Polybrominated diphenyl ethers and gestational weight gain: a multi-center prospective cohort study.

OBJECTIVE: To evaluate the associations of plasma polybrominated diphenyl ether (PBDE) concentrations in early pregnancy with gestational weight gain (GWG). DESIGN: Prospective cohort study. SETTING: US-based, multicentre cohort of pregnant women. POPULATION: We used data from 2052 women without obesity and 397 women with obesity participating in the NICHD Fetal Growth Studies - Singleton Cohort, with first-trimester plasma PBDE concentrations and weight measurements throughout pregnancy. METHODS: We applied generalised linear models and Bayesian kernel machine regression (BKMR) to evaluate both the individual and joint associations of PBDEs with measures of GWG, adjusting for potential confounders. MAIN OUTCOME MEASURES: Total GWG (kg), total and trimester-specific GWG velocities (kg/week), and GWG categories and trajectory groups. RESULTS: Mean pre-pregnancy BMIs were 23.6 and 34.5 kg/m2 for women without and with obesity, respectively. Among women without obesity, there were no associations of PBDEs with any GWG measure. Among women with obesity, one standard deviation increase in log-transformed PBDE 47 was associated with a 1.87 kg higher total GWG (95% CI 0.39-3.35) and a 0.05 kg/week higher total GWG velocity (95% CI 0.01-0.09). Similar associations were found for PBDE 47 in BKMR among women with obesity, and PBDE 47, 99 and 100 were associated with lower odds of being in the low GWG trajectory group. CONCLUSIONS: PBDEs were not associated with GWG among individuals without obesity. Among those with obesity, only PBDE 47 showed consistent positive associations with GWG measures across multiple statistical methods. Further research is needed to validate this association and explore potential mechanisms.

Use of Chemical Hair Straighteners and Fecundability in a North American Preconception Cohort.

Chemical hair straighteners ("relaxers") are used by millions of North Americans, particularly women of color. Hair relaxers may contain endocrine-disrupting compounds, which can harm fertility. We evaluated the association between hair relaxer use and fecundability among 11,274 participants from Pregnancy Study Online (PRESTO), a North American preconception cohort study. During 2014-2022, participants completed a baseline questionnaire in which they reported their history of relaxer use and completed follow-up questionnaires every 8 weeks for 12 months or until pregnancy, whichever came first. We used multivariable-adjusted proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs). Relative to never use, fecundability was lower among current (FR = 0.81, 95% CI: 0.64, 1.03) and former (FR = 0.89, 95% CI: 0.81, 0.98) users of hair relaxers. FRs for first use of hair relaxers at ages <10, 10-19, and ≥20 years were 0.73 (95% CI: 0.55, 0.96), 0.93 (95% CI: 0.83, 1.04), and 0.85 (95% CI: 0.74, 0.98), respectively. Fecundability was lowest among those with longer durations of use (≥10 years vs. never: FR = 0.71, 95% CI: 0.54, 0.91) and more frequent use (≥5 times/year vs. never: FR = 0.82, 95% CI: 0.60, 1.11), but associations were nonmonotonic. In this preconception cohort study, use of chemical hair straighteners was associated with slightly reduced fecundability.

Urinary phthalate metabolite concentrations and hot flash outcomes: Longitudinal associations in the Midlife Women's Health Study.

Midlife in women is an understudied time for environmental chemical exposures and menopausal outcomes. Recent cross-sectional research links phthalates with hot flashes, but little is known regarding such associations over time. Our objective was to estimate longitudinal associations between repeated measures of urinary phthalate metabolite concentrations and hot flash outcomes in midlife women. Using data from the Midlife Women's Health Study (MWHS), a prospective longitudinal study, we fit generalized linear mixed-effects models (GLMMs) and Cox proportional hazards regression models to repeated measures over a 4-year period. Recruitment occurred in Baltimore and surrounding counties, Maryland, USA between 2006 and 2015. Participants were premenopausal/perimenopausal women (n = 744) aged 45-54 years, who were not pregnant, not taking menopausal symptom medication or oral contraceptives, did not have hysterectomy/oophorectomy, and irrespective of hot flash experience. Baseline mean (SD) age was 48.4 (2.45), and 65% were premenopausal. Main outcome measures included adjusted odds ratios (ORs) for 4 self-reported hot flash outcomes (ever experienced, past 30 days experience, weekly/daily, and moderate/severe), and hazard ratios (HRs) for incident hot flashes. We observed mostly increased odds of certain hot flash outcomes with higher concentrations of metabolites of di (2-ethylhexyl) phthalate (DEHP), monoisobutyl phthalate (MiBP), and a molar summary measure of plasticizer phthalate metabolites (DEHP metabolites, mono-(3-carboxypropyl) phthalate (MCPP), monobenzyl phthalate (MBzP)). Some associations between exposures and outcomes indicated decreased odds. In conclusion, phthalate metabolites were associated with certain hot flash outcomes in midlife women. Midlife may be a sensitive period for higher phthalate metabolite concentrations with respect to menopausal symptoms.

