Phthalate Metabolite Concentrations Research Articles

The associations between pre-conception urinary phthalate concentrations, the serum metabolome, and live birth among women undergoing assisted reproduction

BackgroundPhthalates are ubiquitous endocrine disruptors. Past studies have shown an association between higher preconception urinary concentrations of phthalate metabolites and lower fertility in women; however, the biological mechanisms remain unclear. Our exploratory study aimed to understand the metabolites and pathways associated with maternal preconception phthalate exposure and examine if any may underline the association between phthalate exposure and live birth using untargeted metabolomics. MethodsParticipants (n = 183) were part of the Environment and Reproductive Health (EARTH) study, a prospective cohort that followed women undergoing in vitro fertilization (IVF) at the Massachusetts General Hospital Fertility Center (2005–2016). On the same day, women provided a serum sample during controlled ovarian stimulation, which was analyzed for metabolomics using liquid chromatography coupled with high-resolution mass spectrometry and two chromatography columns, and a urine sample, which was analyzed for 11 phthalate metabolites using targeted approaches. We used multivariable generalized linear models to identified metabolic features associated with urinary phthalate metabolite concentrations and live birth, followed by enriched pathway analysis. We then used a meet-in-the-middle approach to identify overlapping pathways and features. ResultsMetabolic pathway enrichment analysis revealed 43 pathways in the C18 negative and 32 pathways in the HILIC positive columns that were significantly associated (p < 0.05) with at least one of the 11 urinary phthalate metabolites or molar sum of di-2-ethylhexyl phthalate metabolites. Lipid, amino acid, and carbohydrate metabolism were the most common pathways associated with phthalate exposure. Five pathways, tryptophan metabolism, tyrosine metabolism, biopterin metabolism, carnitine shuttle, and vitamin B6 metabolism, were also identified as being associated with at least one phthalate metabolite and live birth following IVF. ConclusionOur study provides further insight into the metabolites and metabolomics pathways, including amino acid, lipid, and vitamin metabolism that may underlie the observed associations between phthalate exposures and lower fertility in women.

Cohort profile: the Environmental Reproductive and Glucose Outcomes (ERGO) Study (Boston, Massachusetts, USA) — a prospective pregnancy cohort study of the impacts of environmental exposures on parental cardiometabolic health

PurposePregnancy and the postpartum period are increasingly recognised as sensitive windows for cardiometabolic disease risk. Growing evidence suggests environmental exposures, including endocrine-disrupting chemicals (EDCs), are associated with an increased risk...

Extracellular Vesicles in Environmental Toxicological Studies: Association between Urinary Concentrations of Phthalate Metabolites and Exosomal miRNA Expression Profiles.

Phthalates are chemical compounds, mainly used as additives in plastics, which are known to induce harmful impacts to the environment and human health due to their ability to act as hormone-mimics. Few studies have been reported on the relationship between human exposure to phthalates and the level of circulating microRNAs (miRs), especially those miRs encapsulated in extracellular vesicles/exosomes or exosome-like vesicles (ELVs). We examined the relationship of ELV-miR expression patterns and urine of adult men with five phthalate metabolites (i.e., mono isobutyl phthalate, mono-n-butyl phthalate, mono benzyl phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, mono-(2-ethylhexyl) phthalate) to identify potential biomarkers and relevant pathways. We found significant positive associations which were further confirmed by multivariable analysis. Overall, our analyses showed that the Σ phthalate metabolite concentration was associated with a significant increase in the expression level of two miRs found in ELV: miR-202 and miR-543. Different pathways including cancer and immune-related responses were predicted to be involved in this relationship. Analyzing the specific downstream target genes of miR-202 and miR-543, we identified the phosphatase and tensin homolog (PTEN) as the key gene in several converging pathways. In summary, the obtained results demonstrate that exposure to environmental phthalates could be related to altered expression profiles of specific ELV-miRs in adult men, thereby demonstrating the potential of miRs carried by exosomes to act as early effect biomarkers.

Serum Phthalate Concentrations and Biomarkers of Oxidative Stress in Adipose Tissue in a Spanish Adult Cohort.

