A multi-environmental source approach to explore associations between metals exposure and olfactory identification among school-age children residing in northern Italy.

BACKGROUND: Metal exposures can adversely impact olfactory function. Few studies have examined this association in children. Further, metal exposure occurs as a mixture, yet previous studies of metal-associated olfactory dysfunction only examined individual metals. Preventing olfactory dysfunctions can improve quality of life and prevent neurodegenerative diseases with long-term health implications. OBJECTIVE: We aimed to test the association between exposure to a mixture of 12 metals measured in environmental sources and olfactory function among children and adolescents residing in the industrialized province of Brescia, Italy. METHODS: We enrolled 130 children between 6 and 13 years old (51.5% females) and used the "Sniffin' Sticks" test to measure olfactory performance in identifying smells. We used a portable X-ray fluorescence instrument to determine concentrations of metals (arsenic (As), calcium, cadmium (Cd), chromium, copper, iron, manganese, lead (Pb), antimony, titanium, vanadium and zinc) in outdoor and indoor deposited dust and soil samples collected from participants' households. We used an extension of weighted quantile sum (WQS) regression to test the association between exposure to metal mixtures in multiple environmental media and olfactory function adjusting for age, sex, socio-economic status, intelligence quotient and parents' smoking status. RESULTS: A higher multi-source mixture was significantly associated with a reduced Sniffin' Sticks identification score (ß = -0.228; 95% CI -0.433, -0.020). Indoor dust concentrations of Pb, Cd and As provided the strongest contributions to this association (13.8%, 13.3% and 10.1%, respectively). The metal mixture in indoor dust contributed more (for 8 metals out of 12) to the association between metals and olfactory function compared to soil or outdoor dust. IMPACT STATEMENT: Among a mixture of 12 metals measured in three different environmental sources (soil, outdoor and indoor dust), we identified Pb, Cd and As measured in indoor dust as the main contributors to reduced olfactory function in children and adolescents residing in an industrialized area. Exposure to indoor pollution can be effectively reduced through individual and public health interventions allowing to prevent the deterioration of olfactory functions. Moreover, the identification of the factors that can deteriorate olfactory functions can be a helpful instrument to improve quality of life and prevent neurodegenerative diseases as long-term health implications.

Using the delayed spatial alternation task to assess environmentally associated changes in working memory in very young children.

BACKGROUND: Working memory (WM) is critical for problem solving and reasoning. Beginning in infancy, children show WM capacity increasing with age but there are few validated tests of WM in very young children. Because rapid brain development may increase susceptibility to adverse impacts of prenatal neurotoxicant exposure, such as lead, tests of WM in very young children would help to delineate onset of developmental problems and windows of susceptibility. PURPOSE: Our objective was to assess the feasibility of administering a Delayed Spatial Alternation Task (DSAT) to measure WM among 18- and 24-month old children enrolled in an ongoing longitudinal birth cohort study and compare DSAT performance with age and general cognitive development. We further explored whether prenatal lead exposure impacted DSAT performance. METHODS: We assessed 457 mother-child pairs participating in the Programming Research in Obesity, GRowth, Environment and Social Stressors (PROGRESS) Study in Mexico City. The DSAT and Bayley Scales of Infant Development (BSID-III) were administered at 18- and 24-months. Lead was measured in maternal blood collected during pregnancy (MBPb) and in a subsample of children at 24-months (CBPb). We regressed DSAT measures on MBPb and CBPb, child sex, and maternal age, education, socioeconomic status, and household smoking. We compared DSAT performance to BSID-III performance with adjusted residuals. RESULTS: 24-month children perform better on the DSAT than 18-month children; 24-month subjects reached a higher level on the DSAT (3.3 (0.86) vs. 2.4 (0.97), p < 0.01), and had a higher number of correct responses (20.3 vs. 17.2, p < 0.01). In all DSAT parameters, females performed better than males. Maternal education predicted better DSAT performance; household smoking predicted worse DSAT performance. A higher number of correct responses was associated with higher BSID-III Cognitive scales at 18 months (r = 0.20, p < 0.01) and 24 months (r = 0.27, p < 0.01). MBPb and CPBb did not significantly predict DSAT performance. CONCLUSION: Improved performance on the DSAT with increasing age, the positive correlation with the BSID-III cognitive and language scales and the correlation with common sociodemographic predictors of neurodevelopment demonstrate the validity of the DSAT as a test of infant development.

