Environmental Health Journal Abstracts

The following journal articles are intended for readers interested in pursuing the scientific details of Environmental Health Research as concerns autism and neurodevelopment in general. These papers represent much of the recent scholarship on the subject, though hundreds of investigations and review articles exist in the literature and it was not possible to include the full breadth of these publications. One major consideration in selecting this list was their free availability. While a couple important publications requiring payment (usually $20 to $35) are included here (marked with $), most are free. There is a movement within the academic community to demand that all articles become freely available, at least beginning 12 months after their publications, so in the coming months and years more will become available and will be added to this list. As well, we welcome suggestions for additional articles to add at any time. Articles are assigned levels of difficulty to help guide you. key text within each abstract has been bolded to help you locate articles of interest with ease.

In order to access the full articles, click on the article titles and on the subsequent page, click on ‘Full Text (PDF)’ or ‘PDF’ (requires Adobe Reader, a free program) or, if you prefer, ‘Full Text (HTML)’.

Autism Epidemiology
 Blaxill, M.F. "What's going on? The question of time trends in autism. [Review] [96 refs]", Public Health Reports., vol. 119, no. 6, pp. 536-551.

Abstract: Increases in the reported prevalence of autism and autistic spectrum disorders in recent years have fueled concern over possible environmental causes. The author reviews the available survey literature and finds evidence of large increases in prevalence in both the United States and the United Kingdom that cannot be explained by changes in diagnostic criteria or improvements in case ascertainment. Incomplete ascertainment of autism cases in young child populations is the largest source of predictable bias in prevalence surveys; however, this bias has, if anything, worked against the detection of an upward trend in recent surveys. Comparison of autism rates by year of birth for specific geographies provides the strongest basis for trend assessment. Such comparisons show large recent increases in rates of autism and autistic spectrum disorders in both the U.S. and the U.K. Reported rates of autism in the United States increased from 30 per 10,000 children in the 1990s, a 10-fold increase. In the United Kingdom, autism rates rose from < 10 per 10,000 in the 1980s to roughly 30 per 10,000 in the 1990s. Reported rates for the full spectrum of autistic disorders rose from the 5 to 10 per 10,000 range to the 50 to 80 per 10,000 range in the two countries. A precautionary approach suggests that the rising incidence of autism should be a matter of urgent public concern.

 Eskenazi, B., Marks, A.R., Bradman, A., Harley, K., Barr, D.B., Johnson, C., Morga, N. & Jewell, N.P. "Organophosphate pesticide exposure and neurodevelopment in young Mexican-American children", Environmental Health Perspectives, vol. 115, no. 5, pp. 792-798; Epub 2007 Jan 4.

Abstract: BACKGROUND: Organophosphate (OP) pesticides are widely used in agriculture and homes. Animal studies suggest that even moderate doses are neurodevelopmental toxicants, but there are few studies in humans. OBJECTIVES: We investigated the relationship of prenatal and child OP urinary metabolite levels with children's neurodevelopment. METHODS: Participating children were from a longitudinal birth cohort of primarily Latino farm-worker families in California. We measured six nonspecific dialkylphosphate (DAP) metabolites in maternal and child urine as well as metabolites specific to malathion (MDA) and chlorpyrifos (TCPy) in maternal urine. We examined their association with children's performance at 6 (n = 396), 12 (n = 395), and 24 (n = 372) months of age on the Bayley Scales of Infant Development [Mental Development (MDI) and Psychomotor Development (PDI) Indices] and mother's report on the Child Behavior Checklist (CBCL) (n = 356). RESULTS: Generally, pregnancy DAP levels were negatively associated with MDI, but child measures were positively associated. At 24 months of age, these associations reached statistical significance [per 10-fold increase in prenatal DAPs: beta = -3.5 points; 95% confidence interval (CI), -6.6 to -0.5; child DAPs: beta = 2.4 points; 95% CI, 0.5 to 4.2]. Neither prenatal nor child DAPs were associated with PDI or CBCL attention problems, but both prenatal and postnatal DAPs were associated with risk of pervasive developmental disorder [per 10-fold increase in prenatal DAPs: odds ratio (OR) = 2.3, p = 0.05; child DAPs OR = 1.7, p = 0.04]. MDA and TCPy were not associated with any outcome. CONCLUSIONS: We report adverse associations of prenatal DAPs with mental development and pervasive developmental problems at 24 months of age. Results should be interpreted with caution given the observed positive relationship with postnatal DAPs.

