Hypertensive Disorders of Pregnancy and Maternal Cardiovascular Disease Risk Factor Development: An Observational Cohort Study.

Background: Women with a history of hypertensive disorders of pregnancy (HDP) are nearly twice as likely to develop cardiovascular disease (CVD) as those who are normotensive during pregnancy. However, the emergence of CVD risk factors after HDP is less well-understood. Objective: To identify associations between HDP and maternal CVD risk factors and chart the trajectory of risk factor development after pregnancy. Design: Observational cohort study. Setting: United States. Participants: 58 671 parous NHS II (Nurses' Health Study II) participants who did not have CVD or risk factors of interest at baseline. Measurements: Women were followed for self-reported physician diagnosis of chronic hypertension and hypercholesterolemia and confirmed type 2 diabetes mellitus (T2DM) from their first birth through 2013; mean follow-up ranged from 25 to 32 years across these end points. Multivariable Cox proportional hazards models estimated hazard ratios (HRs) and 95% CIs, with adjustment for prepregnancy confounders. Results: Compared with women who were normotensive during pregnancy, those with gestational hypertension (2.9%) or preeclampsia (6.3%) in their first pregnancy had increased rates of chronic hypertension (HRs, 2.8 [95% CI, 2.6 to 3.0] and 2.2 [CI, 2.1 to 2.3], respectively), T2DM (HRs, 1.7 [CI, 1.4 to 1.9] and 1.8 [CI, 1.6 to 1.9], respectively), and hypercholesterolemia (HRs, 1.4 [CI, 1.3 to 1.5] and 1.3 [CI, 1.3 to 1.4], respectively). Although these women were more likely to develop CVD risk factors throughout follow-up, the relative risk for chronic hypertension was strongest within 5 years after their first birth. Recurrence of HDP further elevated risks for all end points. Limitation: Participants self-reported HDP. Conclusion: Women with HDP in their first pregnancy had increased rates of chronic hypertension, T2DM, and hypercholesterolemia that persisted for several decades. These women may benefit from lifestyle intervention and early screening to reduce lifetime risk for CVD. Primary Funding Source: National Institutes of Health.

Trimester-specific phthalate concentrations and glucose levels among women from a fertility clinic.

BACKGROUND: Subfertile women are at increased risk of glucose intolerance in pregnancy. Based on epidemiologic studies, exposure to certain phthalates is associated with diabetes, elevated glucose, and increased insulin resistance. OBJECTIVES: To evaluate the association between urinary phthalate metabolites and pregnancy glucose levels in women seeking medically assisted reproduction. METHODS: We evaluated 245 women participating in a prospective cohort study based at a large fertility clinic who delivered live births and had data on pregnancy urinary phthalate metabolite concentrations and blood glucose levels. Urinary phthalate metabolite concentrations were from single spot urine samples collected in 1st and 2nd trimesters. Blood glucose data was abstracted from medical records for non-fasting 50-g glucose challenge tests at 24-28 weeks gestation. Multivariable linear regression models were used to evaluate associations between 7 urinary phthalate metabolites in quartiles and mean glucose adjusted for potential confounders. RESULTS: Eighteen percent of women had glucose levels ≥ 140 mg/dL. Second trimester monoethyl phthalate (MEP) concentrations were positively associated with glucose levels, with adjusted mean (95%CI) glucose levels of 121 mg/dl (114, 128) vs. 109 mg/dL (103, 116) for women in highest and lowest quartiles, respectively. Women in the highest quartile of second trimester mono-isobutyl phthalate (MiBP) concentrations had a mean glucose level 14 mg/dL lower compared to women in the lowest quartile. No other urinary phthalate metabolites were associated with glucose levels. CONCLUSIONS: MEP and MiBP-metabolites of diethyl phthalate and dibutyl phthalate, respectively-were associated with higher pregnancy glucose in subfertile women-a population at high risk of glucose intolerance in pregnancy.

The association between phthalates and metabolic syndrome: the National Health and Nutrition Examination Survey 2001-2010.

