Abeer Hassoun

Prenatal exposure to antibiotics, cesarean section and risk of childhood obesity

Background/Objectives:Cesarean section (CS) and antibiotic use during pregnancy may alter normal maternal-offspring microbiota exchange, thereby contributing to aberrant microbial colonization of the infant gut and increased susceptibility to obesity later in life. We hypothesized that (i) maternal use of antibiotics in the second or third trimester of pregnancy and (ii) CS are independently associated with higher risk of childhood obesity in the offspring.Subjects/Methods:Of the 727 mothers enrolled in the Northern Manhattan Mothers and Children Study, we analyzed the 436 mother–child dyads followed until 7 years of age with complete data. We ascertained prenatal antibiotic use by a questionnaire administered late in the third trimester, and delivery mode by medical record. We derived age- and sex-specific body mass index (BMI) z-scores using the CDC SAS Macro, and defined obesity as BMI z⩾95th percentile. We used binary regression with robust variance and linear regression models adjusted for maternal age, ethnicity, pre-gravid BMI, maternal receipt of public assistance, birth weight, sex, breastfeeding in the first year and gestational antibiotics or delivery mode.Results:Compared with children not exposed to antibiotics during the second or third trimester, those exposed had 84% (33–154%) higher risk of obesity, after multivariable adjustment. Second or third trimester antibiotic exposure was also positively associated with BMI z-scores, waist circumference and % body fat (all P<0.05). Independent of prenatal antibiotic usage, CS was associated with 46% (8–98%) higher offspring risk of childhood obesity. Associations were similar for elective and non-elective CS.Conclusions:In our cohort, CS and exposure to antibiotics in the second or third trimester were associated with higher offspring risk of childhood obesity. Future studies that address the limitations of our study are warranted to determine if prenatal antibiotic use is associated with offspring obesity. Research is also needed to determine if alterations in neonatal gut microbiota underlie the observed associations.

Association of Childhood Obesity With Maternal Exposure to Ambient Air Polycyclic Aromatic Hydrocarbons During Pregnancy

There are concerns that prenatal exposure to endocrine-disrupting chemicals increases childrens risk of obesity. African-American and Hispanic children born in the Bronx or Northern Manhattan, New York (1998-2006), whose mothers underwent personal air monitoring for polycyclic aromatic hydrocarbon (PAH) exposure during pregnancy, were followed up to ages 5 (n = 422) and 7 (n = 341) years. At age 5 years, 21% of the children were obese, as were 25% of those followed to age 7 years. After adjustment for childs sex, age at measurement, ethnicity, and birth weight and maternal receipt of public assistance and prepregnancy obesity, higher prenatal PAH exposures were significantly associated with higher childhood body size. In adjusted analyses, compared with children of mothers in the lowest tertile of PAH exposure, children of mothers in the highest exposure tertile had a 0.39-unit higher body mass index z score (95% confidence interval (CI): 0.08, 0.70) and a relative risk of 1.79 (95% CI: 1.09, 2.96) for obesity at age 5 years, and they had a 0.30-unit higher body mass index z score (95% CI: 0.01, 0.59), a 1.93-unit higher percentage of body fat (95% CI: 0.33, 3.54), and a relative risk of 2.26 (95% CI: 1.28, 4.00) for obesity at age 7 years. The data indicate that prenatal exposure to PAHs is associated with obesity in childhood.

Bone age advancement in prepubertal children with obesity and premature adrenarche: possible potentiating factors.