The relationship between phthalates, a group of chemical pollutants classified as endocrine disruptors, and oxidative stress is not fully understood. The aim of the present hospital-based study was to explore the associations between circulating levels of 10 phthalate metabolites and 8 biomarkers of oxidative stress in adipose tissue. The study population (n = 143) was recruited in two hospitals in the province of Granada (Spain). Phthalate metabolite concentrations were analyzed by isotope diluted online-TurboFlow-LC-MS/MS in serum samples, while oxidative stress markers were measured by commercially available kits in adipose tissue collected during routine surgery. Statistical analyses were performed by MM estimators' robust linear regression and weighted quantile sum regression. Mainly, positive associations were observed of monomethyl phthalate (MMP), monoiso-butyl phthalate (MiBP), and mono-n-butyl phthalate (MnBP) (all low molecular weight phthalates) with glutathione peroxidase (GPx) and thiobarbituric acid reactive substances (TBARS), while an inverse association was found between monoiso-nonyl phthalate (MiNP) (high molecular weight phthalate) and the same biomarkers. WQS analyses showed significant effects of the phthalate mixture on GSH (β = -30.089; p-value = 0.025) and GSSG levels (β = -19.591; p-value = 0.030). Despite the limitations inherent to the cross-sectional design, our novel study underlines the potential influence of phthalate exposure on redox homeostasis, which warrants confirmation in further research.

Urinary concentrations of phthalate metabolites in relation to preeclampsia and other hypertensive disorders of pregnancy in the environmental influences on child health outcomes (ECHO) program

BackgroundPhthalate exposure may contribute to hypertensive disorders of pregnancy (HDP), including preeclampsia/eclampsia (PE/E), but epidemiologic studies are lacking. ObjectivesTo evaluate associations of pregnancy phthalate exposure with development of PE/E and HDP. MethodsUsing data from 3,430 participants in eight Environmental influences on Child Health Outcomes (ECHO) Program cohorts (enrolled from 1999 to 2019), we quantified concentrations of 13 phthalate metabolites (8 measured in all cohorts, 13 in a subset of four cohorts) in urine samples collected at least once during pregnancy. We operationalized outcomes as PE/E and composite HDP (PE/E and/or gestational hypertension). After correcting phthalate metabolite concentrations for urinary dilution, we evaluated covariate-adjusted associations of individual phthalates with odds of PE/E or composite HDP via generalized estimating equations, and the phthalate mixture via quantile-based g-computation. We also explored effect measure modification by fetal sex using stratified models. Effect estimates are reported as odds ratios (OR) with 95% confidence intervals (95% CIs). ResultsIn adjusted analyses, a doubling of mono-benzyl phthalate (MBzP) and of mono (3-carboxypropyl) phthalate (MCPP) concentrations was associated with higher odds of PE/E as well as composite HDP, with somewhat larger associations for PE/E. For example, a doubling of MCPP was associated with 1.12 times the odds of PE/E (95%CI 1.00, 1.24) and 1.02 times the odds of composite HDP (95%CI 1.00, 1.05). A quartile increase in the phthalate mixture was associated with 1.27 times the odds of PE/E (95%CI 0.94, 1.70). A doubling of mono-carboxy isononyl phthalate (MCiNP) and of mono-carboxy isooctyl phthalate (MCiOP) concentrations were associated with 1.08 (95%CI 1.00, 1.17) and 1.11 (95%CI 1.03, 1.19) times the odds of PE/E. Effect estimates for PE/E were generally larger among pregnancies carrying female fetuses. DiscussionIn this study, multiple phthalates were associated with higher odds of PE/E and HDP. Estimates were precise and some were low in magnitude. Interventions to reduce phthalate exposures during pregnancy may help mitigate risk of these conditions.

Endocrine-disrupting chemical concentrations in follicular fluid and follicular reproductive hormone levels.

To determine correlations between chemicals in follicular fluid (FF) and follicular reproductive hormone levels. The analysis was part of a larger cohort study to determine associations between exposure to EDCs and in vitro fertilization (IVF) outcomes. FF was aspirated from a single leading follicle per participant. Demographics and data on exposure to EDCs were self-reported by the participants using a questionnaire. The concentrations of estradiol (E2), progesterone (PG), anti-Mullerian hormone (AMH), and inhibin B, as well as that of 12 phthalate metabolites and 12 phenolic chemicals were measured in each FF sample. Multivariate linear regression model was used to identify the drivers of hormone levels based on participant's age, BMI, smoking status, and chemical exposure for the monitored chemicals detected in more than 50% of the samples. Benjamini-Hochberg false discovery rate (FDR) correction was applied on the resulting p values (q value). FF samples were obtained from 72 women (mean age 30.9years). Most of the phthalates and phenolic substances monitored (21/24, 88%) were identified in FF. Ten compounds (7 phthalate metabolites, 3 phenols) were found in more than 50% of samples. In addition, there were positive associations between E2 levels and mono-n-butyl phthalate (MnBP) (beta = 0.01) and mono-isobutyl phthalate (MiBP) (beta = 0.03) levels (q value < 0.05). Higher concentrations of several phthalate metabolites, present among others in personal care products, were associated with increased E2 levels in FF. The results emphasize the need to further investigate the mechanisms of action of such EDCs on hormonal cyclicity and fertility in women.