BACKGROUND: Higher exposure to certain phthalates is associated with a diabetes and insulin resistance, with sex differences seen. Yet, little is known about the association between phthalates and metabolic syndrome (MetS), particularly with consideration for differences by sex and menopausal status. METHODS: We analyzed data from 2719 participants in the National Health and Nutrition Examination Survey (NHANES) 2001-2010 aged 20-80 years. Five urinary phthalate metabolites (MEP, MnBP, MiBP, MBzP, and MCPP) and DEHP metabolites were analyzed by the Centers for Disease Control and Prevention and were evaluated as population-specific quartiles. MetS was defined by National Cholesterol Education Program's Adult Treatment Panel III report criteria. Prevalence odds ratios (POR) and 95 % confidence intervals (CI) were calculated using multivariable logistic regression, adjusting for potential confounders and stratifying by sex and menopausal status. RESULTS: Participants with MetS (32 % of the study population) had higher concentrations for all urinary phthalate metabolites. After full adjustment, higher DEHP metabolite concentrations were associated with an increased odds of MetS in men, but not women (adj. POR for men Q4 versus Q1: 2.20; 95 % CI: 1.32, 3.68 and adj. POR for women Q4 versus Q1: 1.50; 95 % CI: 0.89, 2.52). When evaluating by menopausal status, pre-menopausal women with higher concentrations of MBzP had close to a 4-fold increased odds of MetS compared to pre-menopausal women with the lowest concentrations of MBzP (adj POR: Q4 versus Q1: 3.88; 95 % CI: 1.59, 9.49). CONCLUSIONS: Higher concentrations of certain phthalate metabolites were associated with an increased odds of MetS. Higher DEHP metabolite concentrations were associated with an increased odds of MetS for men. In women, the strongest association was between higher concentrations of MBzP and MetS, but only among pre-menopausal women.

Gestational age, infant birth weight, and subsequent risk of type 2 diabetes in mothers: Nurses' Health Study II.

INTRODUCTION: Women with a history of gestational diabetes mellitus (GDM) are at higher risk of developing type 2 diabetes (T2DM); however, little is known about the association between other common pregnancy complications (eg, preterm birth, macrosomia) and T2DM risk. We examined the associations between first-pregnancy preterm, postterm birth, low birth weight, and macrosomia with subsequent risk of T2DM. METHODS: We conducted a prospective cohort study of Nurses' Health Study II (NHSII) participants; 51,728 women in the study had a single live birth and complete pregnancy history. NHSII confirmed incident diabetes mellitus through supplemental questionnaires. Participants were followed from year of first birth until 2005. We defined gestational age as very preterm (20 to ≤32 weeks), moderate preterm (33 to ≤37 weeks), term (38 to ≤42 weeks), and postterm (≥43 weeks). We defined low birth weight as an infant born at term weighing less than 5.5 pounds, and we defined macrosomia as an infant born at term weighing 10 pounds or more. We used Cox proportional hazards models, adjusting for potential confounders. RESULTS: Women with a very preterm birth (2%) had an increased T2DM risk (adjusted hazard ratio, 1.34; 95% confidence interval [CI], 1.05-1.71). This increased risk emerged in the decade following pregnancy. Macrosomia (1.5%) was associated with a 1.61 increased T2DM risk, after adjusting for risk factors, including GDM (95% CI, 1.24-2.08). This association was apparent within the first 5 years after pregnancy. Moderate preterm and term low birth weight did not significantly increase the risk of T2DM over the 35-year follow-up time. CONCLUSION: Women who experienced a very preterm birth or had an infant that weighed 10 pounds or more may benefit from lifestyle intervention to reduce T2DM risk. If replicated, these findings could lead to a reduced risk of T2DM through improved primary care for women experiencing a preterm birth or an infant of nonnormal birth weight.

Associations of insulin pump and continuous glucose monitoring use with pregnancy-related outcomes in women with type 1 diabetes.

