Table of Contents

Asking the Right Questions: How Early-Life Exposures Influence Later Development of Disease

Abstract

Background: In utero exposure of the fetus to a stressor can lead to disease in later life. Epigenetic mechanisms are likely mediators of later-life expression of early-life events.

Objectives: We examined the current state of understanding of later-life diseases resulting from early-life exposures in order to identify in utero and postnatal indicators of later-life diseases, develop an agenda for future research, and consider the risk assessment implications of this emerging knowledge.

Methods: This review was developed based on our participation in a National Research Council workshop titled “Use of in Utero and Postnatal Indicators to Predict Health Outcomes Later in Life: State of the Science and Research Recommendations.” We used a case study approach to highlight the later-life consequences of early-life malnutrition and arsenic exposure.

Discussion: The environmental sensitivity of the epigenome is viewed as an adaptive mechanism by which the developing organism adjusts its metabolic and homeostatic systems to suit the anticipated extrauterine environment. Inappropriate adaptation may produce a mismatch resulting in subsequent increased susceptibility to disease. A nutritional mismatch between the prenatal and postnatal environments, or early-life obesogen exposure, may explain at least some of the recent rapid increases in the rates of obesity, type 2 diabetes, and cardiovascular diseases. Early-life arsenic exposure is also associated with later-life diseases, including cardiovascular disease and cancer.

Conclusions: With mounting evidence connecting early-life exposures and later-life disease, new strategies are needed to incorporate this emerging knowledge into health protective practices.

Developmental Fluoride Neurotoxicity: A Systematic Review and Meta-Analysis

Abstract

Background: Although fluoride may cause neurotoxicity in animal models and acute fluoride poisoning causes neurotoxicity in adults, very little is known of its effects on children’s neurodevelopment.

Objective: We performed a systematic review and meta-analysis of published studies to investigate the effects of increased fluoride exposure and delayed neurobehavioral development.

Methods: We searched the MEDLINE, EMBASE, Water Resources Abstracts, and TOXNET databases through 2011 for eligible studies. We also searched the China National Knowledge Infrastructure (CNKI) database, because many studies on fluoride neurotoxicity have been published in Chinese journals only. In total, we identified 27 eligible epidemiological studies with high and reference exposures, end points of IQ scores, or related cognitive function measures with means and variances for the two exposure groups. Using random-effects models, we estimated the standardized mean difference between exposed and reference groups across all studies. We conducted sensitivity analyses restricted to studies using the same outcome assessment and having drinking-water fluoride as the only exposure. We performed the Cochran test for heterogeneity between studies, Begg’s funnel plot, and Egger test to assess publication bias, and conducted meta-regressions to explore sources of variation in mean differences among the studies.

Results: The standardized weighted mean difference in IQ score between exposed and reference populations was –0.45 (95% confidence interval: –0.56, –0.35) using a random-effects model. Thus, children in high-fluoride areas had significantly lower IQ scores than those who lived in low-fluoride areas. Subgroup and sensitivity analyses also indicated inverse associations, although the substantial heterogeneity did not appear to decrease.

Conclusions: The results support the possibility of an adverse effect of high fluoride exposure on children’s neurodevelopment. Future research should include detailed individual-level information on prenatal exposure, neurobehavioral performance, and covariates for adjustment.

Mercury, Cadmium, and Lead Levels in Human Placenta: A Systematic Review

Abstract

Background: Placental tissue may furnish information on the exposure of both mother and fetus. Mercury (Hg), cadmium (Cd), and lead (Pb) are toxicants of interest in pregnancy because they are associated with alterations in child development.

Objectives: The aim of this study was to summarize the available information regarding total Hg, Cd, and Pb levels in human placenta and possible related factors.

Methods: We performed a systematic search of PubMed/MEDLINE, EMBASE, Lilacs, OSH, and Web of Science for original papers on total Hg, Cd, or Pb levels in human placenta that were published in English or Spanish (1976–2011). Data on study design, population characteristics, collection and analysis of placenta specimens, and main results were extracted using a standardized form.

