Dataset Information

Early pregnancy phthalates and replacements in relation to fetal growth: The human placenta and phthalates study.

ABSTRACT:

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 (β: -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.

SUBMITTER: Stevens DR

PROVIDER: S-EPMC10201455 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

Early pregnancy phthalates and replacements in relation to fetal growth: The human placenta and phthalates study.

Stevens Danielle R DR Rosen Emma M EM Van Wickle Kimi K McNell Erin E EE Bommarito Paige A PA Calafat Antonia M AM Botelho Julianne C JC Sinkovskaya Elena E Przybylska Ann A Saade George G Abuhamad Alfred A Ferguson Kelly K KK

Environmental research 20230423

<h4>Background</h4>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.<h4>Objective</h4>Characterize associations between urinary phthalate and repla ...[more]

PMID: 37094650

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Project description:BackgroundBisphenols and phthalates are high production volume chemicals used as additives in a variety of plastic consumer products leading to near ubiquitous human exposure. These chemicals have established endocrine disrupting properties and have been linked to a range of adverse reproductive and developmental outcomes. Here, we investigated exposure in relation to fetal growth.MethodsParticipants included 855 mother-fetal pairs enrolled in the population-based New York University Children's Health and Environment Study (NYU CHES). Bisphenols and phthalates were measured in maternal urine collected repeatedly during pregnancy. Analyses included 15 phthalate metabolites and 2 bisphenols that were detected in 50 % of participants or more. Fetal biometry data were extracted from electronic ultrasonography records and estimated fetal weight (EFW) was predicted for all fetuses at 20, 30, and 36 weeks gestation. We used quantile regression adjusted for covariates to model exposure-outcome relations across percentiles of fetal weight at each gestational timepoint. We examined sex differences using stratified models.ResultsFew statistically significant associations were observed across chemicals, gestational time periods, percentiles, and sexes. However, within gestational timepoints, we found that among females, the molar sums of the phthalates DiNP and DnOP were generally associated with decreases in EFW among smaller babies and increases in EFW among larger babies. Among males, the opposite trend was observed. However, confidence intervals were generally wide at the tails of the distribution.ConclusionIn this sample, exposure to bisphenols and phthalates was associated with small sex-specific shifts in fetal growth; however, few associations were observed at the median of fetal weight and confidence intervals in the tails were wide. Findings were strongest for DiNP and DnOP, which are increasingly used as replacements for DEHP, supporting the need for future research on these contaminants.

Project description:Humans are exposed to complex mixtures of phthalates. Gestational exposure to phthalates has been linked to preeclampsia and preterm birth through potential pathways such as endocrine disruption, oxidative stress, and inflammation. Eicosanoids are bioactive signaling lipids that are related to a variety of homeostatic and inflammatory processes. We investigated associations between urinary phthalates and their mixtures with plasma eicosanoid levels during pregnancy using the PROTECT cohort in Puerto Rico (N = 655). After adjusting for covariates, we estimated pair-wise associations between the geometric mean of individual phthalate metabolite concentrations across pregnancy and eicosanoid biomarkers using multivariable linear regression. We used bootstrapping of adaptive elastic net regression (adENET) to evaluate phthalate mixtures associated with eicosanoids and subsequently create environmental risk scores (ERS) to represent weighted sums of phthalate exposure for each individual. After adjusting for false-discovery, in single-pollutant analysis, 14 of 20 phthalate metabolites or parent compound indices showed significant and primarily negative associations with multiple eicosanoids. In our mixture analysis, associations with several metabolites of low molecular weight phthalates - DEP, DBP, and DIBP - became prominent. Additionally, MEHHTP and MECPTP, metabolites of a new phthalate replacement, DEHTP, were selected as important predictors for determining the concentrations of multiple eicosanoids from different pathway groups. A unit increase in phthalate ERS derived from bootstrapping of adENET was positively associated with several eicosanoids mainly from Cytochrome P450 pathway. For example, an increase in ERS was associated with 11(S)-HETE (β = 1.6, 95% CI: 0.020, 3.180), (±)11,12-DHET (β = 2.045, 95% CI: 0.250, 3.840), 20(S)-HETE (β = 0.813, 95% CI: 0.147, 1.479), and 9 s-HODE (β = 2.381, 95% CI: 0.657, 4.104). Gestational exposure to phthalates and phthalate mixtures were associated with eicosanoid levels during pregnancy. Results from the mixture analyses underscore the complexity of physiological impacts of phthalate exposure and call for further in-depth studies to examine these relationships.

