Stephen Rauch

In Utero and Childhood Polybrominated Diphenyl Ether (PBDE) Exposures and Neurodevelopment in the CHAMACOS Study

background: California children’s exposures to polybrominated diphenyl ether flame retardants (PBDEs) are among the highest worldwide. PBDEs are known endocrine disruptors and neurotoxicants in animals. Objective: Here we investigate the relation of in utero and child PBDE exposure to neurobehavioral development among participants in CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas), a California birth cohort. Methods: We measured PBDEs in maternal prenatal and child serum samples and examined the association of PBDE concentrations with children’s attention, motor functioning, and cognition at 5 (n = 310) and 7 years of age (n = 323). Results: Maternal prenatal PBDE concentrations were associated with impaired attention as measured by a continuous performance task at 5 years and maternal report at 5 and 7 years of age, with poorer fine motor coordination—particularly in the nondominant—at both age points, and with decrements in Verbal and Full-Scale IQ at 7 years. PBDE concentrations in children 7 years of age were significantly or marginally associated with concurrent teacher reports of attention problems and decrements in Processing Speed, Perceptual Reasoning, Verbal Comprehension, and Full-Scale IQ. These associations were not altered by adjustment for birth weight, gestational age, or maternal thyroid hormone levels. Conclusions: Both prenatal and childhood PBDE exposures were associated with poorer attention, fine motor coordination, and cognition in the CHAMACOS cohort of school-age children. This study, the largest to date, contributes to growing evidence suggesting that PBDEs have adverse impacts on child neurobehavioral development.

The Effects of Temperature and Use of Air Conditioning on Hospitalizations

Several investigators have documented the effect of temperature on mortality, although fewer have studied its impact on morbidity. In addition, little is known about the effectiveness of mitigation strategies such as use of air conditioners (ACs). The authors investigated the association between temperature and hospital admissions in California from 1999 to 2005. They also determined whether AC ownership and usage, assessed at the zip-code level, mitigated this association. Because of the unique spatial pattern of income and climate in California, confounding of AC effects by other local factors is less likely. The authors included only persons who had a temperature monitor within 25 km of their residential zip code. Using a time-stratified case-crossover approach, the authors observed a significantly increased risk of hospitalization for multiple diseases, including cardiovascular disease, ischemic heart disease, ischemic stroke, respiratory disease, pneumonia, dehydration, heat stroke, diabetes, and acute renal failure, with a 10°F increase in same-day apparent temperature. They also found that ownership and usage of ACs significantly reduced the effects of temperature on these health outcomes, after controlling for potential confounding by family income and other socioeconomic factors. These results demonstrate important effects of temperature on public health and the potential for mitigation.

Prenatal Polybrominated Diphenyl Ether Exposures and Neurodevelopment in U.S. Children through 5 Years of Age: The HOME Study

Background: Polybrominated diphenyl ethers (PBDEs) are persistent chemicals that have been widely used as flame retardants in furniture, carpet padding, car seats, and other consumer products during the past three decades. Objective: We examined whether in utero exposure to PBDEs is associated with child cognitive function and behavior in a U.S. study sample. Methods: In a prospective birth cohort, we measured maternal serum concentrations of BDE-47 and other PBDE congeners in 309 women at 16 weeks of gestation during 2003–2006 and followed their children in Cincinnati, Ohio. We measured cognitive and motor abilities using the Bayley Scales of Infant Development-II at ages 1, 2, and 3 years; intelligence using the Wechsler Preschool and Primary Scale of Intelligence-III at age 5 years; and children’s behaviors using the Behavioral Assessment System for Children-2 annually at ages 2–5 years. We used linear mixed models or generalized estimating equations with adjustment for potential confounders to estimate associations between these outcomes and log10-transformed PBDE concentrations. Results: The geometric mean of BDE-47 in maternal serum (20.1 ng/g lipid) was comparable with U.S. adult national reference values. Prenatal BDE-47 was not significantly associated with Bayley Mental or Psychomotor Development Indices at 1–3 years, but a 10-fold increase in prenatal BDE-47 was associated with a 4.5-point decrease (95% CI: –8.8, –0.1) in Full-Scale IQ and a 3.3-point increase (95% CI: 0.3, 6.3) in the hyperactivity score at age 5 years. Conclusions: Prenatal exposure to PBDEs was associated with lower IQ and higher hyperactivity scores in children. Citation: Chen A, Yolton K, Rauch SA, Webster GM, Hornung R, Sjödin A, Dietrich KN, Lanphear BP. 2014. Prenatal polybrominated diphenyl ether exposures and neurodevelopment in U.S. children through 5 years of age: the HOME study. Environ Health Perspect 122:856–862; http://dx.doi.org/10.1289/ehp.1307562