Results: We found a total of 79 papers (73 different studies). Hg, Cd, and Pb levels were reported in 24, 46, and 46 studies, respectively. Most studies included small convenience samples of healthy pregnant women. Studies were heterogeneous regarding populations selected, processing of specimens, and presentation of results. Hg concentrations > 50 ng/g were found in China (Shanghai), Japan, and the Faroe Islands. Cd levels ranged from 1.2 ng/g to 53 ng/g and were highest in the United States, Japan, and Eastern Europe. Pb showed the greatest variability, with levels ranging from 1.18 ng/g in China (Shanghai) to 500 ng/g in a polluted area of Poland.

Conclusion: The use of the placenta as a biomarker to assess heavy metals exposure is not properly developed because of heterogeneity among the studies. International standardized protocols are needed to enhance comparability and increase the usefulness of this promising tissue in biomonitoring studies.

Research

GSTM1, GSTT1, and GSTP1 Polymorphisms and Associations between Air Pollutants and Markers of Insulin Resistance in Elderly Koreans

Jin Hee Kim and
Yun-Chul Hong

Abstract

Background: Previous studies have suggested that diabetes mellitus (DM) is an outcome of exposure to air pollution, and metabolic detoxification genes affect air pollution–related outcomes.

Objectives: We evaluated associations between air pollutants and markers of insulin resistance (IR), an underlying mechanism of type 2 DM, and effect modification by GSTM1, GSTT1, and GSTP1 genotypes among elderly participants in the Korean Elderly Environmental Panel (KEEP) study.

Methods: We recruited 560 people ≥ 60 years of age and obtained blood samples from them up to three times between 2008 and 2010. For air pollution exposure, we used ambient air pollutant [i.e., particulate matter ≤ 10 µm in diameter (PM₁₀), sulfur dioxide (SO₂), ozone (O₃), and nitrogen dioxide (NO₂)] monitoring data. We measured levels of fasting glucose and insulin and derived the homeostatic model assessment (HOMA) index to assess IR. Mixed-effect models were used to estimate associations between air pollutants and IR indices on the same day or lagged up to 10 days prior, and effect modification by GSTM1, GSTT1, and GSTP1 genotypes.

Results: Interquartile range increases in PM₁₀, O₃, and NO₂ were significantly associated with IR indices, depending on the lag period. Associations were stronger among participants with a history of DM and among those with GSTM1-null, GSTT1-null, and GSTP1 AG or GG genotypes.

Conclusions: Our results suggest that PM₁₀, O₃, and NO₂ may increase IR in the elderly, and that GSTM1-null, GSTT1-null, and GSTP1 AG or GG genotypes may increase susceptibility to potential effects of ambient air pollutants on IR.

Winter Temperature Inversions and Emergency Department Visits for Asthma in Salt Lake County, Utah, 2003–2008

This article is a correction of

Abstract

Background: Winter temperature inversions—layers of air in which temperature increases with altitude—trap air pollutants and lead to higher pollutant concentrations. Previous studies have evaluated associations between pollutants and emergency department (ED) visits for asthma, but none have considered inversions as independent risk factors for ED visits for asthma.

Objective: We aimed to assess associations between winter inversions and ED visits for asthma in Salt Lake County, Utah.

Methods: We obtained electronic records of ED visits for asthma and data on inversions, weather, and air pollutants for Salt Lake County, Utah, during the winters of 2003 through 2004 to 2007 through 2008. We identified 3,425 ED visits using a primary diagnosis of asthma. We used a time-stratified case-crossover design, and conditional logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to estimate rate ratios of ED visits for asthma in relation to inversions during a 4-day lag period and prolonged inversions. We evaluated interactions between inversions and weather and pollutants.

Results: After adjusting for dew point and mean temperatures, the OR for ED visits for asthma associated with inversions 0–3 days before the visit compared with no inversions during the lag period was 1.14 (95% CI: 1.00, 1.30). The OR for each 1-day increase in the number of inversion days during the lag period was 1.03 (95% CI: 1.00, 1.07). Associations were only apparent when PM₁₀ and maximum and mean temperatures were above median levels.

Conclusions: Our results provide evidence that winter inversions are associated with increased rates of ED visits for asthma.

Associations between Nighttime Traffic Noise and Sleep: The Finnish Public Sector Study

Erratum: Halonen et al. “Associations between Nighttime Traffic Noise and Sleep: The Finnish Public Sector Study” [120:1391–1396 (2012)]

Abstract

Background: Associations between traffic noise and sleep problems have been detected in experimental studies, but population-level evidence is scarce.

Objectives: We studied the relationship between the levels of nighttime traffic noise and sleep disturbances and identified vulnerable population groups.