Functional connectivity of the reading network is associated with prenatal polybrominated diphenyl ether concentrations in a community sample of 5 year-old children: A preliminary study.

Genetic factors explain 60 percent of variance in reading disorder. Exposure to neurotoxicants, including polybrominated diphenyl ethers (PBDEs), may be overlooked risk factors for reading problems. We used resting-state functional magnetic resonance imaging (rs-fMRI) to examine associations between prenatal PBDE concentrations and functional connectivity of a reading-related network (RN) in a community sample of 5-year-old children (N = 33). Maternal serum PBDE concentrations (∑PBDE) were measured at 12.2 ±â€¯2.8 weeks gestation (mean ±â€¯SD). The RN was defined by 12 regions identified in prior task-based fMRI meta-analyses; global efficiency (GE) was used to measure network integration. Linear regression evaluated associations between ∑PBDE, word reading, and GE of the RN and the default mode network (DMN); the latter to establish specificity of findings. Weighted quantile sum regression analyses evaluated the contributions of specific PBDE congeners to observed associations. Greater RN efficiency was associated with better word reading in these novice readers. Children with higher ∑PBDE showed reduced GE of the RN; ∑PBDE was not associated with DMN efficiency, demonstrating specificity of our results. Consistent with prior findings, ∑PBDE was not associated word reading at 5-years-old. Altered efficiency and integration of the RN may underlie associations between ∑PBDE concentrations and reading problems observed previously in older children.

A preliminary study on prenatal polybrominated diphenyl ether serum concentrations and intrinsic functional network organization and executive functioning in childhood.

BACKGROUND: The prenatal period is a period of vulnerability during which neurotoxic exposures exert persistent changes in brain development and behavior. Polybrominated diphenyl ethers (PBDEs), used as flame retardants in commercial products, are known to be developmental neurotoxicants. PBDEs were phased out of use in the United States a decade ago, but exposure remains widespread due to their release from existing products and biopersistence. Despite consistent animal and epidemiological evidence of developmental neurotoxicity, the neural substrates linking prenatal PBDE serum concentrations to impaired neurodevelopment are poorly understood. METHODS: In the present study, we used resting state functional magnetic resonance imaging (fMRI) to examine associations between prenatal PBDE concentrations measured in maternal serum and intrinsic functional network organization (i.e., global and local efficiency; estimated using a graph-theoretical approach) in 5-year-old children (n = 34). We explored whether PBDE serum concentrations were associated with executive functioning (EF) assessed using a parent-report questionnaire (BRIEF-P) (n = 106) and whether changes in intrinsic functional network organization linked the association between prenatal PBDE serum concentrations and EF problems. RESULTS: Children with higher prenatal PBDE serum concentrations showed: (a) increased global efficiency of brain areas involved in visual attention (e.g., inferior occipital gyrus) (ß's = .01, FDR-corrected p's ≤ .05); (b) more reported EF problems (ß's = .001, FDR-corrected p's ≤ .05). Higher global efficiency of brain areas involved in visual attention was associated with more EF problems (ß's = .01, FDR-corrected p's < .05). CONCLUSIONS: Intrinsic functional network organization of visual attention brain areas linked prenatal PBDE concentrations to EF problems in childhood. Visual attention may contribute to the development of higher-order cognitive functions, such as EF, which could be explored in future studies.

Cocaine addiction severity exacerbates the negative association of lifetime lead exposure with blood pressure levels: Evidence from a pilot study.