 Szpir, M. "Tracing the origins of autism: a spectrum of new studies", Environmental Health Perspectives., vol. 114, no. 7, pp. A412-8.

This review addresses the increased focus of the research community and the mainstream media on the rising rates of ASDs. Several new studies are addressing potential gene-environment interactions involved in the etiology of the condition, including the Autism Birth Cohort (Norway), California Autism Twin Study (Kaiser Permanente), Centers for Autism and Developmental Disabilities Research and Epidemiology (Johns Hopkins and elsewhere), Childhood Autism Risks from Genetics and the Environment (UC Davis), Early Markers of Autsim (Kaiser Permanente), and Markers for Autism Risk in Babies—Learning Early Signs (UC Davis). These, as well as other important Children's Environmental Health studies, are discussed.

$ Palmer, R.F., Blanchard, S., Stein, Z., Mandell, D. & Miller, C. "Environmental mercury release, special education rates, and autism disorder: an ecological study of Texas. ", Health & Place., vol. 12, no. 2, pp. 203-209.

Abstract: The association between environmentally released mercury, special education and autism rates in Texas was investigated using data from the Texas Education Department and the United States Environmental Protection Agency. A Poisson regression analysis adjusted for school district population size, economic and demographic factors was used. There was a significant increase in the rates of special education students and autism rates associated with increases in environmentally released mercury. On average, for each 1,000 lb of environmentally released mercury, there was a 43% increase in the rate of special education services and a 61% increase in the rate of autism. The association between environmentally released mercury and special education rates were fully mediated by increased autism rates. This ecological study suggests the need for further research regarding the association between environmentally released mercury and developmental disorders such as autism. These results have implications for policy planning and cost analysis.

or Palmer RF, Blanchard S, Wood R. "Proximity to point sources of environmental mercury release as a predictor of autism prevalence." Health Place. 2008 Feb 12. [Epub ahead of print]

 Roberts, E.M., English, P.B., Grether, J.K., Windham, G.C., Somberg, L. & Wolff, C. "Maternal residence near agricultural pesticide applications and autism spectrum disorders among children in the California Central Valley. ", Environmental Health Perspectives., vol. 115, no. 10, pp. 1482-1489.

Abstract: BACKGROUND: Ambient levels of pesticides ("pesticide drift") are detectable at residences near agricultural field sites. OBJECTIVE: Our goal was to evaluate the hypothesis that maternal residence near agricultural pesticide applications during key periods of gestation could be associated with the development of autism spectrum disorders (ASD) in children. METHODS: We identified 465 children with ASD born during 1996-1998 using the California Department of Developmental Services electronic files, and matched them by maternal date of last menstrual period to 6,975 live-born, normal-birth-weight, term infants as controls. We determined proximity to pesticide applications using California Department of Pesticide Regulation records refined using Department of Water Resources land use polygons. A staged analytic design applying a priori criteria to the results of conditional logistic regressions was employed to exclude associations likely due to multiple testing error. RESULTS: Of 249 unique hypotheses, four that described organochlorine pesticide applications--specifically those of dicofol and endosulfan--occurring during the period immediately before and concurrent with central nervous system embryogenesis (clinical weeks 1 through 8) met a priori criteria and were unlikely to be a result of multiple testing. Multivariate a posteriori models comparing children of mothers living within 500 m of field sites with the highest nonzero quartile of organochlorine poundage to those with mothers not living near field sites suggested an odds ratio for ASD of 6.1 (95% confidence interval, 2.4-15.3). ASD risk increased with the poundage of organochlorine applied and decreased with distance from field sites. CONCLUSIONS: The association between residential proximity to organochlorine pesticide applications during gestation and ASD among children should be further studied.

 Windham, G.C., Zhang, L., Gunier, R., Croen, L.A. & Grether, J.K. "Autism spectrum disorders in relation to distribution of hazardous air pollutants in the San Francisco Bay Area", Environmental Health Perspectives., vol. 114, no. 9, pp. 1438-1444.

