Search

Abstract Introduction Preterm birth continues to be a significant public heath concern and is a leading cause of perinatal and infant mortality. Environmental exposures to phenols and parabens are suspected to potentially contribute to the pathology of preterm birth, yet limited human studies have characterized the extent to which these toxicants are associated with birth outcomes. Methods We examined the associations between phenols, parabens, and preterm birth, within pregnant women who were recruited early in gestation into the LIFECODES cohort at Brigham and Women's Hospital in Boston, Massachusetts. Urine samples were collected at up to 4 time points in pregnancy and analyzed for phenols and parabens. We selected 130 cases of preterm birth (defined as delivery before 37 weeks gestation), and 350 random controls. We categorized preterm birth subtypes based on clinical presentation and identified 75 cases of spontaneous preterm birth (characterized by spontaneous preterm labor and/or preterm premature rupture of membranes), and 37 cases of placental preterm birth (characterized by preeclampsia and/or intrauterine growth restriction). We used multivariate logistic regression with visit specific and geometric averages of phenols and parabens to determine associations with preterm birth. Results We observed moderate variability in urinary phenol and paraben concentrations over pregnancy with intraclass correlation coefficients ranging between 0.45 and 0.68. Regression analyses indicated mostly null associations. We observed inverse associations, notably between 2,5-dichlorophenol and overall preterm birth (adjusted odds ratio [95% confidence interval, CI]: 0.79 [0.67 – 0.94]), and this relationship was consistent by study visit. Conversely, ethyl paraben was associated with increased risk for placental preterm birth (adjusted odds ratio [95% CI]: 1.47 [1.14 – 1.91]). Bisphenol-S detection at visit 4 was associated with overall preterm birth (adjusted odds ratio [95% CI]: 2.05 [1.09, 3.89]). Conclusions While the findings from this study largely indicate null associations, we observed some relationships between select phenols, parabens and preterm birth, which warrants further investigation of these toxicants and birth outcomes. Highlights • We measured ten unique phenol compounds in this case-control study of preterm birth. • Ethyl paraben was associated with increased risk for placental preterm birth. • 2,5-Dichlorophenol was associated with decreased risk for overall preterm birth. • A majority of the phenols were not associated with birth outcomes. [ABSTRACT FROM AUTHOR]

