associated with smaller fetal and newborn growth parameters in a nonlinear fashion. At 18-25 wk, fetuses in the second, third, and fourth quartiles of exposure (Q2-Q4) had 26g [95% confidence intervals (CI):-38, -13], 35g (95% CI: -55, -15), and 27g (95% CI: -54, 1) lower EFW compared with those in the first quartile (Q1). A similar dose-response pattern was observed at >25wk, but all effect sizes were smaller, and no association was observed comparing Q4 to Q1. At birth, we observed no differences in weight between Q1-Q2 or Q1-Q3. However, fetuses in Q4 had 91g (95% CI: -258, 76) lower birth weight in comparison with those in Q1. Results observed at 18-25 and >25wk were similar for femur length; however, no differences were observed at birth. No associations were observed for head circumference.DiscussionHigher exposure to a mixture of phthalates, bisphenols, and OP pesticides was associated with lower EFW in the midpregnancy period. In late pregnancy, these differences were similar but less pronounced. At birth, the only associations observed appeared when comparing individuals from Q1 and Q4. This finding suggests that even low levels of exposure may be sufficient to influence growth in early pregnancy, whereas higher levels may be necessary to affect birth weight. Joint exposure to nonpersistent chemicals may adversely impact fetal growth, and because these exposures are widespread, this impact could be substantial. https://doi.org/10.1289/EHP9178.
| S-EPMC8612241 | biostudies-literature
Project description:BackgroundWhile fetal growth is a tightly regulated process, it is sensitive to environmental exposures that occur during pregnancy. Many commonly used consumer products contain chemicals that can disturb processes underlying fetal growth. However, mixtures of these chemicals have been minimally examined. We investigated associations between prenatal exposure to 33 consumer product chemicals (nine organophosphate ester flame retardant [OPE] metabolites, 12 phthalate metabolites, and 12 phenols) and the odds of small- or large-for-gestational age (SGA and LGA) births.MethodsThis case-control study was comprised of SGA (N = 31), LGA (N = 28), and appropriate for gestational age control (N = 31) births selected from the larger LIFECODES cohort. Biomarkers of exposure to consumer product chemicals were quantified in maternal urine collected from up to three study visits during pregnancy. In a single-pollutant approach, odds ratios (OR) and 95% confidence intervals (CI) of SGA and LGA associated with an interquartile range (IQR)-increase in exposure biomarkers were estimated using multinomial logistic regression. In a multi-pollutant approach, quantile g-computation was used to jointly estimate the OR (95% CI) of SGA and LGA per simultaneous one quartile-change in all biomarkers belonging to each chemical class.ResultsAmong the 33 biomarkers analyzed, 20 were detected in at least 50% of the participants. After adjusting for potential confounders, we observed reduced odds of LGA in association with higher urinary concentrations of several exposure biomarkers. For example, an IQR-increase in the OPE metabolite, diphenyl phosphate, was associated with lower odds of LGA (OR: 0.40 [95% CI: 0.18, 0.87]). Using quantile g-computation, we estimated lower odds of an LGA birth for higher OPE metabolite concentrations (OR: 0.49 [95% CI: 0.27, 0.89]) and phthalate metabolite concentrations (OR: 0.23 [95% CI: 0.07, 0.73]). Associations between consumer product chemicals and SGA were largely null.ConclusionsJoint exposure to OPEs and phthalates was associated with lower odds of delivering LGA. Associations with LGA could indicate a specific impact of these exposures on the high end of the birth weight spectrum. Future work to understand this nuance in the associations between consumer product chemical mixtures and fetal growth is warranted.
| S-EPMC8194159 | biostudies-literature
Project description:BackgroundChemicals found in personal care products and plastics have been associated with asthma, allergies, and lung function, but methods to address real life exposure to mixtures of these chemicals have not been applied to these associations.MethodsWe quantified urinary concentrations of eleven phthalate metabolites, four parabens, and five other phenols in mothers twice during pregnancy and assessed probable asthma, aeroallergies, and lung function in their age seven children. We implemented Bayesian Profile Regression (BPR) to cluster women by their exposures to these chemicals and tested the clusters for differences in outcome measurements. We used Bayesian Kernel Machine Regression (BKMR) to fit biomarkers into one model as joint independent variables.ResultsBPR clustered women into seven groups characterized by patterns of personal care product and plastic use, though there were no significant differences in outcomes across clusters. BKMR showed that monocarboxyisooctyl phthalate and 2,4-dichlorophenol were associated with probable asthma (predicted probability of probable asthma per IQR of biomarker z-score (standard deviation) = 0.08 (0.09) and 0.11 (0.12), respectively) and poorer lung function (predicted probability per IQR = -0.07 (0.05) and -0.07 (0.06), respectively), and that mono(3-carboxypropyl) phthalate and bisphenol A were associated with aeroallergies (predicted probability per IQR = 0.13 (0.09) and 0.11 (0.08), respectively). Several biomarkers demonstrated positive additive effects on other associations.ConclusionsBPR and BKMR are useful tools to evaluate associations of biomarker concentrations within a mixture of exposure and should supplement single-chemical regression models when data allow.