Methods: Noise levels of nighttime–outdoor traffic were modeled based on the traffic intensities in the cities of Helsinki and Vantaa, Finland. In these cities, 7,019 public sector employees (81% women) responded to postal surveys on sleep and health. We linked modeled outdoor noise levels to the residences of the employees who responded to the postal survey. We used logistic regression models to estimate associations of noise levels with subjectively assessed duration of sleep and symptoms of insomnia (i.e., difficulties falling asleep, waking up frequently during the night, waking up too early in the morning, nonrestorative sleep). We also used stratified models to investigate the possibility of vulnerable subgroups.

Results: For the total study population, exposure to levels of nighttime–outside (L_{night, outside}) traffic noise > 55 dB was associated with any insomnia symptom ≥ 2 nights per week [odds ratio (OR) = 1.32; 95% confidence interval (CI): 1.05, 1.65]. Among participants with higher trait anxiety scores, which we hypothesized were a proxy for noise sensitivity, the ORs for any insomnia symptom at exposures to L_{night, outside} traffic noises 50.1–55 dB and > 55 dB versus ≤ 45 dB were 1.34 (95% CI: 1.00, 1.80) and 1.61 (95% CI: 1.07, 2.42), respectively.

Conclusions: Nighttime traffic noise levels > 50 dB L_{night, outside} was associated with insomnia symptoms among persons with higher scores for trait anxiety. For the total study population, L_{night, outside} > 55 dB was positively associated with any symptoms.

Phthalate Excretion Pattern and Testicular Function: A Study of 881 Healthy Danish Men

Abstract

Background: In animals, some phthalates impair male reproductive development and function. Epidemiological studies have reported inconsistent evidence of associations between phthalates and markers of human testicular function.

Objectives: We aimed to provide estimates of the effects of phthalate exposure on reproductive hormone levels and semen quality in healthy men.

Methods: A total of 881 men gave urine, serum, and semen samples. Serum levels of testosterone, estradiol (E₂), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and inhibin-B; semen quality; and urinary concentrations of 14 phthalate metabolites, including metabolites of di(2-ethylhexyl) phthalate (DEHP) and diisononyl phthalate (DiNP), were assessed. The proportions of DEHP and DiNP excreted as their respective primary metabolites [mono(2-ethylhexyl) phthalate (MEHP) and mono-isononyl phthalate (MiNP)] were calculated and expressed as percentages (%MEHP and %MiNP, respectively).

Results: The free androgen index was 15% lower [95% confidence interval (CI): –23, –8%] for men in the highest %MiNP quartile compared to the lowest quartile (p < 0.001) after adjusting for confounders, and 9% lower (95% CI: –16, –1%) in the highest %MEHP quartile (p = 0.02). %MEHP and %MiNP were negatively associated with the ratio of testosterone/LH and testosterone/FSH. %MEHP was negatively associated with total testosterone, free testosterone, and ratio of testosterone/E₂. %MiNP was positively associated with SHBG. There was little evidence of associations between urinary phthalate metabolites or sums of phthalates with reproductive hormones or semen quality

Conclusion: Our data suggest that both testosterone production and pituitary–hypothalamic feedback may be compromised in individuals excreting a high proportion of primary metabolites of long-chained phthalates relative to the proportion of secondary metabolites.

Health Benefits from Large-Scale Ozone Reduction in the United States

Abstract

Background: Exposure to ozone has been associated with adverse health effects, including premature mortality and cardiopulmonary and respiratory morbidity. In 2008, the U.S. Environmental Protection Agency (EPA) lowered the primary (health-based) National Ambient Air Quality Standard (NAAQS) for ozone to 75 ppb, expressed as the fourth-highest daily maximum 8-hr average over a 24-hr period. Based on recent monitoring data, U.S. ozone levels still exceed this standard in numerous locations, resulting in avoidable adverse health consequences.

Objectives: We sought to quantify the potential human health benefits from achieving the current primary NAAQS standard of 75 ppb and two alternative standard levels, 70 and 60 ppb, which represent the range recommended by the U.S. EPA Clean Air Scientific Advisory Committee (CASAC).

