Ellen M. Wells

Estimating risk from ambient concentrations of acrolein across the United States.

Background Estimated ambient concentrations of acrolein, a hazardous air pollutant, are greater than the U.S. Environmental Protection Agency (EPA) reference concentration throughout the United States, making it a concern for human health. However, there is no method for assessing the extent of risk under the U.S. EPA noncancer risk assessment framework. Objectives We estimated excess risks from ambient concentrations of acrolein based on dose–response modeling of a study in rats with a relationship between acrolein and residual volume/total lung capacity ratio (RV/TLC) and specific compliance (sCL), markers for altered lung function. Methods Based on existing literature, we defined values above the 90th percentile for controls as “adverse.” We estimated the increase over baseline response that would occur in the human population from estimated ambient concentrations of acrolein, taken from the U.S. EPA’s National-Scale Air Toxics Assessment for 1999, after standard animal-to-human conversions and extrapolating to doses below the experimental data. Results The estimated median additional number of adverse sCL outcomes across the United States was approximately 2.5 cases per 1,000 people. The estimated range of additional outcomes from the 5th to the 95th percentile of acrolein concentration levels across census tracts was 0.28–14 cases per 1,000. For RV/TLC, the median additional outcome was 0.002 per 1,000, and the additional outcome at the 95th percentile was 0.13 per 1,000. Conclusions Although there are uncertainties in estimating human risks from animal data, this analysis demonstrates a method for estimating health risks for noncancer effects and suggests that acrolein could be associated with decreased respiratory function in the United States.

Body burdens of mercury, lead, selenium and copper among Baltimore newborns.

Umbilical cord blood or serum concentrations of mercury, lead, selenium and copper were measured with inductively coupled plasma mass spectrometry in a population of 300 infants born in Baltimore, Maryland. Geometric mean values were 1.37 μg/L (95% confidence interval: 1.27, 1.48) for mercury; 0.66 μg/dL (95% CI: 0.61, 0.71) for lead; and 38.62 μg/dL (95% CI: 36.73, 40.61) for copper. Mean selenium was 70.10 μg/L (95% CI: 68.69, 70.52). Mercury, selenium and copper levels were within exposure ranges reported among similar populations, whereas the distribution of lead levels was lower than prior reports; only one infant had a cord blood lead above 10 μg/dL. Levels of selenium were significantly correlated with concentrations of lead (Spearmans ρ=0.20) and copper (Spearmans ρ=0.51). Multivariable analyses identified a number of factors associated with one of more of these exposures. These included: increase in maternal age (increased lead); Asian mothers (increased mercury and lead, decreased selenium and copper); higher umbilical cord serum n-3 fatty acids (increased mercury, selenium and copper), mothers using Medicaid (increased lead); increasing gestational age (increased copper); increasing birthweight (increased selenium); older neighborhood housing stock (increased lead and selenium); and maternal smoking (increased lead). This work provides additional information about contemporary prenatal element exposures and can help identify groups at risk of atypical exposures.

Prenatal mercury concentration is associated with changes in DNA methylation at TCEANC2 in newborns

BACKGROUND Human exposure to the widespread environmental contaminant mercury is a known risk factor for common diseases such as cancer, cardiovascular disease and neurological disorders through poorly characterized mechanisms. Evidence suggests mercury exposure may alter DNA methylation levels, but to date, the effects in early life on a genome-wide scale have not been investigated. METHODS A study sample of 141 newborns was recruited in Baltimore, MD, USA and total mercury and methylmercury were measured in cord blood samples. We quantified genome-wide DNA methylation data using CHARM 2.0, an array-based method, and used region-finding analyses to identify concentration-associated differentially methylated regions (DMRs). To test for replication of these identified DMRs in the pilot, or Vanguard, phase of the National Childrens Study (NCS), we compared bisulfite-pyrosequenced DNA at candidate regions from 85 whole cord blood samples with matched first trimester maternal mercury concentration measures. RESULTS Total mercury concentration was associated with methylation at DMRs inside ANGPT2 and near PRPF18 genes [false discovery rate (FDR) < 0.05], as well as DMRs near FOXD2 and within TCEANC2 (FDR< 0.1) genes. Methylmercury concentration was associated with an overlapping DMR within TCEANC2 (FDR< 0.05). In NCS replication analyses, methylation levels at three of four cytosine-guanine DNA dinucleotides (CpG sites) within the TCEANC2 DMR were associated with total mercury concentration (P < 0.05), and this association was diminished after adjusting for estimated cell proportions. CONCLUSIONS Evidence for an association between mercury and DNA methylation at the TCEANC2 region was found, which may represent a mercury-associated shift in cord blood cell composition or a change in methylation within blood cell types. Further confirmatory studies are needed.