Associations of Prenatal Exposure to Organophosphate Pesticide Metabolites with Gestational Age and Birth Weight

Background: Prenatal exposure to organophosphate (OP) insecticides, a widely used class of pesticides, may be associated with decreased gestational age and lower birth weight. Single nucleotide polymorphisms in paroxanase (PON1) enzyme genotypes may modify the relationships between OP exposure and perinatal outcomes. Objective: We examined the relationship of prenatal OP insecticide exposure, measured using urinary dialkyl phosphate (DAP) metabolite concentrations, with gestational age and birth weight. Methods: We measured the concentrations of six nonspecific DAP metabolites of OP insecticides in two maternal spot urine samples collected in a prospective birth cohort. We performed multivariable regression to examine associations between the sum of six DAP concentrations (ΣDAP) with gestational age and birth weight. We also examined whether these associations differed according to infant PON1192 and PON1–108 genotypes. Results: Among 306 mother–infant dyads, a 10-fold increase in ΣDAP concentrations was associated with a decrease in covariate-adjusted gestational age [–0.5 weeks; 95% confidence interval (CI): –0.8, –0.1] and birth weight (–151 g; CI: –287, –16); the decrements in birth weight were attenuated after adjusting for gestational age. The relationship between ΣDAP concentrations and gestational age was stronger for white (–0.7 weeks; CI: –1.1, –0.3) than for black (–0.1 weeks; 95% CI: –0.9, 0.6) newborns. In contrast, there was a greater decrease in birth weight with increasing urinary ΣDAP concentrations for black (–188 g; CI: –395, 19) than for white (–118 g; CI: –296, 60) newborns. Decrements in birth weight and gestational age associated with ΣDAP concentrations were greatest among infants with PON1192QR and PON–108CT genotypes. Conclusions: Prenatal urinary ΣDAP concentrations were associated with shortened gestation and reduced birth weight in this cohort, but the effects differed by race/ethnicity and PON1192/108 genotypes.

Low-level lead exposure and mortality in US adults: a population-based cohort study

BACKGROUND Lead exposure is a risk factor for cardiovascular disease mortality, but the number of deaths in the USA attributable to lead exposure is poorly defined. We aimed to quantify the relative contribution of environmental lead exposure to all-cause mortality, cardiovascular disease mortality, and ischaemic heart disease mortality. METHODS Our study population comprised a nationally representative sample of adults aged 20 years or older who were enrolled in the Third National Health and Nutrition Examination Survey (NHANES-III) between 1988 and 1994 and followed up to Dec 31, 2011. Participants had completed a medical examination and home interview and had results for concentrations of lead in blood, cadmium in urine, and other relevant covariates. Individuals were linked with the National Death Index. This study presents extended follow-up of an earlier analysis. FINDINGS We included 14 289 adults in our study. The geometric mean concentration of lead in blood was 2·71 μg/dL (geometric SE 1·31). 3632 (20%) participants had a concentration of lead in blood of at least 5 μg/dL (≥0·24 μmol/L). During median follow-up of 19·3 years (IQR 17·6-21·0), 4422 people died, 1801 (38%) from cardiovascular disease and 988 (22%) from ischaemic heart disease. An increase in the concentration of lead in blood from 1·0 μg/dL to 6·7 μg/dL (0·048 μmol/L to 0·324 μmol/L), which represents the tenth to 90th percentiles, was associated with all-cause mortality (hazard ratio 1·37, 95% CI 1·17-1·60), cardiovascular disease mortality (1·70, 1·30-2·22), and ischaemic heart disease mortality (2·08, 1·52-2·85). The population attributable fraction of the concentration of lead in blood for all-cause mortality was 18·0% (95% CI 10·9-26·1), which is equivalent to 412 000 deaths annually. Respective fractions were 28·7% (15·5-39·5) for cardiovascular disease mortality and 37·4% (23·4-48·6) for ischaemic heart disease mortality, which correspond to 256 000 deaths a year from cardiovascular disease and 185 000 deaths a year from ischaemic heart disease. INTERPRETATION Low-level environmental lead exposure is an important, but largely overlooked, risk factor for cardiovascular disease mortality in the USA. A comprehensive strategy to prevent deaths from cardiovascular disease should include efforts to reduce lead exposure. FUNDING The Artemis Fund and Simon Fraser University.

