Faculty Bibliography

A previous report documented that endocrine disrupting chemicals contribute substantially to certain forms of disease and disability. In the present analysis, our main objective was to update a range of health and economic costs that can be reasonably attributed to endocrine disrupting chemical exposures in the European Union, leveraging new burden and disease cost estimates of female reproductive conditions from accompanying report. Expert panels evaluated the epidemiologic evidence, using adapted criteria from the WHO Grading of Recommendations Assessment, Development and Evaluation Working Group, and evaluated laboratory and animal evidence of endocrine disruption using definitions recently promulgated by the Danish Environmental Protection Agency. The Delphi method was used to make decisions on the strength of the data. Expert panels consensus was achieved for probable (>20%) endocrine disrupting chemical causation for IQ loss and associated intellectual disability; autism; attention deficit hyperactivity disorder; endometriosis; fibroids; childhood obesity; adult obesity; adult diabetes; cryptorchidism; male infertility, and mortality associated with reduced testosterone. Accounting for probability of causation, and using the midpoint of each range for probability of causation, Monte Carlo simulations produced a median annual cost of euro163 billion (1.28% of EU Gross Domestic Product) across 1000 simulations. We conclude that endocrine disrupting chemical exposures in the EU are likely to contribute substantially to disease and dysfunction across the life course with costs in the hundreds of billions of Euros per year. These estimates represent only those endocrine disrupting chemicals with the highest probability of causation; a broader analysis would have produced greater estimates of burden of disease and costs.

OBJECTIVE: Asthma is a leading cause of pediatric admissions. While several factors including race have been linked to increased overall asthma morbidity and mortality, few studies have explored factors associated with inpatient asthma outcomes. We examined factors associated with mortality and morbidity in children admitted for asthma. DESIGN/METHODS: Data were obtained from the US Nationwide Inpatient Sample for 2007-2011. Patients 2-18 years old with a primary diagnosis of asthma were included. Predictor variables were sociodemographic and hospital factors and acute/chronic secondary diagnoses. Outcomes were mortality, intubation, length of stay (LOS), and costs. Weighted national estimates were calculated. Multivariable analyses were performed. RESULTS: There were 97,379 (478,546 weighted) asthma admissions. Most patients were male (60.6%); 30% were white, 28% black, and 18% Hispanic. Mortality rate was 0.03%. 0.3% were intubated. Median (IQR) LOS was 2 (1-3) days. Median (IQR) costs were $2760 ($1860-4320). Native American race, older age (13-18 years), and West region were significant independent predictors of mortality. Intubation rate was lower in Hispanic compared to white children (p=0.028). LOS was shorter in Asian compared to white children (p=0.022) but longer in children with public insurance and from low income areas (p <0.001). Average costs were higher in black, Hispanic, and Asian compared to white children (p<0.05). CONCLUSIONS: With the exception of Native Americans, race/ethnicity is not associated with inpatient asthma mortality and has varied effects on morbidity. Recognition of factors associated with increased asthma mortality and morbidity may allow for earlier, more effective treatment and avoidance of complications.

AIM: We examined whether children of mothers with a medical condition diagnosed before or during pregnancy took longer to achieve gross motor milestones up to age 24 months. METHOD: We obtained information on medical conditions using self-reports, birth certificates, and hospital records in 4909 mothers participating in Upstate KIDS, a population-based birth cohort. Mothers reported on their children's motor milestone achievement at 4, 8, 12, 18, and 24 months of age. RESULTS: After adjustment for covariates (including pre-pregnancy body mass index), children of mothers with gestational diabetes took longer to achieve sitting without support (hazard ratio [HR]=0.84, 95% confidence interval [CI] 0.75-0.93), walking with assistance (HR=0.88, 95% CI 0.77-0.98), and walking alone (HR=0.88, 95% CI 0.77-0.99) than children of females with no gestational diabetes. Similar findings emerged for maternal diabetes. Gestational hypertension was associated with a longer time to achieve walking with assistance. These associations did not change after adjustment for gestational age or birthweight. Severe hypertensive disorders of pregnancy were related to a longer time to achieve milestones, but not after adjustment for perinatal factors. INTERPRETATION: Children exposed to maternal diabetes, gestational or pre-gestational, may take longer to achieve motor milestones than non-exposed children, independent of maternal obesity.