Low-Level Lead Exposure and Elevations in Blood Pressure during Pregnancy

Background Lead exposure is associated with elevated blood pressure during pregnancy; however, the magnitude of this relationship at low exposure levels is unclear. Objectives Our goal was to determine the association between low-level lead exposure and blood pressure during late pregnancy. Methods We collected admission and maximum (based on systolic) blood pressures during labor and delivery among 285 women in Baltimore, Maryland. We measured umbilical cord blood lead using inductively coupled plasma mass spectrometry. Multivariable models were adjusted for age, race, median household income, parity, smoking during pregnancy, prepregnancy body mass index, and anemia. These models were used to calculate benchmark dose values. Results Geometric mean cord blood lead was 0.66 μg/dL (95% confidence interval, 0.61–0.70). Comparing blood pressure measurements between those in the highest and those in the lowest quartile of lead exposure, we observed a 6.87-mmHg (1.51–12.21 mmHg) increase in admission systolic blood pressure and a 4.40-mmHg (0.21–8.59 mmHg) increase in admission diastolic blood pressure after adjustment for confounders. Corresponding values for maximum blood pressure increase were 7.72 (1.83–13.60) and 8.33 (1.14–15.53) mmHg. Benchmark dose lower limit values for a 1-SD increase in blood pressure were < 2 μg/dL blood lead for all blood pressure end points. Conclusions A significant association between low-level lead exposures and elevations in maternal blood pressure during labor and delivery can be observed at umbilical blood lead levels < 2 μg/dL.

Activity Change in Response to Bad Air Quality, National Health and Nutrition Examination Survey, 2007–2010

Air pollution contributes to poor respiratory and cardiovascular health. Susceptible individuals may be advised to mitigate effects of air pollution through actions such as reducing outdoor physical activity on days with high pollution. Our analysis identifies the extent to which susceptible individuals changed activities due to bad air quality. This cross-sectional study included 10,898 adults from the National Health and Nutrition Examination Survey (NHANES) 2007–2010. Participants reported if they did something differently when air quality was bad. Susceptible categories included respiratory conditions, cardiovascular conditions and older age (≥65 years). Analyses accounted for complex survey design; logistic regression models controlled for gender, race, education, smoking, and body mass index. 1305 individuals reported doing something differently (12.0%, 95% confidence interval (CI): 10.9, 13.1). This percentage was 14.2% (95% CI: 11.6, 16.8), 25.1% (95% CI: 21.7, 28.6), and 15.5% (95% CI: 12.2, 18.9) among older adults, those with a respiratory condition, and those with a cardiovascular condition, respectively. In adjusted regression models the following were significantly more likely to have changed activity compared to those who did not belong to any susceptible group: respiratory conditions (adjusted odds ratio (aOR): 2.61, 95% CI: 2.03, 3.35); respiratory and cardiovascular conditions (aOR: 4.36, 95% CI: 2.47, 7.69); respiratory conditions and older age (aOR: 3.83; 95% CI: 2.47, 5.96); or all three groups (aOR: 3.52; 95% CI: (2.33, 5.32). Having cardiovascular conditions alone was not statistically significant. Some individuals, especially those with a respiratory condition, reported changing activities due to poor air quality. However, efforts should continue to educate the public about air quality and health.