Ongoing exposure to endocrine disrupting phthalates and alternative plasticizers in neonatal intensive care unit patients

Due to endocrine disrupting effects, di-(2-ethylhexyl) phthalate (DEHP), a plasticizer used to soften plastic medical devices, was restricted in the EU Medical Devices Regulation (EU MDR 2017/745) and gradually replaced by alternative plasticizers. Neonates hospitalized in the neonatal intensive care unit (NICU) are vulnerable to toxic effects of plasticizers. From June 2020 to August 2022, urine samples (n = 1070) were repeatedly collected from premature neonates (n = 132, 4–10 samples per patient) born at <31 weeks gestational age and/or <1500 g birth weight in the Antwerp University Hospital, Belgium. Term control neonates (n = 21, 1 sample per patient) were included from the maternity ward. Phthalate and alternative plasticizers’ metabolites were analyzed using liquid-chromatography coupled to tandem mass spectrometry. Phthalate metabolites were detected in almost all urine samples. Metabolites of alternative plasticizers, di-(2-ethylhexyl)-adipate (DEHA), di-(2-ethylhexyl)-terephthalate (DEHT) and cyclohexane-1,2-dicarboxylic-di-isononyl-ester (DINCH), had detection frequencies ranging 30–95 %. Urinary phthalate metabolite concentrations were significantly higher in premature compared to control neonates (p = 0.023). NICU exposure to respiratory support devices and blood products showed increased phthalate metabolite concentrations (p < 0.001). Phthalate exposure increased from birth until four weeks postnatally. The estimated phthalate intake exceeded animal-derived no-effect-levels (DNEL) in 10 % of samples, with maximum values reaching 24 times the DNEL. 29 % of premature neonates had at least once an estimated phthalate intake above the DNEL. Preterm neonates are still exposed to phthalates during NICU stay, despite the EU Medical Devices Regulation. NICU exposure to alternative plasticizers is increasing, though currently not regulated, with insufficient knowledge on their hazard profile.

Association between Biomarkers of Phthalate Exposure and Serum Folate Concentrations in Children: A Population-Based Cross-Sectional Study of the NHANES from 2011 to 2016

BackgroundAlthough adverse health effects of phthalates have been reported, very few studies have assessed the associations between biomarkers of phthalate exposure and serum folate concentrations in children. ObjectivesWe aimed to examine the association between urinary phthalate metabolites, as biomarkers of exposure to phthalates, and total serum folate concentrations in children using national data from the United States. MethodsWe conducted cross-sectional analyses of 2100 individuals aged 6–18 y enrolled in the National Health and Nutrition Examination Survey, 2011–2016. Multivariable linear regression was applied to examine the relationship between natural logarithm (ln)-transformed urinary phthalate metabolites and serum folate concentrations. The quantile-based g-computation was used to assess the association of urinary phthalate metabolite mixture with serum folate levels. Subgroup analyses were conducted by sex, age, and race/ethnicity, and the interactions were assessed by adding interaction terms of these stratifying variables and phthalates and modeling through the Wald test. ResultsIn multiple linear regression models, for participants in the highest tertile of MEHHP, MEOHP, DEHP, MCPP, and MCOP, total serum folate concentrations were 1.566 [β: −1.566; 95% confidence interval: −2.935, −0.196], 1.423 (−1.423; −2.689, −0.157), 1.309 (−1.309; −2.573, −0.044), 1.530 (−1.530; −2.918, −0.142), and 1.381 (−1.381; −2.641, −0.122) ng/mL lower than those in the lowest tertile. The inverse associations were consistent in different subgroups by sex, age, and race/ethnicity (P for interaction ≥0.083 for all). In addition, the phthalate mixture showed a strong inverse correlation with serum folate; a quartile increase in the phthalate mixture on the ln scale was associated with 0.888 (−0.888; −1.677, −0.099) ng/mL decrease in the serum folate. ConclusionsHigher concentrations of urinary phthalate metabolites were associated with lower serum folate concentrations in children. Although our findings should be validated through additional population and mechanistic studies, they support a potential adverse effect of phthalate exposure on folate metabolism in children.