Use of personal care products during pregnancy and birth outcomes - A pilot study.

Prenatal exposure to endocrine disrupting chemicals (EDCs) from personal care products may be associated with birth outcomes including preterm birth and low birth weight. There is limited research examining the role of personal care product use during pregnancy on birth outcomes. Our pilot study consisted of 164 participants in the Environmental Reproductive and Glucose Outcomes (ERGO) study (Boston, MA), with data on self-reported personal care product use at four study visits throughout pregnancy (product use in the 48 h before a study visit and hair product use in the month before a study visit). We used covariate-adjusted linear regression models to estimate differences in mean gestational age at delivery, birth length, and sex-specific birth weight-for-gestational age (BW-for-GA) Z-score based on personal care product use. Hair product use in the past month prior to certain study visits was associated with decreased mean sex-specific BW-for-GA Z-scores. Notably, hair oil use in the month prior to study visit 1 was associated with a lower mean BW-for-GA Z-score (V1: -0.71, 95% confidence interval: -1.12, -0.29) compared to non-use. Across all study visits (V1-V4), increased mean birth length was observed among nail polish users vs. non-users. In comparison, decreased mean birth length was observed among shave cream users vs. non-users. Liquid soap, shampoo, and conditioner use at certain study visits were significantly associated with higher mean birth length. Suggestive associations were observed across study visits for other products including hair gel/spray with BW-for-GA Z-score and liquid/bar soap with gestational age. Overall, use of a variety of personal care products throughout pregnancy was observed to be associated with our birth outcomes of interest, notably hair oil use during early pregnancy. These findings may help inform future interventions/clinical recommendations to reduce exposures linked to adverse pregnancy outcomes.

Associations of urinary metabolite concentrations of phthalates and phthalate replacements with body composition from mid-childhood to early adolescence.

BACKGROUND: Phthalates may adversely influence body composition by lowering anabolic hormones and activating peroxisome-proliferator activated receptor gamma. However, data are limited in adolescence when body mass distributions rapidly change and bone accrual peaks. Also, potential health effects of certain phthalate/replacements [e.g., di-2-ethylhexyl terephthalate (DEHTP)] have not been well studied. METHODS: Among 579 children in the Project Viva cohort, we used linear regression to evaluate associations of urinary concentrations of 19 phthalate/replacement metabolites from mid-childhood (median: 7.6 years; 2007-2010) with annualized change in areal bone mineral density (aBMD) and lean, total fat, and truncal fat mass as measured by dual-energy X-ray absorptiometry between mid-childhood and early adolescence (median: 12.8 years). We used quantile g-computation to assess associations of the overall chemical mixture with body composition. We adjusted for sociodemographics and tested for sex-specific associations. RESULTS: Urinary concentrations were highest for mono-2-ethyl-5-carboxypentyl phthalate [median (IQR): 46.7 (69.1) ng/mL]. We detected metabolites of most replacement phthalates in a relatively small number of participants [e.g., 28% for mono-2-ethyl-5-hydrohexyl terephthalate (MEHHTP; metabolite of DEHTP)]. Detectable (vs. non-detectable) MEHHTP was associated with less bone and greater fat accrual in males and greater bone and lean mass accrual in females [e.g., change in aBMD Z-score/year (95% CI): -0.049 (-0.085, -0.013) in males versus 0.042 (0.007, 0.076) in females; pinteraction<0.01]. Children with higher concentrations of mono-oxo-isononyl phthalate and mono-3-carboxypropyl phthalate (MCPP) had greater bone accrual. Males with higher concentrations of MCPP and mono-carboxynonyl phthalate had greater accrual of lean mass. Other phthalate/replacement biomarkers, and their mixtures, were not associated with longitudinal changes in body composition. CONCLUSIONS: Concentrations of select phthalate/replacement metabolites in mid-childhood were associated with changes in body composition through early adolescence. As use of phthalate replacements such as DEHTP may be increasing, further investigation can help better understand the potential effects of early-life exposures.