Cross-Sectional Associations of Serum Perfluoroalkyl Acids and Thyroid Hormones in U.S. Adults: Variation According to TPOAb and Iodine Status (NHANES 2007–2008)

Background: Perfluoroalkyl acids (PFASs) are suspected thyroid toxicants, but results from epidemiological studies are inconsistent. Objectives: We examined associations between serum PFASs and thyroid hormones (THs) in a representative, cross-sectional sample of U.S. adults. We hypothesized that people with high thyroid peroxidase antibodies and low iodine would be more susceptible to PFAS-induced thyroid disruption. Methods: Our sample included 1,525 adults (≥ 18 years) from the 2007–2008 NHANES study with available serum PFASs and THs. We examined associations between four serum PFASs [perfluorohexane sulfonate (PFHxS), perfluorononanoate (PFNA), perfluorooctanoate (PFOA), and perfluorooctane sulfonate (PFOS)], and serum THs [free triiodothyronine (fT3), free thyroxine (fT4), fT3/fT4, thyroid-stimulating hormone (TSH), total T3 (TT3), and total T4 (TT4)] using multivariable linear regression. We stratified subjects into four groups by two indicators of thyroid “stress”: thyroid peroxidase antibody (TPOAb ≥ 9 IU/mL) and iodine status (< 100 μg/L urine). Results: Of 1,525 participants, 400 (26%) had low iodine only (T0I1), 87 (6%) had high TPOAb only (T1I0), and 26 (2%) had both high TPOAb and low iodine (T1I1). In general, associations were similar among participants in the groups with neither (T0I0) or only one thyroid stressor (T0I1 or T1I0), suggesting that PFAS–TH associations were not modified by high TPOAb or low iodine alone. However, PFHxS and PFOS were negatively associated (p < 0.05) with fT4, and all four PFASs were positively associated (p < 0.05) with fT3, fT3/fT4, TSH, and TT3 in the group with joint exposure to high TPOAb and low iodine (T1I1). Conclusions: We found evidence of PFAS-associated thyroid disruption in a subset of U.S. adults with high TPOAb (a marker of autoimmune hypothyroidism) and low iodine status, who may represent a vulnerable subgroup. However, the small sample size, cross-sectional design, and possibility of reverse causation are limitations of this work. Citation: Webster GM, Rauch SA, Ste Marie N, Mattman A, Lanphear BP, Venners SA. 2016. Cross-sectional associations of serum perfluoroalkyl acids and thyroid hormones in U.S. adults: variation according to TPOAb and iodine status (NHANES 2007–2008). Environ Health Perspect 124:935–942; http://dx.doi.org/10.1289/ehp.1409589

Prevention of Disability in Children: Elevating the Role of Environment.

Much public attention and many resources are focused on medical research to identify risk factors and mitigate symptoms of disability for individual children. But this focus will inevitably fail to prevent disabilities. Stephen Rauch and Bruce Lanphear argue for a broader focus on environmental influences that put entire populations at risk. They argue that identifying and eliminating or controlling environmental risk factors that incrementally increase the prevalence of disability is the key to preventing many disorders.Rauch and Lanphear examine emerging evidence that many disabilities of childhood have their roots in the environment—from toxins in air, water, and soil, to the stressors of poverty, to marketing practices that encourage unhealthy choices or discourage healthy ones. They review research on well-known environmental causes of disability, such as exposures to lead, cigarette smoke, and industrial air pollution. They point to new evidence suggesting that chemicals found in commonly used plastics may have subtle but serious effects on child development, and that many disabilities spring from the complex interplay of environmental risk factors and genetic susceptibility.Rauch and Lanphear make a case for turning our attention to societal or population-level interventions that would rely less on medical and genetic technology and more on policies and regulations that would reduce childrens exposure to ubiquitous environmental risks. Examples include required testing of new chemicals for developmental toxicity before they are put on the market; zoning regulations that separate residential communities from industrial areas; and restrictions on advertising of unhealthy products, such as tobacco, alcohol, and junk foods, to children. Rauch and Lanphear outline and assess the effectiveness of interventions that could be adopted, and suggest what a healthy modern community might look like. Such interventions, they acknowledge, are likely to be highly controversial, require both long-term investments and shifts in societal thinking, and produce less well-defined outcomes than individual medical treatments. But in the long run, the authors contend, such interventions could prevent many of the disabilities that now afflict millions of children and adults.

Association of prenatal urinary phthalate metabolite concentrations and childhood bmi and obesity.

