Attention Deficit/Hyperactivity Disorder: A Focused Overview for Children’s Environmental Health Researchers

Objectives

Attention deficit/hyperactivity disorder (ADHD) is the most frequently diagnosed childhood neurobehavioral disorder. Much research has been done to identify genetic, environmental, and social risk factors for ADHD; however, we are still far from fully understanding its etiology. In this review we provide an overview of diagnostic criteria for ADHD and what is known about its biological basis. We also review the neuropsychological functions that are affected in ADHD. The goal is to familiarize the reader with the behavioral deficits that are hallmarks of ADHD and to facilitate comparisons with neurobehavioral deficits associated with environmental chemical exposures.

Data sources

Relevant literature on ADHD is reviewed, focusing in particular on meta-analyses conducted between 2004 and the present that evaluated associations between measures of neuropsychological function and ADHD in children. Meta-analyses were obtained through searches of the PubMed electronic database using the terms “ADHD,” “meta-analysis,” “attention,” “executive,” and “neuropsychological functions.” Although meta-analyses are emphasized, nonquantitative reviews are included for particular neuropsychological functions where no meta-analyses were available.

Data synthesis

The meta-analyses indicate that vigilance (sustained attention), response inhibition, and working memory are impaired in children diagnosed with ADHD. Similar but somewhat less consistent meta-analytic findings have been reported for impairments in alertness, cognitive flexibility, and planning. Additionally, the literature suggests deficits in temporal information processing and altered responses to reinforcement in children diagnosed with ADHD. Findings from brain imagining and neurochemistry studies support the behavioral findings.

Conclusions

Behavioral, neuroanatomical, and neurochemical data indicate substantial differences in attention and executive functions between children diagnosed with ADHD and non-ADHD controls. Comparisons of the neurobehavioral deficits associated with ADHD and those associated with exposures to environmental chemicals may help to identify possible environmental risk factors for ADHD and/or reveal common underlying biological mechanisms.     

Lead Exposure and Behavior among Young Children in Chennai,India

Background

Lead exposure has long been associated with deficits in IQ among children. However, few studies have assessed the impact of lead on specific domains of behavior and cognition.

Objective

We evaluated the associations between lead and different domains of neurobehavior and their relative sensitivity to lead.

Methods

We determined blood lead levels using a LeadCare instrument in 756 children 3–7 years of age attending pre- and elementary schools in Chennai, India. Anxiety, social problems, inattention, hyperactivity, and attention deficit hyperactivity disorder (ADHD), as well as executive function were assessed in children by their schoolteachers using Conners’ Teacher Rating Scales-39, Conners’ ADHD/Diagnostic and Statistical Manual for Mental Disorders, 4th Edition Scales (CADS), and the Behavior Rating Inventory of Executive Function questionnaires, with higher scores denoting worse behavior. Analyses were carried out using multivariate generalized estimating equations with comparisons of outcome Z-scores to assess the relative strengths of the associations between log-blood lead and the different domains of behavior.

Results

Mean blood lead level was 11.4 ± 5.3 μg/dL. Blood lead was associated with higher anxiety (β = 0.27, p = 0.01), social problems (β = 0.20, p = 0.02), and higher scores in the ADHD index (β = 0.17; p = 0.05). The effect estimate was highest for global executive function (β = 0.42; p< 0.001).

Conclusions

Higher blood lead levels in this population of young children is associated with increased risk of neurobehavioral deficits and ADHD, with executive function and attention being particularly vulnerable domains to the effects of lead.     

Environmental Lead Exposure and Attention Deficit/Hyperactivity Disorder Symptom Domains in a Community Sample of South Korean School-Age Children

Background

Low-level environmental exposure to lead has been associated with both reduced intelligence and symptoms of attention deficit/hyperactivity disorder (ADHD). However, few studies have estimated the association of lead and intelligence independent of ADHD, and it is not clear from previous studies whether lead is associated with both inattention and impulsivity ADHD symptoms.

Objectives

We estimated mutually adjusted associations of environmental lead exposure with both intelligence and ADHD symptoms, and associations between lead and specific ADHD-related domains.

Methods

Blood lead concentrations were measured in a general population of 1,001 children 8–11 years of age. We used multivariable linear regression models to estimate associations of blood lead concentrations with IQ scores, teacher and parent ratings of ADHD symptoms, and measures of inattention and impulsivity. Models were adjusted for demographic variables and other environmental exposures (blood levels of mercury and manganese, urinary concentrations of cotinine, phthalate metabolites, and bisphenol A).

