Bisphenol A Exposure, Adipogenic Mechanism and Effect on Childhood Adiposity

Bisphenol A (BPA) is a common component in plastic consumer products and epoxy resin linings. Initially developed in the 1930s-40s as a synthetic hormone treatment, it is now widely considered an endocrine disrupting chemical (EDC). A growing body of epidemiological literature suggests that ubiquitous exposures to BPA may be contributing to the global epidemic of obesity, with children a particularly vulnerable population. Obesity in children, defined by a body mass index (BMI) greater than or equal to the 95th percentile for age and sex, is an epidemic of great concern in the United States. As with other chemicals, the prenatal and early life period are critical windows of exposure to BPA; however, the mechanism by which BPA may influence the development of body size in children remains unclear. Experimental studies have found that BPA influences adipogenesis in both murine and adult human preadipocyte cell lines and BPA is hypothesized to play a role in enhancing adipogenic regulation by nuclear receptors such as peroxisome proliferator-activated receptor gamma (PPARγ). While the timeline of the processes involved in adipogenesis in humans is not universally agreed upon, it is accepted that PPARγ is highly expressed in adipose tissue and considered to be the master regulator of adipogenesis. To answer the question of both timing and developmental origin of BPA effects on adipogensis, we employed both an epidemiological approach, and experimental methodologies using primordial cell lines, mesenchymal stem cells (MSCs). Our study characterizes early life exposures to BPA, explores the adipogenic mechanism of BPA in human MSCs via cellular morphometrics and PPARγ gene expression, and identifies associations between early life exposure to BPA and childhood obesity and adiposity. For our epidemiological assessments, we studied a birth cohort of African American and Dominican mother and child dyads in New York City. BPA was measured in spot urine samples collected during pregnancy and at child ages 3, 5, and 7 years, from mothers and children (n=568 dyads) in the Columbia Center for Children’s Environmental Health (CCCEH). We compared BPA concentrations across paired samples. We explored relationships between BPA and the class of phthalate chemicals, another common plasticizer. BPA was detected in nearly all urine samples from prenatal third trimester and childhood ages 3 years, 5 years and 7 years. Prenatal urinary BPA concentrations were significantly lower than postnatal urinary BPA concentrations (p<0.001). BPA and phthalate metabolites were correlated prenatally and at 3, 5, and 7 years (all p-values < 0.02). BPA concentrations were correlated with phthalate metabolite concentrations prenatally, and at 3, 5 and 7 years(all p-values < 0.05). Geometric means of BPA were higher among African Americans than among Dominicans in prenatal (p<0.01), 5 year (p<0.001) and 7 year (p=0.02) samples. Postnatal BPA concentrations were significantly higher among children with mothers who had never marrried marital status and were significantly higher in summer than in all other seasons (all p-values < 0.05). These findings reveal widespread BPA exposure in an inner-city minority population. Our in vitro experiment was a feasibility study which sought to determine whether exposure to BPA by human umbilical cord mesenchymal stem cells (HUMSC) induces morphological changes and PPARγ gene expression during adipogenesis. An anonymous sample of n=18 umbilical cords was collected at delivery from mothers registered at New York-Presbyterian Sloane Hospital for Women and New York-Presbyterian Allen Hospital in New York City. HUMSCs were harvested from umbilical cords using an adhesion technique. HUMSCs were then induced in culture to differentiate into adipocytes using: a standard differentiation induction mix medium, a negative vehicle control medium, a positive control medium and experimental control media. Differences in cell surface area and cell count in all cultures were assessed using ImageJ software (version 1.49n, 2014). Gene expression of PPARγ in all cultures was evaluated by RT-PCR. Cell morphometric results were based on 11,676 cells from 3 umbilical cord samples. PPARγ1 and PPARγ2 gene expression was assessed during differntiation phase and early terminal phase adipogenesis (0 to 72 hours). Cell morphometrics were assessed during middle to late terminal phase adipogenesis (days 14 and 21). No differences in cell count were observed for experimental conditions compared to standard induction medium. A significant decrease in surface area was seen in cells exposed to 100 μM concentration of BPA as compared to exposure to standard induction medium at day 14 (t=-37.02 p=0.001). Differences in cell surface area were not observed at day 21. A twofold increased expression of PPARγ1 was observed in cells exposed to 10 μM concentration of BPA by 72 hours of adipogenic induction which was higher than the increase in expression observed for cells exposed to the positive control induction medium containing 10 μM concentration of rosiglitazone. All induction media conditions had negligible effects on PPARγ2 expression. As BPA increases expression of PPARγ1 in HUMSCs during the transition into the early terminal differentiation phase of adipogenesis, HUMSCs may be an approximate target tissue for evaluating BPA effects in adipogenesis. Finally, using a longitudinal research design, we analyzed the possible effect of prenatal and postnatal BPA exposures, measured in urine, on childhood anthropometric outcome measures. Participants in the CCCEH have been followed since the third trimester of pregnancy, providing us with anthropometric data on children from birth through the age of seven years. Available anthropometric outcome measures include body mass index z-scores (BMIZ) at 5 and 7 years, as well as fat mass index (FMI), percent body fat (%BF), and waist circumference (WC) at 7 years. Prenatal urinary BPA concentrations were positively associated with child age 7 FMI (beta=0.31 kg/m2, p-value=0.04, [95%CI 0.01, 0.60]), %BF (beta=0.79, p-value=0.04, [95%CI 0.03, 1.55]), and WC (beta=1.29 cm, p-value=0.01, [95%CI 0.29, 2.30]). Child urinary BPA concentrations were not associated with childhood BMI or other anthropometric outcomes. As the prenatal exposures were associated with childhood measures of adiposity, prenatal BPA exposure may have an effect on adiposity as children age that cannot be determined by the use of BMI alone. Our results suggest BPA may contribute to the developmental origins of obesity and adiposity