Associations of concentrations of eight urinary phthalate metabolites with the frequency of use of common adult consumer and personal-care products

This study analyzed the relationship between urine concentrations of phthalate metabolites (UCOM) and personal care products (PCPs) used in adults and examined the change in UCOM according to the usage frequency of PCPs based on raw data from the 3rd Korean National Environmental Health Survey conducted between 2015 and 2017. The relationship between PCP use frequency and UCOM was analyzed using multiple regression analysis, adjusting for baseline factors. The regression model consisted of a Crude Model with log-transformed UCOM before and after adjustment for urine creatinine concentrations. Model 1 was additionally adjusted for age, sex, and obesity, while Model 2 was additionally adjusted for smoking, alcohol consumption, pregnancy history, average monthly income of the household, and PCP exposure within the past 2 days. PCP usage frequency was significantly associated with the UCOM without adjustment for urine creatinine and correlated with demographic characteristics, urine creatinine concentration, and PCP exposure within the past 2 days. This study on exposure to urinary phthalates will play a crucial role in Korean public health by aligning with the fundamentals of research priorities and providing representative data on phthalate exposure for conducting population-level studies.

Association of maternal phthalates exposure and metabolic gene polymorphisms with congenital heart diseases: a multicenter case-control study

BackgroundThe majority of congenital heart diseases (CHDs) are thought to result from the interactions of genetics and the environment factors. This study aimed to assess the association of maternal non-occupational phthalates exposure, metabolic gene polymorphisms and their interactions with risk of CHDs in offspring.MethodsA multicenter case-control study of 245 mothers with CHDs infants and 268 control mothers of health infant was conducted from six hospitals. Maternal urinary concentrations of eight phthalate metabolites were measured by ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Twenty single nucleotide polymorphisms (SNPs) in cytochrome P450 family 2 subfamily C member 9 (CYP2C9) and 19 (CYP2C19), uridine diphosphate (UDP) glucuronosyl transferase family 1 member A7 (UGT1A7), family 2 member B7 (UGT2B7) and B15(UGT2B15) genes were genotyped. The multivariate logistic regressions were used to estimate the association between maternal phthalates exposure or gene polymorphisms and risk of CHDs. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene–gene and gene–phthalates exposure interactions.ResultsThere was no significant difference in phthalate metabolites concentrations between the cases and controls. No significant positive associations were observed between maternal exposure to phthalates and CHDs. The SNPs of UGT1A7 gene at rs4124874 (under three models, log-additive: aOR = 1.74, 95% CI:1.28–2.37; dominant: aOR = 1.86, 95% CI:1.25–2.78; recessive: aOR = 2.50, 95% CI: 1.26–4.94) and rs887829 (under the recessive model: aOR = 13.66, 95% CI: 1.54–121) were significantly associated with an increased risk of CHDs. Furthermore, the associations between rs4124874 (under log-additive and dominant models) of UGT1A7 were statistically significant after the false discovery rate correction. No significant gene-gene or gene-phthalate metabolites interactions were observed.ConclusionsThe polymorphisms of maternal UGT1A7 gene at rs4124874 and rs887829 were significantly associated with an increased risk of CHDs. More large-scale studies or prospective study designs are needed to confirm or refute our findings in the future.

485 Association between perinatal phthalate metabolite concentrations and postpartum glucose levels: a prospective observational study

485 Association between perinatal phthalate metabolite concentrations and postpartum glucose levels: a prospective observational study

Associations between Phthalate Metabolite Concentrations in Follicular Fluid and Reproductive Outcomes among Women Undergoing in Vitro Fertilization/Intracytoplasmic Sperm Injection Treatment.

