Faculty Bibliography

OBJECTIVE:, suggesting that elevated suPAR levels may reflect a heightened inflammatory response in preeclamptic pregnancies rather than serving as a pre-clinical indicator. No data currently exist on the trajectory of suPAR across pregnancy. In the present study, we investigated if and how plasma suPAR levels change across gestation and examined whether this change and the levels in each trimester varied between women with and without HDP. STUDY DESIGN/METHODS:Participants included pregnant individuals enrolled in the [study name removed for blinding], a prospective birth cohort designed to study an array of exposures and conditions relevant to maternal and child health. Maternal blood was collected at up to three time points during pregnancy and plasma suPAR levels were analyzed by enzyme-linked immunosorbent assay. Information on maternal HDP was abstracted from electronic medical records. Study participants with suPAR data in any trimester and information about HDP were eligible for inclusion (n=393); 64 non-HDP participants who had chronic hypertension (n=5), gestational diabetes mellitus (n=55), lupus (n=1), type 1 diabetes (n=1) or type 2 diabetes (n=2) were excluded, resulting in a final analytic sample of 329. The study was approved by the Institutional Review Board of the [institution removed for blinding] and all participants provided written informed consent. We first regressed suPAR levels on gestational age at the time of sample collection to assess change over the course of pregnancy. We did this for the sample overall and stratified by HDP status. Among the subset of participants with repeated measures, we used paired Wilcoxon signed-rank tests to assess the within-person change in suPAR across trimesters in both groups. Finally, we used Wilcoxon signed-rank tests to assess whether suPAR levels in each trimester and averaged over pregnancy were different among participants with and without HDP. RESULTS:and ranged from 16.8-50.1; 44% of the sample was overweight or obese defined by a BMI ≥ 25. The majority had at least a high school degree (90.1%) and reported never smoking cigarettes (92.9%). Participants with HDP (n=44) were older and had higher BMI; other participant characteristics did not significantly vary by HDP status. suPAR levels did not significantly differ between those with and without HDP at any gestational timepoint (Table 1), although the association was marginal when considering the third trimester such that those with HDP had higher suPAR levels (2.43 ng/mL vs. 2.12 ng/mL, p=0.11). In the sample overall, suPAR levels decreased by 1.1% per week of advancing gestation (p-value< 0.001); however, when stratified by HDP status, suPAR levels only significantly decreased among those without HDP (1.2% per week, p<0.001), while remaining more stable among the cases (0.8% per week, p=0.17) (Figure 1). This finding was also apparent when examining the subset of participants with repeated measures. Among those with paired samples that did not have HDP, the median suPAR level in early gestation (2.79 ng/mL) was significantly higher than late gestation (2.30 ng/mL) with a p-value <0.001 and large effect size r=0.634. In contrast, among those with paired samples and HDP, the median suPAR level in early gestation (2.37 ng/mL) was not significantly different than late gestation (2.45 ng/mL) with a p-value=0.578 and small effect size r=0.256. It is notable however that the sample size of participants with repeated measures and HDP was small (n=7) and the timing of HDP onset was variable across participants. CONCLUSIONS:Although HDP is a primary cause of morbidity and mortality in pregnancy, predictive biomarkers are lacking. suPAR levels decrease with advancing gestation among healthy women, but remain stable in women with HDP, which may reflect a heightened inflammatory state. Additional research is needed to understand how suPAR correlates with other biomarkers of HDP and whether stable suPAR levels can predict HDP accurately in clinical practice.

Endocrine-disrupting chemicals (EDCs) are a prime concern for the environment and health globally. Research shows that in developing countries such as India both the environment and human populations are severely exposed to EDCs and consequently experience rising incidents of adverse health effects such as diabetes and cancers. In this paper, we discuss the current EDC management approach in India, critically assess its limitations, and describe opportunities for potential improvements. Foremost, current EDC management actions and interventions in India are fragmented and outdated, and far behind the modern and comprehensive approaches adopted in the European Union and other developed countries. Strong and well-planned actions are required on various fronts of science, policy, commerce, and public engagement. These actions include the adoption of a dedicated and modern regulatory framework for managing EDCs, enhancing capacity and infrastructure for EDC monitoring in the environment and human population, employing public-private partnership programs for not only managing EDCs but also in the sectors that indirectly contribute toward the mismanagement of EDCs in the country, and raising awareness on EDCs and promoting health-preserving consumption habits among the public. As India hosts a large proportion of the global human population and biodiversity, the success or failure of its actions will substantially affect the direction of global efforts to manage EDCs and set an example for other developing countries.