The relationship of blood lead with immunoglobulin E, eosinophils, and asthma among children: NHANES 2005-2006.

Early life lead exposure may alter immune function and predispose a child to develop asthma. In an initial exploration of this hypothesis, we examined the association between blood lead, and serum immunoglobulin E (IgE), eosinophils, and asthma prevalence in a cross-sectional study of 1788 children from the National Health and Nutrition Examination Survey 2005-2006. Geometric mean blood lead, serum IgE, and percent eosinophils were 1.13 μg/dL (95% confidence interval (CI): 1.04, 1.22), 46.3 kU/L (95% CI: 40.3, 53.1), and 2.82 percent (95% CI 2.67, 2.98), respectively. Prevalence of asthma, atopic asthma, and atopy were 11.8% (95% CI: 9.5, 14.2), 8.1% (6.2, 9.9), and 44.4% (40.1, 48.7), respectively. Regression models controlled for season, age, sex, race/ethnicity, education, passive smoke exposure, and body mass index. Based on these models, there was an 11.1% (95% CI: 5.6, 16.9) increase in IgE and a 4.9% (95% CI: 2.3, 7.6) increase in eosinophils per 1 μg/dL increase in blood lead. In independent stratified analyses, lead was found to increase IgE and eosinophils among non-Hispanic whites, but not other children; and stronger associations were observed among children who lived with a smoker vs. not. Lead was not associated with asthma, atopic asthma, or general atopy. This study provides additional evidence of a cross-sectional association between lead with IgE and new evidence for eosinophils. This may be a mechanism for development of downstream allergic disease. The mechanisms that determine ultimate development of allergic disease are currently unknown, but are the focus of ongoing studies.

Cord Blood Methylmercury and Fetal Growth Outcomes in Baltimore Newborns: Potential Confounding and Effect Modification by Omega-3 Fatty Acids, Selenium, and Sex

Background Methylmercury (MeHg) may affect fetal growth; however, prior research often lacked assessment of mercury speciation, confounders, and interactions. Objective Our objective was to assess the relationship between MeHg and fetal growth as well as the potential for confounding or interaction of this relationship from speciated mercury, fatty acids, selenium, and sex. Methods This cross-sectional study includes 271 singletons born in Baltimore, Maryland, 2004–2005. Umbilical cord blood was analyzed for speciated mercury, serum omega-3 highly unsaturated fatty acids (n-3 HUFAs), and selenium. Multivariable linear regression models controlled for gestational age, birth weight, maternal age, parity, prepregnancy body mass index, smoking, hypertension, diabetes, selenium, n-3 HUFAs, and inorganic mercury (IHg). Results Geometric mean cord blood MeHg was 0.94 μg/L (95% CI: 0.84, 1.07). In adjusted models for ponderal index, βln(MeHg) = –0.045 (g/cm3) × 100 (95% CI: –0.084, –0.005). There was no evidence of a MeHg × sex interaction with ponderal index. Contrastingly, there was evidence of a MeHg × n-3 HUFAs interaction with birth length [among low n-3 HUFAs, βln(MeHg) = 0.40 cm, 95% CI: –0.02, 0.81; among high n-3 HUFAs, βln(MeHg) = –0.15, 95% CI: –0.54, 0.25; p-interaction = 0.048] and head circumference [among low n-3 HUFAs, βln(MeHg) = 0.01 cm, 95% CI: –0.27, 0.29; among high n-3 HUFAs, βln(MeHg) = –0.37, 95% CI: –0.63, –0.10; p-interaction = 0.042]. The association of MeHg with birth weight and ponderal index was affected by n-3 HUFAs, selenium, and IHg. For birth weight, βln(MeHg) without these variables was –16.8 g (95% CI: –75.0, 41.3) versus –29.7 (95% CI: –93.9, 34.6) with all covariates. Corresponding values for ponderal index were –0.030 (g/cm3) × 100 (95% CI: –0.065, 0.005) and –0.045 (95% CI: –0.084, –0005). Conclusion We observed an association of increased MeHg with decreased ponderal index. There is evidence for interaction between MeHg and n-3 HUFAs; infants with higher MeHg and n-3 HUFAs had lower birth length and head circumference. These results should be verified with additional studies. Citation Wells EM, Herbstman JB, Lin YH, Jarrett J, Verdon CP, Ward C, Caldwell KL, Hibbeln JR, Witter FR, Halden RU, Goldman LR. 2016. Cord blood methylmercury and fetal growth outcomes in Baltimore newborns: potential confounding and effect modification by omega-3 fatty acids, selenium, and sex. Environ Health Perspect 124:373–379; http://dx.doi.org/10.1289/ehp.1408596