Results

Associations of blood lead with lower IQ and higher impulsivity were robust to adjustment for a variety of covariates. When adjusted for demographic characteristics, other environmental exposures, and ADHD symptoms or IQ, a 10-fold increase in blood lead concentration was associated with lower Full-Scale IQ (–7.23; 95% CI: –13.39, –1.07) and higher parent- and teacher-rated hyperactivity/impulsivity scores (ADHD Rating Scale, 1.99; 95% CI: 0.17, 3.81 and 3.66; 95% CI: 1.18, 6.13, respectively) and commission errors (Continuous Performance Test, 12.27; 95% CI: –0.08, 24.62). Blood lead was not significantly associated with inattention in adjusted models.

Conclusions

Low-level lead exposure was adversely associated with intelligence in school-age children independent of ADHD, and environmental lead exposure was selectively associated with impulsivity among the clinical features of ADHD.

Citation

Hong SB, Im MH, Kim JW, Park EJ, Shin MS, Kim BN, Yoo HJ, Cho IH, Bhang SY, Hong YC, Cho SC. 2015. Environmental lead exposure and attention deficit/hyperactivity disorder symptom domains in a community sample of South Korean school-age children. Environ Health Perspect 123:271–276; http://dx.doi.org/10.1289/ehp.1307420     

Environmental Exposure,Obesity, and Parkinson’s Disease: Lessons from Fat and Old Worms

Background

A common link has been exposed, namely, that metal exposure plays a role in obesity and in Parkinson’s disease (PD). This link may help to elucidate mechanisms of neurotoxicity.

Objective

We reviewed the utility of the nematode, Caenorhabditis elegans, as a model organism to study neurodegeneration in obesity and Parkinson’s disease (PD), with an emphasis on the neurotransmitter, dopamine (DA).

Data sources

A PubMed literature search was performed using the terms “obesity” and any of the following: “C. elegans,” “central nervous system,” “neurodegeneration,” “heavy metals,” “dopamine” or “Parkinson’s disease.” We reviewed the identified studies, including others cited therein, to summarize the current evidence of neurodegeneration in obesity and PD, with an emphasis on studies carried out in C. elegans and environmental toxins in the etiology of both diseases.

Data extraction and data synthesis

Heavy metals and DA have both been linked to diet-induced obesity, which has led to the notion that the mechanism of environmentally induced neurodegeneration in PD may also apply to obesity. C. elegans has been instrumental in expanding our mechanism-based knowledge of PD, and this species is emerging as a good model of obesity. With well-established toxicity and neurogenetic assays, it is now feasible to explore the putative link between metal-and chemical-induced neurodegeneration.

Conclusions

One side effect of an aging population is an increase in the prevalence of obesity, metabolic disorders, and neurodegenerative orders, diseases that are likely to co-occur. Environmental toxins, especially heavy metals, may prove to be a previously neglected part of the puzzle.     

Prenatal and Postnatal Tobacco Exposure and Behavioral Problems in 10-Year-Old Children: Results from the GINI-plus Prospective Birth Cohort Study

Background

Prenatal and postnatal tobacco exposure have been reported to be associated with behavioral problems. However, the magnitude of the association with tobacco exposure at specific periods of exposure is unclear.

Objective

We assessed the relative risk of behavioral problems in children who had been exposed to tobacco smoke in utero and postnatally.

Methods

We analyzed data from a prospective birth cohort study in two cities in Germany: the German Infant Nutrition Intervention. Our sample included 5,991 children born between 1995 and 1998 as well as their parents. We measured behavioral problems using the Strength and Difficulties Questionnaire (SDQ) at follow-up 10 years after birth. According to prespecified SDQ cutoff values, children were classified as “normal,” “borderline,” or “abnormal” according to the subscales “emotional symptoms,” “conduct problems,” “hyperactivity/inattention,” “peer-relationship problems,” and a total difficulties score. Smoke exposure and further covariates were assessed using parent questionnaires.

Results

Compared with children not exposed to tobacco smoke, children exposed both pre- and postnatally to tobacco smoke had twice the estimated risk [95% confidence interval (CI), 1.4–3.1] of being classified as abnormal according to the total difficulties score of the SDQ at 10 years of age. Children who were only prenatally exposed had a 90% higher relative risk (95% CI, 0.9–4.0), whereas children who were only postnatally exposed had a 30% higher relative risk (95% CI, 0.9–1.9). These results could not be explained by confounding by parental education, father’s employment, child’s time spent in front of computer or television screen, being a single father or mother, or mother’s age.