| S-EPMC7255953 | biostudies-literature
Project description:BackgroundAfrican Americans (AAs) experience higher rates of preterm birth and fetal growth restriction relative to other pregnant populations. Differential in utero exposure to environmental chemicals may partially explain these health disparities, as AAs are disproportionately exposed to environmental hazards.ObjectiveWe examined the individual and mixture effects of non-persistent chemicals and persistent organic pollutants (POPs) on gestational age at birth and birthweight for gestational age z-scores within a prospective cohort of pregnant AAs.MethodsFirst-trimester serum and urine samples obtained from participants within the Atlanta African American Maternal-Child cohort were analyzed for 43 environmental chemicals, including per-and polyfluoroalkyl substances (PFAS), polybrominated diphenyl ethers (PBDEs), organochlorine pesticides, pyrethroid insecticides, phthalates, bisphenol A, nicotine, and the primary metabolite of delta-9-tetrahydrocannabinol. Linear regression was used to estimate individual associations between chemicals and gestational age and birthweight z-scores (N ranging from 107 to 523). Mixture associations were estimated using quantile g-computation, principal component (PC) analyses, and hierarchical Bayesian kernel machine regression among complete cases (N = 86).ResultsUsing quantile g-computation, increasing all chemical exposures by one quantile was modestly associated with a reduction in gestational age (mean change per quartile increase = -0.47, 95% CI = -1.56, 0.61) and birthweight z-scores (mean change per quartile increase = -0.49, 95% CI = -1.14, 0.15). All PCs were associated with a reduction in birthweight z-scores; associations were greatest in magnitude for the two PCs reflecting exposure to combined tobacco, insecticides, PBDEs, and phthalates. In single pollutant models, we observed inconsistent and largely non-significant associations.SignifanceWe conducted multiple targeted exposure assessment methods to quantify levels of environmental chemicals and leveraged mixture methods to quantify their joint effects on gestational age and birthweight z-scores. Our findings suggest that prenatal exposure to multiple classes of persistent and non-persistent chemicals is associated with reduced gestational age and birthweight z-scores in AAs.ImpactAfrican Americans (AAs) experience higher rates of preterm birth and fetal growth restriction relative to other pregnant populations. Differential in utero exposure to environmental chemicals may partially explain these health disparities, as AAs are disproportionately exposed to environmental hazards. In the present study, we analyzed serum and urine samples for levels of 43 environmental chemicals. We used quantile g-computation, principal component analysis, and BKMR to assess associations between chemical exposure mixtures and adverse birth outcomes. Our findings suggest that prenatal exposure to multiple classes of chemicals is associated with reduced birthweight z-scores, a proxy for fetal growth, in AAs.
| S-EPMC10450095 | biostudies-literature
Project description:BackgroundPrevious studies of prenatal phthalate exposure and childhood asthma are inconsistent. These studies typically model phthalates as individual, rather than co-occurring, exposures. We investigated whether prenatal phthalates are associated with childhood wheeze and asthma using a mixtures approach.MethodsWe studied dyads from two prenatal cohorts in the ECHO-PATHWAYS consortium: CANDLE, recruited 2006-2011 and TIDES, recruited 2011-2013. Parents reported child respiratory outcomes at age 4-6 years: ever asthma, current wheeze (symptoms in past 12 months) and current asthma (two affirmative responses from ever asthma, recent asthma-specific medication use, and/or current wheeze). We quantified 11 phthalate metabolites in third trimester urine and estimated associations with child respiratory outcomes using weighted quantile sum (WQS) logistic regression, using separate models to estimate protective and adverse associations, adjusting for covariates. We examined effect modification by child sex and maternal asthma.ResultsOf 1481 women, most identified as White (46.6%) or Black (44.6%); 17% reported an asthma history. Prevalence of ever asthma, current wheeze and current asthma in children was 12.3%, 15.8% and 12.3%, respectively. Overall, there was no adverse association with respiratory outcomes. In sex-stratified analyses, boys' phthalate index was adversely associated with all outcomes (e.g., boys' ever asthma: adjusted odds ratio per one quintile increase in WQS phthalate index (AOR): 1.42; 95% confidence interval (CI): 1.08, 1.85, with mono-ethyl phthalate (MEP) weighted highest). Adverse associations were also observed in dyads without maternal asthma history, driven by MEP and mono-butyl phthalate (MBP), but not in those with maternal asthma history. We observed protective associations between the phthalate index and respiratory outcomes in analysis of all participants (e.g., ever asthma: AOR; 95% CI: 0.81; 0.68, 0.96), with di(2-ethylhexyl)phthalate (DEHP) metabolites weighted highest.ConclusionsResults suggest effect modification by child sex and maternal asthma in associations between prenatal phthalate mixtures and child asthma and wheeze.
