Epidemiological investigation of infant health and environmental exposures

The impact of “place” on health is a classical and key element of epidemiology. Recent advances in geographic information systems have facilitated the use of spatial methods to investigate public health issues. Such approaches are particularly helpful when a public health phenomenon is relatively new and adequate environmental exposure information is lacking. The overarching objective of the present epidemiological investigation is to use spatial methods to explore relationships between several infant and children’s health outcomes and potential environmental exposures. The public health significance of this work is to identify possible sources of harmful exposures that may motivate further research, primary prevention efforts, and eventually policies to further limit exposures in these sensitive populations. It is well known that the embryo/fetus is particularly sensitive to the effects of environmental agents. Early life exposures are of public health significance since they may harm infant health and also have further adverse consequences in childhood and adulthood. The present work encompasses two relatively new but growing areas of interest related to fetal, infant, and children’s health: 1) unconventional natural gas development and adverse birth outcomes, and 2) sources of air toxics and childhood autism spectrum disorder (ASD). Geographic information systems are used to spatially link health outcomes, including birth weight, small for gestational age, preterm birth, and ASD, with nearby sources or with aggregated (e.g., census tract-level) estimates of exposure. Logistic regression is conducted to determine associations between risk for each of the above health effects and the exposures of interest, adjusting for other sociodemographic and personal risk factors. Overall, results indicate that environmental factors have a small but important role to play in the health of infants and children, even after accounting for other potentially confounding factors. Since spatial surrogates for exposure are the primary focus of this investigation, future work will benefit from improved individual exposure assessment and a prospective study design to confirm and further explain these associations

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

Maternal and Child Risk Factors for Geocoded versus Not Geocoded Residences and Those With versus Without at Least One Well Within 10-miles.

<p>Maternal and Child Risk Factors for Geocoded versus Not Geocoded Residences and Those With versus Without at Least One Well Within 10-miles.</p

Unadjusted and adjusted odds ratios (OR) and 95% confidence intervals (CI) for prematurity (adjusted for mom’s age, mom’s education, pre-pregnancy weight, gender of infant, prenatal visits, smoking during pregnancy, gestational diabetes, WIC, race, and birth order).

<p>Key: Referent (First quartile), <0.87 wells per mile; Second quartile (2Q), 0.87 to 2.59 wells per mile; Third quartile (3Q), 2.60 to 5.99 wells per mile; Fourth quartile (4Q), ≥6.00 wells per mile.</p

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

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

Identification of a Human Airway Epithelial Cell Subpopulation with Altered Biophysical, Molecular, and Metastatic Properties.

Lung cancers are documented to have remarkable intratumoral genetic heterogeneity. However, little is known about the heterogeneity of biophysical properties, such as cell motility, and its relationship to early disease pathogenesis and micrometastatic dissemination. In this study, we identified and selected a subpopulation of highly migratory premalignant airway epithelial cells that were observed to migrate through microscale constrictions at up to 100-fold the rate of the unselected immortalized epithelial cell lines. This enhanced migratory capacity was found to be Rac1-dependent and heritable, as evidenced by maintenance of the phenotype through multiple cell divisions continuing more than 8 weeks after selection. The morphology of this lung epithelial subpopulation was characterized by increased cell protrusion intensity. In a murine model of micrometastatic seeding and pulmonary colonization, the motility-selected premalignant cells exhibit both enhanced survival in short-term assays and enhanced outgrowth of premalignant lesions in longer-term assays, thus overcoming important aspects of "metastatic inefficiency." Overall, our findings indicate that among immortalized premalignant airway epithelial cell lines, subpopulations with heritable motility-related biophysical properties exist, and these may explain micrometastatic seeding occurring early in the pathogenesis of lung cancer. Understanding, targeting, and preventing these critical biophysical traits and their underlying molecular mechanisms may provide a new approach to prevent metastatic behavior. Cancer Prev Res; 10(9); 514-24. ©2017 AACRSee related editorial by Hynds and Janes, p. 491

Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality