Maternal steroids during pregnancy and their associations with exposure to lifetime stressful life events, prenatal stress appraisal and psychological functioning.

BACKGROUND: During pregnancy, steroids enable physiological adaptations in response to many factors, including maternal stress or psychological functioning. While stress and psychological dysfunction can have endocrine-disrupting effects beyond cortisol disruption, associations between prenatal maternal stress or related psychological dysfunction and the broader steroid milieu remain understudied. AIM: To assess associations between independent and joint maternal stress and psychological functioning measures and steroid profiles in pregnancy (22-40 gestational weeks) in the Programming of Intergenerational Stress Mechanisms (PRISM) birth cohort (n = 334). METHODS: Serum metabolomics detected 42 steroids and their metabolites, which were grouped into five classes (pregnenolone, androgens, estrogens, progestin, and corticosteroids). The Perceived Stress Scale, Life Stressor Checklist-Revised, and Edinburgh Postnatal Depression Scale indexed lifetime traumatic/non-traumatic stressors, global prenatal stress appraisal, and depressive symptoms during pregnancy, respectively. Exposures were categorized as high-low using the corresponding 3rd quartiles. We assessed associations between both individual and joint stress exposures with steroid classes using linear mixed effect models and with individual steroids using linear regressions. We also examined fetal sex-specific effects. RESULTS: High prenatal perceived stress was independently associated with lower levels of androgens and estrogens in the overall sample [ß (95%CI): androgens: -0.13 (-0.25;-0.01); estrogens: -0.16 (-0.31;-0.01)], particularly among women carrying males [androgens: -0.22 (-0.39;-0.05); estrogens: -0.28 (-0.50;-0.07)]. Results on estrogens were consistent when considering joint exposure to both greater lifetime stressors and higher prenatal perceived stress. We also found a single testosterone metabolite-5alpha-androstan-3alpha,17alpha-diol disulfate-negatively associated with both individual high perceived stress and joint exposure to high lifetime stressors and high perceived stress among women carrying males. CONCLUSIONS: Increased maternal perceived stress experienced in pregnancy was independently associated with lower maternal androgen and estrogen levels during pregnancy in the overall sample, particularly among women carrying males. Results on estrogens were consistent when we considered the joint exposure of increased lifetime stressors and higher prenatal perceived stress.

Biomarkers of maternal lead exposure during pregnancy using micro-spatial child deciduous dentine measurements.

BACKGROUND: Lead is a toxic chemical of public health concern, however limited biomarkers are able to reconstruct prior lead exposures in early-life when biospecimens are not collected and stored. Although child tooth dentine measurements accurately assess past child perinatal lead exposure, it has not been established if they reflect maternal exposure in pregnancy. AIM: To assess the prenatal relationship between child tooth dentine and maternal blood lead measurements and to estimate maternal lead exposure during the 2nd and 3rd trimesters of pregnancy from weekly child dentine profiles. METHODS: We measured early-life lead exposure in child tooth dentine and maternal blood from 419 child-mother dyads enrolled in the Programming Research in Obesity, Growth, Environment and Social Stress (PROGRESS) cohort. We employed the Super-Learner algorithm to determine the relationship of dentine lead data with maternal blood lead concentrations and to predict maternal lead from child dentine lead data in blinded analyses. We validated and quantified the bias of our results internally. RESULTS: Mothers had moderate blood lead levels (trimesters: 2nd = 29.45 ug/L, 3rd = 31.78 ug/L). Trimester-averaged and weekly child dentine lead measurements were highly correlated with maternal blood levels in the corresponding trimesters. The predicted trimester-specific maternal lead levels were significantly correlated with actual measured blood values (trimesters: 2nd = 0.83; 3rd = 0.88). Biomarkers of maternal lead exposure discriminated women highly exposed to lead (>mean) with 85 % and 96 % specificity in the 2nd and 3rd trimesters, respectively, with 80 % sensitivity. DISCUSSION: Weekly child dentine lead levels can serve as biomarkers of past child and maternal lead exposures during pregnancy.

Prenatal exposure to multiple organochlorine compounds and childhood body mass index.

Background: Prenatal exposure to organochlorine compounds (OCs) has been associated with increased childhood body mass index (BMI); however, only a few studies have focused on longitudinal BMI trajectories, and none of them used multiple exposure mixture approaches. Aim: To determine the association between in-utero exposure to eight OCs and childhood BMI measures (BMI and BMI z-score) at 4 years and their yearly change across 4-12 years of age in 279 Rhea child-mother dyads. Methods: We applied three approaches: (1) linear mixed-effect regressions (LMR) to associate individual compounds with BMI measures; (2) Bayesian weighted quantile sum regressions (BWQSR) to provide an overall OC mixture association with BMI measures; and (3)Bayesian varying coefficient kernel machine regressions (BVCKMR) to model nonlinear and nonadditive associations. Results: In the LMR, yearly change of BMI measures was consistently associated with a quartile increase in hexachlorobenzene (HCB) (estimate [95% Confidence or Credible interval] BMI: 0.10 [0.06, 0.14]; BMI z-score: 0.02 [0.01, 0.04]). BWQSR results showed that a quartile increase in mixture concentrations was associated with yearly increase of BMI measures (BMI: 0.10 [0.01, 0.18]; BMI z-score: 0.03 [0.003, 0.06]). In the BVCKMR, a quartile increase in dichlorodiphenyldichloroethylene concentrations was associated with higher BMI measures at 4 years (BMI: 0.33 [0.24, 0.43]; BMI z-score: 0.19 [0.15, 0.24]); whereas a quartile increase in HCB and polychlorinated biphenyls (PCB)-118 levels was positively associated with BMI measures yearly change (BMI: HCB:0.10 [0.07, 0.13], PCB-118:0.08 [0.04, 012]; BMI z-score: HCB:0.03 [0.02, 0.05], PCB-118:0.02 [0.002,04]). BVCKMR suggested that PCBs had nonlinear relationships with BMI measures, and HCB interacted with other compounds. Conclusions: All analyses consistently demonstrated detrimental associations between prenatal OC exposures and childhood BMI measures.