Determinants of urinary phthalate biomarker concentrations in pre- and perimenopausal women with consideration of race.

BACKGROUND/OBJECTIVES: Phthalates are endocrine disruptors in consumer plastics and personal care products. Our objectives were to identify determinants of phthalate biomarkers in women during the hormonally-sensitive midlife period, and to consider differences between non-Hispanic White and Black women. METHODS: We used information from the Midlife Women's Health Study of pre- and peri-menopausal women from Baltimore, Maryland (enrolled 2006-2015). We collected sociodemographic/health information via baseline questionnaires or during clinic visits and measured nine phthalate metabolites in pools of 2-4 urines collected across one menstrual cycle. We calculated molar sums of metabolites to estimate exposure to di(2-ethylhexyl) phthalate (ΣDEHP), personal care product phthalates (ΣPCPs), and phthalates in plastics (ΣPlastics). Accounting for meaningful predictors from bivariable analyses, our multivariable linear regression models evaluated determinants of phthalate biomarkers in all women (n = 689), non-Hispanic White women only (n = 467), or non-Hispanic Black women only (n = 195). RESULTS: In multivariable analyses of all women, those who were perimenopausal, widowed/divorced, non-Hispanic Black, with higher family income, with lower BMI, or who reported more frequent nausea had higher monoethyl phthalate (MEP) and ΣPCP. Non-Hispanic White women who were perimenopausal had lower mono-(3-carboxypropyl) phthalate (MCPP) and monobutyl phthalate (MBP), those who consume alcohol had higher mono-isobutyl phthalate (MiBP), and those with higher BMI had lower MEP and higher MCPP. Alternatively, widowed/divorced Black women had higher ΣDEHP, monobenzyl phthalate (MBzP), and ΣPlastics, whereas Black women with higher income had higher MEP and ΣPCP. Black women who described themselves as having "as much" physical activity as others or who reported a skin condition had lower MBzP and MCPP, respectively. CONCLUSION: We identified important determinants of phthalate biomarkers in midlife women and observed some differences by race. Future studies could consider reasons for these differences when developing interventions to reduce phthalate disparities and related health effects.

Urinary polycyclic aromatic hydrocarbon excretion and regional body fat distribution: evidence from the U.S. National Health and Nutrition Examination Survey 2001-2016.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants that may contribute to the etiology of obesity. However, it is unclear whether PAHs from environmental sources are associated with regional body fat distribution, and whether the association varies across racial/ethnic groups who may have differential PAH exposure patterns. OBJECTIVES: To examine correlations between PAHs and body fat distribution, and potential racial/ethnic differences among U.S. adults. METHODS: Ten PAHs were measured in spot urine samples from 2691 non-smoking adults (age ≥ 20 years) in the NHANES 2001-2016. Dual-energy X-ray absorptiometry was used to measure fat mass percent (FM%). Partial Pearson correlation coefficients (r) with multivariable adjustment were used to assess PAH-FM% associations. RESULTS: In the total population, 1-naphthalene, 3-fluorene, and 1-pyrene were inversely correlated with total FM% or trunk FM% (adjusted r ranged: - 0.06 to - 0.08), while 2-naphthalene, 9-fluorene, and 4-phenanthrene were positively correlated with the FM% measurements (r: 0.07-0.11). PAH levels are highest among non-Hispanic Blacks, followed by Hispanics and Whites and some of the correlations were different by these races/ethnicities. Among non-Hispanic Whites, no PAH was correlated with FM%. In contrast, 9-fluorene was positively correlated with total FM% (r = 0.20) and trunk FM% (r = 0.22) among Blacks, and 4-phenanthrene was positively correlated with total FM% (r = 0.23) and trunk FM% (r = 0.24) among Hispanics (P-interaction: 0.010-0.025). DISCUSSION: In this US adult population, certain PAHs are significantly associated with higher body fat contents among non-Hispanic Blacks and Hispanics but not non-Hispanic Whites, suggesting that minority groups might be particularly susceptible to PAH's obesogenic effects or the effects of other factors that determine the PAH exposure levels. Alternatively, differences in body composition may contribute to differential PAH metabolism in minority groups. Future studies are warranted to explore the racial/ethnic disparity in PAH exposures, drivers of these exposure differences, and mechanisms through which PAHs may influence body composition by races/ethnicities.

