Faculty Bibliography

BACKGROUND: Preterm birth (PTB) rates (11.4% in 2013) in the United States (US) remain high and are a substantial cause of morbidity. Studies of prenatal exposure have associated particulate matter <2.5microns in diameter (PM2.5) and other ambient air pollutants with adverse birth outcomes, yet, to our knowledge, burden and costs of PM 2.5-attributable PTB have not been estimated in the US. OBJECTIVES: To estimate burden of PTB in the US and economic costs attributable to PM2.5 exposure in 2010. METHODS: Annual deciles of PM2.5 were obtained from US EPA. We converted PTB odds ratio (OR), identified in a previous meta-analysis (1.15 per 10microg/m3 for our base case, 1.07-1.16 for low- and high-end scenarios) to relative risk (RRs), to obtain an estimate that better represents the true relative risk. A reference level (RL) of 8.8microg/m3 was applied. We then used the RR estimates and county-level PTB prevalence to quantify PM2.5 attributable PTB. Direct medical costs were obtained from the 2007 Institute of Medicine report, and lost economic productivity (LEP) was estimated using a meta-analysis of PTB-associated IQ loss, and well-established relationships of IQ loss with LEP. All costs were calculated using 2010 dollars. RESULTS: An estimated 3.32% of PTBs nationally (corresponding to15,808 PTBs) in 2010 could be attributed to PM2.5 (PM2.5>8.8 microg/m3). Attributable PTBs cost were estimated at $4.33 billion (SA: $2.06-8.22B), of which $760 million were spent for medical care (SA: $362M-1.44B). The estimated PM2.5-attributable fraction (AF) of PTB was highest in urban counties, with highest AFs in the Ohio valley and Southern US. CONCLUSIONS: PM2.5 may contribute substantially to burden and costs of PTB in the US, and considerable health and economic benefits could be achieved through environmental regulatory interventions that reduce PM2.5 exposure in pregnancy.

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.

We estimated the economic costs of female reproductive disorders attributable to endocrine disrupting chemical exposures. These may contribute substantially to fibroids and endometriosis, costing nearly euro1.5 billion annually.

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.

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.

OBJECTIVE: Recent evidence has suggested that polycyclic aromatic hydrocarbons (PAHs) may contribute to cardiometabolic and kidney dysfunction by increasing oxidative stress, but little is known about impacts in childhood. STUDY DESIGN: We performed cross-sectional analyses of 660 adolescents aged 12-19 years in the 2003-2008 National Health and Nutrition Examination Survey (NHANES), using levels of 10 monohydroxylated urinary PAH metabolites as our exposure. Our primary outcomes of interest were biomarkers of oxidative stress and renal function, including estimated glomerular filtration rate (eGFR), urinary albumin to creatinine ratio (ACR), insulin resistance, and serum uric acid, gamma glutamyl transferase (GGT) and C-reactive protein (CRP). RESULTS: We observed statistically significant associations between PAH metabolites and levels of serum GGT, CRP, uric acid and eGFR. Each 100% increase in 2-hydroxyphenanthrene was related to a 3.36% increase in uric acid (95% CI: 0.338-6.372; p=0.032), a 3.86% increase in GGT (95% CI: 1.361-6.362; p=0.005) and a 16.78% increase in CRP (95% CI: 1.848-31.689; p=0.029). Each 100% increase in 4-hydroxyphenanthrene was associated with a 6.18% increase in GGT (95% CI: 4.064-8.301; p<0.001) and a 13.66% increase in CRP (95% CI: 2.764-24.564; p=0.017). Each 100% increase in 9-hydroxyfluorene was associated with a 2.58% increase in GGT (95% CI: 0.389-4776; p=0.024). Each 100% increase in 3-hydroxyphenanthrene was associated with a 2.66% decrease in eGFR (95% CI: -4.979 to -0.331; p=0.028). CONCLUSIONS: Urinary PAH metabolites were associated with serum uric acid, GGT and CRP, suggesting possible impacts on cardiometabolic and kidney function in adolescents. Prospective work is needed to investigate the potential long-term health consequences of these findings.

BACKGROUND:Cesarean delivery may reduce placental-fetal transfusion and thus increase the risk of early childhood anemia compared with vaginal delivery, but this notion has not been carefully studied in longitudinal cohorts. OBJECTIVE:The aim was to assess the association of cesarean delivery with anemia in infants and children in 2 longitudinal Chinese birth cohorts from different socioeconomic settings. DESIGN/METHODS:Cohort 1 was recruited from 5 counties in northeastern China and cohort 2 from 21 counties or cities in southeastern China. Cohort 1 involved 17,423 infants born during 2006-2009 to mothers with early pregnancy baseline hemoglobin concentrations ranging from 100 to 177 g/L, whereas cohort 2 involved 122,777 children born during 1993-1996 to mothers with baseline hemoglobin concentrations ranging from 60 to 190 g/L. The main outcomes were anemia at 6 and 12 mo in cohort 1 and at 58 mo in cohort 2. Multiple logistic regressions were used to estimate adjusted ORs of anemia for cesarean compared with vaginal delivery. Stratified analyses were performed by pre- and postlabor cesarean delivery and according to maternal baseline hemoglobin concentration (≤109, 110-119, 120-129, and ≥130 g/L). RESULTS:Cesarean delivery was not associated with anemia at 6 mo in cohort 1 (adjusted OR: 1.05; 95% CI: 0.93, 1.19); however, cesarean delivery was associated with increased anemia at 12 mo in cohort 1 (adjusted OR: 1.19; 95% CI: 1.04, 1.37) and at 58 mo in cohort 2 (adjusted OR: 1.11; 95% CI: 1.08, 1.15). The positive associations for anemia at 12 and 58 mo were consistent across maternal hemoglobin subgroups and persisted for cesarean delivery subtypes. CONCLUSION/CONCLUSIONS:Cesarean delivery is likely associated with anemia in children, which suggests a possible need for exploring changes in obstetric care that might prevent anemia in cesarean-delivered children.

OBJECTIVE:To compare the prevalence of hospitalizations for ambulatory care sensitive conditions (ACSC) in children with and without autism spectrum disorder (ASD) and to compare inpatient health care utilization (total charges and length of stay) for the same conditions in children with and without ASD. METHODS:The 2009 Kids' Inpatient Database was used to examine hospitalizations for ACSC in children within 3 cohorts: those with ASD, those with chronic conditions (CC) without ASD, and those with no CC. RESULTS:The proportion of hospitalizations for ACSC in the ASD cohort was 55.9%, compared with 28.2% in the CC cohort and 22.9% in the no-CC cohort (P < .001). Hospitalized children with ASD were more likely to be admitted for a mental health condition, epilepsy, constipation, pneumonia, dehydration, vaccine-preventable diseases, underweight, and nutritional deficiencies compared with the no-CC cohort. Compared with the CC cohort, the ASD cohort was more likely to be admitted for mental health conditions, epilepsy, constipation, dehydration, and underweight. Hospitalized children with ASD admitted for mental health conditions had significantly higher total charges and longer LOS compared with the other 2 cohorts. CONCLUSIONS:The proportion of potentially preventable hospitalizations is higher in hospitalized children with ASD compared with children without ASD. These data underscore the need to improve outpatient care of children with ASD, especially in the areas of mental health care and seizure management. Future research should focus on understanding the reasons for increased inpatient health care utilization in children with ASD admitted for mental health conditions.