Faculty Bibliography

Urinary bisphenol A (BPA), a widely used biomarker of exposure to BPA, has been associated with cardiometabolic derangements in laboratory studies and with low-grade albuminuria in Chinese adults. Despite the known unique vulnerability of children to environmental chemicals, no studies have examined associations of urinary BPA with albuminuria in children. As exposure to BPA is widespread in the United States population, we examined data from 710 children in the 2009-10 National Health and Nutrition Examination Survey with urinary BPA measurements and first morning urine samples with creatinine values. Controlled for a broad array of sociodemographic and environmental risk factors as well as insulin resistance and elevated cholesterol, children with the highest compared with the lowest quartile of urinary BPA had a significant 0.91 mg/g higher albumin-to-creatinine ratio, adjusted for the urinary BPA concentration. When the multivariable model was reprised substituting continuous measures of BPA, a significant 0.28 mg/g albumin-to-creatinine ratio increase was identified for each log unit increase in urinary BPA. Thus, an association of BPA exposure with low-grade albuminuria is consistent with previous results found in Chinese adults and documents this in children in the United States. Our findings broaden the array of adverse effects of BPA to include endothelial dysfunction as evidenced by the low-grade albuminuria and support proactive efforts to prevent harmful exposures.Kidney International advance online publication, 9 January 2013; doi:10.1038/ki.2012.422.

BACKGROUND: Phthalates have antiandrogenic effects and may disrupt lipid and carbohydrate metabolism. Racial/ethnic subpopulations have been documented to have varying urinary phthalate concentrations and prevalences of childhood obesity. OBJECTIVE: We examined associations between urinary phthalate metabolites and body mass outcomes in a nationally representative sample of US children and adolescents. METHODS: We performed stratified and whole-sample cross-sectional analyses of 2,884 children 6-19 years of age who participated in the 2003-2008 National Health and Nutrition Examination Survey. Multivariable linear and logistic analyses of body mass index Z-score, overweight, and obesity were performed against molar concentrations of low-molecular weight (LMW), high-molecular weight (HMW) and di-2-ethylhexylphthalate (DEHP) metabolites, controlling for gender, television watching, caregiver education, caloric intake, poverty-income ratio, race/ethnicity, serum cotinine, and age group. Sensitivity analysis examined robustness of results to removing sample weighting, normalizing phthalate concentrations for molecular weight and examination of different dietary intake covariates. RESULTS: In stratified, multivariable models, each log unit (roughly threefold) increase in LMW metabolites was associated with 21% and 22% increases in odds (95% CIs 1.05-1.39 and 1.07-1.39, respectively) of overweight and obesity, and a 0.090 SD unit increase in BMI Z-score (95% CI 0.003-0.18), among non-Hispanic blacks. Significant associations were not identified in any other racial/ethnic subgroup or in the study sample as a whole after controlling for potential confounders, associations were not significant for HMW or DEHP metabolites, and results did not change substantially with sensitivity analysis. CONCLUSIONS: We identify a race/ethnicity-specific association of phthalates with childhood obesity in a nationally representative sample. Further study is needed to corroborate the association, and evaluate genetic/epigenomic predisposition and/or increased phthalate exposure as possible explanations for differences among racial/ethnic subgroups.

OBJECTIVE: Prior research on the physical health of children exposed to the World Trade Center (WTC) attacks has largely relied on parental report via questionnaire. We examined the impact of clinically-reported exposures on the physical health of children who lived and/or attended school in downtown Manhattan on September 11, 2001. STUDY DESIGN: We performed a cross-sectional study of 148 patients who presented to the WTC Environmental Health Center/Survivors Health Program, and were /=1day in their home between September 11 and 18, 2001; and 25.7% reported home dust exposure. New-onset nasal/sinus congestion was reported in 52.7%, while nearly one-third reported new gastroesophageal reflux (GERD) symptoms. Prehypertension or hypertension was identified in 45.5%. Multivariable regression with exposure variables, body mass index category, and age as covariates identified strongest associations of dust cloud with spirometry (17.1% decrease in maximum midexpiratory flow). Younger children experienced increased peripheral eosinophils (+0.098% per year, p=0.023), while older children experienced more new-onset GERD (OR 1.17, p=0.004), headaches (OR 1.10, p=0.011), and prehypertension (OR 1.09, p=0.024). Home dust exposure was associated with reduced high-density lipoprotein (-10.3mg/dL, p=0.027) and elevated triglycerides (+36.3mg/dL, p=0.033). CONCLUSIONS: While these findings cannot be assumed to generalize to all children exposed to the WTC attacks, they strongly suggest the need for more extensive study of respiratory, metabolic, and cardiovascular consequences.