AIMS: To examine insulin pump and continuous glucose monitoring (CGM) use with pregnancy-related outcomes in women with type 1 diabetes. METHODS: We abstracted medical records of 646 pregnancies in 478 women with type 1 diabetes, with information on insulin pump versus multiple daily injection (MDI) use and CGM use. We analyzed the associations of pump vs. MDI use, CGM use vs. non-use and pregnancy-related outcomes using mixed effect models. RESULTS: Pump use was associated with lower HbA1c levels in the first [ß (95% CI) = -0.33 (-0.51, -0.15) %] and second trimester [ß (95% CI) = -0.13 (-0.24, -0.02) %], increased birth weight [ß (95% CI) = 0.14 (0.02, 0.26) kg], birth weight percentile [ß (95% CI) = 4.87 (0.49, 9.26) %], higher odds of large for gestational age [OR (95% CI) = 1.65 (1.06, 2.58)] and macrosomia [OR (95% CI) = 1.81 (1.03, 3.18)]. CGM use was associated with lower first [ß (95% CI) = -0.38 (-0.64, -0.13) %] and third trimester [ß (95% CI) = -0.17 (-0.33, -0.00) %] HbA1c levels. CONCLUSIONS: Women with type 1 diabetes who used pump or CGM had better glycemic control during pregnancy; however, pump use was associated with higher birth weight measures.

Impact of "healthier" materials interventions on dust concentrations of per- and polyfluoroalkyl substances, polybrominated diphenyl ethers, and organophosphate esters.

Per- and polyfluoroalkyl substances (PFAS), polybrominated diphenyl ethers (PBDEs), and organophosphate esters (OPEs) are found in building materials and associated with thyroid disease, infertility, and impaired development. This study's objectives were to (1) compare levels of PFAS, PBDEs, and OPEs in dust from spaces with conventional versus "healthier" furniture and carpet, and (2) identify other product sources of flame retardants in situ. We measured 15 PFAS, 8 PBDEs, and 19 OPEs in dust from offices, common areas, and classrooms having undergone either no intervention (conventional rooms in older buildings meeting strict fire codes; n = 12), full "healthier" materials interventions (rooms with "healthier" materials in buildings constructed more recently or gut-renovated; n = 7), or partial interventions (other rooms with at least "healthier" foam furniture but more potential building contamination; n = 28). We also scanned all materials for bromine and phosphorus as surrogates of PBDEs and OPEs respectively, using x-ray fluorescence. In multilevel regression models, rooms with full "healthier" materials interventions had 78% lower dust levels of PFAS than rooms with no intervention (p < 0.01). Rooms with full "healthier" interventions also had 65% lower OPE levels in dust than rooms with no intervention (p < 0.01) and 45% lower PBDEs than rooms with only partial interventions (p < 0.10), adjusted for covariates related to insulation, electronics, and furniture. Bromine loadings from electronics in rooms were associated with PBDE concentrations in dust (p < 0.05), and the presence of exposed insulation was associated with OPE dust concentrations (p < 0.001). Full "healthier" materials renovations successfully reduced chemical classes in dust. Future interventions should address electronics, insulation, and building cross-contamination.