Project description:Background/objectivesPregnant women are exposed to multiple phthalates and their replacements, which are endocrine disrupting chemicals associated with adverse maternal and child health outcomes. Identifying maternal characteristics associated with phthalate/replacement exposure during pregnancy is important.MethodsWe evaluated 13 maternal sociodemographic and lifestyle factors, enrollment year, and conception season as determinants of exposure biomarkers of phthalates and their replacements in 482 pregnant women from the Illinois Kids Development Study (I-KIDS, enrolled 2013-2018). We quantified 19 phthalate/replacement metabolites in pools of five first-morning urines collected across pregnancy. K-means clustering identified women with distinct patterns of biomarker concentrations and principal component analysis (PCA) identified principal component (PC) profiles of biomarkers that exist together. We used multivariable regression models to evaluate associations of predictors with identified k-means clusters and PCs.ResultsK-means clustering identified two clusters of women: 1) low phthalate/di(2-ethylhexyl) terephthalate (∑DEHTP) and 2) high phthalate/∑DEHTP biomarker concentrations. PCA identified four PCs with loadings heaviest for biomarkers of plasticizer phthalates [di-isononyl, di-isodecyl, di-n-octyl phthalates] (PC1), of other phthalates [dibenzyl, di-n-butyl, di-iso-butyl phthalates] (PC2), of phthalate replacements [∑DEHTP, di(isononyl) cyclohexane-1,2-dicarboxylate (∑DiNCH)] (PC3), and of monoethyl phthalate [MEP] (PC4). Overall, age, marital status, income, parity, pre-pregnancy BMI, caffeine intake, enrollment year, and conception season were independently associated with k-means cluster membership and at least one PC. Additionally, race/ethnicity, education, employment, pregnancy intention, smoking status, alcohol intake, and diet were associated with at least one PC. For instance, women who conceived in the spring, summer, and/or fall months had lower odds of high phthalate/∑DEHTP cluster membership and had lower plasticizer phthalate, phthalate replacement, and MEP PC scores.ConclusionsConception season, enrollment year, and several sociodemographic/lifestyle factors were predictive of phthalate/replacement biomarker profiles. Future studies should corroborate these findings, with a special focus on replacements to which pregnant women are becoming increasingly exposed.

Project description:BackgroundFetal growth restriction (FGR) is a pregnancy complication in which a newborn fails to achieve its growth potential, increasing the risk of perinatal morbidity and mortality. Chronic maternal gestational hypoxia, as well as placental insufficiency are associated with increased FGR incidence; however, the molecular mechanisms underlying FGR remain unknown.MethodsPregnant mice were subjected to acute or chronic hypoxia (12.5% O2) resulting in reduced fetal weight. Placenta oxygen transport was assessed by blood oxygenation level dependent (BOLD) contrast magnetic resonance imaging (MRI). The placentae were analyzed via immunohistochemistry and in situ hybridization. Human placentae were selected from FGR and matched controls and analyzed by immunohistochemistry (IHC). Maternal and cord sera were analyzed by mass spectrometry.ResultsWe show that murine acute and chronic gestational hypoxia recapitulates FGR phenotype and affects placental structure and morphology. Gestational hypoxia decreased labyrinth area, increased the incidence of red blood cells (RBCs) in the labyrinth while expanding the placental spiral arteries (SpA) diameter. Hypoxic placentae exhibited higher hemoglobin-oxygen affinity compared to the control. Placental abundance of Bisphosphoglycerate mutase (BPGM) was upregulated in the syncytiotrophoblast and spiral artery trophoblast cells (SpA TGCs) in the murine gestational hypoxia groups compared to the control. Hif1α levels were higher in the acute hypoxia group compared to the control. In contrast, human FGR placentae exhibited reduced BPGM levels in the syncytiotrophoblast layer compared to placentae from healthy uncomplicated pregnancies. Levels of 2,3 BPG, the product of BPGM, were lower in cord serum of human FGR placentae compared to control. Polar expression of BPGM was found in both human and mouse placentae syncytiotrophoblast, with higher expression facing the maternal circulation. Moreover, in the murine SpA TGCs expression of BPGM was concentrated exclusively in the apical cell side, in direct proximity to the maternal circulation.ConclusionsThis study suggests a possible involvement of placental BPGM in maternal-fetal oxygen transfer, and in the pathophysiology of FGR.FundingThis work was supported by the Weizmann Krenter Foundation and the Weizmann - Ichilov (Tel Aviv Sourasky Medical Center) Collaborative Grant in Biomedical Research, by the Minerva Foundation, by the ISF KillCorona grant 3777/19.

