Re-scaling and small area estimation of behavioral risk survey guided by social vulnerability data.

BACKGROUND: Local governments and other public health entities often need population health measures at the county or subcounty level for activities such as resource allocation and targeting public health interventions, among others. Information collected via national surveys alone cannot fill these needs. We propose a novel, two-step method for rescaling health survey data and creating small area estimates (SAEs) of smoking rates using a Behavioral Risk Factor Surveillance System survey administered in 2015 to participants living in Allegheny County, Pennsylvania, USA. METHODS: The first step consisted of a spatial microsimulation to rescale location of survey respondents from zip codes to tracts based on census population distributions by age, sex, race, and education. The rescaling allowed us, in the second step, to utilize available census tract-specific ancillary data on social vulnerability for small area estimation of local health risk using an area-level version of a logistic linear mixed model. To demonstrate this new two-step algorithm, we estimated the ever-smoking rate for the census tracts of Allegheny County. RESULTS: The ever-smoking rate was above 70% for two census tracts to the southeast of the city of Pittsburgh. Several tracts in the southern and eastern sections of Pittsburgh also had relatively high (> 65%) ever-smoking rates. CONCLUSIONS: These SAEs may be used in local public health efforts to target interventions and educational resources aimed at reducing cigarette smoking. Further, our new two-step methodology may be extended to small area estimation for other locations and health outcomes.

Maternal Obesity, Birth Size, and Risk of Childhood Cancer Development.

Infants and children are particularly vulnerable to in utero and early-life exposures. Thus, a mother's exposures before and during pregnancy could have important consequences for her child's health, including cancer development. We examined whether birth certificate-derived maternal anthropometric characteristics were associated with increased risk of subsequent childhood cancer development, accounting for established maternal and infant risk factors. Pennsylvania birth and cancer registry files were linked by the state Department of Health, yielding a virtual cohort of births and childhood cancers from 2003 through 2016. The analysis included 1,827,875 infants (13,785,309 person-years at risk), with 2,352 children diagnosed with any cancer and 747 with leukemia before age 14 years. Children born to mothers with a body mass index (weight (kg)/height (m)2) of ≥40 had a 57% (95% confidence interval: 12, 120) higher leukemia risk. Newborn size of ≥30% higher than expected was associated with 2.2-fold and 1.8-fold hazard ratios for total childhood cancer and leukemia, respectively, relative to those with expected size. Being <30% below expected size also increased the overall cancer risk (P for curvilinearity < 0.0001). Newborn size did not mediate the association between maternal obesity and childhood cancer. The results suggest a significant role of early-life exposure to maternal obesity- and fetal growth-related factors in childhood cancer development.

Patterns, Variability, and Predictors of Urinary Triclosan Concentrations during Pregnancy and Childhood.

Exposure to triclosan, an antimicrobial used in many consumer products, is ubiquitous in the United States, yet only limited data are available on the predictors and variability of exposure, particularly in children. We examined the patterns, variability, and predictors of urinary triclosan concentrations in 389 mother-child pairs enrolled in the Health Outcomes and Measures of the Environment Study from 2003 to 2006. We quantified triclosan in 3 urine samples collected from women between 16 weeks of pregnancy and birth and 6 urine samples collected from children between the ages of 1-8 years. For maternal and child samples, we calculated intraclass correlation coefficients (ICCs) to assess triclosan reproducibility and identified sociodemographic predictors of triclosan. Among 8 year old children, we examined associations between triclosan and personal-care product use. We detected triclosan in >70% of urine samples. Median maternal triclosan varied across pregnancy from 17 to 11 ng/mL, while in children, median concentrations increased from 3.6 to 17 ng/mL over the first 4 years of life, declining slightly at later ages. Triclosan reproducibility was fair to good during pregnancy and for child samples taken weeks apart (ICCs = 0.4-0.6) but poor for annual child samples (ICCs = 0.2-0.4). Triclosan was 66% (95% CI: 29-113) higher in 8 year olds using hand soap compared to nonusers and increased monotonically with hand-washing frequency. Toothpaste use in children was also positively associated with triclosan. Our results suggest that urinary triclosan concentrations have modest stability over weeks to months; children are exposed to triclosan through the use of some personal-care products.

Patterns, Variability, and Predictors of Urinary Bisphenol A Concentrations during Childhood.