Abstract: OBJECTIVE: To explore possible associations between autism spectrum disorders (ASD) and environmental exposures, we linked the California autism surveillance system to estimated hazardous air pollutant (HAP) concentrations compiled by the U.S. Environmental Protection Agency. METHODS: Subjects included 284 children with ASD and 657 controls, born in 1994 in the San Francisco Bay area. We assigned exposure level by census tract of birth residence for 19 chemicals we identified as potential neurotoxicants, developmental toxicants, and/or endocrine disruptors from the 1996 HAPs database. Because concentrations of many of these were highly correlated, we combined the chemicals into mechanistic and structural groups, calculating summary index scores. We calculated ASD risk in the upper quartiles of these group scores or individual chemical concentrations compared with below the median, adjusting for demographic factors. RESULTS: The adjusted odds ratios (AORs) were elevated by 50% in the top quartile of chlorinated solvents and heavy metals [95% confidence intervals (CIs) , 1.1-2.1], but not for aromatic solvents. Adjusting for these three groups simultaneously led to decreased risks for the solvents and increased risk for metals (AORs for metals: fourth quartile = 1.7 ; 95% CI, 1.0-3.0 ; third quartile = 1.95 ; 95% CI, 1.2-3.1) . The individual compounds that contributed most to these associations included mercury, cadmium, nickel, trichloroethylene, and vinyl chloride. CONCLUSIONS: Our results suggest a potential association between autism and estimated metal concentrations, and possibly solvents, in ambient air around the birth residence, requiring confirmation and more refined exposure assessment in future studies.

Developmental Neurotoxicology
 $ Grandjean, P. & Landrigan, P.J. "Developmental neurotoxicity of industrial chemicals", Lancet, vol. 368, no. 9553, pp. 2167-2178.


Abstract: Neurodevelopmental disorders such as autism, attention deficit disorder, mental retardation, and cerebral palsy are common, costly, and can cause lifelong disability. Their causes are mostly unknown. A few industrial chemicals (eg, lead, methylmercury, polychlorinated biphenyls [PCBs], arsenic, and toluene) are recognized causes of neurodevelopmental disorders and subclinical brain dysfunction. Exposure to these chemicals during early fetal development can cause brain injury at doses much lower than those affecting adult brain function. Recognition of these risks has led to evidence-based programmes of prevention, such as elimination of lead additives in petrol. Although these prevention campaigns are highly successful, most were initiated only after substantial delays. Another 200 chemicals are known to cause clinical neurotoxic effects in adults. Despite an absence of systematic testing, many additional chemicals have been shown to be neurotoxic in laboratory models. The toxic effects of such chemicals in the developing human brain are not known and they are not regulated to protect children. The two main impediments to prevention of neurodevelopmental deficits of chemical origin are the great gaps in testing chemicals for developmental neurotoxicity and the high level of proof required for regulation. New, precautionary approaches that recognise the unique vulnerability of the developing brain are needed for testing and control of chemicals.

 Szpir, M. "New thinking on neurodevelopment", Environmental Health Perspectives., vol. 114, no. 2, pp. A100-7.

This essay addresses environmental chemicals shown or suspected to impact neurodevelopment. It also discusses the interconnectedness of the body’s different systems, and how impacts to any of these systems may reverberate to cause developmental changes in many systems, including the brain. Challenges of study design, including accurate and sensitive exposure assessment are important issues facing researchers, and are reviewed here as well.

Gene-Environment Interaction
 $ Herbert, M.R., Russo, J.P., Yang, S., Roohi, J., Blaxill, M., Kahler, S.G., Cremer, L. & Hatchwell, E. "Autism and environmental genomics. [Review] [101 refs]", Neurotoxicology, vol. 27, no. 5, pp. 671-684.

Abstract: Autism spectrum disorders (ASD) are defined by behavior and diagnosed by clinical history and observation but have no biomarkers and are presumably, etiologically and biologically heterogeneous. Given brain abnormalities and high monozygotic concordance, ASDs have been framed as neurobiologically based and highly genetic, which has shaped the research agenda and in particular criteria for choosing candidate ASD genes. Genetic studies to date have not uncovered genes of strong effect, but a move toward "genetic complexity" at the neurobiological level may not suffice, as evidence of systemic abnormalities (e.g. gastrointestinal and immune), increasing rates and less than 100% monozygotic concordance support a more inclusive reframing of autism as a multisystem disorder with genetic influence and environmental contributors. We review this evidence and also use a bioinformatic approach to explore the possibility that "environmentally responsive genes" not specifically associated with the nervous system, but potentially associated with systemic changes in autism, have not hitherto received sufficient attention in autism genetics investigations. We overlapped genes from NIEHS Environmental Genome Project, the Comparative Toxicogenomics Database, and the SeattleSNPs database of genes relevant to the human immune and inflammatory response with linkage regions identified in published autism genome scans. We identified 135 genes in overlap regions, of which 56 had never previously been studied in relation to autism and 47 had functional SNPs (in coding regions). Both our review and the bioinformatics exercise support the expansion of criteria for evaluating the relevance of genes to autism risk to include genes related to systemic impact and environmental responsiveness. This review also suggests the utility of environmental genomic resources in highlighting the potential relevance of particular genes within linkage regions. Environmental responsiveness and systems impacts consistent with system-wide findings in autism are thus supported as important considerations in identifying the numerous and complex modes of gene-environment interaction in autism.