Methods: We applied health impact assessment methodology to estimate numbers of deaths and other adverse health outcomes that would have been avoided during 2005, 2006, and 2007 if the current (or lower) NAAQS ozone standards had been met. Estimated reductions in ozone concentrations were interpolated according to geographic area and year, and concentration–response functions were obtained or derived from the epidemiological literature.

Results: We estimated that annual numbers of avoided ozone-related premature deaths would have ranged from 1,410 to 2,480 at 75 ppb to 2,450 to 4,130 at 70 ppb, and 5,210 to 7,990 at 60 ppb. Acute respiratory symptoms would have been reduced by 3 million cases and school-loss days by 1 million cases annually if the current 75-ppb standard had been attained. Substantially greater health benefits would have resulted if the CASAC-recommended range of standards (70–60 ppb) had been met.

Conclusions: Attaining a more stringent primary ozone standard would significantly reduce ozone-related premature mortality and morbidity.

Concentration–Response Function for Ozone and Daily Mortality: Results from Five Urban and Five Rural U.K. Populations

Abstract

Background: Short-term exposure to ozone has been associated with increased daily mortality. The shape of the concentration–response relationship—and, in particular, if there is a threshold—is critical for estimating public health impacts.

Objective: We investigated the concentration–response relationship between daily ozone and mortality in five urban and five rural areas in the United Kingdom from 1993 to 2006.

Methods: We used Poisson regression, controlling for seasonality, temperature, and influenza, to investigate associations between daily maximum 8-hr ozone and daily all-cause mortality, assuming linear, linear-threshold, and spline models for all-year and season-specific periods. We examined sensitivity to adjustment for particles (urban areas only) and alternative temperature metrics.

Results: In all-year analyses, we found clear evidence for a threshold in the concentration–response relationship between ozone and all-cause mortality in London at 65 µg/m³ [95% confidence interval (CI): 58, 83] but little evidence of a threshold in other urban or rural areas. Combined linear effect estimates for all-cause mortality were comparable for urban and rural areas: 0.48% (95% CI: 0.35, 0.60) and 0.58% (95% CI: 0.36, 0.81) per 10-µg/m³ increase in ozone concentrations, respectively. Seasonal analyses suggested thresholds in both urban and rural areas for effects of ozone during summer months.

Conclusions: Our results suggest that health impacts should be estimated across the whole ambient range of ozone using both threshold and nonthreshold models, and models stratified by season. Evidence of a threshold effect in London but not in other study areas requires further investigation. The public health impacts of exposure to ozone in rural areas should not be overlooked.

Rice Consumption and Urinary Arsenic Concentrations in U.S. Children

Element of Surprise? Rice as a Source of Arsenic in Children’s Diets

This article is a correction of

Abstract

Background: In adult populations, emerging evidence indicates that humans are exposed to arsenic by ingestion of contaminated foods such as rice, grains, and juice; yet little is known about arsenic exposure among children.

Objectives: Our goal was to determine whether rice consumption contributes to arsenic exposure in U.S. children.

Methods: We used data from the nationally representative National Health and Nutrition Examination Survey (NHANES) to examine the relationship between rice consumption (measured in 0.25 cups of cooked rice per day) over a 24-hr period and subsequent urinary arsenic concentration among the 2,323 children (6–17 years of age) who participated in NHANES from 2003 to 2008. We examined total urinary arsenic (excluding arsenobetaine and arsenocholine) and dimethylarsinic acid (DMA) concentrations overall and by age group: 6–11 years and 12–17 years.

Results: The median [interquartile range (IQR)] total urinary arsenic concentration among children who reported consuming rice was 8.9 μg/L (IQR: 5.3–15.6) compared with 5.5 μg/L (IQR: 3.1–8.4) among those who did not consume rice. After adjusting for potentially confounding factors, and restricting the study to participants who did not consume seafood in the preceding 24 hr, total urinary arsenic concentration increased 14.2% (95% confidence interval: 11.3, 17.1%) with each 0.25 cup increase in cooked rice consumption.

Conclusions: Our study suggests that rice consumption is a potential source of arsenic exposure in U.S. children.

450K Epigenome-Wide Scan Identifies Differential DNA Methylation in Newborns Related to Maternal Smoking during Pregnancy

Errata

Pattern of Clues: Evidence of Distinct DNA Methylation in Newborns of Smoking Women

Abstract

Background: Epigenetic modifications, such as DNA methylation, due to in utero exposures may play a critical role in early programming for childhood and adult illness. Maternal smoking is a major risk factor for multiple adverse health outcomes in children, but the underlying mechanisms are unclear.