Decline in urinary bisphenol A concentrations in the United States.

To the Editor: Bisphenol A (BPA) is a highvolume production chemical used in polycarbonate plastics and epoxy resins. Human exposure occurs when BPA leaches from packaging into food or water. BPA has been associated with adverse reproductive, cardiometabolic, and behavioral outcomes, resulting in public and scientific concern.1–4 This concern, particularly for children, has led to the production of BPA-free products.2,5 Prior reports noted a possible decrease in urinary BPA after 2003–20043,6; however, more recent data are now available. We assessed time trends, especially among children, using National Health and Nutrition Examination Survey (NHANES) 2003–2010 data. Spot urine samples were obtained in 10,415 persons from four consecutive 2-year NHANES cycles (www.cdc. gov/nchs/nhanes.htm). Urinary BPA was analyzed using high-performance liquid chromatography-tandem mass spectrometry; this method did not change over time. The limit of detection (LOD) was 0.4 ng/ml: LOD/√2 was used for values below LOD (7.0%) (see eTable 1, http:// links.lww.com/EDE/A634). To account for urine dilution, BPA was creatininecorrected (BPAcorr) or adjusted for creatinine in models. We carried out statistical analyses using Stata 11.2 (College Station, TX), accounting for survey design and incorporating appropriate sample weights. Geometric mean BPAcorr levels by year were calculated. We assessed the percentage difference in BPA over time, adjusting for creatinine, age, sex, race/ethnicity, and income, using linear regression models with 2003–2004 as the reference category. To determine when substantial changes in BPA concentrations occurred within the study time frame, we further examined the percentage difference between consecutive survey cycles. Geometric mean BPAcorr was 2.09 μg/g creatinine (95% confidence interval [CI] = 2.02–2.16). BPA concentrations were higher in 2003–2004 compared with later years (eTable 2, h t tp : / / l inks . lww.com/EDE/A634; Fig.). In adjusted models, among 6to 11-year-olds, 12to 19-year-olds, and those 20 years or older, the percentage difference in BPA comparing 2009– 2010 to 2003–2004 was −45 (95% CI = −55 to −32), −40 (−49 to −28), and −20 (−23 to −2), respectively (eTable3, h t tp : / / l inks . lww.com/EDE/A634; Fig.). When comparing each cycle with the previous one, we observed significant decreases from 2003–2004 to 2005–2006 among all age groups and from 2007–2008 to 2009–2010 among 6to 11-year-olds, but a significant increase from 2005–2006 to 2007–2008 among those 20 years or older (eTable 4, http://links.lww.com/EDE/A634). Urinary BPA concentrations declined from 2003 to 2010 among younger children; however, among young people of age 12–19 years and those 20 years or older, there was a decline only from 2003–2004 to 2005–2006. This analysis is consistent with prior reports but includes more recent data and specifically focused on time trends. As has been suggested previously, this decline might represent random variation6; however, it is also plausible that there has been a true reduction in BPA exposure. As early as 2003, public concern about BPA generated advice on how to avoid exposure,7 by changing consumption habits; this has been shown to affect urinary BPA concentrations.8 In addition, removal of BPA from products would reduce exposures. It will be important to continue monitoring BPA concentrations, as additional removal of BPA from products may further reduce body burdens. It is also important to consider what is used as a substitute, to avoid merely replacing one endocrine disruptor with another.5 In conclusion, BPA concentrations have declined among 6to 11-year-olds in recent years, but remain highest in this age group, which may be the most vulnerable to environmental toxicants.1 Additional research should consider the health effects of BPA exposure particularly in the pediatric population, where outcomes—especially those related to obesity and cardiovascular risk—remain relatively understudied.