Prenatal Insecticide Exposures and Birth Weight and Length among an Urban Minority Cohort

We reported previously that insecticide exposures were widespread among minority women in New York City during pregnancy and that levels of the organophosphate chlorpyrifos in umbilical cord plasma were inversely associated with birth weight and length. Here we expand analyses to include additional insecticides (the organophosphate diazinon and the carbamate propoxur), a larger sample size (n = 314 mother–newborn pairs), and insecticide measurements in maternal personal air during pregnancy as well as in umbilical cord plasma at delivery. Controlling for potential confounders, we found no association between maternal personal air insecticide levels and birth weight, length, or head circumference. For each log unit increase in cord plasma chlorpyrifos levels, birth weight decreased by 42.6 g [95% confidence interval (CI), −81.8 to −3.8, p = 0.03] and birth length decreased by 0.24 cm (95% CI, −0.47 to −0.01, p = 0.04). Combined measures of (ln)cord plasma chlorpyrifos and diazinon (adjusted for relative potency) were also inversely associated with birth weight and length (p < 0.05). Birth weight averaged 186.3 g less (95% CI, −375.2 to −45.5) among newborns with the highest compared with lowest 26% of exposure levels (p = 0.01). Further, the associations between birth weight and length and cord plasma chlorpyrifos and diazinon were highly significant (p ≤ 0.007) among newborns born before the 2000–2001 U.S. Environmental Protection Agency’s regulatory actions to phase out residential use of these insecticides. Among newborns born after January 2001, exposure levels were substantially lower, and no association with fetal growth was apparent (p > 0.8). The propoxur metabolite 2-isopropoxyphenol in cord plasma was inversely associated with birth length, a finding of borderline significance (p = 0.05) after controlling for chlorpyrifos and diazinon. Results indicate that prenatal chlorpyrifos exposures have impaired fetal growth among this minority cohort and that diazinon exposures may have contributed to the effects. Findings support recent regulatory action to phase out residential uses of the insecticides

Using Text Messaging to Improve Access to Prenatal Health Information in Urban African American and Afro-Caribbean Immigrant Pregnant Women: Mixed Methods Analysis of Text4baby Usage.