BACKGROUND: High blood pressure (BP) is associated independently with cocaine use and lead exposure. It is not known whether cocaine use and lead exposure act jointly to disrupt cardiovascular health. OBJECTIVE: To determine whether cocaine use modifies the association between cumulative lead levels and elevated BP. MATERIALS AND METHODS: We measured cumulative tibia lead levels in 35 adults: 20 with cocaine use disorder (CUD) and 15 non-CUD controls using in vivo K-shell X-ray fluorescence. Generalized estimating equation regression determined associations between log2-transformed lead and BP (systolic, diastolic, and mean arterial pressure) and assessed the modifying association of cocaine use (as addiction severity) on the lead-BP relationship, adjusting for age, sex, smoking, and education. Sensitivity analyses included correction for potential selection bias. RESULTS: Cases and controls differed by sex (%male: 90% vs. 67%), age (50.7 vs. 39.9 years), education (12.8 vs. 14.4 years), and tibia lead (3.50 vs. 2.35 µg/g). Lead was positively associated with systolic (P = 0.01) and diastolic BP (P = 0.01). We observed an interaction between lead and addiction severity on BP (P values for systolic BP: 0.01, diastolic BP: 0.003, and mean arterial BP: <0.0001); the association was stronger among individuals with more severe cocaine addiction: Systolic BP: Est.: 17.89, 95% confidence interval (CI): 9.52; 26.26, diastolic BP Est.: 17.89, 95% CI: 7.33; 13.79, mean arterial BP: Est.: 13.09, 95% CI: 10.34; 15.83. CONCLUSIONS: Lead was adversely associated with BP. This association was strongest among individuals with more severe cocaine addiction. The results from this small pilot study suggest that the interaction between lead and cocaine should be considered in studies of substance abuse-related health outcomes.

Neuroimaging is a novel tool to understand the impact of environmental chemicals on neurodevelopment.

PURPOSE OF REVIEW: The prevalence of childhood neurodevelopmental disorders has been increasing over the last several decades. Prenatal and early childhood exposure to environmental toxicants is increasingly recognized as contributing to the growing rate of neurodevelopmental disorders. Very little information is known about the mechanistic processes by which environmental chemicals alter brain development. We review the recent advances in brain imaging modalities and discuss their application in epidemiologic studies of prenatal and early childhood exposure to environmental toxicants. RECENT FINDINGS: Neuroimaging techniques (volumetric and functional MRI, diffusor tensor imaging, and magnetic resonance spectroscopy) have opened unprecedented access to study the developing human brain. These techniques are noninvasive and free of ionization radiation making them suitable for research applications in children. Using these techniques, we now understand much about structural and functional patterns in the typically developing brain. This knowledge allows us to investigate how prenatal exposure to environmental toxicants may alter the typical developmental trajectory. SUMMARY: MRI is a powerful tool that allows in-vivo visualization of brain structure and function. Used in epidemiologic studies of environmental exposure, it offers the promise to causally link exposure with behavioral and cognitive manifestations and ultimately to inform programs to reduce exposure and mitigate adverse effects of exposure.

Brain anomalies in children exposed prenatally to a common organophosphate pesticide.

Prenatal exposure to chlorpyrifos (CPF), an organophosphate insecticide, is associated with neurobehavioral deficits in humans and animal models. We investigated associations between CPF exposure and brain morphology using magnetic resonance imaging in 40 children, 5.9-11.2 y, selected from a nonclinical, representative community-based cohort. Twenty high-exposure children (upper tertile of CPF concentrations in umbilical cord blood) were compared with 20 low-exposure children on cortical surface features; all participants had minimal prenatal exposure to environmental tobacco smoke and polycyclic aromatic hydrocarbons. High CPF exposure was associated with enlargement of superior temporal, posterior middle temporal, and inferior postcentral gyri bilaterally, and enlarged superior frontal gyrus, gyrus rectus, cuneus, and precuneus along the mesial wall of the right hemisphere. Group differences were derived from exposure effects on underlying white matter. A significant exposure × IQ interaction was derived from CPF disruption of normal IQ associations with surface measures in low-exposure children. In preliminary analyses, high-exposure children did not show expected sex differences in the right inferior parietal lobule and superior marginal gyrus, and displayed reversal of sex differences in the right mesial superior frontal gyrus, consistent with disruption by CPF of normal behavioral sexual dimorphisms reported in animal models. High-exposure children also showed frontal and parietal cortical thinning, and an inverse dose-response relationship between CPF and cortical thickness. This study reports significant associations of prenatal exposure to a widely used environmental neurotoxicant, at standard use levels, with structural changes in the developing human brain.