Socioeconomic and racial/ethnic differences in use of endocrine-disrupting chemical-associated personal care product categories among pregnant women.

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.

Identifying windows of susceptibility to endocrine disrupting chemicals in relation to gestational weight gain among pregnant women attending a fertility clinic.

BACKGROUND: Exposure to endocrine disrupting chemicals (EDC), such as phthalates and phenols, during pregnancy may be associated with excessive gestational weight gain (GWG), an important predictor of future health of the mother and the offspring. There is however a paucity of literature examining this association, and no study has accounted for the complex nature of EDCs exposure as a time-varying mixture of chemicals. OBJECTIVE: We examined the association between trimester-specific EDCs mixture and GWG in pregnant women attending a fertility clinic, to identify windows of susceptibility to such exposures, and assess the individual contribution of each chemical over pregnancy. METHODS: We included 243 pregnant women from the Environment and Reproductive Health (EARTH) Study, who provided up to 3 urine samples (one per trimester), and with available data on GWG. Urinary concentrations of 7 phthalate metabolites, bisphenol A, and 2 parabens, corrected for specific gravity, were included in the analysis. The association between trimester-specific EDCs mixture and GWG was evaluated using multiple regression models - categorizing exposures into concentration quartiles- and with Bayesian Kernel Machine Regression (BKMR), while adjusting for potential confounders. Hierarchical BKMR (hBKMR) was used to account for the time-varying nature of chemical concentrations over pregnancy, identifying the most important trimester and most important EDC within each trimester. RESULTS: During 1st trimester, higher GWG was observed at higher sum of metabolites of di (2-ethylhexyl) phthalate (ΣDEHP) from both multiple regression (e.g. comparing the 4th quartile with the 1st: ß = 2.36 kg, 95% CI: 0.47, 5.19) and BKMR. During 2nd and 3rd trimesters, positive associations with mono-n-butyl phthalate and propylparaben, and negative with ΣDEHP and methylparaben were observed. When evaluating exposures as a time-varying mixture with hBKMR, 1st trimester was the most important exposure window when evaluating prenatal urinary EDCs in relation to GWG. Within the 1st trimester, urinary ΣDEHP, mono-isobutyl phthalate and propylparaben had the highest contribution in the positive association between the mixture and GWG. CONCLUSION: We observed positive associations between urinary EDCs during pregnancy, especially DEHP metabolites, and GWG. Our results suggest the 1st trimester of pregnancy as the time window of highest susceptibility to the effects of EDCs on GWG, with potential indication for the design of public health interventions, informing prevention strategies for reducing sources of exposure at specific time points.

Urinary phthalate metabolite concentrations and hot flashes in women from an urban convenience sample of midlife women.

CONTEXT: Phthalate exposure is associated with altered reproductive function, but little is known about associations of phthalate exposure with risk of hot flashes. OBJECTIVE: To investigate associations of urinary phthalate metabolite levels with four hot flash outcomes in midlife women. DESIGN: A cross-sectional study of the first year of a prospective cohort of midlife women, the Midlife Women's Health Study (2006-2015), a convenience sample from an urban setting. PARTICIPANTS: 728 multi-racial/ethnic pre- and perimenopausal women aged 45-54 years. OUTCOME MEASURES: Women completed questionnaires about hot flash experience and provided 1-4 urine samples over four consecutive weeks that were pooled for analysis. Phthalate metabolites were assessed individually and as molar sums representative of common compounds (all phthalates: Æ©Phthalates; DEHP: Æ©DEHP), exposure sources (plastics: Æ©Plastic; personal care products: Æ©PCP), and modes of action (anti-androgenic: Æ©AA). Covariate-adjusted logistic regression models were used to assess associations of continuous natural log-transformed phthalate metabolite concentrations with hot flash outcomes. Analyses were conducted to explore whether associations differed by menopause status, body mass index (BMI), race/ethnicity, and depressive symptoms. RESULTS: Overall, 45% of women reported a history of hot flashes. Compared to women who never experienced hot flashes, every two-fold increase in Æ©Plastic was associated with 18% (OR: 1.18; 95%CI: 0.98, 1.43) and 38% (OR: 1.38; 95%CI: 1.11, 1.70) higher odds of experiencing hot flashes in the past 30 days and experiencing daily/weekly hot flashes, respectively. Some associations of phthalates with certain hot flash outcomes differed by menopause status, BMI, race/ethnicity, and depressive symptoms. CONCLUSIONS: This study suggests that phthalates are associated with hot flash experience and may impact hot flash risk in women who are susceptible to experiencing hot flashes.