Objective: We investigated epigenome-wide methylation in cord blood of newborns in relation to maternal smoking during pregnancy.

Methods: We examined maternal plasma cotinine (an objective biomarker of smoking) measured during pregnancy in relation to DNA methylation at 473,844 CpG sites (CpGs) in 1,062 newborn cord blood samples from the Norwegian Mother and Child Cohort Study (MoBa) using the Infinium HumanMethylation450 BeadChip (450K).

Results: We found differential DNA methylation at epigenome-wide statistical significance (p-value < 1.06 × 10^–7) for 26 CpGs mapped to 10 genes. We replicated findings for CpGs in AHRR, CYP1A1, and GFI1 at strict Bonferroni-corrected statistical significance in a U.S. birth cohort. AHRR and CYP1A1 play a key role in the aryl hydrocarbon receptor signaling pathway, which mediates the detoxification of the components of tobacco smoke. GFI1 is involved in diverse developmental processes but has not previously been implicated in responses to tobacco smoke.

Conclusions: We identified a set of genes with methylation changes present at birth in children whose mothers smoked during pregnancy. This is the first study of differential methylation across the genome in relation to maternal smoking during pregnancy using the 450K platform. Our findings implicate epigenetic mechanisms in the pathogenesis of the adverse health outcomes associated with this important in utero exposure.

Maternal Concentrations of Polyfluoroalkyl Compounds during Pregnancy and Fetal and Postnatal Growth in British Girls

Abstract

Background: Prenatal exposures to polyfluoroalkyl compounds (PFCs) may be associated with adverse changes in fetal and postnatal growth.

Objective: We explored associations of prenatal serum concentrations of perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexane sulfonate (PFHxS) with fetal and postnatal growth in girls.

Methods: We studied a sample of 447 singleton girls and their mothers participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Data on weight and length were obtained at birth and at 2, 9, and 20 months. Serum samples were obtained in 1991–1992, from mothers during pregnancy. We explored associations between prenatal PFC concentrations and weight at birth as well as longitudinal changes in weight-for-age SD scores between birth and 20 months.

Results: PFOS (median, 19.6 ng/mL), PFOA (median, 3.7 ng/mL), and PFHxS (median, 1.6 ng/mL) were detected in 100% of samples. On average, girls born to mothers with prenatal concentrations of PFOS in the upper tertile weighed 140 g less [95% confidence interval (CI): –238, –42] at birth than girls born to mothers with concentrations in the lower tertile in adjusted models. Similar patterns were seen for PFOA (–133 g; 95% CI: –237, –30) and PFHxS (–108 g; 95% CI: –206, –10). At 20 months, however, girls born to mothers with prenatal concentrations of PFOS in the upper tertile weighed 580 g more (95% CI: 301, 858) when compared with those in the lower tertile. No differences in weight were found for PFOA and PFHxS.

Conclusions: Girls with higher prenatal exposure to each of the PFCs examined were smaller at birth than those with lower exposure. In addition, those with higher exposure to PFOS were larger at 20 months.

Lactational Exposure to Polybrominated Diphenyl Ethers and Its Relation to Social and Emotional Development among Toddlers

Abstract

Background: Polybrominated diphenyl ethers (PBDEs) have been widely used as flame retardants and are ubiquitous environmental contaminants. PBDEs have been linked to adverse neurodevelopment in animals and humans.

Objectives: We investigated the association between breast milk PBDE levels and social and emotional development in toddlers.

Methods: The Pregnancy Infection and Nutrition (PIN) and PIN Babies studies followed a cohort of North Carolina pregnant women and their children through 36 months of age. Breast milk samples obtained at 3 months postpartum were analyzed for PBDEs. The Infant–Toddler Social and Emotional Assessment (ITSEA) was completed by mothers when children were approximately 30 months of age (n = 222). We assessed the relationship between breast milk concentrations of five PBDE congeners—BDEs 28, 47, 99, 100, and 153—and children’s social and emotional development, adjusting for other factors.