OBJECTIVE:We examined the longitudinal associations of age at achieving gross motor milestones and children's development in a US cohort of singletons and twins. METHODS:In the Upstate KIDS study, a population-based study of children born between 2008 and 2010, information on age at achievement of motor milestones and developmental skills was available in 599 children (314 singletons, 259 twins, and 26 triplets). Mothers reported their children's major motor milestones at ∼4, 8, 12, 18, and 24 months. At age 4 years, children's development was clinically assessed by using the Battelle Developmental Inventory, Second Edition (BDI-2). Primary analyses by using multivariate linear regressions were conducted in singletons. We also examined the associations in twins. RESULTS:Later achievement of standing with assistance predicted lower BDI-2 scores in singletons in adjusted models (B per SD of age at achievement, -21.9 [95% confidence interval (CI), -41.5 to -2.2]). Post hoc analysis on age of standing with assistance showed that associations were driven by differences in adaptive skills (B = -5.3 [95% CI, -9.0 to -1.6]) and cognitive skills (B = -5.9 [95% CI, -11.5 to -0.4]). Analyses restricted to twins suggested no association between the age at achievement of milestones and total BDI-2 score after adjustment for gestational age and birth weight. CONCLUSIONS:This study provides evidence that the age of achieving motor milestones may be an important basis for various aspects of later child development. In twins, key predictors of later development (eg, perinatal factors) overshadow the predictive role of milestones in infancy.

BACKGROUND: Few studies have used GPS data to analyze the relationship between Walk Score, transportation choice and walking. Additionally, the influence of Walk Score is understudied using trips rather than individuals as statistical units. The purpose of this study is to examine associations at the trip level between Walk Score, transportation mode choice, and walking among Paris adults who were tracked with GPS receivers and accelerometers in the RECORD GPS Study. METHODS: In the RECORD GPS Study, 227 participants were tracked during seven days with GPS receivers and accelerometers. Participants were also surveyed with a GPS-based web mapping application on their activities and transportation modes for all trips (6969 trips). Walk Score, which calculates neighborhood walkability, was assessed for each origin and destination of every trip. Multilevel logistic and linear regression analyses were conducted to estimate associations between Walk Score and walking in the trip or accelerometry-assessed number of steps for each trip, after adjustment for individual/neighborhood characteristics. RESULTS: The mean overall Walk Scores for trip origins were 87.1 (SD = 14.4) and for trip destinations 87.1 (SD = 14.5). In adjusted trip-level associations between Walk Score and walking only in the trip, we found that a walkable neighborhood in the trip origin and trip destination was associated with increased odds of walking in the trip assessed in the survey. The odds of only walking in the trip were 3.48 (95% CI: 2.73 to 4.44) times higher when the Walk Score for the trip origin was "Walker's Paradise" compared to less walkable neighborhoods (Very/Car-Dependent or Somewhat Walkable), with an identical independent effect of trip destination Walk Score on walking. The number of steps per 10 min (as assessed with accelerometry) was cumulatively higher for trips both originating and ending in walkable neighborhoods (i.e., "Very Walkable"). CONCLUSIONS: Walkable neighborhoods were associated with increases in walking among adults in Paris, as documented at the trip level. Creating walkable neighborhoods (through neighborhood design increased commercial activity) may increase walking trips and, therefore, could be a relevant health promotion strategy to increase physical activity.

Perchlorate is an endocrine-disrupting chemical that interferes with the normal functioning of the thyroid gland. Maternal thyroid dysfunction during gestation may alter fetal brain development. Perchlorate contamination is widespread: it is present in the body of all Americans tested and the majority of foods tested. The main sources of food contamination appear to be hypochlorite bleach, a disinfectant and sanitizer, that when poorly managed quickly degrades to perchlorate and perchlorate-laden plastic food packaging for dry food or localized contamination from manufacturing or processing of the chemical. Eliminating perchlorate from food packaging and improving bleach management, such as reducing concentration and storage time and temperature, would result in reduced perchlorate contamination of food and water.

BACKGROUND: Dietary composition has been associated with sleep indexes. However, most of the evidence is based on cross-sectional data, and studies in young children are lacking. OBJECTIVE: The aim of this study was to explore the longitudinal associations of macronutrient composition of the diet with sleep duration and consolidation (number of awakenings) in infancy and early childhood. METHODS: The study was performed in 3465 children from the Generation R Study, a population-based cohort study in the Netherlands. Mothers reported their child's food intake at 13 mo of age by using a validated food-frequency questionnaire and their child's sleep patterns at 2 and 3 y of age. We used nutrient substitution models to assess the associations of relative macronutrient intakes with sleep indexes and adjusted the models for sociodemographic and lifestyle factors. RESULTS: Isocaloric substitution of fat intake by protein or carbohydrate in infancy was associated with longer total sleep duration at 2 but not 3 y of age. For each 5% increase in energy intake of either protein or carbohydrate at the expense of fat, sleep duration at 2 y of age was longer by 6 min (95% CI: 0.4, 12 min) and 4 min (95% CI: 2, 6 min), respectively. Further exploration of macronutrient subtypes indicated no consistent differences between saturated or unsaturated fat and that intake of plant compared with animal protein or Trp did not explain the association of higher total protein intake with longer sleep duration at 2 y of age. Replacing unsaturated with saturated fat was associated with 7 min (95% CI: -13, -1 min) shorter total sleep duration at 3 y of age. Macronutrient intakes were not associated with sleep consolidation. CONCLUSIONS: Our results suggest that the macronutrient composition of the diet is associated with sleep duration in young children. Future research should further study the causality of this association and explore the underlying mechanisms.