Objectives:To examine the associations of antibiotic exposures during the first 2 years of life and the development of body mass over the first 7 years of life.Design:Longitudinal birth cohort study.Subjects:A total of 11 532 children born at >/=2500 g in the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based study of children born in Avon, UK in 1991-1992.Measurements:Exposures to antibiotics during three different early-life time windows (<6 months, 6-14 months, 15-23 months), and indices of body mass at five time points (6 weeks, 10 months, 20 months, 38 months and 7 years).Results:Antibiotic exposure during the earliest time window (<6 months) was consistently associated with increased body mass (+0.105 and +0.083 s.d. unit, increase in weight-for-length Z-scores at 10 and 20 months, P<0.001 and P=0.001, respectively; body mass index (BMI) Z-score at 38 months +0.067 s.d. units, P=0.009; overweight OR 1.22 at 38 months, P=0.029) in multivariable, mixed-effect models controlling for known social and behavioral obesity risk factors. Exposure from 6 to 14 months showed no association with body mass, while exposure from 15 to 23 months was significantly associated with increased BMI Z-score at 7 years (+0.049 s.d. units, P=0.050). Exposures to non-antibiotic medications were not associated with body mass.Conclusions:Exposure to antibiotics during the first 6 months of life is associated with consistent increases in body mass from 10 to 38 months. Exposures later in infancy (6-14 months, 15-23 months) are not consistently associated with increased body mass. Although effects of early exposures are modest at the individual level, they could have substantial consequences for population health. Given the prevalence of antibiotic exposures in infants, and in light of the growing concerns about childhood obesity, further studies are needed to isolate effects and define life-course implications for body mass and cardiovascular risks.

Context: Bisphenol A (BPA) is an environmental endocrine disruptor that has been linked to many reproductive disorders in animal models and humans. One such disorder is polycystic ovary syndrome (PCOS), which has been correlated with increased BPA levels in adult women. However, little is known about the role of serum BPA in adolescents with PCOS and its correlation with the metabolic profile. Objectives: To measure BPA levels in adolescent with PCOS as compared to a body mass index (BMI)-matched control group. To correlate serum BPA levels with disease severity, as measured by biochemical and radiologic features. Design: A retrospective chart review of clinical, biochemical, and ultrasonographic data in adolescents with PCOS and controls. Serum BPA was measured and compared between groups and correlated with biochemical (testosterone, insulin resistance) and ovarian ultrasound findings. Setting: Urban tertiary academic medical center. Participants: Study groups included 15 overweight/obese adolescent females with PCOS (mean age 15.27 years, mean BMI 32.84) and 14 BMI-matched female controls (mean age 14.1 years, mean BMI 31). Results: Biochemical data showed a mean free testosterone of 7.06 pg/mL and mean LH:FSH ratio of 1.93 in the PCOS group as compared to mean testosterone of 4.51 pg/mL and mean LH:FSH ratio of 1.12 in the control group (P=0.08 and 0.012, respectively). The index of insulin resistance (HOMA-IR) was 1.65 in the PCOS group and 1.82 in the control group (P=0.75). Serum BPA levels were 0.624 +/-1.29 ng/mL in the PCOS group versus 0.28 +/-0.11 ng/mL in controls (P=0.325). No correlation was found between serum BPA levels and biochemical and radiologic markers of PCOS severity. Conclusions: The results of this exploratory study pose many interesting questions about BPA exposure in adolescents. Although the results are not statistically significant, both adult studies and animal models have shown a strong correlation between serum BPA and severity of PCOS. The weaker relationship in adolescents may be explained in part by shorter duration of exposure to BPA in years. Further studies are warranted to clarify the correlation of PCOS and the endocrine disruptor BPA in a larger setting

OBJECTIVE:To assess the association of the severity of obesity with diagnosis and health education, and to identify any differences within demographic or other subgroups.DESIGN:Clinician visits for 2-18 year olds from the 2005-2008 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey were combined. Descriptive, bivariate and multivariate analyses were used to compare diagnosis of obesity and health education (nutrition, exercise and weight reduction) across elevated body mass index (BMI) groups (overweight, obese and extreme or very obese, defined as >120% of the 95th percentile for age and gender), patient socio-demographic characteristics, physician specialty and type of visit (well child visits (WCV) versus non-well child visits (non-WCV).RESULTS:A total of 17 808 visits had a calculated BMI, of which 5.8% were extremely obese, 13% were obese and 15.2% were overweight, with the highest percentages among older children, blacks and Hispanics. Diagnosis and weight reduction education were higher among children with an extreme BMI. Nutrition and exercise education were not correlated with severity of obesity. Race, ethnicity or gender biases were not identified. Severity of obesity was significantly associated with presentation to a non-WCV rather than a WCV. CONCLUSION:Extremely obese children have higher, but still insufficient, rates of diagnosis and health education. Nutrition and exercise education are not prevalent throughout all age groups. Providers may be relying inconsistently and insufficiently on visual cues to drive their obesity prevention practices. Furthermore, lower rates of diagnosis and education at non-WCV may result in a missed opportunity to prevent comorbidities. This is of particular concern as overweight children are less likely to be seen at WCV than non-WCV.