Per- and polyfluoroalkyl substance plasma concentrations and metabolomic markers of type 2 diabetes in the Diabetes Prevention Program trial.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are widely used chemicals, some of which have been linked to type 2 diabetes. We tested whether PFAS concentrations were cross-sectionally associated with metabolites previously shown to predict incident type 2 diabetes using the Diabetes Prevention Program (DPP), a trial of individuals at high risk of type 2 diabetes. METHODS: We evaluated 691 participants enrolled in the DPP with baseline measures of 10 PFAS (including total perfluorooctanesulfonic acid (PFOS), total perfluorooctanoic acid (PFOA), and Sb-PFOA [branched isomers of PFOA]) and 77 metabolites. We used log2-transformed PFAS concentrations as exposures and standardized metabolite concentrations as outcomes in linear regression models adjusted for age, sex, race/ethnicity, use of anti-hyperlipidemic or triglyceride-lowering medication, income, years of education, marital status, smoking, and family history of diabetes, with Benjamini-Hochberg linear step-up false discovery rate correction. RESULTS: Sb-PFOA was associated with the largest number of tested metabolites (29 of 77). Each doubling in Sb-PFOA was associated with higher leucine (ß = 0.07 [95%CI: 0.02, 0.11] SD) and lower glycine (-0.08 [95%CI: 0.03, -0.13] SD). Each doubling of either total PFOA or n-PFOA was associated with -0.13 [95%CI: 0.04, -0.22] SD lower glycine. PFOA and Sb-PFOA were positively associated with multiple triacylglycerols and diacylglycerols, and total PFOS, total PFOA, and Sb-PFOA were positively associated with phosphatidylethanolamines. CONCLUSIONS: PFAS concentrations are associated with metabolites linked to type 2 diabetes (particularly amino acid, glycerolipid and glycerophospholipid pathways). Further prospective research is needed to test whether these metabolites mediate associations of PFAS and type 2 diabetes.

Per- and Polyfluoroalkyl Substance Exposure, Gestational Weight Gain, and Postpartum Weight Changes in Project Viva.

OBJECTIVE: The purpose of this study was to test the extent to which pregnancy per- and polyfluoroalkyl substance (PFAS) concentrations were associated with gestational weight gain and postpartum weight changes. METHODS: This study was composed of 1,614 women recruited between 1999 and 2002 via the Project Viva cohort with pregnancy plasma concentrations of six PFAS, including perfluorooctanesulfonic acid, perfluorooctanoic acid (PFOA), and 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid. Gestational weight gain was defined as the difference between last pregnancy weight and prepregnancy weight, 1-year postpartum weight retention as the difference between 1-year postpartum weight and prepregnancy weight, and 3-year postpartum weight change as the difference between 3-year postpartum weight and prepregnancy weight. RESULTS: During pregnancy, women gained 0.37 kg (95% CI: 0.11-0.62) more weight per doubling of 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid. At 1 year post partum, women retained 0.55 kg (95% CI: 0.07-1.04) more weight per doubling of PFOA. At 3 years post partum, women gained 0.91 kg (95% CI: 0.25-1.56) more weight per doubling in PFOA. Findings were similar after adjustment for all PFAS. Other PFAS were not associated with weight changes. Postpartum associations were stronger among women with higher prepregnancy BMI. Models were adjusted for demographics. CONCLUSIONS: Pregnancy PFAS were associated with greater gestational weight gain, weight retention, and weight gain years after pregnancy.

Pregnancy Per- and Polyfluoroalkyl Substance Concentrations and Postpartum Health in Project Viva: A Prospective Cohort.

CONTEXT: Per- and polyfluoroalkyl substances (PFAS) are environmental chemicals linked to weight gain and type 2 diabetes. OBJECTIVE: We examined the extent to which PFAS plasma concentrations during pregnancy were associated with postpartum anthropometry and biomarkers. DESIGN, PATIENTS, AND MEASURES: We studied women recruited between 1999 and 2002 in the Project Viva prospective cohort with pregnancy plasma concentrations of PFAS, including perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and 2-(N-ethyl-perfluorooctane sulfonamide) acetic acid (EtFOSAA). Three-year postpartum anthropometry measurements were available from 786 to 801 women, blood pressure from 761 women, and blood biomarkers from 450 to 454 women. We used multivariable regression to evaluate the association of log2-transformed PFAS with postpartum anthropometry, blood pressure, and blood biomarkers (leptin, adiponectin, sex hormone binding globulin [SHBG], hemoglobin A1c, interleukin-6 [IL-6], C-reactive protein), adjusting for age, prepregnancy body mass index, marital status, race/ethnicity, education, income, smoking, parity, and breastfeeding history. RESULTS: Pregnancy concentrations of certain PFAS were associated with greater adiposity (eg, 0.4 cm [95% confidence interval [95%CI]: -0.1, 0.9] greater waist circumference per doubling in EtFOSAA; 0.2 cm [95%CI: -0.1, 0.5] greater mid-upper arm circumference per doubling in PFOA; 1.2 mm [95%CI: 0.1, 2.2] thicker sum of subscapular and triceps skinfolds per doubling in PFOS) and higher systolic blood pressure (eg, 1.2 mm Hg [95%CI: 0.3, 2.2] per doubling in PFOS) at 3 years postpartum. Higher EtFOSAA concentrations were also associated with 10.8% higher IL-6 (95%CI: 3.3, 18.9) and 6.1% lower SHBG (95%CI: 0.7, 11.2) per doubling. CONCLUSIONS: Pregnancy concentrations of EtFOSAA, PFOS, and PFOA were associated with adverse postpartum cardiometabolic markers.