Project description:BackgroundPrenatal exposure to bisphenol A (BPA) and phthalates may affect fetal growth; however, previous findings are inconsistent and based on few studies.ObjectivesWe assessed whether prenatal exposure to BPA and phthalates was associated with fetal growth in a Spanish birth cohort of 488 mother-child pairs.MethodsWe measured BPA and eight phthalates [four di(2-ethylhexyl) phthalate metabolites (DEHPm), mono-benzyl phthalate (MBzP), and three low-molecular-weight phthalate metabolites (LMWPm)] in two spot-urine samples collected during the first and third trimester of pregnancy. We estimated growth curves for femur length (FL), head circumference (HC), abdominal circumference (AC), biparietal diameter (BPD), and estimated fetal weight (EFW) during pregnancy (weeks 12-20 and 20-34), and for birth weight, birth length, head circumference at birth, and placental weight.ResultsOverall, results did not support associations of exposure to BPA or DEHPm during pregnancy with fetal growth parameters. Prenatal MBzP exposure was positively associated with FL at 20-34 weeks, resulting in an increase of 3.70% of the average FL (95% CI: 0.75, 6.63%) per doubling of MBzP concentration. MBzP was positively associated with birth weight among boys (48 g; 95% CI: 6, 90) but not in girls (-27 g; 95% CI: -79, 25) (interaction p-value = 0.04). The LMWPm mono-n-butyl phthalate (MnBP) was negatively associated with HC at 12-20 pregnancy weeks [-4.88% of HC average (95% CI: -8.36, -1.36%)].ConclusionsThis study, one of the first to combine repeat exposure biomarker measurements and multiple growth measures during pregnancy, finds little evidence of associations of BPA or phthalate exposures with fetal growth. Phthalate metabolites MBzP and MnBP were associated with some fetal growth parameters, but these findings require replication.CitationCasas M, Valvi D, Ballesteros-Gomez A, Gascon M, Fernández MF, Garcia-Esteban R, Iñiguez C, Martínez D, Murcia M, Monfort N, Luque N, Rubio S, Ventura R, Sunyer J, Vrijheid M. 2016. Exposure to bisphenol A and phthalates during pregnancy and ultrasound measures of fetal growth in the INMA-Sabadell cohort. Environ Health Perspect 124:521-528; http://dx.doi.org/10.1289/ehp.1409190.

Project description:BackgroundPreterm birth (occurring before 37 completed weeks of gestation) affects 15 million infants annually, 7.5% of which die due to related complications. The detection and early diagnosis are therefore paramount in order to prevent the development of prematurity and its consequences. So far, focus has been laid on the association between reduced intrauterine fetal growth during late gestation and prematurity. The aim of the current study was to investigate the association between accelerated fetal growth in early pregnancy and the risk of preterm birth.MethodsThis prospective cohort study included 69,617 singleton pregnancies without congenital malformations and with available biometric measurements during the first and second trimester. Estimation of fetal growth was based on measurements of biparietal diameter (BPD) at first and second trimester scan. We investigated the association between accelerated fetal growth and preterm birth prior to 37 weeks of gestation. The outcome was further stratified into very preterm birth (before 32 weeks of gestation) or moderate preterm birth (between 32 and 37 weeks of gestation) and medically induced or spontaneous preterm birth and was further explored.ResultsThe odds of prematurity were increased among fetuses with accelerated BPD growth (> 90th centile) estimated between first and second ultrasound scan, even after adjustment for possible confounders (aOR 1.36; 95% CI 1.20-1.54). The findings remained significant what regards moderate preterm births but not very preterm births. Regarding medically induced preterm birth, the odds were found to be elevated in the group of fetuses with accelerated growth in early pregnancy (aOR 1.34; 95% CI 1.11-1.63). On the contrary, fetuses with delayed fetal growth exhibited lower odds for both overall and spontaneous preterm birth.ConclusionsFetuses with accelerated BPD growth in early pregnancy, detected by ultrasound examination during the second trimester, exhibited increased odds of being born preterm. The findings of the current study suggest that fetal growth in early pregnancy should be taken into account when assessing the risk for preterm birth.

Dataset Information

Early pregnancy phthalates and replacements in relation to fetal growth: The human placenta and phthalates study.

Background

Objective

Methods

Results

Conclusions

Publications

Early pregnancy phthalates and replacements in relation to fetal growth: The human placenta and phthalates study.

Similar Datasets

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