Faculty Bibliography

Evidence increasingly confirms that synthetic chemicals disrupt the endocrine system and contribute to disease and disability across the lifespan. Despite a United Nations Environment Programme/WHO report affirmed by over 100 countries at the Fourth International Conference on Chemicals Management, 'manufactured doubt' continues to be cast as a cloud over rigorous, peer-reviewed and independently funded scientific data. This study describes the sources of doubt and their social costs, and suggested courses of action by policymakers to prevent disease and disability. The problem is largely based on the available data, which are all too limited. Rigorous testing programmes should not simply focus on oestrogen, androgen and thyroid. Tests should have proper statistical power. 'Good laboratory practice' (GLP) hardly represents a proper or even gold standard for laboratory studies of endocrine disruption. Studies should be evaluated with regard to the contamination of negative controls, responsiveness to positive controls and dissection techniques. Flaws in many GLP studies have been identified, yet regulatory agencies rely on these flawed studies. Peer-reviewed and unbiased research, rather than 'sound science', should be used to evaluate endocrine-disrupting chemicals.

Within a population-based study of 3356 children, we investigated whether infant neuromotor development was associated with cognition in early childhood. Neuromotor development was examined with an adapted version of Touwen's Neurodevelopmental Examination between 9 and 20 weeks. Parents rated their children's executive functioning at 4 years. At age 6 years, children performed intelligence and language comprehension tests, using Dutch test batteries. At age 6-9 years, neuropsychological functioning was assessed in 486 children using the validated NEPSY-II-NL test battery. We showed that less optimal neurodevelopment in infancy may predict poor mental rotation, immediate memory, shifting, and planning; but not nonverbal intelligence or language comprehension.

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.