Time trends in pregnancy-related outcomes among women with type 1 diabetes mellitus, 2004-2017.

OBJECTIVE: To examine time trends in US pregnant women with type 1 diabetes mellitus for maternal characteristics and pregnancy outcomes. STUDY DESIGN: We abstracted clinical data from the medical records of 700 pregnant women from 2004 to 2017. For each time period, means and percentages were calculated. P values for trend were calculated using linear and logistic regression. RESULTS: HbA1c in each trimester was unchanged across the analysis period. The prevalence of nephropathy decreased from 4.8% to 0% (P = 0.002). Excessive gestational weight gain increased (P = 0.01). Gestation length also increased (P = 0.01), as did vaginal deliveries (P = 0.03). There were no change in birthweight over time (P = 0.07) and the percentage of neonates with macrosomia and large for gestational age (LGA) neonates also remained unchanged. CONCLUSION: Obstetric guideline changes may have improved gestation length and mode of delivery; however, other outcomes need more attention, including excessive gestational weight gain, macrosomia, and LGA.

Phthalate metabolite exposures among immigrants living in the United States: findings from NHANES, 1999-2014.

Phthalates exposure has been linked to multiple health risks, and US immigrants may have different exposures to phthalates due to lifestyle differences. Urinary concentrations of eight phthalate metabolites (mono-ethyl phthalate [MEP], mono-n-butyl phthalate [MnBP], mono-isobutyl phthalate [MiBP], mono-(3-carboxypropyl) phthalate [MCPP], mono-benzyl phthalate [MBzP], mono-2-ethylhexyl phthalate [MEHP], mono-(2-ethyl-5-hydroxyhexyl) phthalate [MEHHP], mono-(2-ethyl-5-oxohexyl) phthalate [MEOHP]) were measured in 10318 US-born and 3511 foreign-born individuals from NHANES 1999-2014. Using multivariate adjusted linear regression, we assessed whether phthalate metabolite levels differed by nativity in the whole population, within racial/ethnic groups, and by years in the US. We also tested whether immigrant demographics predicted phthalate metabolite levels. In fully adjusted models, MEP, MnBP, and MiBP were significantly higher, and MBzP significantly lower, among immigrants than US-born participants. Among immigrants, MnBP and MiBP significantly declined with longer time in the US (Ptrend = 0.029 and Ptrend = 0.039, respectively), while MCPP and MBzP significantly rose (Ptrend = 0.019 and Ptrend = 0.043, respectively). Results within each racial/ethnic group were consistent with the whole population. Among immigrants, women had significantly higher metabolite levels than men (all p < 0.01), and MEP, MnBP, and MCPP differed by race/ethnicity. Due to higher phthalate exposures, immigrants may be especially vulnerable to phthalate-associated health problems.

Preterm Delivery and Maternal Cardiovascular Disease Risk Factors: The Nurses' Health Study II.