Conclusions

Prenatal exposure to tobacco smoke is associated with behavioral problems in school-age children. Although our findings do not preclude the influence of postnatal exposure, prenatal exposure seems to be more important.     

A Growing Role for Gender Analysis in Air Pollution Epidemiology

Objective

Epidemiologic studies of air pollution effects on respiratory health report significant modification by sex, although results are not uniform. Importantly, it remains unclear whether modifications are attributable to socially derived gendered exposures, to sex-linked physiological differences, or to some interplay thereof. Gender analysis, which aims to disaggregate social from biological differences between males and females, may help to elucidate these possible sources of effect modification.

Data sources and data extraction

A PubMed literature search was performed in July 2009, using the terms “respiratory” and any of “sex” or “gender” or “men and women” or “boys and girls” and either “PM_2.5” (particulate matter ≥ 2.5 μm in aerodynamic diameter) or “NO₂” (nitrogen dioxide). I reviewed the identified studies, and others cited therein, to summarize current evidence of effect modification, with attention to authors’ interpretation of observed differences. Owing to broad differences in exposure mixes, outcomes, and analytic techniques, with few studies examining any given combination thereof, meta-analysis was not deemed appropriate at this time.

Data synthesis

More studies of adults report stronger effects among women, particularly for older persons or where using residential exposure assessment. Studies of children suggest stronger effects among boys in early life and among girls in later childhood.

Conclusions

The qualitative review describes possible sources of difference in air pollution response between women and men, which may vary by life stage, coexposures, hormonal status, or other factors. The sources of observed effect modifications remain unclear, although gender analytic approaches may help to disentangle gender and sex differences in pollution response. A framework for incorporating gender analysis into environmental epidemiology is offered, along with several potentially useful methods from gender analysis.     

A Workflow to Investigate Exposure and Pharmacokinetic Influences on High-Throughput in Vitro Chemical Screening Based on Adverse Outcome Pathways

Background

Adverse outcome pathways (AOPs) link adverse effects in individuals or populations to a molecular initiating event (MIE) that can be quantified using in vitro methods. Practical application of AOPs in chemical-specific risk assessment requires incorporation of knowledge on exposure, along with absorption, distribution, metabolism, and excretion (ADME) properties of chemicals.

Objectives

We developed a conceptual workflow to examine exposure and ADME properties in relation to an MIE. The utility of this workflow was evaluated using a previously established AOP, acetylcholinesterase (AChE) inhibition.

Methods

Thirty chemicals found to inhibit human AChE in the ToxCast™ assay were examined with respect to their exposure, absorption potential, and ability to cross the blood–brain barrier (BBB). Structures of active chemicals were compared against structures of 1,029 inactive chemicals to detect possible parent compounds that might have active metabolites.

Results

Application of the workflow screened 10 “low-priority” chemicals of 30 active chemicals. Fifty-two of the 1,029 inactive chemicals exhibited a similarity threshold of ≥ 75% with their nearest active neighbors. Of these 52 compounds, 30 were excluded due to poor absorption or distribution. The remaining 22 compounds may inhibit AChE in vivo either directly or as a result of metabolic activation.

Conclusions

The incorporation of exposure and ADME properties into the conceptual workflow eliminated 10 “low-priority” chemicals that may otherwise have undergone additional, resource-consuming analyses. Our workflow also increased confidence in interpretation of in vitro results by identifying possible “false negatives.”

Citation

Phillips MB, Leonard JA, Grulke CM, Chang DT, Edwards SW, Brooks R, Goldsmith MR, El-Masri H, Tan YM. 2016. A workflow to investigate exposure and pharmacokinetic influences on high-throughput in vitro chemical screening based on adverse outcome pathways. Environ Health Perspect 124:53–60; http://dx.doi.org/10.1289/ehp.1409450     

Neurobehavioral Deficits and Increased Blood Pressure in School-Age Children Prenatally Exposed to Pesticides

Background

The long-term neurotoxicity risks caused by prenatal exposures to pesticides are unclear, but a previous pilot study of Ecuadorian school children suggested that blood pressure and visuospatial processing may be vulnerable.

Objectives

In northern Ecuador, where floriculture is intensive and relies on female employment, we carried out an intensive cross-sectional study to assess children’s neurobehavioral functions at 6–8 years of age.

Methods

We examined all 87 children attending two grades in the local public school with an expanded battery of neurobehavioral tests. Information on pesticide exposure during the index pregnancy was obtained from maternal interview. The children’s current pesticide exposure was assessed from the urinary excretion of organophosphate metabolites and erythrocyte acetylcholine esterase activity.