We examined the patterns, variability, and predictors of urinary bisphenol A (BPA) concentrations in 337 children from the Cincinnati, Ohio HOME Study. From 2003 to 2014, we collected two urine samples from women at 16 and 26 weeks of pregnancy and six urine samples from children at 1-5 and 8 years of age. We used linear mixed models to calculate intraclass correlation coefficients (ICCs) as a measure of within-person BPA variability and to identify sociodemographic and environmental predictors. For the 8-year visit, we used multivariable linear regression to explore associations between urinary BPA concentrations and exposure-related factors. We calculated daily intakes using equations estimating creatinine excretion rates and creatinine-standardized BPA concentrations. Urinary BPA concentrations, which decreased over childhood, had a low degree of reproducibility (ICC < 0.2). Estimated daily intakes decreased with age and were below the reference dose of 50 µg/kg body weight/day. BPA concentrations were positively associated with consuming food stored or heated in plastic, consuming canned food and beverages, and handling cash register receipts. Our results suggest that there are multiple sources of BPA exposure in young children. Etiological studies should collect serial urine samples to accurately classify BPA exposure and consider sociodemographic and environmental factors as possible confounders.

Fine particulate matter and the risk of autism spectrum disorder.

The causes of autism spectrum disorder (ASD) are not well known. Recent investigations have suggested that air pollution, including PM2.5, may play a role in the onset of this condition. The objective of the present work was to investigate the association between prenatal and early childhood exposure to fine particulate matter (PM2.5) and risk for childhood ASD. A population-based case-control study was conducted in children born between January 1, 2005 and December 31, 2009 in six counties in Southwestern Pennsylvania. ASD cases were recruited from specialty autism clinics, local pediatric practices, and school-based special needs services. ASD cases were children who scored 15 or above on the Social Communication Questionnaire (SCQ) and had written documentation of an ASD diagnosis. Controls were children without ASD recruited from a random sample of births from the Pennsylvania state birth registry and frequency matched to cases on birth year, gender, and race. A total of 217 cases and 226 controls were interviewed. A land use regression (LUR) model was used to create person- and time-specific PM2.5 estimates for individual (pre-pregnancy, trimesters one through three, pregnancy, years one and two of life) and cumulative (starting from pre-pregnancy) key developmental time periods. Logistic regression was used to investigate the association between estimated exposure to PM2.5 during key developmental time periods and risk of ASD, adjusting for mother's age, education, race, and smoking. Adjusted odds ratios (AOR) were elevated for specific pregnancy and postnatal intervals (pre-pregnancy, pregnancy, and year one), and postnatal year two was significant, (AOR=1.45, 95% CI=1.01-2.08). We also examined the effect of cumulative pregnancy periods; noting that starting with pre-pregnancy through pregnancy, the adjusted odds ratios are in the 1.46-1.51 range and significant for pre-pregnancy through year 2 (OR=1.51, 95% CI=1.01-2.26). Our data indicate that both prenatal and postnatal exposures to PM2.5 are associated with increased risk of ASD. Future research should include multiple pollutant models and the elucidation of the biological mechanism for PM2.5 and ASD.

Air toxics and the risk of autism spectrum disorder: the results of a population based case-control study in southwestern Pennsylvania.

BACKGROUND: Autism spectrum disorders (ASD) constitute a major public health problem affecting one in 68 children. There is little understanding of the causes of ASD despite its serious social impact. Air pollution contains many toxicants known to have adverse effects on the fetus. We conducted a population based case-control study in southwestern Pennsylvania to estimate the association between ASD and 2005 US EPA modeled NATA (National Air Toxics Assessment) levels for 30 neurotoxicants. METHODS: A total of 217 ASD cases born between 2005 and 2009 were recruited from local ASD diagnostic and treatment centers. There were two different control groups: 1) interviewed controls (N = 224) frequency matched by child's year of birth, sex and race with complete residential histories from prior to pregnancy through the child's second birthday, and 2) 5,007 controls generated from a random sample of birth certificates (BC controls) using residence at birth. We used logistic regression analysis comparing higher to first quartile of exposure to estimate odds ratios (ORs) and 95% confidence intervals (CI), adjusting for mother's age, education, race, smoking status, child's year of birth and sex. RESULTS: Comparing fourth to first quartile exposures for all births, the adjusted OR for styrene was 2.04 (95% CI = 1.17-3.58, p = 0.013) for the interviewed case-control analysis and 1.61 (95% CI = 1.08-2.40, p = 0.018) for the BC analysis. In the BC comparison, chromium also exhibited an elevated OR of 1.60 (95% CI = 1.08-2.38, p = 0.020), which was similarly elevated in the interviewed analysis (OR = 1.52, 95% CI = 0.87-2.66). There were borderline significant ORs for the BC comparison for methylene chloride (OR = 1.41, 95% CI = 0.96-2.07, p = 0.082) and PAHs (OR = 1.44, 95% CI = 0.98-2.11, p = 0.064). CONCLUSIONS: Living in areas with higher levels of styrene and chromium during pregnancy was associated with increased risk of ASD, with borderline effects for PAHs and methylene chloride. These results are consistent with other studies. It is unclear, however, whether these chemicals are risk factors themselves or if they reflect the effect of a mixture of pollutants. Future work should include improved spatiotemporal estimates of exposure to air toxics, taking into account the dynamic movement of individuals during daily life.