Persistent organic pollutants and maternal glycemic outcomes in a diverse pregnancy cohort of overweight women.

BACKGROUND: Animal and human studies suggest certain persistent organic pollutants (POPs) may impact glucose metabolism; however, few epidemiologic studies have examined environmental determinants of glycemic outcomes during pregnancy. Our objective is to evaluate associations between exposures to individual and mixture of POPs and measures of prenatal fasting glucose, insulin, and insulin resistance during pregnancy in overweight women. METHODS: A cohort of overweight and obese pregnant women (N = 95) was recruited from California. Blood samples were collected during late first or second trimester (median = 16 weeks' gestation; range = 10-24 weeks). Exposures included serum concentrations of polybrominated diphenyl ethers (PBDEs) and hydroxylated metabolites (OH-PBDEs), polychlorinated biphenyls (PCBs), and poly- and perfluoroalkyl substances (PFASs). Outcomes included serum concentrations of fasting plasma glucose, fasting plasma insulin, and calculated homeostatic model assessment of insulin resistance (HOMA-IR). Generalized linear models were used to evaluate cross-sectional associations between individual and aggregate POPs and mean percent difference in fasting glucose, fasting insulin, and HOMA-IR. Bayesian kernel machine regression (BKMR) was used to assess the relative importance of each exposure to the association with our outcomes, using conditional and group posterior inclusion probabilities (PIPs). RESULTS: Study participants were racially/ethnically diverse and nearly half were below the federal poverty level. Across PBDEs and OH-PBDEs, the direction of associations with fasting glucose, fasting insulin and HOMA-IR were varied. A doubling of PCB-138, PCB-153, PCB-180, and ∑PCBs concentrations was associated with a 2.10% mmol/L (95%CI: 0.49%, 3.74%), 2.10% mmol/L (95%CI: -0.14%, 4.39%), 2.10% mmol/L (95%CI: 0.12%, 4.12%), and 2.81% mmol/L (95%CI: 0.38%, 5.31%) increase in fasting glucose, respectively. Exposure to individual PCBs was positively associated with both fasting insulin and HOMA-IR. All PFAS were inversely associated with fasting glucose, fasting insulin, and HOMA-IR. In BKMR models of fasting glucose, all four chemical classes were important contributors to the overall mixture, with PFASs identified as the most important contributor. DISCUSSION: Prenatal PCB exposure was positively associated while certain PBDE and PFAS analytes were inversely associated with fasting glucose concentrations in overweight women. Further examination of the relationship between POPs exposure and glycemic functioning in a larger study population of women during pregnancy is warranted.

Endocrine disrupting chemical-associated hair product use during pregnancy and gestational age at delivery: a pilot study.

BACKGROUND: Prenatal endocrine disrupting chemical (EDC) exposure has been associated with increased risk of preterm birth. Non-Hispanic Black women have higher incidence of preterm birth compared to other racial/ethnic groups and may be disproportionately exposed to EDCs through EDC-containing hair products. However, research on the use of EDC-associated hair products during pregnancy and risk of preterm birth is lacking. Therefore, the objective of this pilot study was to estimate associations of prenatal hair product use with gestational age at delivery in a Boston, Massachusetts area pregnancy cohort. METHODS: The study population consisted of a subset of participants enrolled in the Environmental Reproductive and Glucose Outcomes (ERGO) Study between 2018 and 2020. We collected self-reported data on demographics and hair product use using a previously validated questionnaire at four prenatal visits (median: 12, 19, 26, 36 weeks' gestation) and abstracted gestational age at delivery from medical records. We compared gestational age and hair product use by race/ethnicity and used linear regression to estimate covariate-adjusted associations of product use and frequency of use at each study visit with gestational age at delivery. Primary models were adjusted for maternal age at enrollment and delivery method. RESULTS: Of the 154 study participants, 7% delivered preterm. Non-Hispanic Black participants had lower mean gestational age at delivery compared to non-Hispanic White participants (38.2 vs. 39.2 weeks) and were more likely to report ever and more frequent use of hair products. In regression models, participants reporting daily use of hair oils at visit 4 had lower mean gestational age at delivery compared to non-users (ß: -8.3 days; 95% confidence interval: -14.9, -1.6). We did not find evidence of associations at earlier visits or with other products. CONCLUSIONS: Frequent use of hair oils during late pregnancy may be associated with shorter gestational duration. As hair oils are more commonly used by non-Hispanic Black women and represent potentially modifiable EDC exposure sources, this may have important implications for the known racial disparity in preterm birth.