Results

Of 84 eligible participants, 35 were exposed to pesticides during pregnancy via maternal occupational exposure, and 23 had indirect exposure from paternal work. Twenty-two children had detectable current exposure irrespective of their prenatal exposure status. Only children with prenatal exposure from maternal greenhouse work showed consistent deficits after covariate adjustment, which included stunting and socioeconomic variables. Exposure-related deficits were the strongest for motor speed (Finger Tapping Task), motor coordination (Santa Ana Form Board), visuospatial performance (Stanford-Binet Copying Test), and visual memory (Stanford-Binet Copying Recall Test). These associations corresponded to a developmental delay of 1.5–2 years. Prenatal pesticide exposure was also significantly associated with an average increase of 3.6 mmHg in systolic blood pressure and a slight decrease in body mass index of 1.1 kg/m². Inclusion of the pilot data strengthened these results.

Conclusions

These findings support the notion that prenatal exposure to pesticides—at levels not producing adverse health outcomes in the mother—can cause lasting adverse effects on brain development in children. Pesticide exposure therefore may contribute to a “silent pandemic” of developmental neurotoxicity.     

Self-Reported Truck Traffic on the Street of Residence and Symptoms of Asthma and Allergic Disease: A Global Relationship in ISAAC Phase 3

Background

Associations between traffic pollution on the street of residence and a range of respiratory and allergic outcomes in children have been reported in developed countries, but little is known about such associations in developing countries.

Methods

The third phase of the International Study of Asthma and Allergies in Childhood (ISAAC) was carried out in 13- to 14-year-old and 6- to 7-year-old children across the world. A question about frequency of truck traffic on the street of residence was included in an additional questionnaire. We investigated the association between self-reported truck traffic on the street of residence and symptoms of asthma, rhinoconjunctivitis, and eczema with logistic regression. Adjustments were made for sex, region of the world, language, gross national income, and 10 other subject-specific covariates.

Results

Frequency of truck traffic on the street of residence was positively associated with the prevalence of symptoms of asthma, rhinoconjunctivitis, and eczema with an exposure–response relationship. Odds ratios (95% confidence intervals) for “current wheeze” and “almost the whole day” versus “never” truck traffic were 1.35 (1.23–1.49) for 13- to 14-year-olds and 1.35 (1.22–1.48) for 6- to 7-year-olds.

Conclusions

Higher exposure to self-reported truck traffic on the street of residence is associated with increased reports of symptoms of asthma, rhinitis, and eczema in many locations in the world. These findings require further investigation in view of increasing exposure of the world’s children to traffic.     

Biological Monitoring for Depleted Uranium Exposure in U.S. Veterans

Background

As part of an ongoing medical surveillance program for U.S. veterans exposed to depleted uranium (DU), biological monitoring of urine uranium (U) concentrations is offered to any veteran of the Gulf War and those serving in more recent conflicts (post-Gulf War veterans).

Objectives

Since a previous report of surveillance findings in 2004, an improved methodology for determination of the isotopic ratio of U in urine (²³⁵U:²³⁸U) has been developed and allows for more definitive evaluation of DU exposure. This report updates previous findings.

Methods

Veterans provide a 24-hr urine specimen and complete a DU exposure questionnaire. Specimens are sent to the Baltimore Veterans Affairs Medical Center for processing. Uranium concentration and isotopic ratio are measured using ICP-MS at the Armed Forces Institute of Pathology.

Results

Between January 2003 and June 2008, we received 1,769 urine specimens for U analysis. The mean urine U measure was 0.009 μg U/g creatinine. Mean urine U concentrations for Gulf War and post-Gulf War veterans were 0.008 and 0.009 μg U/g creatinine, respectively. Only 3 of the 1,700 (0.01%) specimens for which we completed isotopic determination showed evidence of DU. Exposure histories confirmed that these three individuals had been involved in “friendly fire” incidents involving DU munitions or armored vehicles.

Conclusions

No urine U measure with a “depleted” isotopic signature has been detected in U.S. veterans without a history of retained DU embedded fragments from previous injury. These findings suggest that future DU-related health harm is unlikely in veterans without DU fragments.     

Do TETRA (Airwave) Base Station Signals Have a Short-Term Impact on Health and Well-Being? A Randomized Double-Blind Provocation Study

Background

“Airwave” is the new communication system currently being rolled out across the United Kingdom for the police and emergency services, based on the Terrestrial Trunked Radio Telecommunications System (TETRA). Some police officers have complained about skin rashes, nausea, headaches, and depression as a consequence of using their Airwave handsets. In addition, a small subgroup in the population self-report being sensitive to electromagnetic fields (EMFs) in general.