Obesity and premature adrenarche (PA) are both associated with bone age (BA) advancement of unclear etiology, which may lead to earlier puberty, suboptimal final height and obesity in adulthood. Our objective was to understand the hormonal and anthropometric characteristics of BA advancement in a spectrum of prepubertal children with and without obesity and PA. In this cross‐sectional study of 66 prepubertal children (35 PA, 31 control, 5–9 years), BMI z‐score, hormonal values and response to an oral glucose tolerance test were the main outcome measures. Subjects were divided into tertiles by BA divided by chronological age (BA/CA), an index of BA advancement. Subjects in the top tertile for BA/CA had the highest dehydroepiandrosterone sulfate (DHEAS), free testosterone (%), hemoglobin A1C, BMI z‐score, and weight (P < 0.05). BMI z‐score (r = 0.47), weight (r = 0.40), free testosterone (%) (r = 0.34), and DHEAS (r = 0.30) correlated with BA/CA (P < 0.02). Regression analysis showed greater BA/CA in PA compared to controls after controlling for weight (0.21 ± 0.56, P < 0.004). An exploratory stepwise regression model showed that weight, estradiol, and DHEAS were the strongest predictors of BA/CA accounting for 24% of its variance. Obesity was highly associated with BA advancement in this study of prepubertal children. In addition, children with PA had greater BA/CA at any given weight when compared to controls. These findings suggest a possible hormonal factor, which potentiates the effect of obesity on BA advancement in children with obesity and/or PA.

Prenatal Exposure to Phthalates and Childhood Body Size in an Urban Cohort

Background: Phthalate exposures are hypothesized to increase obesity; however, prior research has been largely cross-sectional. Objective: We evaluated associations between prenatal phthalate exposures and body mass index (BMI) at child ages 5 and 7 years. Methods: Nine metabolites of six phthalates—di(2-ethylhexyl) phthalate (DEHP), di-n-octyl-, di-iso-butyl-, di-n-butyl-, butylbenzyl-, and diethyl phthalates—were measured in spot urine samples collected from pregnant African-American and Dominican women during their third trimester, and from their children at ages 3 and 5 years. To reduce multiple comparison issues, we initially used principal component analysis (PCA) to identify major patterns of natural log (ln)-transformed metabolite concentrations. Height and weight were assessed at ages 5 and 7 years, and fat mass and waist circumference at age 7. Linearized generalized estimating equation analyses related maternal component scores to child anthropometric outcomes at ages 5 (n = 326) and 7 (n = 330) years. Results: PCA identified a DEHP component and a non-DEHP component. In boys, higher maternal non-DEHP, but not DEHP, component scores were associated with lower BMI z-score (β = –0.30; 95% CI: –0.50, –0.10, n = 156), lower fat percentage (β = –1.62; 95% CI: –2.91, –0.34, n = 142), and smaller waist circumference (β = –2.02; 95% CI: –3.71, –0.32, n = 124). No significant associations with anthropometric outcomes were seen in girls (for BMI z-score, β = 0.07; 95% CI: –0.18, 0.31, n = 181). Interactions between sex and non-DEHP component association with outcomes were statistically significant (p < 0.01). Conclusions: Contrary to hypotheses, prenatal non-DEHP phthalate exposures were associated with lower BMI z-score, waist circumference, and fat mass in boys during early childhood. Citation: Maresca MM, Hoepner LA, Hassoun A, Oberfield SE, Mooney SJ, Calafat AM, Ramirez J, Freyer G, Perera FP, Whyatt RM, Rundle AG. 2016. Prenatal exposure to phthalates and childhood body size in an urban cohort. Environ Health Perspect 124:514–520; http://dx.doi.org/10.1289/ehp.1408750

Bisphenol A and Adiposity in an Inner-City Birth Cohort.