Phthalates have been reported to impair fertility in various studies. However, evidence exploring the associations between phthalate metabolites in follicular fluid (FF) and reproductive outcomes is lacking. To investigate the associations between phthalate metabolite concentrations in FF and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes among women recruited from a fertility clinic. We included 641 women undergoing IVF/ICSI treatment from December 2018 to January 2020. The levels of eight phthalate metabolites, including monoethyl phthalate (MEP), mono-isobutyl phthalate (MiBP), mono--butyl phthalate (MBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), were quantified in FF collected on the oocyte retrieval day. Associations between quartiles of individual phthalate metabolite concentrations and nine IVF/ICSI outcomes, including oocyte yield, mature oocyte number, two distinct pronuclei (2PN) zygote number, fertilization rate, blastocyst formation rate, implantation, clinical pregnancy, miscarriage, and live birth, were estimated with generalized linear models. The effects of phthalate mixtures on IVF/ICSI outcomes were assessed using Bayesian kernel machine regression (BKMR) models. After adjusting for relevant confounders, elevated quartiles of MBzP, MEHHP, and MEHP in FF were inversely associated with the numbers of retrieved oocytes, mature oocytes, and 2PN zygotes (all for trends ). In comparison with the lowest quartile, the highest quartile of molar sum of di(2-ethylhexyl) phthalate metabolites () was associated with a reduction of 9.1% [95% confidence interval (CI): , ] and 10.3% (95% CI: , ) in yielded oocyte and mature oocyte numbers, respectively. Furthermore, the BKMR models revealed inverse associations between phthalate mixtures and the numbers of retrieved oocytes and mature oocytes. We generally found null results for implantation, clinical pregnancy, miscarriage, and live birth. Certain phthalate metabolites in FF are inversely associated with the numbers of retrieved oocytes, mature oocytes, and 2PN zygotes among women undergoing IVF/ICSI treatment. https://doi.org/10.1289/EHP11998.

Racial and Ethnic Disparities in Phthalate Exposure and Preterm Birth: A Pooled Study of Sixteen U.S. Cohorts.

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

Phthalate metabolites in urine and follicular fluid in relation to menstrual cycle characteristics in women seeking fertility assistance

BackgroundPhthalates have been shown to disrupt the estrous cycle in animal studies. However, epidemiological research investigating their associations with menstrual cycle characteristics is limited. ObjectiveTo explore the relationships between phthalate exposure and menstrual cycle characteristics among women seeking fertility assistance. MethodsWe determined the levels of eight phthalate metabolites in both follicular fluid (FF) and urine specimens collected from 441 women in the Tongji Reproductive and Environmental (TREE) cohort, using high-performance liquid chromatography and tandem mass spectrometry. Information about menstrual cycle parameters was obtained through a questionnaire. The impacts of individual and joint exposure to phthalates on menstrual cycle characteristics were assessed using multivariable linear regression, Poisson regression, and quantile g-computation approaches. ResultsAfter adjusting for relevant covariates, we found that per log10-unit increase in mono(2-ethylhexyl) phthalate (MEHP) level in urine specimens was associated with a decrease of 0.20 days (95 % CI: −0.37, −0.03) in bleeding duration. We also observed that mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) and the sum of di(2-ethylhexyl) phthalate (DEHP) metabolites (∑DEHP) concentrations in FF samples were inversely related to cycle length [β = −1.92 (95 % CI: −3.10, −0.75) and −1.87 (95 % CI: −3.56, −0.19), respectively]. However, we generally observed null associations between phthalate metabolites and irregular cycle, dysmenorrhea, hypomenorrhea, or cycle length variation. Furthermore, we also found that phthalate metabolite mixtures in FF and urine were generally unrelated to menstrual cycle characteristics. ConclusionOur findings suggest that some DEHP metabolites in FF and urine are inversely associated with menstrual cycle length and menstrual bleeding duration in women attending a fertility center.

Paternal and maternal preconception and maternal pregnancy urinary phthalate metabolite and BPA concentrations in relation to child behavior