Background Epidemiological data suggest associations between phthalate exposures to a variety of adverse reproductive outcomes including reduced sperm quality and reproductive success. While mechanisms of these associations are not fully elucidated, oxidative stress has been implicated as a potential mediator. We examined associations of urinary metabolites of phthalates and phthalate alternative plasticizers with oxidative stress among couples seeking fertility treatment. Methods Seventeen urinary plasticizer metabolites and 15-F2t isoprostane, a biomarker of oxidative stress, were quantified in spot samples from 50 couples seeking fertility treatment who enrolled in the Sperm Environmental Epigenetics and Development Study during 2014–2015. Results In multivariable analyses, percent change in isoprostane was positively associated with interquartile range increases for the oxidative metabolites of di-2-ethylhexyl phthalate, [mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP; 20.0%, p=0.02), mono-2-ethyl-5-oxohexyl phthalate (MEOHP; 24.1%, p=0.01), and mono-2-ethyl-5-carboxypentyl phthalate (MECPP; 24.1%, p=0.004)], mono-isobutyl phthalate (MiBP; 17.8%, p=0.02), mono-hydroxyisobutyl phthalate (MHiBP; 27.5%, p=0.003), and cyclohexane-1,2-dicarboxylic acid mono-hydroxy-isononyl ester (MHINCH; 32.3%, p=0.002). Stratification of participants by sex revealed that isoprostane was positively associated with MHiBP (41.4%, p=0.01) and monocarboxy-isononyl phthalate (MCNP; 26.0%, p=0.02) among females and MEOHP (35.8%, p=0.03), MiBP (29.2%, p=0.01), MHiBP (34.7%, p=0.007) and MHINCH (49.0%, p=0.002) among males. Conclusions Our results suggest that exposure to phthalates and phthalate replacements are associated with higher levels of oxidative stress in a sex-specific manner. Additional studies are needed to replicate our findings and to examine the potential health implications of the use of phthalates and alternative phthalates in consumer end products. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are endocrine disruptors resulting from incomplete combustion. Pregnancy represents a particularly vulnerable period to such exposures, given the significant influence of hormone physiology on fetal growth and pregnancy outcomes. Maternal thyroid hormones play crucial roles in fetal development and pregnancy outcomes. However, limited studies have examined gestational PAH exposure and maternal thyroid hormones during pregnancy. Our study included 439 women enrolled in the LIFECODES birth cohort in Boston, aiming to explore the relationship between urinary PAH metabolites and thyroid hormones throughout pregnancy. Urine samples for PAH metabolite analysis and plasma samples for thyroid hormone were measured up to four visits throughout gestation. Single pollutant analyses employed linear mixed effect models to investigate individual associations between each PAH metabolite and thyroid hormone concentration. Sensitivity analyses were conducted to assess potential susceptibility windows and fetal-sex-specific effects of PAH exposure. Mixture analyses utilized quantile g-computation to evaluate the collective impact of eight PAH metabolites on thyroid hormone concentrations. Additionally, Bayesian kernel machine regression (BKMR) was employed to explore potential non-linear associations and interactions between PAH metabolites. Subject-specific random intercepts were incorporated to address intra-individual correlation of serial measurements over time in both single pollutant and mixture analyses. Our findings revealed positive trends in associations between PAH metabolites and thyroid hormones, both individually and collectively as a mixture. Sensitivity analyses indicated that these associations were influenced by the study visit and fetal sex. Mixture analyses suggested non-linear relationships and interactions between different PAH exposures. This comprehensive investigation underscores the critical importance of understanding the impact of PAH exposures on thyroid hormone physiology during pregnancy. The findings highlight the intricate interplay between environmental pollutants and human pregnancy physiology, emphasizing the need for targeted interventions and public health policies to mitigate adverse outcomes associated with prenatal PAH exposure. • Polycyclic aromatic hydrocarbons (PAHs) exposure and thyroid hormone levels were assessed up to four times during pregnancy. • Gestational exposure to PAHs was associated with thyroid hormone concentration during pregnancy. • Associations between PAHs and thyroid hormone concentration varied based on study visit and fetal sex. • Certain PAHs exhibited non-linear associations with thyroid hormones and interacted with other PAHs. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic chemicals widely used in consumer and industrial products. Numerous studies have linked prenatal PFAS exposures to increased risks of adverse pregnancy outcomes such as preterm birth (PTB) and small-for-gestational age (SGA).However, limited evidence is available for the effects of PFAS on PTB subtypes and large-for-gestational age (LGA). To examine the associations of PFAS with PTB [overall, placental (pPTB), spontaneous (sPTB)], BW Z-score, and size-for-gestational age (SGA, LGA). Our nested case-control study included 128 preterm cases and 373 term controls from the LIFECODES cohort between 2006 and 2008 (n = 501). Plasma concentrations of nine PFAS were measured in early pregnancy samples. Logistic regression was used to assess individual PFAS-birth outcome associations, while Bayesian Kernel Machine Regression (BKMR) was used to evaluate the joint effects of all PFAS. Effect modification by fetal sex was examined, and stratified analyses were conducted to obtain fetal sex-specific estimates. Compared to term births, the odds of pPTB were higher from an interquartile range increase in perfluorodecanoic acid (PFDA) (OR = 1.60, 95% CI: 1.00–2.56), perfluorononanoic acid (PFNA) (OR = 1.67, 95% CI: 1.06–2.61), and perfluoroundecanoic acid (PFUA) (OR = 1.77, 95% CI: 1.00–3.12), with stronger associations observed in women who delivered males. BKMR analysis identified PFNA as the most important PFAS responsible for pPTB (conditional PIP = 0.78), with increasing ORs at higher percentiles of PFAS mixture. For LGA, positive associations were observed with PFDA and perfluorooctanoic acid in females only, and with PFUA in males only. BKMR analysis showed increasing, but null effects of PFAS mixture on LGA. The effect of prenatal exposure to single and multiple PFAS on PTB and LGA depended on fetal sex. Future studies should strongly consider examining PTB subtypes and sex-specific effects of PFAS on pregnancy outcomes. • PFNA, PFDA, and PFUA associated with increased odds of placental preterm birth. • PFHP marginally linked with increased odds of spontaneous preterm birth. • PFDA and PFOA associated with increased odds of LGA in female offspring. • Fetal sex-specific effects of PFAS on preterm birth and LGA. [ABSTRACT FROM AUTHOR]

Background Mercury is a global contaminant of concern though little is known about exposures in México. Objectives To characterize mercury levels in pregnant women, children, and commonly consumed seafood samples. Methods Use resources of the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) birth cohorts to measure total mercury levels in archived samples from 348 pregnant women (blood from three trimesters and cord blood), 825 offspring (blood, hair, and urine) and their mothers (hair), and 91 seafood and canned tuna samples from Mexico City. Results Maternal blood mercury levels correlated across three trimesters and averaged 3.4 μg/L. Cord blood mercury averaged 4.7 μg/L and correlated with maternal blood from trimester 3 (but not trimesters 1 and 2). In children, blood, hair and urine mercury levels correlated and averaged 1.8 μg/L, 0.6 μg/g, and 0.9 μg/L, respectively. Hair mercury was 0.5 μg/g in mothers and correlated with child׳s hair. Mean consumption of canned tuna, fresh fish, canned sardine, and shellfish was 3.1, 2.2, 0.5, and 1.0 times per month respectively in pregnant women. Mean mercury content in 7 of 23 seafood species and 5 of 9 canned tuna brands purchased exceeded the U.S. EPA guidance value of 0.3 μg/g. Conclusions Mercury exposures in pregnant women and children from Mexico City, via biomarker studies, are generally 3–5 times greater than values reported in population surveys from the U.S., Canada, and elsewhere. In particular, mercury levels in 29–39% of the maternal participants exceeded the biomonitoring guideline associated with the U.S. EPA reference dose for mercury. [ABSTRACT FROM AUTHOR]