Background: The Text4baby (T4B) mobile health (mHealth) program is acclaimed to provide pregnant women with greater access to prenatal health care, resources, and information. However, little is known about whether urban African American and Afro-Caribbean immigrant pregnant women in the United States are receptive users of innovative health communication methods or of the cultural and systematic barriers that inhibit their behavioral intent to use T4B. Objective: This study aimed to understand the lived experiences of urban African American and Afro-Caribbean immigrant pregnant women with accessing quality prenatal health care and health information; to assess usage of mHealth for seeking prenatal health information; and to measure changes in participants' knowledge, perceptions, and behavioral intent to use the T4B mHealth educational intervention. Methods: An exploratory sequential mixed methods study was conducted among pregnant women and clinical professionals for a phenomenological exploration with focus groups, key informants, interviews, and observations. Qualitative themes were aligned with behavioral and information technology communications theoretical constructs to develop a survey instrument used. repeated-measures pre- and post-test design to evaluate changes in participants' knowledge, attitudes, and beliefs, of mHealth and T4B after a minimum of 4 weeks' exposure to the text message-based intervention. Triangulation and mixing of both qualitative and quantitative data occurred primarily during the survey development and also during final analysis. Results: A total of 9 women participated in phase 1, and 49 patients signed up for T4B and completed a 31-item survey at baseline and again during follow-up. Three themes were identified: (1) patient-provider engagement, (2) social support, and (3) acculturation. With time as a barrier to quality care, inadequate patient-provider engagement left participants feeling indifferent about the prenatal care and information they received in the clinical setting. Of 49 survey participants, 63% (31/49) strongly agreed that T4B would provide them with extra support during their pregnancy. On a Likert scale of 1 to 5, participants' perception of the usefulness of T4B ranked at 4.26, and their perception of the compatibility and relative advantage of using T4B ranked at 4.41 and 4.15, respectively. At follow-up, there was a 14% increase in participants reporting their intent to use T4B and a 28% increase from pretest and posttest in pregnant women strongly agreeing to speak more with their doctor about the information learned through T4B. Conclusions: Urban African American and Afro-Caribbean immigrant pregnant women in Brooklyn endure a number of social and ecological determinants like low health literacy, income, and language that serve as barriers to accessing quality prenatal health care and information, which negatively impacts prenatal health behaviors and outcomes. Our study indicates a number of systematic, political, and other microsystem-level factors that perpetuate health inequities in our study population.VoRSUNY DownstateEnvironmental and Occupational Health SciencesN/

Prenatal exposure to air pollution during the early and middle stages of pregnancy is associated with adverse neurodevelopmental outcomes at ages 1 to 3 years