IMPORTANCE/UNASSIGNED:Physical and social neighborhood attributes may have implications for children's growth and development patterns. The extent to which these attributes are associated with body mass index (BMI) trajectories and obesity risk from childhood to adolescence remains understudied. OBJECTIVE/UNASSIGNED:To examine associations of neighborhood-level measures of opportunity and social vulnerability with trajectories of BMI and obesity risk from birth to adolescence. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study used data from 54 cohorts (20 677 children) participating in the Environmental Influences on Child Health Outcomes (ECHO) program from January 1, 1995, to January 1, 2022. Participant inclusion required at least 1 geocoded residential address and anthropometric measure (taken at the same time or after the address date) from birth through adolescence. Data were analyzed from February 1 to June 30, 2022. EXPOSURES/UNASSIGNED:Census tract-level Child Opportunity Index (COI) and Social Vulnerability Index (SVI) linked to geocoded residential addresses at birth and in infancy (age range, 0.5-1.5 years), early childhood (age range, 2.0-4.8 years), and mid-childhood (age range, 5.0-9.8 years). MAIN OUTCOMES AND MEASURES/UNASSIGNED:BMI (calculated as weight in kilograms divided by length [if aged <2 years] or height in meters squared) and obesity (age- and sex-specific BMI ≥95th percentile). Based on nationwide distributions of the COI and SVI, Census tract rankings were grouped into 5 categories: very low (<20th percentile), low (20th percentile to <40th percentile), moderate (40th percentile to <60th percentile), high (60th percentile to <80th percentile), or very high (≥80th percentile) opportunity (COI) or vulnerability (SVI). RESULTS/UNASSIGNED:Among 20 677 children, 10 747 (52.0%) were male; 12 463 of 20 105 (62.0%) were White, and 16 036 of 20 333 (78.9%) were non-Hispanic. (Some data for race and ethnicity were missing.) Overall, 29.9% of children in the ECHO program resided in areas with the most advantageous characteristics. For example, at birth, 26.7% of children lived in areas with very high COI, and 25.3% lived in areas with very low SVI; in mid-childhood, 30.6% lived in areas with very high COI and 28.4% lived in areas with very low SVI. Linear mixed-effects models revealed that at every life stage, children who resided in areas with higher COI (vs very low COI) had lower mean BMI trajectories and lower risk of obesity from childhood to adolescence, independent of family sociodemographic and prenatal characteristics. For example, among children with obesity at age 10 years, the risk ratio was 0.21 (95% CI, 0.12-0.34) for very high COI at birth, 0.31 (95% CI, 0.20-0.51) for high COI at birth, 0.46 (95% CI, 0.28-0.74) for moderate COI at birth, and 0.53 (95% CI, 0.32-0.86) for low COI at birth. Similar patterns of findings were observed for children who resided in areas with lower SVI (vs very high SVI). For example, among children with obesity at age 10 years, the risk ratio was 0.17 (95% CI, 0.10-0.30) for very low SVI at birth, 0.20 (95% CI, 0.11-0.35) for low SVI at birth, 0.42 (95% CI, 0.24-0.75) for moderate SVI at birth, and 0.43 (95% CI, 0.24-0.76) for high SVI at birth. For both indices, effect estimates for mean BMI difference and obesity risk were larger at an older age of outcome measurement. In addition, exposure to COI or SVI at birth was associated with the most substantial difference in subsequent mean BMI and risk of obesity compared with exposure at later life stages. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cohort study, residing in higher-opportunity and lower-vulnerability neighborhoods in early life, especially at birth, was associated with a lower mean BMI trajectory and a lower risk of obesity from childhood to adolescence. Future research should clarify whether initiatives or policies that alter specific components of neighborhood environment would be beneficial in preventing excess weight in children.

Fetal exposure to phthalates and bisphenols could be associated with kidney function. We aim to assess the association between maternal urine concentrations of phthalates and bisphenols during pregnancy and kidney function and size during childhood. In 1366 pregnant women from a prospective population-based cohort, we measured urine concentrations of phthalates, more specifically phthalic acid and metabolites of low molecular weight phthalates (LMWP) and high molecular weight phthalates (HMWP), with its subgroups of di-2-ethylhexylphthalate (DEHP) and di-n-octylphthalate (DNOP) metabolites, and bisphenol A, S and F during first, second and third trimester. We explored three methods of adjustment for maternal hydration status: creatinine standardization, covariate adjustment for creatinine and covariate-adjusted creatinine standardization plus covariate adjustment. We measured kidney size, calculated estimated glomerular filtration rate (eGFR) and the albumin/creatinine ratio in urine and assessed microalbuminuria at 6 years old. When applying creatinine standardization, we found some associations of higher maternal second trimester urine phthalic acid and overall mean phthalic acid and LMWP concentrations with higher eGFR. These associations were lessened when applying other methods of creatinine adjustment. The associations found when we applied the covariate adjustment for creatinine method were also lessened when applying other methods of creatinine adjustment. Only the association of higher second trimester phthalic acid maternal urine concentrations with higher eGFR at 6 years old remained significant irrespective of the method of creatinine adjustment. There were no consistent associations of maternal bisphenol A, S and F urine concentrations with childhood kidney function. There were no associations of maternal phthalate or bisphenol urine concentrations with kidney volume in children at 6 years old. Concluding, no consistent associations of maternal phthalate or bisphenol urine concentrations with childhood kidney function or volume could be found. Furthermore, the method of adjusting maternal urine phthalate and bisphenol concentrations for urinary dilution had a substantial effect on the associations with childhood kidney function, as it changed the conclusions about the directionality of the associations. Future studies including maternal kidney function are needed to further elucidate these association in humans.

