Patterns of Childhood Body Mass Index Percentile Gains as Predictors of Adolescent Body Mass Index, Waist Circumference, and Blood Pressure.

OBJECTIVE: To examine whether patterns of body mass index (BMI) percentile gains across childhood predict BMI percentile, overweight and obesity, waist circumference, and elevated or prehypertensive blood pressure at age 15. METHODS: Trained technicians in the Study of Early Child Care and Youth Development assessed children's weight and height from birth to 15 years and waist circumference and blood pressure at age 15 (n = 1132). Children's BMI percentile trajectories from age 2 to age 13 along with 28 demographic and social covariates were used to predict BMI percentile, waist circumference, overweight, obesity, and elevated or prehypertensive blood pressure. Linear and logistic regressions were used to predict BMI percentile, overweight, obesity, waist circumference, and elevated or prehypertensive blood pressure. RESULTS: Children were classified into one"?>1 of 4four"?> BMI percentile trajectories: "low stable" (28.4%), "low-to-high" (11.8%), "median stable" (29.0%), and "high rising" (30.7%). Children in trajectory classes characterized by persistent above average BMI percentile or by periods of rapid BMI percentile gains were more likely than their peers to experience poor weight and elevated or prehypertensive outcomes in adolescence. Trajectory class membership explained substantially more variance in adolescent health outcomes than demographic covariates alone. Estimated maternal BMI was a key independent predictor of adolescent outcomes. CONCLUSIONS: Different patterns of BMI percentile gains, namely those with rapid gains or persistently above average BMI percentile, from ages 2 to 13 predicted weight, waist circumference, and elevated or prehypertensive blood pressure at age 15, above and beyond demographic and social characteristics.

Identification of Children's BMI Trajectories and Prediction from Weight Gain in Infancy.

OBJECTIVE: The goal of this study was to identify patterns of BMI changes across childhood (ages 24 months to 13 years) and to assess whether demographic characteristics, birth weight, and percent infant weight gain from birth to 15 months predicted BMI patterns. METHODS: Eleven waves of data from the Study of Early Child Care and Youth Development were used. Trained technicians assessed children's weight at birth and 10 times from 15 months to eighth grade (N = 1364). Latent growth modeling was used to estimate BMI change trajectories, and logistic regression was used to predict membership in trajectory classes. RESULTS: Children in the high-rising and low-to-high BMI patterns had the highest BMI of all trajectory groups during middle childhood. Birth weight and infant weight gain were stronger predictors of trajectory membership than gender or race/ethnicity. Infant weight gain predicted high-rising membership over and above the effect of birth weight. African American children had lower birth weight, faster infant weight increase, and higher odds of being in one of the rising trajectories. Risk algorithms are provided. CONCLUSIONS: Clinicians should monitor weight gain during infancy independent of birth weight. Researchers should continue investigating the lasting physiological effects of early rapid weight gain in infancy.

Estimating serum concentrations of dioxin-like compounds in the U.S. population effective 2005-2006 and 2007-2008: A multiple imputation and trending approach incorporating NHANES pooled sample data.

Dioxin-like compounds (DLCs) are monitored in the U.S. population using data collected with the National Health and Nutrition Examination Survey (NHANES). Until recently, participants' serum samples have been analyzed individually, and summary statistics defining reference ranges by age, gender, and race/ethnicity have served as the background by which other biomonitoring data can be evaluated. In the most recent NHANES DLC data, 2005-2006 and 2007-2008, participants' sera have been physically pooled prior to laboratory analysis, introducing major challenges to their utility as a reference population: variability among individuals and relations with covariates are lost, and individual design effects cannot be applied. Further, the substantial drop in limits of detection (LODs) in pooled sample biennials prevents reliable comparisons to individual data, and has complicated estimates of change over time. In this study, we address the drawbacks introduced by pooled samples by generating U.S. population reference ranges based on individual-level data adjusted to 2005-2006 and 2007-2008 levels. Using publicly available data, multiple imputation (MI) generated four NHANES biennials (2001-2008) of individual DLC data; we then trended the change over time in each DLC by demographic stratum. NHANES 2003-2004 individuals were adjusted by the trended change over time. Population estimates of toxic equivalency (TEQ) concentrations were calculated using traditional MI survey analysis methods and reference tables provided for 2005-2006 and 2007-2008 by age, race, and gender. Demographic differences in TEQ concentrations and trended change are reported, e.g. TEQ continues to drop in young adults aged 20-39, but distributions appear stable in older adults 60+; Mexican Americans have consistently lowest dioxins, furans, and PCBs, with non-Hispanic Blacks dropping to the same levels as non-Hispanic Whites in dioxins and PCBs and significantly below non-Hispanic Whites in furans by 2007-2008. Additionally, the ratio of 95th percentile to mean in DLC distributions was found to vary by age, between dioxins, furans, and PCBs, and across mean, making a simple ratio approach impractical for describing population concentrations using pooled samples. We discuss the practical implications of the pooled sample method, the performance of this trending solution in the context of other methods, and expected effects of distribution assumptions on variability and TEQ estimates, particularly in largely undetected congeners. These updated reference populations of individuals, along with information on trending, provide a common and valid basis for interpreting other individually sampled biomonitoring data.

