65 research outputs found
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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
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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
Association of recent exposure to ambient metals on fractional exhaled nitric oxide in 9–11 year old inner-city children
Exposure to ambient metals in urban environments has been associated with wheeze, and emergency room visits and hospitalizations due to respiratory illness. However, the effect of ambient metals exposure on airway inflammation, and how these associations may be modified by seroatopy, has not been determined. Fractional exhaled nitric oxide (FENO) is a reliable proxy marker of airway inflammation. We hypothesized that recent ambient concentrations of Ni, V, Zn and Fe would be associated differentially with proximal and distal fractions of exhaled NO, and that these associations would be modified by seroatopy. As part of the Columbia Center for Children’s Environmental Health (CCCEH) birth cohort study, 9–11 year old children (n = 192) were evaluated. Ambient measures of Ni, V, Zn and Fe were obtained from a local central monitoring site and averaged over 9 days based on three 24 h measures every third day. Fractional exhaled nitric oxide (FENO) samples were obtained at constant flows of 50 (FENO50), 83 and 100 mL/s, and used to determine surrogate measures for proximal (JNO) and alveolar (Calv) inflammation. Seroatopy was determined by specific IgE at age 7. Data were analyzed using multivariable linear regression. Ambient V and Fe concentrations were associated positively with FENO50 (p = 0.018, p = 0.027). Ambient Fe was associated positively with JNO (p = 0.017). Ambient Ni and V concentrations were associated positively with Calv (p = 0.004, p = 0.018, respectively). A stronger association of Ni concentrations with Calv was observed among the children with seroatopy. These results suggest that ambient metals are associated differentially with different fractions of FENO production, and this relationship may be modified by seroatopy
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Association of recent exposure to ambient metals on fractional exhaled nitric oxide in 9–11 year old inner-city children
Exposure to ambient metals in urban environments has been associated with wheeze, and emergency room visits and hospitalizations due to respiratory illness. However, the effect of ambient metals exposure on airway inflammation, and how these associations may be modified by seroatopy, has not been determined. Fractional exhaled nitric oxide (FENO) is a reliable proxy marker of airway inflammation. We hypothesized that recent ambient concentrations of Ni, V, Zn and Fe would be associated differentially with proximal and distal fractions of exhaled NO, and that these associations would be modified by seroatopy. As part of the Columbia Center for Children’s Environmental Health (CCCEH) birth cohort study, 9–11 year old children (n = 192) were evaluated. Ambient measures of Ni, V, Zn and Fe were obtained from a local central monitoring site and averaged over 9 days based on three 24 h measures every third day. Fractional exhaled nitric oxide (FENO) samples were obtained at constant flows of 50 (FENO50), 83 and 100 mL/s, and used to determine surrogate measures for proximal (JNO) and alveolar (Calv) inflammation. Seroatopy was determined by specific IgE at age 7. Data were analyzed using multivariable linear regression. Ambient V and Fe concentrations were associated positively with FENO50 (p = 0.018, p = 0.027). Ambient Fe was associated positively with JNO (p = 0.017). Ambient Ni and V concentrations were associated positively with Calv (p = 0.004, p = 0.018, respectively). A stronger association of Ni concentrations with Calv was observed among the children with seroatopy. These results suggest that ambient metals are associated differentially with different fractions of FENO production, and this relationship may be modified by seroatopy
Infant rhinitis and watery eyes predict school-age exercise-induced wheeze, emergency department visits and respiratory-related hospitalizations
Background: Rhinitis and conjunctivitis are often linked to asthma development through an allergic pathway. However, runny nose and watery eyes can result from nonallergic mechanisms. These mechanisms can also underlie exercise-induced wheeze (EIW), which has been associated with urgent medical visits for asthma, independent of other indicators of asthma severity or control.
Objective:
To test the hypothesis that rhinitis or watery eyes without cold symptoms (RWWC) in infancy predict development of EIW and urgent respiratory-related medical visits at school age, independent of seroatopy.
Methods:
Within a prospective birth cohort of low-income, urban children (n = 332), RWWC was queried during the first year of life. Relative risks (RRs) for EIW, emergency department (ED) visits, and hospitalizations for asthma and other breathing difficulties at 5 to 7 years of age were estimated with multivariable models. Seroatopy was determined at 7 years of age.