Background: Preterm delivery has been linked to future maternal cardiovascular disease (CVD); however, research investigating clinical CVD risk factors is limited. We evaluated whether women who have delivered an infant preterm are at higher risk of developing CVD risk factors after adjustment for prepregnancy confounders. Materials and Methods: We examined the association between preterm delivery and incident chronic hypertension, type 2 diabetes mellitus (T2DM), and hypercholesterolemia among 57,904 parous women in the Nurses' Health Study II. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between preterm delivery in first pregnancy and each CVD risk factor; adjusted cumulative incidence curves were computed using the Breslow estimator. Results: Preterm delivery (<37 weeks) was associated with HRs of 1.11 (95% CI: 1.06-1.17) for chronic hypertension, 1.17 (95% CI: 1.03-1.33) for T2DM, and 1.07 (95% CI: 1.03-1.11) for hypercholesterolemia, adjusting for age, race/ethnicity, parental education, and prepregnancy confounders (e.g., body mass index, smoking, and family history). HRs were higher in women who delivered very preterm (<32 weeks) and in the first 10 years after first birth. The cumulative incidence of each risk factor was highest in women who delivered very preterm. Conclusions: Women with a history of preterm delivery are at higher risk of developing chronic hypertension, T2DM, and hypercholesterolemia in the years after pregnancy. This increased risk was particularly pronounced in the first 10 years after a preterm delivery, indicating that it may be an important time period to implement lifestyle interventions.

Nonsteroidal anti-inflammatory drugs and change in mammographic density: a cohort study using pharmacy records on over 29,000 postmenopausal women.

BACKGROUND: Use of nonsteroidal anti-inflammatory drugs (NSAID) has been associated with a decrease in breast cancer risk, but it is unknown if they also reduce mammographic density, a strong intermediate marker of breast cancer risk. METHODS: We investigated NSAID use and mammographic density in 29,284 postmenopausal women who had two screening mammograms at Group Health in Seattle. We used pharmacy records to classify women as NSAID nonusers, continuers, initiators, or discontinuers based on use between the two mammograms and nine separate prescription and nonprescription NSAID classes. Using unordered polytomous logistic regression methods, we modeled the odds ratio (OR) of staying not dense, decreasing density, or increasing density relative to remaining dense based on Breast Imaging Reporting Data System classification of density. RESULTS: There was no association with density change from initiation or continuation of NSAIDs. However, both initiators and continuers of any NSAIDs were more likely to stay not dense than stay dense [OR, 1.12; 95% confidence interval (95% CI), 1.04-1.20; OR, 1.25; 95% CI, 1.05-1.49, respectively]. This association with staying not dense for initiators and continuers of any NSAID use was observed primarily among women ages <65 years at first mammogram (OR, 1.24; 95% CI, 1.12-1.36; OR, 1.48; 95% CI, 1.14-1.93, respectively). CONCLUSIONS: Initiation of NSAID use did not reduce mammographic density over the short term. Continuers of NSAID use were more likely to stay not dense compared with nonusers, suggesting that it is plausible that longer-term use of NSAIDs may be needed to reduce density.

Racial and ethnic variations in phthalate metabolite concentration changes across full-term pregnancies.

Higher concentrations of certain phthalate metabolites are associated with adverse reproductive and pregnancy outcomes, as well as poor infant/child health outcomes. In non-pregnant populations, phthalate metabolite concentrations vary by race/ethnicity. Few studies have documented racial/ethnic differences between phthalate metabolite concentrations at multiple time points across the full-course of pregnancy. The objective of the study was to characterize the change in phthalate metabolite concentrations by race/ethnicity across multiple pregnancy time points. Women were participants in a prospectively collected pregnancy cohort who delivered at term (≥37 weeks) and had available urinary phthalate metabolite concentrations for ≥3 time points across full-term pregnancies (n=350 women). We assessed urinary concentrations of eight phthalate metabolites that were log-transformed and specific gravity-adjusted. We evaluated the potential racial/ethnic differences in phthalate metabolite concentrations at baseline (median 10 weeks gestation) using ANOVA and across pregnancy using linear mixed models to calculate the percent change and 95% confidence intervals adjusted for sociodemographic and lifestyle factors. Almost 30% of the population were non-Hispanic black or Hispanic. With the exception of mono-(3-carboxypropyl) (MCPP) and di-ethylhexyl phthalate (DEHP) metabolites, baseline levels of phthalate metabolites were significantly higher in non-whites (P<0.05). When evaluating patterns by race/ethnicity, mono-ethyl phthalate (MEP) and MCPP had significant percent changes across pregnancy. MEP was higher in Hispanics at baseline and decreased in mid-pregnancy but increased in late pregnancy for non-Hispanic blacks. MCPP was substantially higher in non-Hispanic blacks at baseline but decreased later in pregnancy. Across pregnancy, non-Hispanic black and Hispanic women had higher concentrations of certain phthalate metabolites. These differences may have implications for racial/ethnic differences in adverse pregnancy and child health outcomes.