OBJECTIVE: To determine clinical characteristics, demographics and short-term outcomes of neonates diagnosed with fetomaternal haemorrhage (FMH). DESIGN: The authors analysed the Nationwide Inpatient Sample, 1993 to 2008. Singleton births diagnosed with FMH were identified by International Classification of Diseases (ICD-9) code 762.3. Descriptive, univariate and multivariable regression analyses were performed to determine the national annual incidence of FMH over time as well as demographics and clinical characteristics of neonates with FMH. RESULTS: FMH was identified in 12 116 singleton births. Newborns with FMH required high intensity of care: 26.3% received mechanical ventilation, 22.4% received blood product transfusion and 27.8% underwent central line placement. Preterm birth (OR 3.7), placental abruption (OR 9.8) and umbilical cord anomaly (OR 11.4) were risk factors for FMH. Higher patient income was associated with increased likelihood of FMH diagnosis (OR 1.2), and Whites were more likely to be diagnosed than ethnic minorities (OR 1.9). There was reduced frequency of diagnosis in the Southern USA (OR 0.8 vs the Northeastern USA). CONCLUSIONS: Diagnosis of FMH is associated with significant morbidity as well as regional, socioeconomic and racial disparity. Further study is needed to distinguish between diagnostic coding bias and true epidemiology of the disease. This is the first report of socioeconomic and racial/ethnic disparities in FMH, which may represent disparities in detection that require national attention.

Congenital fibrosarcoma (CFS) is a rare fibrous tissue malignancy that usually presents in the first few years of life. It is unique among human sarcomas in that it has an excellent prognosis. We describe a temporal clustering of a number of cases of CFS and investigate the possible associated prenatal risk factors. The Pediatric Environmental History, a questionnaire developed in our clinic that is instrumental in determining environmental risk factors for tumor-related disease, was essential in documenting the presence or absence of risk factors considered as human carcinogens. We found a history of exposure to petroleum products in four cases of CFS that occurred at a greater than expected rate in a short time frame-an apparent cancer cluster. We call attention to the possibility that exposure to petroleum products raises the risk of developing CFS. While future studies should focus on systematic investigation of CFS and its underlying mechanisms, this report suggests the need for proactive measures to avoid exposure to solvents and petroleum products during pregnancy.

CONTEXT: Bisphenol A (BPA), a manufactured chemical, is found in canned food, polycarbonate-bottled liquids, and other consumer products. In adults, elevated urinary BPA concentrations are associated with obesity and incident coronary artery disease. BPA exposure is plausibly linked to childhood obesity, but evidence is lacking to date. OBJECTIVE: To examine associations between urinary BPA concentration and body mass outcomes in children. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analysis of a nationally representative subsample of 2838 participants aged 6 through 19 years randomly selected for measurement of urinary BPA concentration in the 2003-2008 National Health and Nutrition Examination Surveys. MAIN OUTCOME MEASURES: Body mass index (BMI), converted to sex- and age-standardized z scores and used to classify participants as overweight (BMI >/=85th percentile for age/sex) or obese (BMI >/=95th percentile). RESULTS: Median urinary BPA concentration was 2.8 ng/mL (interquartile range, 1.5-5.6). Of the participants, 1047 (34.1% [SE, 1.5%]) were overweight and 590 (17.8% [SE, 1.3%]) were obese. Controlling for race/ethnicity, age, caregiver education, poverty to income ratio, sex, serum cotinine level, caloric intake, television watching, and urinary creatinine level, children in the lowest urinary BPA quartile had a lower estimated prevalence of obesity (10.3% [95% CI, 7.5%-13.1%]) than those in quartiles 2 (20.1% [95% CI, 14.5%-25.6%]), 3 (19.0% [95% CI, 13.7%-24.2%]), and 4 (22.3% [95% CI, 16.6%-27.9%]). Similar patterns of association were found in multivariable analyses examining the association between quartiled urinary BPA concentration and BMI z score and in analyses that examined the logarithm of urinary BPA concentration and the prevalence of obesity. Obesity was not associated with exposure to other environmental phenols commonly used in other consumer products, such as sunscreens and soaps. In stratified analysis, significant associations between urinary BPA concentrations and obesity were found among whites (P < .001) but not among blacks or Hispanics. CONCLUSIONS: Urinary BPA concentration was significantly associated with obesity in this cross-sectional study of children and adolescents. Explanations of the association cannot rule out the possibility that obese children ingest food with higher BPA content or have greater adipose stores of BPA.