Objectives

We conducted a randomized double-blind provocation study to establish whether short-term exposure to a TETRA base station signal has an impact on the health and well-being of individuals with self-reported “electrosensitivity” and of participants who served as controls.

Methods

Fifty-one individuals with self-reported electrosensitivity and 132 age- and sex-matched controls participated in an open provocation test; 48 sensitive and 132 control participants went on to complete double-blind tests in a fully screened semianechoic chamber. Heart rate, skin conductance, and blood pressure readings provided objective indices of short-term physiological response. Visual analog scales and symptom scales provided subjective indices of well-being.

Results

We found no differences on any measure between TETRA and sham (no signal) under double-blind conditions for either controls or electrosensitive participants, and neither group could detect the presence of a TETRA signal at rates greater than chance (50%). When conditions were not double blind, however, the self-reported electrosensitive individuals did report feeling worse and experienced more severe symptoms during TETRA compared with sham.

Conclusions

Our findings suggest that the adverse symptoms experienced by electrosensitive individuals are due to the belief of harm from TETRA base stations rather than to the low-level EMF exposure itself.     

Maternal Bisphenol A Exposure Promotes the Development of Experimental Asthma in Mouse Pups

Background

We recently reported that various environmental estrogens induce mast cell degranulation and enhance IgE-mediated release of allergic mediators in vitro.

Objectives

We hypothesized that environmental estrogens would enhance allergic sensitization as well as bronchial inflammation and responsiveness. To test this hypothesis, we exposed fetal and neonatal mice to the common environmental estrogen bisphenol A (BPA) via maternal loading and assessed the pups’ response to allergic sensitization and bronchial challenge.

Methods

Female BALB/c mice received 10 μg/mL BPA in their drinking water from 1 week before impregnation to the end of the study. Neonatal mice were given a single 5 μg intraperitoneal dose of ovalbumin (OVA) with aluminum hydroxide on postnatal day 4 and 3% OVA by nebulization for 10 min on days 13, 14, and 15. Forty-eight hours after the last nebulization, we assessed serum IgE antibodies to OVA by enzyme-linked immunosorbent assay (ELISA) and airway inflammation and hyperresponsiveness by enumerating eosinophils in bronchoalveolar lavage fluid, whole-body barometric plethysmography, and a forced oscillation technique.

Results

Neonates from BPA-exposed mothers responded to this “suboptimal” sensitization with higher serum IgE anti-OVA concentrations compared with those from unexposed mothers (p < 0.05), and eosinophilic inflammation in their airways was significantly greater. Airway responsiveness of the OVA-sensitized neonates from BPA-treated mothers was enhanced compared with those from unexposed mothers (p < 0.05).

Conclusions

Perinatal exposure to BPA enhances allergic sensitization and bronchial inflammation and responsiveness in a susceptible animal model of asthma.     

A Unified Probabilistic Framework for Dose–Response Assessment of Human Health Effects

Background

When chemical health hazards have been identified, probabilistic dose–response assessment (“hazard characterization”) quantifies uncertainty and/or variability in toxicity as a function of human exposure. Existing probabilistic approaches differ for different types of endpoints or modes-of-action, lacking a unifying framework.

Objectives

We developed a unified framework for probabilistic dose–response assessment.

Methods

We established a framework based on four principles: a) individual and population dose responses are distinct; b) dose–response relationships for all (including quantal) endpoints can be recast as relating to an underlying continuous measure of response at the individual level; c) for effects relevant to humans, “effect metrics” can be specified to define “toxicologically equivalent” sizes for this underlying individual response; and d) dose–response assessment requires making adjustments and accounting for uncertainty and variability. We then derived a step-by-step probabilistic approach for dose–response assessment of animal toxicology data similar to how nonprobabilistic reference doses are derived, illustrating the approach with example non-cancer and cancer datasets.

Results

Probabilistically derived exposure limits are based on estimating a “target human dose” (HD_M^I), which requires risk management–informed choices for the magnitude (M) of individual effect being protected against, the remaining incidence (I) of individuals with effects ≥ M in the population, and the percent confidence. In the example datasets, probabilistically derived 90% confidence intervals for HD_M^I values span a 40- to 60-fold range, where I = 1% of the population experiences ≥ M = 1%–10% effect sizes.