Emerging Science
 Kisby, G.E., Olivas, A., Standley, M., Lu, X., Pattee, P., O'Malley, J., Li, X., Muniz, J. & Nagalla, S.R. "Genotoxicants target distinct molecular networks in neonatal neurons", Environmental Health Perspectives., vol. 114, no. 11, pp. 1703-1712.

Abstract: BACKGROUND: Exposure of the brain to environmental agents during critical periods of neuronal development is considered a key factor underlying many neurologic disorders. OBJECTIVES: In this study we examined the influence of genotoxicants on cerebellar function during early development by measuring global gene expression changes. METHODS: We measured global gene expression in immature cerebellar neurons (i.e., granule cells) after treatment with two distinct alkylating agents, methylazoxymethanol (MAM) and nitrogen mustard (HN2). Granule cell cultures were treated for 24 hr with MAM (10-1,000 microM) or HN2 (0.1-20 microM) and examined for cell viability, DNA damage, and markers of apoptosis. RESULTS: Neuronal viability was significantly reduced (p 500 microM for MAM and > 1.0 microM for HN2; this correlated with an increase in both DNA damage and markers of apoptosis. Neuronal cultures treated with sublethal concentrations of MAM (100 microM) or HN2 (1.0 microM) were then examined for gene expression using large-scale mouse cDNA microarrays (27,648). Gene expression results revealed that a) global gene expression was predominantly up-regulated by both genotoxicants; b) the number of down-regulated genes was approximately 3-fold greater for HN2 than for MAM; and c) distinct classes of molecules were influenced by MAM (i.e, neuronal differentiation, the stress and immune response, and signal transduction) and HN2 (i.e, protein synthesis and apoptosis). CONCLUSIONS: These studies demonstrate that individual genotoxicants induce distinct gene expression signatures. Further study of these molecular networks may explain the variable response of the developing brain to different types of environmental genotoxicants.

 Li, Z., Dong, T., Proschel, C. & Noble, M. "Chemically diverse toxicants converge on Fyn and c-Cbl to disrupt precursor cell function", PLoS Biology., vol. 5, no. 2, pp. e35.

Abstract: Identification of common mechanistic principles that shed light on the action of the many chemically diverse toxicants to which we are exposed is of central importance in understanding how toxicants disrupt normal cellular function and in developing more effective means of protecting against such effects. Of particular importance is identifying mechanisms operative at environmentally relevant toxicant exposure levels. Chemically diverse toxicants exhibit striking convergence, at environmentally relevant exposure levels, on pathway-specific disruption of receptor tyrosine kinase (RTK) signaling required for cell division in central nervous system (CNS) progenitor cells. Relatively small toxicant-induced increases in oxidative status are associated with Fyn kinase activation, leading to secondary activation of the c-Cbl ubiquitin ligase. Fyn/c-Cbl pathway activation by these pro-oxidative changes causes specific reductions, in vitro and in vivo, in levels of the c-Cbl target platelet-derived growth factor receptor-alpha and other c-Cbl targets, but not of the TrkC RTK (which is not a c-Cbl target). Sequential Fyn and c-Cbl activation, with consequent pathway-specific suppression of RTK signaling, is induced by levels of methylmercury and lead that affect large segments of the population, as well as by paraquat, an organic herbicide. Our results identify a novel regulatory pathway of oxidant-mediated Fyn/c-Cbl activation as a shared mechanism of action of chemically diverse toxicants at environmentally relevant levels, and as a means by which increased oxidative status may disrupt mitogenic signaling. These results provide one of a small number of general mechanistic principles in toxicology, and the only such principle integrating toxicology, precursor cell biology, redox biology, and signaling pathway analysis in a predictive framework of broad potential relevance to the understanding of pro-oxidant-mediated disruption of normal development.