Results:
Infant RWWC was common (49% of children) and predicted school-age EIW (RR, 2.8; P < .001), ED visits (RR, 1.8; P = .001), and hospitalizations (RR, 9.8; P = .002). These associations were independent of infant wheeze. They were also independent of birth order, an indicator of increased risk of exposure to viruses in infancy, and infant ear infections, an indicator of sequelae of upper airway infections. The association between infant RWWC and ED visits at 5 to 7 years of age was attenuated (RR, 1.2; P = .23) when EIW at 5 to 7 years of age was included in the model, suggesting EIW mediates the association. Adjustment for seroatopy did not diminish the magnitudes of any of these associations.
Conclusion:
These findings suggest a nonallergic connection between infant nonwheeze symptoms and important consequences of urban respiratory health by school age through EI
Asthma in Inner-City Children at 5–11 Years of Age and Prenatal Exposure to Phthalates: The Columbia Center for Children’s Environmental Health Cohort
Background: Studies suggest that phthalate exposures may adversely affect child respiratory health. Objectives: We evaluated associations between asthma diagnosed in children between 5 and 11 years of age and prenatal exposures to butylbenzyl phthalate (BBzP), di-n-butyl phthalate (DnBP), di(2-ethylhexyl) phthalate (DEHP), and diethyl phthalate (DEP). Methods: Phthalate metabolites were measured in spot urine collected from 300 pregnant inner-city women. Children were examined by an allergist or pulmonologist based on the first parental report of wheeze, other respiratory symptoms, and/or use of asthma rescue/controller medication in the preceding 12 months on repeat follow-up questionnaires. Standardized diagnostic criteria were used to classify these children as either having or not having current asthma at the time of the physician examination. Children without any report of wheeze or the other asthma-like symptoms were classified as nonasthmatics at the time of the last negative questionnaire. Modified Poisson regression analyses were used to estimate relative risks (RR) controlling for specific gravity and potential confounders. Results: Of 300 children, 154 (51%) were examined by a physician because of reports of wheeze, other asthma-like symptoms, and/or medication use; 94 were diagnosed with current asthma and 60 without current asthma. The remaining 146 children were classified as nonasthmatic. Compared with levels in nonasthmatics, prenatal metabolites of BBzP and DnBP were associated with a history of asthma-like symptoms (p 70% higher among children with maternal prenatal BBzP and DnBP metabolite concentrations in the third versus the first tertile. Conclusion: Prenatal exposure to BBzP and DnBP may increase the risk of asthma among inner-city children. However, because this is the first such finding, results require replication. Citation: Whyatt RM, Perzanowski MS, Just AC, Rundle AG, Donohue KM, Calafat AM, Hoepner LA, Perera FP, Miller RL. 2014. Asthma in inner-city children at 5–11 years of age and prenatal exposure to phthalates: the Columbia Center for Children’s Environmental Health Cohort. Environ Health Perspect 122:1141–1146; http://dx.doi.org/10.1289/ehp.130767
Within- and Between-Home Variability in Indoor-Air Insecticide Levels during Pregnancy among an Inner-City Cohort from New York City
BACKGROUND: Residential insecticide use is widespread in the United States, but few data are available on the persistence and variability in levels in the indoor environment. OBJECTIVE: The study aim was to assess within- and between-home variability in indoor-air insecticides over the final 2 months of pregnancy among a cohort of African-American and Dominican women from New York City. METHODS: Women not employed outside the home were enrolled between February 2001 and May 2004 (n = 102); 9 insecticides and an adjuvant were measured in 48-hr personal air samples and 2-week integrated indoor air samples collected sequentially for 7.0 ± 2.3 weeks (n = 337 air samples). RESULTS: Sixty-one percent of the women reported using pest control during the air samplings. Chlorpyrifos, diazinon, and propoxur were detected in 99–100% of personal and indoor samples (range, 0.4–641 ng/m(3)). Piperonyl butoxide (a pyrethroid adjuvant) was detected in 45.5–68.5% (0.2–608 ng/m(3)). There was little within-home variability and no significant difference in air concentrations within homes over time (p ≥ 0.2); between-home variability accounted for 88% of the variance in the indoor air levels of propoxur, 92% in chlorpyrifos, 94% in diazinon, and 62% in piperonyl butoxide (p < 0.001). Indoor and maternal personal air insecticide levels were highly correlated (r = 0.7–0.9, p < 0.001). Diazinon and chlorpyrifos levels declined 5-fold between 2001 and 2004 but were detected in all homes 1.5 and 2.5 years, respectively, after the U.S. Environmental Protection Agency ban on their residential use. CONCLUSION: Results showed that the insecticides were persistent in the home with little variability in air concentrations over the 2 months and contributed to chronic maternal inhalation exposures during pregnancy
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