Results: A small, imprecise, yet consistent positive association was apparent between BDEs 47, 99, and 100 and increased externalizing behaviors, specifically activity/impulsivity behaviors. Externalizing domain T-scores ranged from 30 to 87 with a mean of 47.8. Compared with those with BDE-47 concentrations below the median, adjusted externalizing behavior domain scores were 1.6 [95% confidence interval (CI): –1.2, 4.4] and 2.8 (95% CI –0.1, 5.7) points higher for children born to women with breast milk concentrations in the 3rd and 4th quartiles, respectively. PBDEs were not associated with other social and emotional developmental domains.

Conclusions: Our results, although imprecise, suggest a subtle association between early-life PBDE exposure and increased activity/impulsivity behaviors in early childhood. Confirmation of these results is needed in other longitudinal studies.

A Population-Based Case–Control Study of Extreme Summer Temperature and Birth Defects

Abstract

Background: Although hyperthermia is a recognized animal teratogen and maternal fever has been associated with birth defects in humans, data on the relationship between high environmental temperatures and birth defects are limited.

Objective: To determine whether pregnancies are potentially vulnerable to the weather extremes anticipated with climate change, we evaluated the relationship between extreme summer temperature and the occurrence of birth defects.

Methods: We performed a population-based case–control study by linking the New York State Congenital Malformations Registry to birth certificates for the years 1992–2006. We selected nonmalformed infants from a 10% random sample of live births as controls. We assigned meteorologic data based on maternal residence at birth, summarized universal apparent temperature (UAT; degrees Fahrenheit) across the critical period of embryogenesis, and estimated adjusted odds ratios (aOR) and 95% confidence intervals (CI) with multivariable logistic regression, controlling for confounders available on the birth certificate.

Results: Among 6,422 cases and 59,328 controls that shared at least 1 week of the critical period in summer, a 5-degree increase in mean daily minimum UAT was significantly associated with congenital cataracts (aOR = 1.51; 95% CI: 1.14, 1.99). Congenital cataracts were significantly associated with all ambient temperature indicators as well: heat wave, number of heat waves, and number of days above the 90th percentile. Inconsistent associations with a subset of temperature indicators were observed for renal agenesis/hypoplasia (positive) and anophthalmia/microphthalmia and gastroschisis (negative).

Conclusions: We found positive and consistent associations between multiple heat indicators during the relevant developmental window and congenital cataracts which should be confirmed with other data sources.

Childhood Lead Poisoning Associated with Gold Ore Processing: a Village-Level Investigation—Zamfara State, Nigeria, October–November 2010

Abstract

Background: During May–June 2010, a childhood lead poisoning outbreak related to gold ore processing was confirmed in two villages in Zamfara State, Nigeria. During June–September of that year, villages with suspected or confirmed childhood lead poisoning continued to be identified in Zamfara State.

Objectives: We investigated the extent of childhood lead poisoning [≥ 1 child with a blood lead level (BLL) ≥ 10 µg/dL] and lead contamination (≥ 1 soil/dust sample with a lead level > 400 parts per million) among villages in Zamfara State and identified villages that should be prioritized for urgent interventions.

Methods: We used chain-referral sampling to identify villages of interest, defined as villages suspected of participation in gold ore processing during the previous 12 months. We interviewed villagers, determined BLLs among children < 5 years of age, and analyzed soil/dust from public areas and homes for lead.

Results: We identified 131 villages of interest and visited 74 (56%) villages in three local government areas. Fifty-four (77%) of 70 villages that completed the survey reported gold ore processing. Ore-processing villages were more likely to have ≥ 1 child < 5 years of age with lead poisoning (68% vs. 50%, p = 0.17) or death following convulsions (74% vs. 44%, p = 0.02). Soil/dust contamination and BLL ≥ 45 µg/dL were identified in ore-processing villages only [50% (p < 0.001) and 15% (p = 0.22), respectively]. The odds of childhood lead poisoning or lead contamination was 3.5 times as high in ore-processing villages than the other villages (95% confidence interval: 1.1, 11.3).

Conclusion: Childhood lead poisoning and lead contamination were widespread in surveyed areas, particularly among villages that had processed ore recently. Urgent interventions are required to reduce lead exposure, morbidity, and mortality in affected communities.

Prenatal Methylmercury, Postnatal Lead Exposure, and Evidence of Attention Deficit/Hyperactivity Disorder among Inuit Children in Arctic Québec

Abstract

Background: Prenatal exposure to methylmercury (MeHg) and polychlorinated biphenyls (PCBs) has been associated with impaired performance on attention tasks in previous studies, but the extent to which these cognitive deficits translate into behavioral problems in the classroom and attention deficit/hyperactivity disorder (ADHD) remains unknown. By contrast, lead (Pb) exposure in childhood has been associated with ADHD and disruptive behaviors in several studies.