Conclusions

Although some implementation challenges remain, this unified probabilistic framework can provide substantially more complete and transparent characterization of chemical hazards and support better-informed risk management decisions.

Citation

Chiu WA, Slob W. 2015. A unified probabilistic framework for dose–response assessment of human health effects. Environ Health Perspect 123:1241–1254; http://dx.doi.org/10.1289/ehp.1409385     

Attention Deficit/Hyperactivity Disorder and Childhood Autism in Association with Prenatal Exposure to Perfluoroalkyl Substances: A Nested Case–Control Study in the Danish National Birth Cohort

Background:

Perfluoroalkyl substances (PFASs) are persistent pollutants found to be endocrine disruptive and neurotoxic in animals. Positive correlations between PFASs and neurobehavioral problems in children were reported in cross-sectional data, but findings from prospective studies are limited.

Objectives:

We investigated whether prenatal exposure to PFASs is associated with attention deficit/hyperactivity disorder (ADHD) or childhood autism in children.

Methods:

Among 83,389 mother–child pairs enrolled in the Danish National Birth Cohort during 1996–2002, we identified 890 ADHD cases and 301 childhood autism cases from the Danish National Hospital Registry and the Danish Psychiatric Central Registry. From this cohort, we randomly selected 220 cases each of ADHD and autism, and we also randomly selected 550 controls frequency matched by child’s sex. Sixteen PFASs were measured in maternal plasma collected in early or mid-pregnancy. We calculated risk ratios (RRs) using generalized linear models, taking into account sampling weights.

Results:

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were detected in all samples; four other PFASs were quantified in ≥ 90% of the samples. We did not find consistent evidence of associations between mother’s PFAS plasma levels and ADHD [per natural log nanograms per milliliter increase: PFOS RR = 0.87 (95% CI: 0.74, 1.02); PFOA RR = 0.98 (95% CI: 0.82, 1.16)] or autism [per natural log nanograms per milliliter increase: PFOS RR = 0.92 (95% CI: 0.69, 1.22); PFOA RR = 0.98 (95% CI: 0.73, 1.31)]. We found positive as well as negative associations between higher PFAS quartiles and ADHD in models that simultaneously adjusted for all PFASs, but these estimates were imprecise.

Conclusions:

In this study we found no consistent evidence to suggest that prenatal PFAS exposure increases the risk of ADHD or childhood autism in children.

Citation:

Liew Z, Ritz B, von Ehrenstein OS, Bech BH, Nohr EA, Fei CY, Bossi R, Henriksen TB, Bonefeld-Jørgensen EC, Olsen J. 2015. Attention deficit/hyperactivity disorder and childhood autism in association with prenatal exposure to perfluoroalkyl substances: a nested case–control study in the Danish National Birth Cohort. Environ Health Perspect 123:367–373; http://dx.doi.org/10.1289/ehp.1408412     

Urinary Bisphenol A Levels during Pregnancy and Risk of Preterm Birth

Background

Preterm birth (PTB), a leading cause of infant mortality and morbidity, has a complex etiology with a multitude of interacting causes and risk factors. The role of environmental contaminants, particularly bisphenol A (BPA), is understudied with regard to PTB.

Objectives

In the present study we examined the relationship between longitudinally measured BPA exposure during gestation and PTB.

Methods

A nested case–control study was performed from women enrolled in a prospective birth cohort study at Brigham and Women’s Hospital in Boston, Massachusetts, during 2006–2008. Urine samples were analyzed for BPA concentrations at a minimum of three time points during pregnancy on 130 cases of PTB and 352 randomly assigned controls. Clinical classifications of PTB were defined as “spontaneous,” which was preceded by spontaneous preterm labor or preterm premature rupture of membranes, or “placental,” which was preceded by preeclampsia or intrauterine growth restriction.

Results

Geometric mean concentrations of BPA did not differ significantly between cases and controls. In adjusted models, urinary BPA averaged across pregnancy was not significantly associated with PTB. When examining clinical classifications of PTB, urinary BPA late in pregnancy was significantly associated with increased odds of delivering a spontaneous PTB. After stratification on infant’s sex, averaged BPA exposure during pregnancy was associated with significantly increased odds of being delivered preterm among females, but not males.

Conclusions

These results provide little evidence of a relationship between BPA and prematurity, though further research may be warranted given the generalizability of participant recruitment from a tertiary teaching hospital, limited sample size, and significant associations among females and within the clinical subcategories of PTB.