Background: Early-life exposure to the endocrine disruptor bisphenol A (BPA) may contribute to the development of obesity. Prospective evidence in humans on this topic is limited. Objectives: We examined prenatal and early-childhood BPA exposures in relation to childhood measures of adiposity in the Columbia Center for Children’s Environmental Health (CCCEH) New York City birth cohort. Methods: BPA concentrations were measured in prenatal (n = 375) and child ages 3 (n = 408) and 5 years (n = 518) spot urine samples. Childhood anthropometric and bioelectrical impedance outcomes included body mass index z-scores (BMIZ) at 5 and 7 years, and fat mass index (FMI), percent body fat (%BF), and waist circumference (WC) at 7 years. Associations were evaluated using multiple linear regression with continuous and tertile BPA concentrations. Results: Prenatal urinary BPA concentrations were positively associated with child age 7 FMI (β = 0.31 kg/m2; 95% CI: 0.01, 0.60, p = 0.04), %BF (β = 0.79; 95% CI: 0.03, 1.55, p = 0.04), and WC (β = 1.29 cm; 95% CI: 0.29, 2.30, p = 0.01), but not BMIZ, or change in BMIZ between ages 5 and 7 years (all p-values > 0.1). FMI results were sex-specific. Child urinary BPA concentrations were not associated with child anthropometric outcomes (all p-values > 0.05). Conclusions: Analyses of the CCCEH longitudinal birth cohort found associations between prenatal urinary BPA concentrations and FMI, %BF, and WC. Our results suggest that prenatal BPA exposure may contribute to developmental origins of adiposity. These findings are consistent with several prior studies, raising concern about the pervasiveness of BPA. Citation: Hoepner LA, Whyatt RM, Widen EM, Hassoun A, Oberfield SE, Mueller NT, Diaz D, Calafat AM, Perera FP, Rundle AG. 2016. Bisphenol A and adiposity in an inner-city birth cohort. Environ Health Perspect 124:1644–1650; http://dx.doi.org/10.1289/EHP205

Racial/ethnic Differences in Clinical and Biochemical Type 2 Diabetes Mellitus Risk Factors in Children

To examine whether periadolescent children demonstrate the significant racial/ethnic differences in body fatness relative to BMI and in the prevalence and relationship of body composition to risk factors for type 2 diabetes (T2DM) as in adults.

Retinol binding protein 4 is associated with adiposity-related co-morbidity risk factors in children.

Abstract Objective: In adults, elevated levels of retinol binding protein 4 (RBP4) have been associated with biochemical markers of adiposity-related co-morbidities including insulin resistance, dyslipidemia, hypertension, and abdominal obesity. This study examined the relationship between RBP4 and risk factors for co-morbidities of adiposity in a population of ethnically diverse children in early- to mid-adolescence in the public school system of New York City. Materials/methods: We analyzed anthropometric (body mass index, % body fat, waist circumference), metabolic (lipids, glucose), and inflammatory (TNF-α, interleukin-6, C-reactive protein, adiponectin) markers for adiposity-related co-morbidities and serum alanine aminotransferase (ALT) in 106 school children (65 males, 41 females) 11–15 years of age (mean±SD=13.0±0.1 years) who were enrolled in the Reduce Obesity and Diabetes (ROAD) project. Insulin sensitivity was assessed by quantitative insulin sensitivity check index. Insulin secretory capacity was measured as acute insulin response and glucose disposal index. Results: Serum RBP4 was significantly correlated directly with ALT, triglycerides, and triglyceride z-score, and inversely correlated with adiponectin. Correlations with ALT and adiponectin remained significant when corrected for % body fat, age, and gender. There were significant ethnic differences in the relationship of RBP4 to ALT, glucose disposal index and adiponectin. Conclusions: In early- to mid-adolescents, circulating concentrations of RBP4 are correlated with multiple risk factors for adiposity-related co-morbidities. The observation that many associations persisted when corrected for % body fat, suggests that RBP4 can be viewed as an independent marker of adiposity-related co-morbidity risk in children.