Objectives: In this study we examined the relation of developmental exposure to MeHg, PCBs, and Pb to behavioral problems at school age in Inuit children exposed through their traditional diet.

Methods: In a prospective longitudinal study conducted in the Canadian Arctic, exposure to contaminants was measured at birth and at school age. An assessment of child behavior (n = 279; mean age = 11.3 years) was obtained from the child’s classroom teacher on the Teacher Report Form (TRF) from the Child Behavior Checklist, and the Disruptive Behavior Disorders Rating Scale (DBD).

Results: Cord blood mercury concentrations were associated with higher TRF symptom scores for attention problems and DBD scores consistent with ADHD. Current blood Pb concentrations were associated with higher TRF symptom scores for externalizing problems and with symptoms of ADHD (hyperactive-impulsive type) based on the DBD.

Conclusions: To our knowledge, this study is the first to identify an association between prenatal MeHg and ADHD symptomatology in childhood and the first to replicate previously reported associations between low-level childhood Pb exposure and ADHD in a population exposed to Pb primarily from dietary sources.

Early-Life Cadmium Exposure and Child Development in 5-Year-Old Girls and Boys: A Cohort Study in Rural Bangladesh

Abstract

Background: Cadmium is a commonly occurring toxic food contaminant, but health consequences of early-life exposure are poorly understood.

Objectives: We evaluated the associations between cadmium exposure and neurobehavioral development in preschool children.

Methods: In our population-based mother–child cohort study in rural Bangladesh, we assessed cadmium exposure in 1,305 women in early pregnancy and their children at 5 years of age by measuring concentrations in urine (U-Cd), using inductively coupled plasma mass spectrometry. Children’s IQ at 5 years of age, including Verbal (VIQ), Performance (PIQ), and Full-Scale IQ (FSIQ), were measured by Wechsler Preschool and Primary Scale of Intelligence. Behavior was assessed by the Strengths and Difficulties Questionnaire (SDQ).

Results: In multiple linear regression models, adjusted for sex, home stimulation, socioeconomic status (SES), and maternal and child characteristics, a doubling of maternal U-Cd was inversely associated with VIQ (–0.84 points; 95% confidence interval: –1.3, –0.40), PIQ (–0.64 points; –1.1, –0.18), and FSIQ (–0.80 points; –1.2, –0.39). Concurrent child U-Cd showed somewhat weaker association with VIQ and FSIQ, but not PIQ. Stratification by sex and SES indicated slightly stronger associations with PIQ and FSIQ in girls than in boys and in higher-income compared with lower-income families. Concurrent U-Cd was inversely associated with SDQ-prosocial behavior and positively associated with SDQ-difficult behavior, but associations were close to the null after adjustment. Quantile regression analysis showed similar associations across the whole range of each developmental outcome.

Conclusion: Early-life low-level cadmium exposure was associated with lower child intelligence scores in our study cohort. Further research in this area is warranted.

Adverse Health Effects of Child Labor: High Exposure to Chromium and Oxidative DNA Damage in Children Manufacturing Surgical Instruments

Metal Exposure in Child Workers: Assessing Hazards in Surgical Instrument Manufacturing Workshops

Abstract

Background: A considerable part of the worldwide production of surgical instruments takes place in Sialkot, Pakistan. Many children work in hazardous conditions in this industry.

Objective: We investigated exposure to metals and possible health effects among children working in surgical instruments manufacturing units compared with schoolchildren from the same city.

Methods: In a cross-sectional study we studied a convenience sample of 104 male children (10–14 years of age) working in surgical instruments manufacturing units and 75 male children of similar age from a school in Sialkot, Pakistan. A respiratory questionnaire was administered, spirometry was performed, and blood pressure was measured. In a spot urine sample, concentrations of metals were measured by inductively coupled plasma mass spectrometry and 8-hydroxydeoxyguanosine (8OHdG, reflecting oxidative DNA damage) by ELISA.

