Numerous methods exist to analyze complex environmental mixtures in health studies. As an illustration of the different uses of mixture methods, we employed methods geared toward distinct research questions concerning persistent organic chemicals (POPs) as a mixture and leukocyte telomere length (LTL) as an outcome. With information on 18 POPs and LTL among 1,003 U.S. adults (NHANES, 2001–2002), we used unsupervised methods including clustering to identify profiles of similarly exposed participants, and Principal Component Analysis (PCA) and Exploratory Factor Analysis (EFA) to identify common exposure patterns. We also employed supervised learning techniques, including penalized, weighted quantile sum (WQS), and Bayesian kernel machine (BKMR) regressions, to identify potentially toxic agents, and characterize nonlinear associations, interactions, and the overall mixture effect. Clustering separated participants into high, medium, and low POP exposure groups; longer log-LTL was found among those with high exposure. The first PCA component represented overall POP exposure and was positively associated with log-LTL. Two EFA factors, one representing furans and the other PCBs 126 and 118, were positively associated with log-LTL. Penalized regression methods selected three congeners in common (PCB 126, PCB 118, and furan 2,3,4,7,8-pncdf) as potentially toxic agents. WQS found a positive overall effect of the POP mixture and identified six POPs as potentially toxic agents (furans 1,2,3,4,6,7,8-hxcdf, 2,3,4,7,8-pncdf, and 1,2,3,6,7,8-hxcdf, and PCBs 99, 126, 169). BKMR found a positive linear association with furan 2,3,4,7,8-pncdf, suggestive evidence of linear associations with PCBs 126 and 169, and a positive overall effect of the mixture, but no interactions among congeners. Using different methods, we identified patterns of POP exposure, potentially toxic agents, the absence of interaction, and estimated the overall mixture effect. These applications and results may serve as a guide for mixture method selection based on specific research questions.

Polybrominated Diphenyl Ether (PBDE) flame retardants are environmental chemicals that cross the placenta during pregnancy and have shown evidence of neurotoxicity. As the in utero period is a sensitive developmental window, such exposure may result in adverse childhood outcomes. Associations between in utero PBDE exposure and neurodevelopment are found in animal models and increasingly in human population studies. Here, we review the epidemiological evidence of the association between prenatal exposure to PBDEs and motor, cognitive, and behavioral development in infants and children. Published work suggests a negative association between PBDE concentrations and neurodevelopment despite varying PBDE congeners measured, bio-specimen matrix used, timing of the biological sampling, geographic location of study population, specific developmental tests used, age of children at time of testing, and statistical methodologies. This review includes 16 published studies that measured PBDE exposure in maternal blood during pregnancy or in cord blood at delivery and performed validated motor, cognitive, and/or behavioral testing at one or more time during childhood. We evaluate possible mediation through PBDE-induced perturbations in thyroid function and effect measure modification by child sex. While the majority of studies support an adverse association between PBDEs and neurodevelopment, additional research is required to understand the mechanism of action, possibly through the perturbations in thyroid function either in the pregnant woman or in the child, and the role of biologically relevant effect modifiers such as sex.

Exposure to cold weather can cause cold-related illness and death, which are preventable. To understand the current burden, risk factors, and circumstances of exposure for illness and death directly attributed to cold, we examined hospital discharge, death certificate, and medical examiner data during the cold season from 2005 to 2014 in New York City (NYC), the largest city in the United States. On average each year, there were 180 treat-and-release emergency department visits (average annual rate of 21.6 per million) and 240 hospital admissions (29.6 per million) for cold-related illness, and 15 cold-related deaths (1.8 per million). Seventy-five percent of decedents were exposed outdoors. About half of those exposed outdoors were homeless or suspected to be homeless. Of the 25% of decedents exposed indoors, none had home heat and nearly all were living in single-family or row homes. The majority of deaths and illnesses occurred outside of periods of extreme cold. Unsheltered homeless individuals, people who use substances and become incapacitated outdoors, and older adults with medical and psychiatric conditions without home heat are most at risk. This information can inform public health prevention strategies and interventions.