 Slotkin, T.A., Bodwell, B.E., Levin, E.D. & Seidler, F.J. "Neonatal exposure to low doses of diazinon: long-term effects on neural cell development and acetylcholine systems", Environmental Health Perspectives., vol. 116, no. 3, pp. 340-348.

Abstract: BACKGROUND: The developmental neurotoxicity of organophosphate pesticides involves mechanisms other than their shared property of cholinesterase inhibition. OBJECTIVES: We gave diazinon (DZN) to newborn rats on postnatal days 1-4, using doses (0.5 or 2 mg/kg) spanning the threshold for barely detectable cholinesterase inhibition. METHODS: We then evaluated the lasting effects on indices of neural cell number and size, and on functional markers of acetylcholine (ACh) synapses (choline acetyltransferase, presynaptic high-affinity choline transporter, nicotinic cholinergic receptors) in a variety of brain regions. RESULTS: DZN exposure produced a significant overall increase in cell-packing density in adolescence and adulthood, suggestive of neuronal loss and reactive gliosis; however, some regions (temporal/occipital cortex, striatum) showed evidence of net cell loss, reflecting a greater sensitivity to neurotoxic effects of DZN. Deficits were seen in ACh markers in cerebrocortical areas and the hippocampus, regions enriched in ACh projections. In contrast, there were no significant effects in the midbrain, the major locus for ACh cell bodies. The striatum showed a unique pattern, with robust initial elevations in the ACh markers that regressed in adulthood to normal or subnormal values. CONCLUSIONS: These results indicate that developmental exposures to apparently nontoxic doses of DZN compromise neural cell development and alter ACh synaptic function in adolescence and adulthood. The patterns seen here differ substantially from those seen in earlier work with chlorpyrifos, reinforcing the concept that the various organophosphates have fundamentally different effects on the developmental trajectories of specific neurotransmitter systems, unrelated to their shared action as cholinesterase inhibitors.

Mixtures
 Kortenkamp, A. "Ten years of mixing cocktails: a review of combination effects of endocrine-disrupting chemicals", Environmental Health Perspectives, vol. 115 Suppl 1, pp. 98-105.

Abstract: In the last 10 years, good evidence has become available to show that the combined effects of endocrine disruptors (EDs) belonging to the same category (e.g., estrogenic, antiandrogenic, or thyroid-disrupting agents) can be predicted by using dose addition. This is true for a variety of end points representing a wide range of organizational levels and biological complexity. Combinations of EDs are able to produce significant effect, even when each chemical is present at low doses that individually do not induce observable effects. However, comparatively little is known about mixtures composed of chemicals from different classes of EDs. Nevertheless, I argue that the accumulated evidence seriously undermines continuation with the customary chemical-by-chemical approach to risk assessment for EDs. Instead, we should seriously consider group-wise regulation of classes of EDs. Great care should be taken to define such classes by using suitable similarity criteria. Criteria should focus on common effects, rather than common mechanisms. In this review I also highlight research needs and identify the lack of information about exposure scenarios as a knowledge gap that seriously hampers progress with ED risk assessment. Future research should focus on investigating the effects of combinations of EDs from different categories, with considerable emphasis on elucidating mechanisms. This strategy may lead to better-defined criteria for grouping EDs for regulatory purposes. Also, steps should be taken to develop dedicated mixtures exposure assessment for EDs.

Children's Environmental Health
 Lanphear BP 2005, "Origins and Evolution of Children’s Environmental Health", Environmental Health Perspectives, vol. Essays on the Future of Environmental Health Research, pp. 24.

This essay was included in a special issue of Environmental Health Perspectives celebrating the career of Dr. Kenneth Olden, under whose guidance the NIEHS brought dedicated focus to Children's Environmental Health. Dr. Lanphear reviews the origins of this field in response to environmental disasters and diseases of industrialization and follows its development through the current day and a greater focus on everyday low-level exposures in complex mixtures. A look to the future, including the promise of biomarkers and the understanding of individual genetic characteristics, along with potential challenges and opportunities for prevention are discussed.

 Rice, D. & Barone, S.,Jr. "Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. [Review] [406 refs]", Environmental Health Perspectives., vol. 108 Suppl 3, pp. 511-533.