Citation

Cantonwine DE, Ferguson KK, Mukherjee B, McElrath TF, Meeker JD. 2015. Urinary bisphenol A levels during pregnancy and risk of preterm birth. Environ Health Perspect 123:895–901; http://dx.doi.org/10.1289/ehp.1408126     

Exposure to Polyfluoroalkyl Chemicals and Attention Deficit/Hyperactivity Disorder in U.S. Children 12–15 Years of Age

Background

Polyfluoroalkyl chemicals (PFCs) have been widely used in consumer products. Exposures in the United States and in world populations are widespread. PFC exposures have been linked to various health impacts, and data in animals suggest that PFCs may be potential developmental neurotoxicants.

Objectives

We evaluated the associations between exposures to four PFCs and parental report of diagnosis of attention deficit/hyperactivity disorder (ADHD).

Methods

Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 1999–2000 and 2003–2004 for children 12–15 years of age. Parental report of a previous diagnosis by a doctor or health care professional of ADHD in the child was the primary outcome measure. Perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) levels were measured in serum samples from each child.

Results

Parents reported that 48 of 571 children included in the analysis had been diagnosed with ADHD. The adjusted odds ratio (OR) for parentally reported ADHD in association with a 1-μg/L increase in serum PFOS (modeled as a continuous predictor) was 1.03 [95% confidence interval (CI), 1.01–1.05]. Adjusted ORs for 1-μg/L increases in PFOA and PFHxS were also statistically significant (PFOA: OR = 1.12; 95% CI, 1.01–1.23; PFHxS: OR = 1.06; 95% CI, 1.02–1.11), and we observed a nonsignificant positive association with PFNA (OR = 1.32; 95% CI, 0.86–2.02).

Conclusions

Our results, using cross-sectional data, are consistent with increased odds of ADHD in children with higher serum PFC levels. Given the extremely prevalent exposure to PFCs, follow-up of these data with cohort studies is needed.     

Association of Traffic-Related Air Pollution with Children’s Neurobehavioral Functions in Quanzhou,China

Background

With the increase of motor vehicles, ambient air pollution related to traffic exhaust has become an important environmental issue in China. Because of their fast growth and development, children are more susceptible to ambient air pollution exposure. Many chemicals from traffic exhaust, such as carbon monoxide, nitrogen dioxide, and lead, have been reported to show adverse effects on neurobehavioral functions. Several studies in China have suggested that traffic exhaust might affect neurobehavioral functions of adults who have occupational traffic exhaust exposure. However, few data have been reported on the effects on neurobehavioral function in children.

Objectives

The objective of this study was to explore the association between traffic-related air pollution exposure and its effects on neurobehavioral function in children.

Methods

This field study was conducted in Quanzhou, China, where two primary schools were chosen based on traffic density and monitoring data of ambient air pollutants. School A was located in a clear area and school B in a polluted area. We monitored NO₂ and particulate matter with aerodynamic diameter ≤ 10 μm as indicators for traffic-related air pollution on the campuses and in classrooms for 2 consecutive days in May 2005. The children from second grade (8–9 years of age) and third grade (9–10 years of age) of the two schools (n = 928) participated in a questionnaire survey and manual-assisted neurobehavioral testing. We selected 282 third-grade children (school A, 136; school B, 146) to participate in computer-assisted neurobehavioral testing. We conducted the fieldwork between May and June 2005. We used data from 861 participants (school A, 431; school B, 430) with manual neurobehavioral testing and from all participants with computerized testing for data analyses.

Results

Media concentrations of NO₂ in school A and school B campus were 7 μg/m³ and 36 μg/m³, respectively (p < 0.05). The ordinal logistic regression analyses showed that, after controlling the potential confounding factors, participants living in the polluted area showed poor performance on all testing; differences in results for six of nine tests (66.7%) achieved statistical significance: Visual Simple Reaction Time with preferred hand and with nonpreferred hand, Continuous Performance, Digit Symbol, Pursuit Aiming, and Sign Register.

Conclusion

We found a significant relationship between chronic low-level traffic-related air pollution exposure and neurobehavioral function in exposed children. More studies are needed to explore the effects of traffic exhaust on neurobehavioral function and development.     

Childhood Lead Exposure After the Phaseout of Leaded Gasoline: An Ecological Study of School-Age Children in Kampala,Uganda

Background

Tetraethyl lead was phased out of gasoline in Uganda in 2005. Recent mitigation of an important source of lead exposure suggests examination and re-evaluation of the prevalence of childhood lead poisoning in this country. Ongoing concerns persist about exposure from the Kiteezi landfill in Kampala, the country’s capital.