Abstract Background A large body of data shows that fetal brain development is vulnerable to disruption by air pollution experienced by the mother during pregnancy, adversely affecting cognitive and psychomotor capabilities during childhood (De Asis-Cruz et al., Biol Psychiatry 7:480–90, 2022; Morgan ZEM et al., Environ Health 22:11, 2023). This study has sought to identify gestational windows of susceptibility to prenatal exposure to air pollution. Methods 470 African American and Latina mother/child pairs participated in a prospective cohort study based in the low-income communities of Northern Manhattan and the South Bronx, New York City. Gestational exposure to respirable particulate matter (PM2.5) and nitrogen dioxide (NO₂) was assessed through validated models in relation to cognitive and motor development assessed at ages 1, 2, and 3 years using the Bayley-II Scales. Multiple linear regression models and distributed lag models (DLM) were used to identify critical windows of exposure by trimester and week of pregnancy. Results By linear regression, average exposures to NO₂ during the first and second trimesters and the entire pregnancy were significantly and negatively associated with the mental developmental index (MDI) at age 1. Average exposures to PM2.5 during the second trimester and the entire pregnancy were also significantly, inversely associated with age 1 MDI. No significant associations were found between these exposures and MDI at age 2. NO₂ exposure during the first trimester was significantly negatively associated with MDI at age 3. Using DLM, exposures to NO₂ at lags 29–30 weeks (within the first trimester) and PM2.5 at lags 17–18 weeks (second trimester) were significantly and inversely associated with MDI at age 1. Significant, inverse associations were found between exposures to NO₂ at lag 29 weeks and PM2.5 at lags 27–29 weeks and children’s MDI at age 3. No significant associations were found between psychomotor index (PDI) and prenatal exposures to NO2 or PM2.5 at ages 1, 2 or 3. Conclusions Our finding that prenatal exposure to air pollution in the first and second trimesters was associated with lower scores for cognitive development at ages 1 and 3 is of concern because of the potential consequences of these outcomes for long-term functioning. They underscore the need for stronger policies to protect pregnant individuals and offspring, particularly during vulnerable, early life-stage of development

Prenatal exposure to polycyclic aromatic hydrocarbons and effects on neonatal anthropometric indices and thyroid-stimulating hormone in a Middle Eastern population.

Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) evokes extensive concerns regarding public health. Monitoring the pregnant women's exposure can be considered a suitable alternative to assess the fetus's exposure. This study aimed to monitor pregnant women's exposure (n = 126) to PAHs using a biomonitoring approach to evaluate effects on anthropometric indices and neonatal thyroid-stimulating hormone (TSH) in Shiraz, Iran. PAHs priority compounds were measured by gas chromatography-mass spectrometry (GC-MS) after separating blood serum and liquid-liquid extraction (LLE) method. Information on anthropometric indices, neonatal TSH levels, and data from the respondents was obtained from medical records and questionnaires. The mean PAHs concentrations ranged from 0.29 to 327.91 ng/g lipid. There was no significant difference between the measured PAHs in maternal serum at the seventh month and pregnancy termination except for ACY (p-Value<0.05). Regression analysis results showed a significant correlation (p-value<0.05) between exposure to passive smoke and total PAHs concentrations. There was no significant relationship between exposure to PAHs and weight, height, head circumference, and Apgar score of newborns. The results showed TSH decreased by 0.99 units as ACE increased per unit (β = -0.001). This study is the first to evaluate relationships between prenatal exposure to PAHs and effects on newborn health indicators, including TSH levels in a Middle Eastern population. Future studies are suggested to perform detailed assessments of PAHs intake sources, especially in vulnerable populations such as pregnant women and children.VoRSUNY DownstateEnvironmental and Occupational Health SciencesN/

A survey on the correlation between PM concentration and the incidence of suspected and positive cases of COVID-19 referred to medical centers: A case study of Tehran.

COVID-19, one of the greatest health challenges of the present century, has infected millions of people and caused more than 6 million deaths worldwide. The causative agent of this disease is the new virus SARS-CoV-2; which continues to spread globally and sometimes with new and more complex aspects than before. The present study is an observational study aimed to investigate the role of AQI; PM and its relationship with the incidence of suspected cases (SC) and positive cases (PC) of COVID-19 at different levels of the air quality index (AQI) in Tehran, the capital of Iran in the period from Feb 20th, 2020 to Feb 22nd, 2021. Data on AQI were collected online from the air monitoring website of Air Quality Control Company under the supervision of Tehran Municipality. The data on suspected and positive cases were obtained from the Iranian Ministry of Health. The results and statistical analysis (Pearson correlation test) showed that with the increase of AQI level, the number of suspected cases (SC) and positive cases (PC), also increased (P-value<0.01). The average daily number of suspected and positive COVID-19 cases referred to medical centers, at different levels of the AQI was as follows: level II: yellow, moderate (SC: N = 466; PC: N = 223), level III: orange, unhealthy for sensitive groups (SC: N = 564; PC: N = 275), and Level IV: red, unhealthy (SC: N = 558; PC: N = 294). The results of the GEE for seasonal comparison (winter as reference season), showed that there is an epidemiological pattern in autumn with colder weather compared to other seasons in both suspected (Cl: %95, B = 408.94) and positive (Cl: %95, B = 83.42) cases of COVID-19. The results of this study will serve policymakers as an informative tool for guidance on the importance of the role of air pollution in viral epidemics.VoRSUNY DownstateEnvironmental and Occupational Health SciencesN/