Neighborhood-level disparities and subway utilization during the COVID-19 pandemic in New York City.

The COVID-19 pandemic has yielded disproportionate impacts on communities of color in New York City (NYC). Researchers have noted that social disadvantage may result in limited capacity to socially distance, and consequent disparities. We investigate the association between neighborhood social disadvantage and the ability to socially distance, infections, and mortality in Spring 2020. We combine Census Bureau and NYC open data with SARS-CoV-2 testing data using supervised dimensionality-reduction with Bayesian Weighted Quantile Sums regression. The result is a ZIP code-level index with weighted social factors associated with infection risk. We find a positive association between neighborhood social disadvantage and infections, adjusting for the number of tests administered. Neighborhood disadvantage is also associated with a proxy of the capacity to socially isolate, NYC subway usage data. Finally, our index is associated with COVID-19-related mortality.

Prenatal urinary concentrations of phthalate metabolites and behavioral problems in Mexican children: The Programming Research in Obesity, Growth Environment and Social Stress (PROGRESS) study.

BACKGROUND: Phthalate exposure has been associated with increased childhood behavioral problems. Existing studies failed to include phthalate replacements and did not account for high correlations among phthalates. Phthalates' exposure is higher in Mexico than in U.S. locations, making it an ideal target population for this study. AIM: To examine associations between 15 maternal prenatal phthalate metabolite concentrations and children's behavioral problems. METHODS: We quantified phthalate metabolites in maternal urine samples from maternal-child dyads (n = 514) enrolled in the Programming Research in Obesity, Growth Environment and Social Stress (PROGRESS) birth cohort in Mexico City. We performed least absolute shrinkage and selection operator (LASSO) regressions to identify associations between specific-gravity adjusted log2-transformed phthalate metabolites and parent-reported 4-6 year old behavior on the Behavior Assessment System for Children (BASC-2), accounting for metabolite correlations. We adjusted for socio-demographic and birth-related factors, and examined associations stratified by sex. RESULTS: Higher prenatal mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) urinary concentrations were associated with increased hyperactivity scores in the overall sample (ß = 0.57, 95% CI = 0.17, 1.13) and in girls (ß = 0.54, 95% CI = 0.16, 1.08), overall behavioral problems in boys (ß = 0.58, 95% CI = 0.20, 1.15), and depression scores in boys (ß = 0.44, 95% CI = 0.06, 0.88). Higher prenatal monobenzyl phthalate (MBzP) concentrations were associated with reduced hyperactivity scores in girls (ß = -0.54, 95% CI = -1.08, -0.21). DISCUSSION: Our findings suggested that prenatal concentrations of phthalates and their replacements altered child neurodevelopment and those associations may be influenced sex.

Per- and poly-fluoroalkyl substances and bone mineral density: Results from the Bayesian weighted quantile sum regression.

Per- and poly-fluoroalkyl substances (PFAS) are chemicals, detected in 95% of Americans, that induce osteotoxicity and modulate hormones, thereby influencing bone health. Previous studies found associations between individual PFAS and bone mineral density in adults but did not analyze their combined effects. OBJECTIVE: To extend weighted quantile sum (WQS) regression to a Bayesian framework (Bayesian extension of the WQS regression [BWQS]) and determine the association between a mixture of serum PFAS and mineral density in lumbar spine, total, and neck femur in 499 adults from the 2013 to 2014 National Health and Nutrition Examination Survey (NHANES). METHODS: We used BWQS to assess the combined association of eight PFAS, as a mixture, with bone mineral density in adults. As secondary analyses, we focused on vulnerable populations (men over 50 years and postmenopausal women). Analyses were adjusted for sociodemographic factors. Sensitivity analyses included bone mineral density associations with individual compounds and results from WQS regressions. RESULTS: The mean age was 55 years old (SD = 1) with average spine, total, and neck femur mineral densities of 1.01 (SD = 0.01), 0.95 (SD = 0.01), and 0.78 (SD = 0.01) gm/cm2, respectively. PFAS mixture levels showed no evidence of association with mineral density (spine: ß = -0.004; 95% credible interval [CrI] = -0.04, 0.04; total femur: ß = 0.002; 95% CrI = -0.04, 0.05; femur neck: ß = 0.005; 95%CrI = -0.03, 0.04) in the overall population. Results were also null in vulnerable populations. Findings were consistent across sensitivity analyses. CONCLUSIONS: We introduced a Bayesian extension of WQS and found no evidence of the association between PFAS mixture and bone mineral density.

Assessing capacity to social distance and neighborhood-level health disparities during the COVID-19 pandemic.

The COVID-19 pandemic has yielded disproportionate impacts on communities of color in New York City (NYC). Researchers have noted that social disadvantage may result in limited capacity to socially distance, and consequent disparities. Here, we investigate the role of neighborhood social disadvantage on the ability to socially distance, infections, and mortality. We combine Census Bureau and NYC open data with SARS-CoV-2 testing data using supervised dimensionality-reduction with Bayesian Weighted Quantile Sums regression. The result is a ZIP code-level index with relative weights for social factors facilitating infection risk. We find a positive association between neighborhood social disadvantage and infections, adjusting for the number of tests administered. Neighborhood infection risk is also associated with capacity to socially isolate, as measured by NYC subway data. Finally, infection risk is associated with COVID-19-related mortality. These analyses support that differences in capacity to socially isolate is a credible pathway between disadvantage and COVID-19 disparities.