Methyl mercury, but not inorganic mercury, associated with higher blood pressure during pregnancy

&NA; Prior studies addressing associations between mercury and blood pressure have produced inconsistent findings; some of this may result from measuring total instead of speciated mercury. This cross‐sectional study of 263 pregnant women assessed total mercury, speciated mercury, selenium, and n‐3 polyunsaturated fatty acids in umbilical cord blood and blood pressure during labor and delivery. Models with a) total mercury or b) methyl and inorganic mercury were evaluated. Regression models adjusted for maternal age, race/ethnicity, prepregnancy body mass index, neighborhood income, parity, smoking, n‐3 fatty acids and selenium. Geometric mean total, methyl, and inorganic mercury concentrations were 1.40 &mgr;g/L (95% confidence interval: 1.29, 1.52); 0.95 &mgr;g/L (0.84, 1.07); and 0.13 &mgr;g/L (0.10, 0.17), respectively. Elevated systolic BP, diastolic BP, and pulse pressure were found, respectively, in 11.4%, 6.8%, and 19.8% of mothers. In adjusted multivariable models, a one‐tertile increase of methyl mercury was associated with 2.83 mmHg (0.17, 5.50) higher systolic blood pressure and 2.99 mmHg (0.91, 5.08) higher pulse pressure. In the same models, an increase of one tertile of inorganic mercury was associated with −1.18 mmHg (−3.72, 1.35) lower systolic blood pressure and −2.51 mmHg (−4.49, −0.53) lower pulse pressure. No associations were observed with diastolic pressure. There was a non‐significant trend of higher total mercury with higher systolic blood pressure. We observed a significant association of higher methyl mercury with higher systolic and pulse pressure, yet higher inorganic mercury was significantly associated with lower pulse pressure. These results should be confirmed with larger, longitudinal studies. HighlightsWe compared total, methyl and inorganic mercury with blood pressure in pregnancy.Models controlled for n‐3 fatty acids, selenium, and other variables.Methyl mercury was associated with higher systolic blood pressure and pulse pressure.Inorganic mercury was associated reduced pulse pressure.There were no significant associations of total mercury with blood pressure.

Association of selenium and copper with lipids in umbilical cord blood

Altered levels of selenium and copper have been linked with altered cardiovascular disease risk factors including changes in blood triglyceride and cholesterol levels. However, it is unclear whether this can be observed prenatally. This cross-sectional study includes 274 singleton births from 2004 to 2005 in Baltimore, Maryland. We measured umbilical cord serum selenium and copper using inductively coupled plasma mass spectrometry. We evaluated exposure levels vis-à-vis umbilical cord serum triglyceride and total cholesterol concentrations in multivariable regression models adjusted for gestational age, birth weight, maternal age, race, parity, smoking, prepregnancy body mass index, n-3 fatty acids and methyl mercury. The percent difference in triglycerides comparing those in the highest v. lowest quartile of selenium was 22.3% (95% confidence interval (CI): 7.1, 39.7). For copper this was 43.8% (95% CI: 25.9, 64.3). In multivariable models including both copper and selenium as covariates, copper, but not selenium, maintained a statistically significant association with increased triglycerides (percent difference: 40.7%, 95% CI: 22.1, 62.1). There was limited evidence of a relationship of increasing selenium with increasing total cholesterol. Our findings provide evidence that higher serum copper levels are associated with higher serum triglycerides in newborns, but should be confirmed in larger studies.