Prepregnancy obesity is associated with lower psychomotor development scores in boys at age 3 in a low-income, minority birth cohort

Whether maternal obesity and gestational weight gain (GWG) are associated with early-childhood development in low-income, urban, minority populations, and whether effects differ by child sex remain unknown. This study examined the impact of prepregnancy BMI and GWG on early childhood neurodevelopment in the Columbia Center for Children's Environmental Health Mothers and Newborns study. Maternal prepregnancy weight was obtained by self-report, and GWG was assessed from participant medical charts. At child age 3 years, the Psychomotor Development Index (PDI) and Mental Development Index (MDI) of the Bayley Scales of Infant Intelligence were completed. Sex-stratified linear regression models assessed associations between prepregnancy BMI and pregnancy weight gain z-scores with child PDI and MDI scores, adjusting for covariates. Of 382 women, 48.2% were normal weight before pregnancy, 24.1% overweight, 23.0% obese, and 4.7% underweight. At 3 years, mean scores on the PDI and MDI were higher among girls compared to boys (PDI: 102.3 vs. 97.2, P = 0.0002; MDI: 92.8 vs. 88.3, P = 0.0001). In covariate-adjusted models, maternal obesity was markedly associated with lower PDI scores in boys [b = -7.81, 95% CI: (-13.08, -2.55), P = 0.004], but not girls. Maternal BMI was not associated with MDI in girls or boys, and GWG was not associated with PDI or MDI among either sex (all-P &gt; 0.05). We found that prepregnancy obesity was associated with lower PDI scores at 3 years in boys, but not girls. The mechanisms underlying this sex-specific association remain unclear, but due to elevated obesity exposure in urban populations, further investigation is warranted

Ambient Metals, Elemental Carbon, and Wheeze and Cough in New York City Children through 24 Months of Age

Rationale: The effects of exposure to specific components of ambient fine particulate matter (PM2.5), including metals and elemental carbon (EC), have not been fully characterized in young children. Objectives: To compare temporal associations among PM2.5; individual metal constituents of ambient PM2.5, including nickel (Ni), vanadium (V), and zinc (Zn); and EC and longitudinal reports of respiratory symptoms through 24 months of age. Methods: Study participants were selected from the Columbia Center for Children's Environmental Health birth cohort recruited in New York City between 1998 and 2006. Respiratory symptom data were collected by questionnaire every 3 months through 24 months of age. Ambient pollutant data were obtained from state-operated stationary monitoring sites located within the study area. For each subject, 3-month average inverse-distance weighted concentrations of Ni, V, Zn, EC, and PM2.5 were calculated for each symptom-reporting period based on the questionnaire date and the preceding 3 months. Associations between pollutants and symptoms were characterized using generalized additive mixed effects models, adjusting for sex, ethnicity, environmental tobacco smoke exposure, and calendar time. Measurements and Main Results: Increases in ambient Ni and V concentrations were associated significantly with increased probability of wheeze. Increases in EC were associated significantly with cough during the cold/flu season. Total PM2.5 was not associated with wheeze or cough. Conclusions: These results suggest that exposure to ambient metals and EC from heating oil and/or traffic at levels characteristic of urban environments may be associated with respiratory symptoms among very young children