| S-EPMC7708520 | biostudies-literature
Project description:Prenatal exposure to endocrine disrupting compounds (EDCs) has previously shown to alter epigenetic marks.In this work we explore whether prenatal exposure to mixtures of xenoestrogens has the potential to alter the placenta epigenome, by studying DNA methylation in retrotransposons as a surrogate of global DNA methylation.The biomarker total effective xenoestrogen burden (TEXB) was measured in 192 placentas from participants in the longitudinal INMA Project. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 10 different retrotransposons including 3 different long interspersed nuclear elements (LINEs), 4 short interspersed nuclear elements (SINEs) and 3 human endogenous retroviruses (HERVs). Associations were tested using linear mixed-effects regression models and sex interaction was evaluated.A significant sex interaction was observed for AluYb8 (p-value for interaction <0.001, significant at Bonferroni corrected p-value threshold of 0.0025). Boys with the highest TEXB-alpha levels of exposure (third tertile) presented on average a decrease of 0.84% in methylation compared to those in the first tertile (p-value<0.001), while no significant effects were found in girls (p-value=0.134).Our findings suggest that boys may be more susceptible to the effect of exposure to xenoestrogens during prenatal development, producing shifts in DNA methylation of certain sensitive genomic repetitive sequences in a tissue important for fetal growth and development.
| S-EPMC4122792 | biostudies-literature
Project description:Fragranced product chemical mixtures may be relevant for environmental health, but little is known about exposure. We analyzed results from an olfactory challenge with the synthetic musk fragrance 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopento-γ-2-benzopyran (HHCB), and a questionnaire about attitudes toward chemical safety and use of fragranced products, in a sample of 140 white and 17 black twin pairs attending a festival in Ohio. Data for each product were analyzed using robust ordered logistic regressions with random intercepts for "twin pair" and "sharing address with twin", and fixed effects for sex, age, education, and "ever being bothered by fragrances". Due to the small number of black participants, models were restricted to white participants except when examining racial differences. Overall patterns of association were summarized across product-types through random-effects meta-analysis. Principal components analysis was used to summarize clustering of product use. The dominant axis of variability in fragranced product use was "more vs. less", followed by a distinction between household cleaning products and personal care products. Overall, males used fragranced products less frequently than females (adjusted proportionate odds ratio 0.55, 95% confidence interval 0.33, 0.93). This disparity was driven by personal care products (0.42, 95% CI: 0.19, 0.96), rather than household cleaning products (0.79, 95% CI: 0.49, 1.25) and was particularly evident for body lotion (0.12, 95% CI: 0.05, 0.27). Overall usage differed by age (0.64, 95% CI: 0.43, 0.95) but only hand soap and shampoo products differed significantly. "Ever being bothered by fragrance" had no overall association (0.92, 95% CI: 0.65, 1.30) but was associated with laundry detergent use (0.46, 95% CI: 0.23, 0.93). Similarly, black vs. white differences on average were not significant (1.34, 95% CI: 0.55, 3.28) but there were apparent differences in use of shampoo (0.01, 95% CI: 0.00, 0.69), body lotion (4.67, 95% CI: 1.18, 18.47), and perfume (6.22, 95% CI:1.08, 35.89). There was no overall association with thinking about product risks (0.90, 95% CI: 0.79, 1.02), nor with inability to smell HHCB (0.84, 95% CI: 0.63, 1.12). Exposure to fragranced products may differ demographically. The relevance for health disparities should be studied.
| S-EPMC4344677 | biostudies-literature
Project description:OBJECTIVES:We applied three statistical approaches for evaluating associations between prenatal urinary concentrations of a mixture of phthalate metabolites and birth weight. METHODS:We included 300 women who provided 732 urine samples during pregnancy and delivered a singleton infant. We measured urinary concentrations of metabolites of di(2-ethylhexyl)-phthalate, di-isobutyl-, di-n-butyl-, butylbenzyl-, and diethyl phthalates. We applied 1) linear regressions; 2) classification methods [principal component analysis (PCA) and structural equation models (SEM)]; and 3) Bayesian kernel machine regression (BKMR), to evaluate associations between phthalate metabolite mixtures and birth weight adjusting for potential confounders. Data were presented as mean differences (95% CI) in birth weight (grams) as each phthalate increased from the 10th to the 90th percentile. RESULTS:When analyzing individual phthalate metabolites using linear regressions, each metabolite demonstrated a modest inverse association with birth weight [from -93 (-206, 21) to -49 (-164, 65)]. When simultaneously including all metabolites in a multivariable model, inflation of the estimates and standard errors were noted. PCA identified two principal components, both inversely associated with birth weight [-23 (-68, 22), -27 (-71, 17), respectively]. These inverse associations were confirmed when applying SEM. BKMR further identified that monoethyl and mono(2-ethylhexyl) phthalate and phthalate concentrations were linearly related to lower birth weight [-51(-164, 63) and -122 (-311, 67), respectively], and suggested no evidence of interaction between metabolites. CONCLUSIONS:While none of the methods produced significant results, we demonstrated the potential issues arising using linear regression models in the context of correlated exposures. Among the other selected approaches, classification techniques identified common sources of exposures with implications for interventions, while BKMR further identified specific contributions of individual metabolites.
| S-EPMC5866233 | biostudies-literature