BackgroundEpidemiologic studies on health effects of parental preconception exposures are limited despite emerging evidence from toxicological studies suggesting that such exposures, including to environmental chemicals, may affect offspring health. ObjectiveWe investigated whether maternal and paternal preconception and maternal pregnancy urinary phthalate metabolite and bisphenol A (BPA) concentrations were associated with child behavior. MethodsWe analyzed data from the Preconception Environmental exposure And Childhood health Effects (PEACE) Study, an ongoing prospective cohort study of children aged 6–11 years whose parent(s) previously enrolled in the prospective preconception Environment and Reproductive Health (EARTH) study. Using linear mixed models, we estimated covariate-adjusted associations of 11 urinary phthalate metabolite and BPA concentrations collected prior to conception and during pregnancy with Behavioral Assessment System for Children-3 (BASC-3) T-scores (higher scores indicate more problem behaviors). ResultsThis analysis included 134 mothers, 87 fathers and 157 children (24 sets of twins); parents were predominantly non-Hispanic white (mothers and fathers86%). Higher maternal preconception or pregnancy monobenzyl phthalate (MBzP) concentrations were related to higher mean externalizing problems T-scores in their children (β = 1.3 per 1-loge unit increase; 95 % CI: −0.2, 2.4 and β = 2.1, 95 % CI: 0.7, 3.6, respectively). Higher maternal preconception monocarboxyoctyl phthalate (MCOP) was suggested to be related to lower mean externalizing problems T-scores (β = -0.9; 95 % CI: −1.8, 0.0). Higher paternal preconception MCOP was suggestively associated with lower internalizing problems (β = -0.9; 95 %CI:-1.9, 0.1) and lower Behavioral Symptoms Index (BSI) T-scores (β = -1.3; 95 % CI: −2.1, −0.4). ConclusionIn this cohort, higher maternal preconception and pregnancy MBzP were associated with worse parent-reported child behavior, while higher maternal and paternal preconception MCOP concentrations were related to lower BASC-3 scores.

BMI-specific inflammatory response to phthalate exposure in early pregnancy: findings from the TMCHESC study.

Studies that have evaluated associations between phthalate metabolites and inflammation have reported inconsistent results among pregnant women, and it is unclear how body mass index (BMI) affects such relationships. Therefore, the present study aimed to examine the association between urinary phthalate metabolite concentrations and the levels of inflammatory biomarkers in the general circulation among 394 pregnant women selected from the Tianjin Maternal and Child Health Education and Service Cohort (TMCHESC) and to determine the role that BMI plays in the relationship. The concentrations of eight inflammatory biomarkers and three phthalate metabolites were measured in serum and urine samples, respectively. Multivariable linear modeling was conducted to examine the association between each phthalate and inflammatory biomarker while controlling for potential confounding factors in BMI-stratified subgroups. Restricted cubic splines were also utilised to explore potential non-linear relationships. In the high-BMI group, positive associations were observed between the levels of mono-n-butyl phthalate (MBP) and interleukin 1 beta (IL-1β) (β = 0.192; 95% CI: 0.033, 0.351), monoethyl phthalate (MEP), and C-reaction protein (CRP) (β = 0.129; 95% CI 0.024, 0.233), and mono-ethylhexyl phthalate (MEHP) and interleukin 6 (IL-6) (β = 0.146; 95% CI 0.016, 0.277). Restricted cubic spline models also revealed non-linear associations between the levels of MBP and interleukins 10 and 17A (IL-10 and IL-17A) and between MEP and interleukin 8 (IL-8) and tumor necrosis factor alpha (TNF-α) in pregnant women. These results suggest that phthalate exposure plays a potential role in promoting inflammation in the high-BMI group. While the precise mechanisms underlying the proinflammatory effects of phthalates are not fully understood, these findings suggest that BMI may play a role.

Urinary Bisphenol A and Bis(2-Ethylhexyl) Phthalate Metabolite Concentrations in Children with Obesity: A Case-Control Study

Introduction: Obesity is a worldwide public health problem. Experimental animal and in vitro studies suggest that the exposure to BPA and phthalates are associated to a higher risk of obesity. Objective: The objective of the study was to determine urinary excretion of bisphenol A and phthalates in obese and normal weight children. Methods: A case-control study was conducted in 122 children. Sixty-six obese children, 36 girls (mean age 8.41 ± 1.27 years), and 30 boys (mean age 8.51 ± 1.33 years) and 56 normal weight children, 27 girls (mean age 7.64 ± 1.49 years), and 29 boys (mean age 7.77 ± 1.56 years) were studied. Urinary BPA and bis(2-ethylhexyl) phthalate (DEHP) metabolites (MEHP, MEHHP, and MEOHP) were measured, respectively, by gas chromatography and high-performance liquid chromatography. Individual determinants of exposure were evaluated through “ad hoc” questionnaires. Results: BPA and DEHP metabolites were detectable in obese and normal weight children. Obese girls showed significantly higher BPA concentrations in comparison with normal weight girls (means 10.77, 95% CI = 7.02–16.53 vs. 5.50, 95% CI = 3.93–7.71 μg/g creatinine, respectively, p p p Conclusions: These findings show that a higher exposure to BPA is associated with the risk of obesity in girls. Further studies are needed to unveil the cause-effect relationship.