Excessive gestational weight gain is associated with long-term body fat and weight retention at 7 y postpartum in African American and Dominican mothers with underweight, normal, and overweight prepregnancy BMI

BACKGROUND Excessive gestational weight gain (GWG) is associated with postpartum weight retention (PPWR) and abdominal adiposity, but long-term effects are understudied in low-income and minority populations at high risk of obesity and associated sequelae. OBJECTIVE We examined associations between GWG and long-term PPWR and adiposity in a prospective cohort of African American and Dominican mothers in the Bronx and Northern Manhattan. DESIGN Women (n = 302) were enrolled during pregnancy and were followed for 7 y postpartum. Linear regression was used to relate excessive GWG [greater than 2009 Institute of Medicine (IOM) guidelines] to outcomes [percentage body fat and long-term PPWR (change in weight from prepregnancy to 7 y postpartum)], adjusting for covariates and included an interaction term between prepregnancy body mass index (BMI; in kg/m(2)) and GWG. RESULTS Mean ± SD prepregnancy BMI and total GWG were 25.6 ± 5.8 (42% of women had BMI ≥25) and 16.6 ± 7.8 kg (64% of women had total GWG greater than IOM guidelines), respectively. Associations between GWG and long-term PPWR and the percentage body fat varied by prepregnancy BMI (P-interaction ≤ 0.06); excessive GWG was associated with a higher percentage body fat and greater long-term PPWR in mothers with lower prepregnancy BMI. To illustrate the interaction, a predicted covariate-adjusted model, which was used to derive estimates for the percentage body fat and PPWR associated with excessive GWG, was estimated for 2 prepregnancy BMI examples. For a woman with prepregnancy BMI of 22, excessive GWG was associated with 3.0% higher body fat (P < 0.001) and a 5.6-kg higher PPWR (P < 0.001); however, for a woman with a prepregnancy BMI of 30, excessive GWG was associated with 0.58% higher body fat (P = 0.55) and 2.06 kg PPWR (P = 0.24). CONCLUSIONS Long-term adiposity and PPWR in low-income African American and Dominican mothers were predicted by interacting effects of prepregnancy BMI and excessive GWG. The provision of support for mothers to begin pregnancy at a healthy weight and to gain weight appropriately during pregnancy may have important lasting implications for weight-related health in this population. This study was registered at clinicaltrials.gov as NCT00043498.

Clinical and metabolic characteristics of an obese, Dominican, pediatric population.

The prevalence of obesity is particularly high in Black and Latino pediatric populations. A limited number of metabolic studies suggest that race plays a role in the development of obesity-related co-morbidities. We evaluated clinical and metabolic characteristics of 428 obese (mean BMI z-score 2.63) children and adolescents ranging in age from 2-20 years, of primarily Dominican ancestry attending the obesity clinic at Childrens Hospital of New York Presbyterian over a 5-year period (1998-2003). Of 193 patients available for detailed metabolic analysis, abnormalities were found for elevated systolic blood pressure (19%), diastolic blood pressure (11%), total cholesterol (18%), LDL (12%), triglycerides (10%), AST (<1%), ALT (4%), low HDL (47%), impaired fasting glucose (5%), impaired glucose tolerance 7%, diabetes mellitus by fasting criteria(<1%), and metabolic syndrome (14%). Despite extraordinary family histories of obesity and diabetes mellitus, the metabolic syndrome and abnormalities of glucose regulation were relatively infrequent compared to studies of obese, pediatric Latino patients of primarily Mexican and Puerto Rican ancestry. This finding suggests that Latinos from different areas of origin may have different risks of obesity-related conditions.

Autoimmune thyroid disease following alemtuzumab therapy and hematopoietic cell transplantation in pediatric patients with sickle cell disease

Allogenic hematopoietic cell transplantation (alloHCT) is currently the only curative treatment option for patients with sickle cell disease. Alemtuzumab is a monoclonal antibody directed against CD52 positive cells used in myeloablative conditioning regimens for alloHCT. Its use has been associated with development of autoimmune disease in adult patients with rheumatologic conditions. We report on three cases of new onset autoimmune thyroid disease after alloHCT treatment with alemtuzumab in pediatric patients with sickle cell disease. Pediatr Blood Cancer 2014;61:2307–2309.