A Review of the Human Health Impacts of Unconventional Natural Gas Development.

PURPOSE OF REVIEW: This review summarizes the recent epidemiologic literature examining health outcomes in communities living close to unconventional natural gas development (UNGD) and identifies areas requiring further study. RECENT FINDINGS: To date, these studies have been primarily retrospective in design and used self-report of health symptoms or electronic health databases to obtain outcome information. Proximity to UNGD is often used as a surrogate for exposure. There is preliminary evidence linking respiratory outcomes, including asthma exacerbations, and birth outcomes, such as reduced fetal growth and preterm birth, to UNGD; however, results differ across study populations and regions. SUMMARY: Although small, the current body of literature suggests that living near UNGD may have negative health consequences for surrounding communities, but additional work using more granular estimates of exposure or personalized monitoring is urgently needed.

Early life bisphenol A exposure and neurobehavior at 8years of age: Identifying windows of heightened vulnerability.

BACKGROUND: Early life BPA exposure could affect neurobehavior, but few studies have investigated whether there are developmental periods when the fetus or child is more vulnerable to these potential effects. OBJECTIVES: We explored windows of vulnerability to BPA exposure in a multiethnic cohort of 228 mothers and their children from Cincinnati, Ohio. METHODS: We measured urinary BPA concentrations at up to two prenatal and six postnatal time points from the 2nd trimester of pregnancy until the child was age 8years. At age 8years, we administered the Behavioral Assessment System for Children-2 (BASC-2), Behavior Rating Inventory of Executive Function, and Wechsler Intelligence Scale for Children-IV. We estimated covariate-adjusted differences in composite scores from each instrument using a multiple informant model designed to identify heightened windows of vulnerability. RESULTS: Among all children, there was not strong evidence that the associations between BPA and neurobehavior varied by the timing of exposure (Visit x BPA p-values≥0.16). However, child sex modified the associations of repeated BPA measures with BASC-2 scores (Visit x Sex x BPA p-values=0.02-0.23). For example, each 10-fold increase in prenatal BPA was associated with more externalizing behaviors in girls (ß=6.2, 95% CI: 0.8, 11.6), but not boys (ß=-0.8, 95% CI: -5.0, 3.4). In contrast, a 10-fold increase in 8-year BPA was associated with more externalizing behaviors in boys (ß=3.9, 95% CI: 0.6, 7.2), but not girls (ß=0.3, 95% CI: -3.5, 4.1). CONCLUSIONS: We found that sex-dependent associations between BPA and child neurobehavior may depend on the timing of BPA exposure.

Prenatal environmental chemical exposures and longitudinal patterns of child neurobehavior.