Impact of prenatal exposure to piperonyl butoxide and permethrin on 36-month neurodevelopment.

OBJECTIVE: Recent pesticide-monitoring results suggest that a shift in residential pesticide exposure from organophosphorus insecticides to pyrethroid insecticides has occurred. Pyrethroid insecticides are potential neurodevelopmental toxicants and have not been evaluated for developmental toxicity. Our objective was to explore the association between prenatal exposure to permethrin (a common pyrethroid) and piperonyl butoxide (a pyrethroid synergist) and 36-month neurodevelopment. METHODS: Participants is this study were part of a prospective cohort of black and Dominican mothers and newborns living in low-income neighborhoods in New York City. We examined 36-month cognitive and motor development (using the Bayley Scales of Infant Development, second edition) as a function of permethrin levels measured in maternal and umbilical cord plasma collected on delivery and permethrin and piperonyl butoxide levels measured in personal air collected during pregnancy. All models were controlled for gender, gestational age, ethnicity, maternal education, maternal intelligence, quality of the home environment, and prenatal exposure to environmental tobacco smoke and chlorpyrifos. RESULTS: Prenatal exposure to permethrin in personal air and/or plasma was not associated with performance scores for the Bayley Mental Developmental Index or the Psychomotor Developmental Index. After data adjustment, children more highly exposed to piperonyl butoxide in personal air samples (>4.34 ng/m(3)) scored 3.9 points lower on the Mental Developmental Index than those with lower exposures (95% confidence interval: -0.25 to -7.49). CONCLUSIONS: Prenatal exposure to piperonyl butoxide was negatively associated with 36-month neurodevelopment.

Neonatology and the Environment: Impact of Early Exposure to Airborne Environmental Toxicants on Infant and Child Neurodevelopment.

Environmental contaminants pose a threat to infant neurodevelopment. In this current paper, we discuss evidence for the potentially harmful impact of fetal and early childhood exposure to polycyclic aromatic hydrocarbons (PAHs), environmental tobacco smoke (ETS), and organophosphorus (OP) insecticides. We focus on effects resulting from chronic and low-level exposure during the prenatal period and early childhood, when the brain is still undergoing rapid developmental changes.

Endocrine-disrupting effects of cattle feedlot effluent on an aquatic sentinel species, the fathead minnow.

Over the last decade, research has examined the endocrine-disrupting action of various environmental pollutants, including hormones, pharmaceuticals, and surfactants, in sewage treatment plant effluent. Responding to the growth of concentrated animal feeding operations (CAFOs) and the pollutants present in their wastewater (e.g., nutrients, pharmaceuticals, and hormones), the U.S. Environmental Protection Agency developed a new rule that tightens the regulation of CAFOs. In this study, we collected wild fathead minnows (Pimephales promelas) exposed to feedlot effluent (FLE) and observed significant alterations in their reproductive biology. Male fish were demasculinized (having lower testicular testosterone synthesis, altered head morphometrics, and smaller testis size). Defeminization of females, as evidenced by a decreased estrogen:androgen ratio of in vitro steroid hormone synthesis, was also documented. We did not observe characteristics in either male or female fish indicative of exposure to environmental estrogens. Using cells transfected with the human androgen receptor, we detected potent androgenic responses from the FLE. Taken together, our morphologic, endocrinologic, and in vitro gene activation assay data suggest two hypotheses: a) there are potent androgenic substance(s) in the FLE, and/or b) there is a complex mixture of androgenic and estrogenic substances that alter the hypothalamic-pituitary-gonadal axis, inhibiting the release of gonadotropin-releasing hormone or gonadotropins. This is the first study demonstrating that the endocrine and reproductive systems of wild fish can be adversely affected by FLE. Future studies are needed to further investigate the effects of agricultural runoff and to identify the biologically active agents, whether natural or pharmaceutical in origin.