Ambient PM gross ß-activity and glucose levels during pregnancy.

BACKGROUND: Exposure to ionizing radiation has been associated with insulin resistance and type 2 diabetes. In light of recent work showing an association between ambient particulate matter (PM) gross ß-activity and gestational diabetes mellitus (GDM) among pregnant women, we examined pregnancy glucose levels in relation to PM gross ß-activity to better understand this pathway. METHODS: Our study included 103 participants receiving prenatal care at Beth Israel Deaconess Medical Center in Boston, MA. PM gross ß-activity was obtained from US Environmental Protection Agency's RadNet program monitors, and blood glucose levels were obtained from the non-fasting glucose challenge test performed clinically as the first step of the 2-step GDM screening test. For each exposure window we examined (i.e., moving average same-day, one-week, first-trimester, and second-trimester PM gross ß-activity), we fitted generalized additive models and adjusted for clinical characteristics, socio-demographic factors, temporal variables, and PM with an aerodynamic diameter ≤ 2.5 µm (PM2.5). Subgroup analyses by maternal age and by body mass index were also conducted. RESULTS: An interquartile range increase in average PM gross ß-activity during the second trimester of pregnancy was associated with an increase of 17.5 (95% CI: 0.8, 34.3) mg/dL in glucose concentration. Associations were stronger among younger and overweight/obese participants. Our findings also suggest that the highest compared to the lowest quartile of one-week exposure was associated with 17.0 (95% CI: - 4.0, 38.0) mg/dL higher glucose levels. No associations of glucose were observed with PM gross ß-activity during same-day and first-trimester exposure windows. PM2.5 was not associated with glucose levels during any exposure window in our data. CONCLUSIONS: Exposure to higher levels of ambient PM gross ß-activity was associated with higher blood glucose levels in pregnant patients, with implications for how this novel environmental factor could impact pregnancy health.

SARS-CoV-2 in diabetic pregnancies: a systematic scoping review.

BACKGROUND: Currently, we suffer from an increasing diabetes pandemic and on the other hand from the SARS-CoV-2 pandemic. Already at the beginning of the SARS-CoV-2 pandemic, it was quickly assumed that certain groups are at increased risk to suffer from a severe course of COVID-19. There are serious concerns regarding potential adverse effects on maternal, fetal, and neonatal outcomes. Diabetic pregnancies clearly need special care, but clinical implications as well as the complex interplay of diabetes and SARS-CoV-2 are currently unknown. We summarized the evidence on SARS-CoV-2 in diabetic pregnancies, including the identification of novel potential pathophysiological mechanisms and interactions as well as clinical outcomes and features, screening, and management approaches. METHODS: We carried out a systematic scoping review in MEDLINE (PubMed), EMBASE, CINAHL, Cochrane Library, and Web of Science Core Collection in September 2020. RESULTS: We found that the prognosis of pregnant women with diabetes mellitus and COVID-19 may be associated with potential underlying mechanisms such as a simplified viral uptake by ACE2, a higher basal value of pro-inflammatory cytokines, being hypoxemic as well as platelet activation, embolism, and preeclampsia. In the context of "trans-generational programming" and COVID-19, life-long consequences may be "programmed" during gestation by pro-inflammation, hypoxia, over- or under-expression of transporters and enzymes, and epigenetic modifications based on changes in the intra-uterine milieu. COVID-19 may cause new onset diabetes mellitus, and that vertical transmission from mother to baby might be possible. CONCLUSIONS: Given the challenges in clinical management, the complex interplay between COVID-19 and diabetic pregnancies, evidence-based recommendations are urgently needed. Digital medicine is a future-oriented and effective approach in the context of clinical diabetes management. We anticipate our review to be a starting point to understand and analyze mechanisms and epidemiology to most effectively treat women with SARS-COV-2 and diabetes in pregnancy.

Climate factors and gestational diabetes mellitus risk - a systematic review.