BACKGROUND: Prenatal chemical exposures may adversely affect neurodevelopment, but few studies have examined the persistence of these associations. We examined whether associations between prenatal bisphenol A (BPA) or polybrominated diphenyl ether (PBDE) exposures persist or resolve as children age. METHODS: We followed 346 mother-child pairs (enrolled 2003-2006) from Cincinnati, OH from pregnancy until children were 8 years old. We measured BPA in urine collected at 16 and 26 weeks gestation and PBDE-47 in serum collected at 16 weeks gestation. We administered repeated measures of children's behavior, mental/psychomotor development, and IQ from ages 1-8 years. We determined if associations of BPA or PBDE-47 with child neurobehavior persisted or resolved as children aged using linear mixed models and estimated neurobehavioral measure reproducibility using intraclass correlation coefficients (ICCs). RESULTS: Higher BPA in girls and higher PBDE-47 in both boys and girls were associated with more externalizing behaviors; these associations persisted from ages 2-8 years (exposure×age interaction p-values≥0.36). Higher PBDE-47 concentrations were associated with decreases in MDI from ages 1-3 years (PBDE-47x age interaction p-value=0.03) and persistently lower IQ at ages 5 and 8 years (PBDE-47×age interaction p-value=0.56). Mental/psychomotor abilities had fair reproducibility from ages 1-3 years (ICCs∼0.4), cognitive abilities from ages 5 to 8 years had excellent reproducibility (ICCs=0.7-0.8), and parent-reported behaviors from ages 2-8 years had poor to good reproducibility (ICCs=0.38-0.59). CONCLUSIONS: Prenatal BPA and PBDE-47 concentrations were persistently associated with more externalizing behaviors. PBDE-47 concentrations were inversely associated with cognitive abilities that strengthened over time.

Is there an association of circulatory hospitalizations independent of mining employment in coal-mining and non-coal-mining counties in west virginia?

OBJECTIVE: Exposures associated with coal mining activities, including diesel fuel exhaust, products used in coal processing, and heavy metals and other forms of particulate matter, may impact the health of nearby residents. We investigated the relationships between county-level circulatory hospitalization rates (CHRs) in coal and non-coal-mining communities of West Virginia, coal production, coal employment, and sociodemographic factors. METHODS: Direct age-adjusted CHRs were calculated using West Virginia hospitalizations from 2005 to 2009. Spatial regressions were conducted to explore associations between CHR and total, underground, and surface coal production. RESULTS: After adjustment, neither total, nor surface, nor underground coal production was significantly related to rate of hospitalization for circulatory disease. CONCLUSIONS: Our findings underscore the significant role sociodemographic and behavioral factors play in the health and well-being of coal mining communities.

Perinatal outcomes and unconventional natural gas operations in Southwest Pennsylvania.

Unconventional gas drilling (UGD) has enabled extraordinarily rapid growth in the extraction of natural gas. Despite frequently expressed public concern, human health studies have not kept pace. We investigated the association of proximity to UGD in the Marcellus Shale formation and perinatal outcomes in a retrospective cohort study of 15,451 live births in Southwest Pennsylvania from 2007-2010. Mothers were categorized into exposure quartiles based on inverse distance weighted (IDW) well count; least exposed mothers (first quartile) had an IDW well count less than 0.87 wells per mile, while the most exposed (fourth quartile) had 6.00 wells or greater per mile. Multivariate linear (birth weight) or logistical (small for gestational age (SGA) and prematurity) regression analyses, accounting for differences in maternal and child risk factors, were performed. There was no significant association of proximity and density of UGD with prematurity. Comparison of the most to least exposed, however, revealed lower birth weight (3323 ± 558 vs 3344 ± 544 g) and a higher incidence of SGA (6.5 vs 4.8%, respectively; odds ratio: 1.34; 95% confidence interval: 1.10-1.63). While the clinical significance of the differences in birth weight among the exposure groups is unclear, the present findings further emphasize the need for larger studies, in regio-specific fashion, with more precise characterization of exposure over an extended period of time to evaluate the potential public health significance of UGD.

Global risk assessment of aflatoxins in maize and peanuts: are regulatory standards adequately protective?

The aflatoxins are a group of fungal metabolites that contaminate a variety of staple crops, including maize and peanuts, and cause an array of acute and chronic human health effects. Aflatoxin B1 in particular is a potent liver carcinogen, and hepatocellular carcinoma (HCC) risk is multiplicatively higher for individuals exposed to both aflatoxin and chronic infection with hepatitis B virus (HBV). In this work, we sought to answer the question: do current aflatoxin regulatory standards around the world adequately protect human health? Depending upon the level of protection desired, the answer to this question varies. Currently, most nations have a maximum tolerable level of total aflatoxins in maize and peanuts ranging from 4 to 20ng/g. If the level of protection desired is that aflatoxin exposures would not increase lifetime HCC risk by more than 1 in 100,000 cases in the population, then most current regulatory standards are not adequately protective even if enforced, especially in low-income countries where large amounts of maize and peanuts are consumed and HBV prevalence is high. At the protection level of 1 in 10,000 lifetime HCC cases in the population, however, almost all aflatoxin regulations worldwide are adequately protective, with the exception of several nations in Africa and Latin America.