BackgroundAlthough experiments in animals suggest that phthalates may have obesogenic effects, studies on prenatal exposure in children show inconsistent results.MethodsWe measured urinary concentrations of 11 phthalate metabolites collected twice during pregnancy from mothers participating in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort study (N=345). Height, weight, waist circumference, and percent body fat were assessed in their children between 5 and 12 years of age. We used generalized estimating equations to examine associations at each age and tested for interaction by sex.ResultsMetabolites of diethyl phthalate (DEP), di-n-butyl phthalate (DBP), butyl benzyl phthalate, and di(2-ethylhexyl) phthalate (DEHP) were positively associated with BMI z-score, waist circumference z-score, and percent body fat at multiple ages. At age 12, we observed increased odds of being overweight/obese with each doubling of prenatal concentrations of DEP (odds ratio=1.3; 95% confidence intervals: 1.1, 1.4), DBP (1.2; 1.0, 1.4), and DEHP (1.3; 1.0, 1.6) metabolites. Results were similar in boys and girls except for DBP metabolites and the non-specific metabolite mono-(3-carboxypropyl) phthalate, which showed positive associations only in boys.ConclusionIn utero exposure to certain phthalates is associated with increased BMI and risk for overweight/obesity in childhood.

Serum Dioxin Concentrations and Bone Density and Structure in the Seveso Women's Health Study

Background: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a widespread environmental contaminant, is a known endocrine disruptor. In animal studies, TCDD exposure impairs bone metabolism and increases fragility. To our knowledge, no epidemiologic studies have examined this association. Objectives: On 10 July 1976, a chemical explosion in Seveso, Italy, resulted in the highest known residential exposure to TCDD. In 1996, we initiated the Seveso Women’s Health Study, a retrospective cohort study of the health of the women. In 2008, we followed up the cohort. Here, we evaluated the association between TCDD exposure and bone structure and geometry in adulthood, and considered whether timing of TCDD exposure before achievement of peak bone mass (assumed to occur 2 years after onset of menarche) modified the association. Methods: Individual TCDD concentration was measured in archived serum collected soon after the explosion. In 2008, 350 women who were < 20 years old in 1976 underwent a dual-energy X-ray absorptiometry (DXA) bone scan. Bone mineral density was measured at the lumbar spine and hip, and hip geometry was extracted from hip DXA scans using the hip structural analysis method. Results: Among premenopausal women, TCDD serum levels were associated with some indexes indicating better bone structure in women exposed before peak bone mass (n = 219), with stronger associations in those exposed before 5 years of age (n = 46). In contrast, among postmenopausal women, TCDD levels were associated with evidence of better bone structure in women exposed after peak bone mass (n = 48) than in other women (n = 18). Conclusions: Our current results do not support the hypothesis that postnatal TCDD exposure adversely affects adult bone health. Continued follow-up of women who were youngest at exposure is warranted. Future studies should also focus on those exposed in utero. Citation: Eskenazi B, Warner M, Sirtori M, Fuerst T, Rauch SA, Brambilla P, Mocarelli P, Rubinacci A. 2014. Serum dioxin concentrations and bone density and structure in the Seveso Women’s Health Study. Environ Health Perspect 122:51–57; http://dx.doi.org/10.1289/ehp.1306788

DNA methylation of LINE-1 and Alu repetitive elements in relation to sex hormones and pubertal timing in Mexican-American children

Background:The molecular mechanisms linking environmental exposures to earlier pubertal development are not well characterized. Epigenetics may play an important role, but data on the relationship between epigenetic marks and puberty, particularly in humans, is limited.Methods:We used pyrosequencing to measure Alu and long interspersed nucleotide elements (LINE-1) methylation in DNA isolated from whole blood samples collected from newborns and 9-y-old children (n = 266). Tanner staging was completed six times between ages 9 and 12 y to determine pubertal status, and hormone levels were measured in 12-y-old boys.Results:Among girls, we observed a suggestive trend of increased odds of breast and pubic hair development with higher Alu and LINE-1 methylation in 9-y-old blood, respectively. The strongest association identified was an inverse association of LINE-1 methylation in 9-y-old girls with odds of experiencing menarche by age 12 (OR (95% CI): 0.63 (0.46, 0.87); P = 0.005). We observed a consistent inverse relationship for Alu and LINE-1 methylation at 9 y with luteinizing hormone (LH), testosterone and follicle-stimulating hormone levels in boys but it was only significant between LINE-1 and LH.Conclusion:DNA methylation of Alu and LINE-1 may be involved in puberty initiation and development. This relationship should be confirmed in future studies.