Comparison of in vivo genotoxic and carcinogenic potency to augment mode of action analysis: Case study with hexavalent chromium.

Recent analyses-highlighted by the International Workshops on Genotoxicity Testing Working Group on Quantitative Approaches to Genetic Toxicology Risk Assessment-have identified a correlation between (log) estimates of a carcinogen's in vivo genotoxic potency and in vivo carcinogenic potency in typical laboratory animal models, even when the underlying data have not been matched for tissue, species, or strain. Such a correlation could have important implications for risk assessment, including informing the mode of action (MOA) of specific carcinogens. When in vivo genotoxic potency is weak relative to carcinogenic potency, MOAs other than genotoxicity (e.g., endocrine disruption or regenerative hyperplasia) may be operational. Herein, we review recent in vivo genotoxicity and carcinogenicity data for hexavalent chromium (Cr(VI)), following oral ingestion, in relevant tissues and species in the context of the aforementioned correlation. Potency estimates were generated using benchmark doses, or no-observable-adverse-effect-levels when data were not amenable to dose-response modeling. While the ratio between log values for carcinogenic and genotoxic potency was ≥1 for many compounds, the ratios for several Cr(VI) datasets (including in target tissue) were less than unity. In fact, the ratios for Cr(VI) clustered closely with ratios for chloroform and diethanolamine, two chemicals posited to have non-genotoxic MOAs. These findings suggest that genotoxicity may not play a major role in the cancers observed in rodents following exposure to high concentrations of Cr(VI) in drinking water-a finding consistent with recent MOA and adverse outcome pathway (AOP) analyses concerning Cr(VI). This semi-quantitative analysis, therefore, may be useful to augment traditional MOA and AOP analyses. More case examples will be needed to further explore the general applicability and validity of this approach for human health risk assessment.

Duodenal crypt health following exposure to Cr(VI): Micronucleus scoring, γ-H2AX immunostaining, and synchrotron X-ray fluorescence microscopy.

Lifetime exposure to high concentrations of hexavalent chromium [Cr(VI)] in drinking water results in intestinal damage and an increase in duodenal tumors in B6C3F1 mice. To assess whether these tumors could be the result of a direct mutagenic or genotoxic mode of action, we conducted a GLP-compliant 7-day drinking water study to assess crypt health along the entire length of the duodenum. Mice were exposed to water (vehicle control), 1.4, 21, or 180 ppm Cr(VI) via drinking water for 7 consecutive days. Crypt enterocytes in Swiss roll sections were scored as normal, mitotic, apoptotic, karyorrhectic, or as having micronuclei. A single oral gavage of 50mg/kg cyclophosphamide served as a positive control for micronucleus induction. Exposure to 21 and 180 ppm Cr(VI) significantly increased the number of crypt enterocytes. Micronuclei and γ-H2AX immunostaining were not elevated in the crypts of Cr(VI)-treated mice. In contrast, treatment with cyclophosphamide significantly increased numbers of crypt micronuclei and qualitatively increased γ-H2AX immunostaining. Synchrotron-based X-ray fluorescence (XRF) microscopy revealed the presence of strong Cr fluorescence in duodenal villi, but negligible Cr fluorescence in the crypt compartment. Together, these data indicate that Cr(VI) does not adversely effect the crypt compartment where intestinal stem cells reside, and provide additional evidence that the mode of action for Cr(VI)-induced intestinal cancer in B6C3F1 mice involves chronic villous wounding resulting in compensatory crypt enterocyte hyperplasia.