BACKGROUND: Current and projected increases in global temperatures and extreme climate events have led to heightened interest in the impact of climate factors (i.e. ambient temperature, season/seasonality, and humidity) on human health. There is growing evidence that climate factors may impact metabolic function, including insulin sensitivity. Gestational diabetes mellitus (GDM) is a common pregnancy complication, with an estimated global prevalence of up to 14%. While lifestyle and genetic risk factors for GDM are well established, environmental factors may also contribute to GDM risk. Previous reviews have summarized the growing evidence of environmental risk factors for GDM including endocrine disrupting chemicals and ambient air pollution. However, studies of the effects of climate factors on GDM risk have not been systematically evaluated. Therefore, we conducted a systematic review to summarize and evaluate the current literature on the associations of climate factors with GDM risk. METHODS: We conducted systematic searches in PubMed and EMBASE databases for original research articles on associations of climate factors (i.e. ambient temperature, season/seasonality, and humidity) with GDM and/or related glycemic outcomes for all publication dates through September 20th, 2020. RESULTS: Our search identified 16 articles on the associations of ambient temperature and/or season with GDM and maternal glycemic outcomes during pregnancy, which were included in this review. Despite inconsistencies in exposure and outcome assessment, we found consistent evidence of a seasonal effect on GDM risk, with higher prevalence of GDM and higher pregnancy glucose levels in summer months. We found suggestive evidence of an association between higher ambient temperature and elevated glucose levels from GDM screening tests. CONCLUSION: Climate factors may be associated with GDM risk. However, further research is needed to evaluate these associations and to elucidate the specific mechanisms involved.

Perinatal urinary benzophenone-3 concentrations and glucose levels among women from a fertility clinic.

BACKGROUND: Subfertile women have higher risk of glucose intolerance during pregnancy. Studies suggest associations between several endocrine disrupting chemicals (EDCs) and pregnancy glucose levels. However, the association between benzophenone-3 (BP-3), an EDC widely found in sunscreen, and pregnancy glucose levels remains unclear. We aimed to assess the association between perinatal exposures to BP-3 and pregnancy glucose levels in subfertile women. METHODS: We evaluated 217 women from a prospective cohort based at a fertility clinic who had urinary BP-3 concentrations measured during 3-month preconception, first and/or second trimesters, and blood glucose measured at glucose load tests (GLTs) during late pregnancy. Multivariable linear and logistic regression models were used to assess associations between time-specific BP-3 in quartiles (Q1 - Q4) and mean glucose levels, as well as odds of abnormal GLT (glucose level ≥ 140 mg/dL), adjusting for potential confounders. Effect modification was assessed by age, season, BMI, infertility diagnosis, sex of fetus (es) and physical activity. RESULTS: Women with higher first trimester BP-3 concentrations had lower mean glucose levels [mean glucose (95% CI) for Q4 vs Q1 = 103.4 (95.0, 112.5) vs. 114.6 (105.8, 124.2) mg/dL]. Women with higher second trimester BP-3 concentrations had lower odds of abnormal GLT [OR (95% CI) for Q3 vs. Q1 = 0.12 (0.01, 0.94)]. The associations between BP-3 and glucose levels were modified by several factors: women with female-factor infertility, urine collected during summer, older age, lower BMI, or carried female fetus (es) had the strongest inverse associations between BP-3 and glucose levels, while no associations were observed in the remaining subgroups. CONCLUSIONS: Time-specific inverse associations between BP-3 and pregnancy glucose levels existed in subfertile women, and especially among certain subgroups of this high-risk-population.

Serum beta-carotene modifies the association between phthalate mixtures and insulin resistance: The National Health and Nutrition Examination Survey 2003-2006.

Animal models suggest a protective role of antioxidants against the adverse effect of di-2-ethylhexyl phthalate (DEHP) on insulin resistance. However, no epidemiologic study has examined the effects observed in the animal model. We conduct a study to examine associations of urinary concentrations of phthalate metabolites (individually and as a mixture) with insulin resistance, along with potential effect modification by serum antioxidant concentrations. This cross-sectional study included 1605 participants (51% males) aged 12-85 from the National Health and Nutrition Examination Surveys (2003-2006). Urinary concentrations of 9 phthalate metabolites were measured from spot urine samples. Antioxidant (vitamin A, C, E, and carotenoids) concentrations were measured from a fasting serum sample. We used Bayesian Kernel Machine Regression (BKMR) to evaluate associations between phthalate metabolite mixtures and insulin resistance, and examined whether serum antioxidant levels modified these associations, while accounting for the correlations of multiple concurrent exposures. A change in urinary ΣDEHP concentrations from the 25th to the 75th percentile was associated with a higher log HOMA-IR of 0.07 (95% CI = 0.01, 0.14) (4.85% increase in HOMA-IR). In contrast, the same change in urinary monoethyl phthalate (MEP) was associated with a lower HOMA-IR of -0.07 (95% CI = -0.14, -0.02) (6.68% decrease in HOMA-IR). The positive association between ΣDEHP and HOMA-IR became weaker at higher concentrations of serum ß-carotene. The relationship between MEP and HOMA-IR, however, was not modified by the serum antioxidants examined. The remaining phthalate metabolites were unrelated to HOMA-IR. In this cross-sectional study, the positive association between DEHP exposure and insulin resistance weakened among participants with higher concentrations of serum ß-carotene. As this is the first human report on the protective role of serum ß-carotene on DEHP induced insulin resistance, future studies are needed.