BACKGROUND:Phthalates and bisphenols are non-persistent endocrine disrupting chemicals that are ubiquitously present in our environment and may have long-lasting health effects following fetal exposure. A potential mechanism underlying these exposure-outcome relationships is differential DNA methylation. Our objective was to examine the associations of maternal phthalate and bisphenol concentrations during pregnancy with DNA methylation in cord blood using a chemical mixtures approach. METHODS:This study was embedded in a prospective birth cohort study in the Netherlands and included 306 participants. We measured urine phthalates and bisphenols concentrations in the first, second and third trimester. Cord blood DNA methylation in their children was processed using the Illumina Infinium HumanMethylation450 BeadChip using an epigenome-wide association approach. Using quantile g-computation, we examined the association of increasing all mixture components by one quartile with cord blood DNA methylation. RESULTS:) of the first trimester maternal mixture of phthalates and bisphenols and three suggestive associations of the second trimester maternal mixture of phthalates and bisphenols with DNA methylation in cord blood. CONCLUSIONS:Although we did not identify genome-wide significant results, we identified some suggestive associations of exposure to a maternal mixture of phthalates and bisphenols in the first and second trimester with DNA methylation in cord blood that need further exploration in larger study samples.

BACKGROUND:Prior research has demonstrated bidirectional associations between gestational diabetes mellitus (GDM) and perinatal maternal depression. However, the association between GDM, prenatal depression, and postpartum depression (PPD) has not been examined in a prospective cohort longitudinally. METHODS:Participants in the current analysis included 5,822 women from the National Institutes of Health's Environmental influences on Child Health Outcomes (ECHO) Research Program: N = 4,606 with Neither GDM nor Prenatal Maternal Depression (Reference Category); N = 416 with GDM only; N = 689 with Prenatal Maternal Depression only; and N = 111 with Comorbid GDM and Prenatal Maternal Depression. The PROMIS-D scale was used to measure prenatal and postnatal maternal depressive symptoms. Primary analyses consisted of linear regression models to estimate the independent and joint effects of GDM and prenatal maternal depression on maternal postpartum depressive symptoms. RESULTS:A higher proportion of women with GDM were classified as having prenatal depression (N = 111; 21%) compared to the proportion of women without GDM who were classified as having prenatal depression (N = 689; 13%), however this finding was not significant after adjustment for covariates. Women with Comorbid GDM and Prenatal Maternal Depression had significantly increased postpartum depressive symptoms measured by PROMIS-D T-scores compared to women with Neither GDM nor Prenatal Maternal Depression (mean difference 7.02, 95% CI 5.00, 9.05). Comorbid GDM and Prenatal Maternal Depression was associated with an increased likelihood of PPD (OR 7.38, 95% CI 4.05, 12.94). However, women with GDM only did not have increased postpartum PROMIS-D T-scores or increased rates of PPD. CONCLUSIONS:Our findings underscore the importance of universal depression screening during pregnancy and in the first postpartum year. Due to the joint association of GDM and prenatal maternal depression on risk of PPD, future studies should examine potential mechanisms underlying this relation.

Fetal exposure to environmental chemicals has been associated with adverse health outcomes in children and later into adulthood. While several studies have examined correlations and variability of non-persistent chemical exposures throughout pregnancy, many do not capture more recent exposures, particularly in New York City. Our goal was to characterize exposure to phthalates, bisphenols, polycyclic aromatic hydrocarbons, and organophosphate pesticides among pregnant women residing in New York City who enrolled in the New York University Children's Health and Environment Study (NYU CHES) between 2016 and 2018. We measured urinary chemical metabolite concentrations in 671 women at early, mid, and late pregnancy (median 10.8, 20.8, and 29.3 weeks, respectively). We calculated Spearman correlation coefficients among chemical concentrations at each measurement time point. We compared changes in population-level urinary metabolites at each stage using paired Wilcoxon signed-rank tests and calculated intraclass correlation coefficients (ICCs) to quantify intra-individual variability of metabolites across pregnancy. Geometric means and ICCs were compared to nine other pregnancy cohorts that recruited women in 2011 or later as well as nationally reported levels from women of child-bearing age. Compared with existing cohorts, women in NYU CHES had higher geometric means of organophosphate pesticides (Σdiethylphosphates = 28.7 nmol/g cr, Σdimethylphosphates = 57.3 nmol/g cr, Σdialkyl phosphates = 95.9 nmol/g cr), bisphenol S (0.56 μg/g cr), and 2-naphthalene (8.98 μg/g cr). Five PAH metabolites and two phthalate metabolites increased between early to mid and early to late pregnancy at the population level. Spearman correlation coefficients for chemical metabolites were generally below 0.50. Intra-individual exposures varied over time, as indicated by low ICCs (0.22-0.88, median = 0.38). However, these ICCs were often higher than those observed in other pregnancy cohorts. These results provide a general overview of the chemical metabolites measured in NYU CHES in comparison to other contemporary pregnancy cohorts and highlight directions for future studies.