Racial/ethnic disparities in environmental endocrine disrupting chemicals and women's reproductive health outcomes: epidemiological examples across the life course.

Disparities in women's reproductive health outcomes across the life course have been well-documented. Endocrine disrupting chemicals may be one factor driving disparities, as studies suggest exposure to certain environmental endocrine disrupting chemicals, such as certain phthalates, bisphenol A, parabens and polybrominated diphenyl ethers are higher in non-whites. Yet, a limited amount of research has focused on these chemical exposures as a potential mediator of racial/ethnic differences in women's reproductive health outcomes, such as pubertal development, fibroids, infertility, and pregnancy complications. Given that race/ethnicity is a social construct, the purpose of this review was to present the current state of the literature on racial/ethnic disparities in both environmental endocrine disrupting chemicals, as well as associations between these chemicals and selected women's reproductive health outcomes. Our goal was to evaluate literature from populations based in the United States to: 1) characterize racial/ethnic differences in environmental endocrine disrupting chemicals and 2) systematically review literature on environmental endocrine disrupting chemicals and selected women's health outcomes in populations containing more than one racial/ethnic group. This review highlights the need for future work in determining whether higher exposures to some environmental endocrine disrupting chemicals might partly explain differences in women's reproductive health outcomes in these higher-exposure and high-risk groups.

Pregnancy urinary phthalate metabolite concentrations and gestational diabetes risk factors.

BACKGROUND: Epidemiologic studies suggest phthalate metabolite concentrations are associated with type 2 diabetes. GDM is a strong risk factor for type 2 diabetes. Little is known about phthalates and GDM risk factors (i.e. 1st trimester body mass index (BMI), gestational weight gain (GWG), and 2nd trimester glucose levels). METHODS: A total of 350 women participating in Lifecodes pregnancy cohort (Boston, MA), delivered at term and had pregnancy urinary phthalate metabolite concentrations. Nine specific gravity-adjusted urinary phthalate metabolites were evaluated. General linear regression was used to assess associations between quartiles of phthalate metabolites and continuous 1st trimester BMI and late 2nd trimester blood glucose. Linear mixed models were used for total GWG. Multivariable logistic regression was used for phthalate concentrations and categorized GWG and impaired glucose tolerance defined as glucose≥140mg/dL based on a 50-gram glucose load test. Models were adjusted for potential confounders. RESULTS: There were no associations between 1st trimester urinary phthalate metabolite concentrations and 1st trimester BMI. Mono-ethyl phthalate concentrations averaged across pregnancy were associated with a 2.17 increased odds of excessive GWG (95% CI: 0.98, 4.79). Second trimester mono-ethyl phthalate was associated with increased odds of impaired glucose tolerance (adj. OR: 7.18; 95% CI: 1.97, 26.15). A summary measure of di-2-ethylhexyl phthalate metabolite concentrations were inversely associated with impaired glucose tolerance (adj. OR: 0.25; adj. 95% CI: 0.08, 0.85). CONCLUSIONS: Higher exposure to mono-ethyl phthalate, a metabolite of the parent compound of di-ethyl phthalate, may be associated with excessive GWG and impaired glucose tolerance; higher di-2-ethylhexyl phthalate was associated with reduced odds of impaired glucose tolerance.