Urinary concentrations of parabens mixture and pregnancy glucose levels among women from a fertility clinic.

BACKGROUND: A number of endocrine disrupting chemicals (EDC) have been associated with gestational diabetes (GDM) risk factors. However, no human study has investigated the association between pregnancy exposure to parabens, a class of EDCs, and pregnancy glucose levels, a risk factor for GDM. Furthermore, little is known about this association in subfertile women-a group at high risk of GDM. METHODS: A total of 241 women from the Environment and Reproductive Health Study had data available on 1st and/or 2nd trimester urinary methylparaben, propylparaben, and butylparaben concentrations, and blood glucose levels after the glucose loading test (GLT), a non-fasting 50 g glucose loading test taken at late 2nd trimester. Trimester-specific associations between specific gravity adjusted methylparaben, butylparaben, and propylparaben with adjusted mean of pregnancy glucose levels were evaluated in linear regression models, using quartiles of each paraben's distribution, and as a paraben mixture, using mutual adjustment and Bayesian kernel machine regression (BKMR), a recently proposed method for investigating chemical mixtures that flexibly models the joint effect of chemicals. RESULTS: Investigating parabens one at the time did not provide any significant results. When investigating parabens as a chemical mixture with both multiple regression and BKMR, we observed positive associations of butylparaben (e.g comparing the 4th and 1st quartiles) with glucose levels, for both the 1st trimester (adjusted difference=12.5 mg/dL; 95% CI: 0.9, 24.2) and 2nd trimester (adjusted difference=11.2 mg/dL; 95% CI: 0.2, 22.3), and a negative association between 1st trimester propylparaben and glucose (adjusted difference=-22.3 mg/dL; 95% CI: -43.2, -1.4). CONCLUSIONS: We found 1st trimester butylparaben and propylparaben urinary concentrations to be associated with glucose levels in a pregnancy cohort of women at high risk of GDM, even after adjusting for potential confounders. Because exposure to parabens is widespread, these findings may suggest further investigating the effects of this chemical class on pregnancy health.

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.

Hair product use, age at menarche and mammographic breast density in multiethnic urban women.

BACKGROUND: Select hair products contain endocrine disrupting chemicals (EDCs) that may affect breast cancer risk. We hypothesize that, if EDCs are related to breast cancer risk, then they may also affect two important breast cancer risk factors: age at menarche and mammographic breast density. METHODS: In two urban female cohorts (N = 248): 1) the New York site of the National Collaborative Perinatal Project and 2) the New York City Multiethnic Breast Cancer Project, we measured childhood and adult use of hair oils, lotions, leave-in conditioners, root stimulators, perms/relaxers, and hair dyes using the same validated questionnaire. We used multivariable relative risk regression models to examine the association between childhood hair product use and early age at menarche (defined as <11 years of age) and multivariable linear regression models to examine the association between childhood and adult hair product use and adult mammographic breast density. RESULTS: Early menarche was associated with ever use of childhood hair products (RR 2.3, 95% CI 1.1, 4.8) and hair oil use (RR 2.5, 95% CI 1.2, 5.2); however, additional adjustment for race/ethnicity, attenuated associations (hair products RR 1.8, 95% CI 0.8, 4.1; hair oil use RR 2.3, 95% CI 1.0, 5.5). Breast density was not associated with adult or childhood hair product or hair oil use. CONCLUSIONS: If confirmed in larger prospective studies, these data suggest that exposure to EDCs through hair products in early life may affect breast cancer risk by altering timing of menarche, and may operate through a mechanism distinct from breast density.