A Mixture of Urinary Phthalate Metabolite Concentrations During Pregnancy and Offspring Social Responsiveness Scale Scores.

Phthalates are a group of chemicals with ubiquitous exposure worldwide. Exposures to phthalates during pregnancy may play a role in autism spectrum disorder (ASD) etiology by disrupting hormone levels or directly impacting fetal neurodevelopment. However, there is little research quantifying the aggregate effect of phthalates on child ASD-related behaviors. We used data from two prospective pregnancy and birth cohorts-the Health Outcomes and Measures of the Environment (HOME) and the Early Autism Risk Longitudinal Investigation (EARLI). HOME is a general population cohort while participants in EARLI were at higher familial risk for ASD. Using quantile g-computation and linear regression models, we assessed the joint and individual associations of a mixture of six phthalate metabolites during pregnancy with child ASD-related traits measured by Social Responsiveness Scale (SRS) scores at ages 3-8 years. Our analyses included 271 participants from HOME and 166 participants from EARLI. There were imprecise associations between the phthalate mixture and SRS total raw scores in HOME (difference in SRS scores per decile increase in every phthalate = 1.3; 95% confidence interval [CI] = -0.2, 2.8) and EARLI (difference in SRS scores per decile increase in every phthalate = -0.9; 95% CI = -3.5, 1.7). The cohort-specific effect sizes of the pthalates-SRS associations were small and CIs were imprecise. These results suggest that if there are associations between phthalate metabolites during pregnancy and child SRS scores, they may differ across populations with different familial liabilities. Further studies with larger sample sizes are warranted.

Maternal concentrations of phthalates and Attention-Deficit Hyperactivity Disorder (ADHD-) related symptoms in children aged 2 to 4 years from Odense child cohort

BackgroundPhthalates are endocrine disrupting chemicals used in everyday consumer products. Several epidemiological studies have examined the association between prenatal phthalate concentration and Attention-Deficit Hyperactivity Disorder (ADHD) in offspring, but the findings have been inconclusive. ObjectivesTo investigate the association between maternal urinary concentrations of phthalate metabolites during pregnancy and ADHD related symptoms in children at 2 to 4 years in a large prospective cohort. MethodsIn the Odense Child Cohort from Denmark were women recruited in early pregnancy from 2010 to 2012. Phthalate concentrations were measured in urine samples collected in 3rd trimester and separated into low and high weight phthalates. Parents filled in the Child Behavior Checklist for ages 1.5 to 5 years (CBCL/1½-5), including a 6-item ADHD symptom scale at children aged 2 to 4 years. Data were analysed by use of adjusted negative binomial regression. ResultsA total of 658 mother–child pairs were included. Urinary phthalate metabolite concentrations were generally low compared to previous cohorts. A doubling in maternal concentration of the low-weighted phthalate metabolite MCPP was significantly associated with lower ADHD symptoms score in children (IRR: 0.95 (95 % CI 0.91–0.98)), strongest in girls (IRR: 0.92 (0.87–0.98)). Sex differences were observed. High maternal phthalate metabolite concentrations were associated with lower ADHD symptom score in girls, significant trends across tertile of MCPP and MnBP (p = 0.018, p = 0.038, respectively). In boys, maternal concentrations of high-molecular-weight phthalates (MBzP, ∑DiNP and ∑DEHP) were associated with an almost significantly higher ADHD symptom score (IRR for a doubling in concentration: 1.04 (95 % CI: 0.99–1.10), IRR: 1.05 (95 % CI: 0.97–1.13), IRR: 1.04 (95 % CI: 0.99–1.10), respectively). ConclusionMaternal concentration of the low-weighted phthalate metabolite MCPP was significantly associated with a lower ADHD symptom score in children, strongest in girls. Maternal concentrations of high-molecular-weight phthalates were associated with non-significant increase in ADHD symptom score in boys.

The associations of preconception urinary phthalate metabolite concentrations with the serum metabolome and outcomes of infertility treatment

The associations of preconception urinary phthalate metabolite concentrations with the serum metabolome and outcomes of infertility treatment