Vitamin D facilitates the absorption of calcium but may also increase absorption of other metals; the literature is conflicting. To examine whether 25OHD in the first trimester of pregnancy was associated with subsequent metals levels in the late second trimester of pregnancy. We used data from a sample of women in the LIFECODES pregnancy cohort (N = 381). 25-hydroxyvitamin D (25OHD) was measured with a chemiluminescence immunoassay in plasma samples drawn at 10 weeks of gestation. A panel of 17 metals and elements was measured in urine collected at 26 weeks of gestation. We used linear or logistic regression to estimate associations between 25OHD (dichotomous, linear, and in tertiles) and either urinary metal concentrations or the proportion of samples below the limit of detection, respectively. Multivariable models included urinary specific gravity, age, race/ethnicity, education, body mass index, insurance type, gestational age, and season. After multivariable adjustment, low 25OHD was associated with a 47% increase in lead level, a 60% increase in tin level, and 1.58 times the odds of detectable tungsten. A 10 ng/ml increase in 25OHD was associated with a 12% decrease in tin and an 8% increase in molybdenum. While we had a small sample size, we found some evidence of effect modification by race. Women who reported their race as Black or were classified in the other race category, who also had low 25OHD, had 40% higher thallium than women with higher 25OHD and were more likely to have detectable beryllium and tungsten. These metals were not associated with low 25OHD in women who reported their race as White. Tin and lead were higher in women with low 25OHD in all race groups. In total, further research is warranted to determine if vitamin D levels alter metal levels, and to elucidate the shape of the association for each metal across a range of corresponding 25OHD levels, and longitudinally, across pregnancy. This is especially true for pregnant people as exposure to metals during pregnancy has health consequences for the fetus. • Vitamin D facilitates the absorption of calcium but may also increase absorption of other metals. • After adjustment, low 25OHD was associated with 47% higher lead, 60% higher tin, and higher odds of detectable tungsten. • While the sample size was small, there was some evidence of effect modification by race. • Further research is warranted to determine if vitamin D levels alter metal levels longitudinally, particularly during pregnancy. [ABSTRACT FROM AUTHOR]

Personal care products (PCPs) are important and modifiable sources of exposure to endocrine disrupting chemicals (EDCs). Research is limited on how EDC-associated PCP use differs by race/ethnicity and socioeconomic status (SES), particularly during the sensitive period of pregnancy. We investigated differences in PCP use by race/ethnicity and SES among 497 participants in the LIFECODES pregnancy cohort (Boston, Massachusetts). Participants self-reported race/ethnicity, SES indicators (maternal education; insurance status), and recent PCP use via questionnaire at ≤4 prenatal visits. We evaluated trimester-specific differences in use of individual PCP categories by race/ethnicity and SES indicators. We used Poisson regression to estimate trimester-specific mean total product categories used by race/ethnicity and SES indicators. In the first trimester, compared to non-Hispanic White women, Hispanic women reported higher use of hair gel (45% vs. 28%), perfume (75% vs. 39%), and "other" hair products (37% vs. 19%). Compared to women with a college degree, women without a college degree reported higher use of perfume (79% vs. 41%) and bar soap (74% vs. 56%); patterns were similar for insurance status. The estimated mean total product categories used was significantly lower in Asian compared to non-Hispanic White women in all trimesters (e.g., Trimester 1: 4.8 vs. 6.7 categories; p<0.001). Patterns of PCP use differed by race/ethnicity and SES, with implications for potentially modifiable differential EDC exposure and associated pregnancy outcomes. • Endocrine disrupting chemicals (EDCs) are associated with adverse pregnancy outcomes. • Racial/ethnic and socioeconomic disparities in these exposures and outcomes exist. • Personal care products (PCPs) represent modifiable EDC sources. • PCP use during pregnancy differed by race/ethnicity and socioeconomic status. • Asian women used significantly fewer total categories of products than other groups. [ABSTRACT FROM AUTHOR]

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. 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 (n = 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. 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. 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. • We examined associations between urinary trace metals and oxidative stress in pregnancy. • Higher oxidative stress was observed with increasing levels of urinary selenium. • Higher oxidative stress was also observed with increasing levels of urinary copper. • Increasing cumulative trace metals was also associated with higher oxidative stress. [ABSTRACT FROM AUTHOR]