Faculty Bibliography

Objectives:To assess associations of caesarean section with body mass from birth through adolescence.Design:Longitudinal birth cohort study, following subjects up to 15 years of age.Setting and participants:Children born in 1991-1992 in Avon, UK who participated in the Avon Longitudinal Study of Parents and Children (ALSPAC) (n=10 219).Outcome measures:Primary outcome: standardized measures of body mass (weight-for length z-scores at 6 weeks, 10 and 20 months; and body mass index (BMI) z-scores at 38 months, 7, 9, 11 and 15 years). Secondary outcome: categorical overweight or obese (BMI >/=85th percentile) for age and gender, at 38 months, 7, 9, 11 and 15 years.Results:Of the 10 219 children, 926 (9.06%) were delivered by caesarean section. Those born by caesarean had lower-birth weights than those born vaginally (-46.1 g, 95% confidence interval(CI): 14.6-77.6 g; P=0.004). In mixed multivariable models adjusting for birth weight, gender, parental body mass, family sociodemographics, gestational factors and infant feeding patterns, caesarean delivery was consistently associated with increased adiposity, starting at 6 weeks (+0.11 s.d. units, 95% CI: 0.03-0.18; P=0.005), through age 15 (BMI z-score increment+0.10 s.d. units, 95% CI: 0.001-0.198; P=0.042). By age 11 caesarean-delivered children had 1.83 times the odds of overweight or obesity (95% CI: 1.24-2.70; P=0.002). When the sample was stratified by maternal pre-pregnancy weight, the association among children born of overweight/obese mothers was strong and long-lasting. In contrast, evidence of an association among children born of normal-weight mothers was weak.Conclusion:Caesarean delivery is associated with increased body mass in childhood and adolescence. Research is needed to further characterize the association in children of normal weight women. Additional work is also needed to understand the mechanism underlying the association, which may involve relatively enduring changes in the intestinal microbiome.International Journal of Obesity advance online publication, 14 May 2013; doi:10.1038/ijo.2013.49.

The impact of air pollution on fetal growth remains controversial, in part, because studies have been limited to sub-regions of the United States with limited variability. No study has examined air pollution impacts on neonatal health care utilization. We performed descriptive, univariate and multivariable analyses on administrative hospital record data from 222,359 births in the 2000, 2003 and 2006 Kids Inpatient Database linked to air pollution data drawn from the US Environmental Protection Agency's Aerometric Information Retrieval System. In this study, air pollution exposure during the birth month was estimated based on birth hospital address. Although air pollutants were not individually associated with mean birth weight, a three-pollutant model controlling for hospital characteristics, demographics, and birth month identified 9.3% and 7.2% increases in odds of low birth weight and very low birth weight for each mug/m(3) increase in PM(2.5) (both P<0.0001). PM(2.5) and NO(2) were associated with -3.0% odds/p.p.m. and +2.5% odds/p.p.b. of preterm birth, respectively (both P<0.0001). A four-pollutant multivariable model indicated a 0.05 days/p.p.m. NO(2) decrease in length of the birth hospitalization (P=0.0061) and a 0.13 days increase/p.p.m. CO (P=0.0416). A $1166 increase in per child costs was estimated for the birth hospitalization per p.p.m. CO (P=0.0002) and $964 per unit increase in O(3) (P=0.0448). A reduction from the 75th to the 25th percentile in the highest CO quartile for births predicts annual savings of $134.7 million in direct health care costs. In a national, predominantly urban, sample, air pollutant exposures during the month of birth are associated with increased low birth weight and neonatal health care utilization. Further study of this database, with enhanced control for confounding, improved exposure assessment, examination of exposures across multiple time windows in pregnancy, and in the entire national sample, is supported by these initial investigations.Journal of Exposure Science and Environmental Epidemiology advance online publication, 23 January 2013; doi:10.1038/jes.2012.124.

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.