Objectives

We determined blood lead distributions among Kampala schoolchildren and identified risk factors for elevated blood lead levels (EBLLs; ≥ 10 μg/dL).

Analytical approach

Using a stratified, cross-sectional design, we obtained blood samples, questionnaire data, and soil and dust samples from the homes and schools of 163 4- to 8-year-old children representing communities with different risks of exposure.

Results

The mean blood lead level (BLL) was 7.15 μg/dL; 20.5% of the children were found to have EBLL. Multivariable analysis found participants whose families owned fewer household items, ate canned food, or used the community water supply as their primary water source to have higher BLLs and likelihood of EBLLs. Distance < 0.5 mi from the landfill was the factor most strongly associated with increments in BLL (5.51 μg/dL, p < 0.0001) and likelihood of EBLL (OR = 4.71, p = 0.0093). Dust/soil lead was not significantly predictive of BLL/EBLL.

Conclusions

Lead poisoning remains highly prevalent among school-age children in Kampala. Confirmatory studies are needed, but further efforts are indicated to limit lead exposure from the landfill, whether through water contamination or through another mechanism. Although African nations are to be lauded for the removal of lead from gasoline, this study serves as a reminder that other sources of exposure to this potent neurotoxicant merit ongoing attention.     

Organophosphate pesticide exposure and attention in young Mexican-American children: the CHAMACOS study

Background

Exposure to organophosphate (OP) pesticides, well-known neurotoxicants, has been associated with neurobehavioral deficits in children.

Objectives

We investigated whether OP exposure, as measured by urinary dialkyl phosphate (DAP) metabolites in pregnant women and their children, was associated with attention-related outcomes among Mexican-American children living in an agricultural region of California.

Methods

Children were assessed at ages 3.5 years (n = 331) and 5 years (n = 323). Mothers completed the Child Behavior Checklist (CBCL). We administered the NEPSY-II visual attention subtest to children at 3.5 years and Conners’ Kiddie Continuous Performance Test (K-CPT) at 5 years. The K-CPT yielded a standardized attention deficit/hyperactivity disorder (ADHD) Confidence Index score. Psychometricians scored behavior of the 5-year-olds during testing using the Hillside Behavior Rating Scale.

Results

Prenatal DAPs (nanomoles per liter) were nonsignificantly associated with maternal report of attention problems and ADHD at age 3.5 years but were significantly related at age 5 years [CBCL attention problems: β = 0.7 points; 95% confidence interval (CI), 0.2–1.2; ADHD: β = 1.3; 95% CI, 0.4–2.1]. Prenatal DAPs were associated with scores on the K-CPT ADHD Confidence Index > 70th percentile [odds ratio (OR) = 5.1; 95% CI, 1.7–15.7] and with a composite ADHD indicator of the various measures (OR = 3.5; 95% CI, 1.1–10.7). Some outcomes exhibited evidence of effect modification by sex, with associations found only among boys. There was also limited evidence of associations between child DAPs and attention.

Conclusions

In utero DAPs and, to a lesser extent, postnatal DAPs were associated adversely with attention as assessed by maternal report, psychometrician observation, and direct assessment. These associations were somewhat stronger at 5 years than at 3.5 years and were stronger in boys.     

Bootstrap-after-Bootstrap Model Averaging for Reducing Model Uncertainty in Model Selection for Air Pollution Mortality Studies

Background

Concerns have been raised about findings of associations between particulate matter (PM) air pollution and mortality that have been based on a single “best” model arising from a model selection procedure, because such a strategy may ignore model uncertainty inherently involved in searching through a set of candidate models to find the best model. Model averaging has been proposed as a method of allowing for model uncertainty in this context.

Objectives

To propose an extension (double BOOT) to a previously described bootstrap model-averaging procedure (BOOT) for use in time series studies of the association between PM and mortality. We compared double BOOT and BOOT with Bayesian model averaging (BMA) and a standard method of model selection [standard Akaike’s information criterion (AIC)].

Method

Actual time series data from the United States are used to conduct a simulation study to compare and contrast the performance of double BOOT, BOOT, BMA, and standard AIC.

Results

Double BOOT produced estimates of the effect of PM on mortality that have had smaller root mean squared error than did those produced by BOOT, BMA, and standard AIC. This performance boost resulted from estimates produced by double BOOT having smaller variance than those produced by BOOTand BMA.

Conclusions

Double BOOT is a viable alternative to BOOT and BMA for producing estimates of the mortality effect of PM.