Abstract: Vulnerable periods during the development of the nervous system are sensitive to environmental insults because they are dependent on the temporal and regional emergence of critical developmental processes (i.e., proliferation, migration, differentiation, synaptogenesis, myelination, and apoptosis). Evidence from numerous sources demonstrates that neural development extends from the embryonic period through adolescence. In general, the sequence of events is comparable among species, although the time scales are considerably different. Developmental exposure of animals or humans to numerous agents (e.g., X-ray irradiation, methylazoxymethanol, ethanol, lead, methyl mercury, or chlorpyrifos) demonstrates that interference with one or more of these developmental processes can lead to developmental neurotoxicity. Different behavioral domains (e.g., sensory, motor, and various cognitive functions) are subserved by different brain areas. Although there are important differences between the rodent and human brain, analogous structures can be identified. Moreover, the ontogeny of specific behaviors can be used to draw inferences regarding the maturation of specific brain structures or neural circuits in rodents and primates, including humans. Furthermore, various clinical disorders in humans (e.g., schizophrenia, dyslexia, epilepsy, and autism) may also be the result of interference with normal ontogeny of developmental processes in the nervous system. Of critical concern is the possibility that developmental exposure to neurotoxicants may result in an acceleration of age-related decline in function. This concern is compounded by the fact that developmental neurotoxicity that results in small effects can have a profound societal impact when amortized across the entire population and across the life span of humans.

 Weiss, B. & Landrigan, P.J. "The developing brain and the environment: an introduction", Environmental Health Perspectives., vol. 108 Suppl 3, pp. 373-374.

This paper serves as introduction to a special issue of Environmental Health Perspectives, following the conference, 'Environmental Influences on Children: Brain, Development, and Behavior' held in New York City on 24-25 May 1999, and convened specifically to consider the intersection between neurodevelopmental impairment, environmental chemicals, and prevention. Over 300 health scientists, pediatricians, and public health professionals examined the growing body of evidence linking environmental toxins to neurobehavioral disorders. The conference began by reviewing well-known examples of deleterious effects of environmental chemicals, including lead and PCBs, on children's brains. The conferees then considered the potential impact of environmental chemicals on neurological disorders with particular focus on ADHD, autism, and Parkinson's disease. The inclusion of Parkinson's disease was intended to signal the notion that exposures in early life may have an influence on the evolution of neurological disease in later life. Support for the Mount Sinai conference came from the Superfund Basic Research Program (NIEHS); The Pew Charitable Trusts; the Institute for Health and the Environment at the University of Albany School of Public Health; the Agency for Toxic Substances and Disease Research (ATSDR); the Ambulatory Pediatric Association; Myron A. Mehlman, PhD; the National Center for Environmental Assessment (EPA); the National Center for Environmental Health (CDC); the National Institute of Child Health and Human Development; the Office of Children's Health Protection (EPA); Physicians for Social Responsibility; The New York Academy of Medicine; The New York Community Trust; and the Wallace Genetic Foundation. The impact of environmental toxins on children's health has become a topic of major concern in the federal government. Eight new research centers in children's environmental health have been established in the past 2 years with joint funding from EPA and NIEHS. Clinical units that specialize in the treatment of children with environmentally induced illness have been developed across the nation with grant support from ATSDR. The American Academy of Pediatrics has just published its Handbook of Pediatric Environmental Health 17, the "Green Book," which is available to pediatricians throughout the Americas. Children's environmental health has climbed to a critical position as we launch the new millennium. This monograph marks a significant milestone in the evolution of this emerging discipline.

Environmental Health Education
 Brown, V.J. "Setting a new syllabus: environmental health science in the classroom", Environmental Health Perspectives., vol. 112, no. 14, pp. A814-9.

Abstract: Environmental health is a subject that has only relatively recently become prominent in the social consciousness. Even as its significance becomes known, finding ways to integrate the subject into education for primary and secondary students is difficult because of federal testing requirements under the No Child Left Behind Act of 2001 and other demands placed on teachers. A number of efforts are under way, however, to provide teachers with resources to help them bring environment health into their classrooms.

Independent and dependent contributions of advanced maternal and paternal ages to autism risk
Janie F. Shelton1,Daniel J. Tancredi, Irva Hertz-Picciotto   Autism Research Volume3, Issue 1, pages 30-39, February 2010 

Healthy Report by Ted Schettler