Results: The working children reported more asthma (10% vs. 0%; p = 0.005) and dry cough at night (36% vs. 20%; p = 0.02) than did the schoolchildren, but there were no significant differences in pulmonary function or blood pressure. The urinary concentration of chromium was 35 times higher in working children [geometric mean, 23.0 µg/L; 25th–75th percentile, 8.38–58.6] than in schoolchildren [0.66 µg/L; 0.38–1.09)], and largely in excess of the occupational Biological Exposure Index for adult workers (25 µg/L). Urinary 8-OHdG concentrations were not significantly higher in working children than in schoolchildren (19.3 vs. 17.6 µg/g creatinine, p = 0.4), but were significantly correlated with urinary nickel (r = 0.41; p < 0.0001) and with a composite index of metal exposure (r = 0.46; p < 0.0001).

Conclusions: Children working in the surgical instruments manufacturing industry had substantial exposure to several metals, especially chromium and nickel, which are established carcinogens. Exposure to nickel was associated with evidence of increased oxidative DNA damage.

Prenatal Exposure to Butylbenzyl Phthalate and Early Eczema in an Urban Cohort

Abstract

Background: Recent cross-sectional studies suggest a link between butylbenzyl phthalate (BBzP) in house dust and childhood eczema.

Objectives: We aimed to evaluate whether concentrations of monobenzyl phthalate (MBzP), the main BBzP metabolite in urine, during pregnancy are associated prospectively with eczema in young children, and whether this association varies by the child’s sensitization to indoor allergens or serological evidence of any allergies.

Methods: MBzP was measured in spot urine samples during the third trimester of pregnancy from 407 African-American and Dominican women residing in New York City in 1999–2006. Repeated questionnaires asked mothers whether their doctor ever said their child had eczema. Child blood samples at 24, 36, and 60 months of age were analyzed for total, anti-cockroach, dust mite, and mouse IgE. Relative risks (RR) were estimated with multivariable modified Poisson regression. Analyses included a multinomial logistic regression model for early- and late-onset eczema versus no eczema through 60 months of age.

Results: MBzP was detected in > 99% of samples (geometric mean = 13.6; interquartile range: 5.7–31.1 ng/mL). By 24 months, 30% of children developed eczema, with the proportion higher among African Americans (48%) than among Dominicans (21%) (p < 0.001). An interquartile range increase in log MBzP concentration was associated positively with early-onset eczema (RR = 1.52 for eczema by 24 months; 95% confidence interval: 1.21, 1.91, p = 0.0003, n = 113 reporting eczema/376 total sample), adjusting for urine specific gravity, sex, and race/ethnicity. MBzP was not associated with allergic sensitization, nor did seroatopy modify consistently the MBzP and eczema association.

Conclusions: Prenatal exposure to BBzP may influence the risk of developing eczema in early childhood.

Surrounding Greenness and Pregnancy Outcomes in Four Spanish Birth Cohorts

Abstract

Background: Green spaces have been associated with improved physical and mental health; however, the available evidence on the impact of green spaces on pregnancy is scarce.

Objectives: We investigated the association between surrounding greenness and birth weight, head circumference, and gestational age at delivery.

Methods: This study was based on 2,393 singleton live births from four Spanish birth cohorts (Asturias, Gipuzkoa, Sabadell, and Valencia) located in two regions of the Iberian Peninsula with distinct climates and vegetation patterns (2003–2008). We defined surrounding greenness as average of satellite-based Normalized Difference Vegetation Index (NDVI) (Landsat 4–5 TM data at 30 m × 30 m resolution) during 2007 in buffers of 100 m, 250 m, and 500 m around each maternal place of residence. Separate linear mixed models with adjustment for potential confounders and a random cohort effect were used to estimate the change in birth weight, head circumference, and gestational age for 1-interquartile range increase in surrounding greenness.

Results: Higher surrounding greenness was associated with increases in birth weight and head circumference [adjusted regression coefficients (95% confidence interval) of 44.2 g (20.2 g, 68.2 g) and 1.7 mm (0.5 mm, 2.9 mm) for an interquartile range increase in average NDVI within a 500-m buffer] but not gestational age. These findings were robust against the choice of the buffer size and the season of data acquisition for surrounding greenness, and when the analysis was limited to term births. Stratified analyses indicated stronger associations among children of mothers with lower education, suggesting greater benefits from surrounding greenness.

Conclusions: Our findings suggest a beneficial impact of surrounding greenness on measures of fetal growth but not pregnancy length.

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