Good morning. I am pleased to have this opportunity to speak with you about research needs in protecting our children from adverse environmental effects and about the ways in which the National Institute of Environmental Health Sciences and other federal agencies are addressing these needs. My name is Ken Olden and I serve as Director of the National Institute of Environmental Health Sciences (NIEHS). Located in the Research Triangle Park, North Carolina, the NIEHS is the component of the National Institutes of Health (NIH) charged with studying how environmental factors affect human health.
CHILDREN'S HEALTH - A MIXED REVIEW
Children are the nation's most precious resource. So, it is critical that they have the opportunity to develop into healthy and productive citizens. We can be proud of the fact that the health and safety of children is better than at any time in recorded history. Yet, the report card on the well being of our children is a mixture of success and failure. Infant mortality rate is at a record low, but is still higher than in many countries. Academic achievement is up, but still lags behind many industrialized nations. Of the sixty million children younger than 15 years in the U.S., more than forty-seven thousand died in 1994 from preventable diseases (Schneider and Northridge, Amer. J. Public Health 89:155,1999; National Center for Health Statistics). Thirty-five percent of adolescents have been diagnosed with one or more chronic health problems (US DHHS, National Health Interview Survey, 1998). Approximately two million children in any given year are classified as learning disabled (Digest of Education Statistics). The high rates of homicides, suicides, unintentional injuries, poverty, violence, alcohol and tobacco use, asthma, autism, and developmental and behavioral disorders suggest that many challenges remain.
Much of the progress achieved can be attributed to research that has advanced our understanding of children's health issues. In fact, many of the research programs supported by the various federal agencies represented on this panel have served as the basis for policy decisions and the development of activities to prevent and track childhood health problems. But in spite of past and ongoing efforts, significant gaps persist in our understanding of the causes of children's health problems. Too many holes exist in the children's environmental health and safety net. In most instances, we lack adequate information to determine which are the most significant health problems and what should be done about them. Only recently have efforts been initiated to develop a coordinated, well thought-out, government-wide agenda focused around research and prevention. The President's Executive Order (#13045) on Children's Environmental Health and Safety, the development of the Children's Environmental Health and Disease Prevention Centers, and this Special Hearing are three recent efforts to develop a coordinated children's environmental health and protection agenda.
IMPORTANT NIEHS-SUPPORTED RESEARCH ON CHILDREN'S ENVIRONMENTAL HEALTH AND SAFETY
NIEHS research has been vital to the design of our Nation's environmental policies to protect our population at this critical stage of life. This work continues and today I would like to tell you about some of our new initiatives and the collaborations we have brokered with other federal agencies. I can only present some of the highlights of our work in the time allotted, so I am providing an attachment that gives a more complete overview of the NIEHS portfolio in children's environmental health.
Children's Environmental Health and Disease Prevention Centers
The NIEHS teamed with the Environmental Protection Agency (EPA) and the Centers for Disease Control and Prevention (CDC) to create a network of eight Children's Environmental Health and Disease Prevention Research Centers throughout the country. These centers focus on identifying the environmental underpinnings of common childhood disabilities such as asthma and developmental disorders. As is true of all environmental health research, the ultimate goal is to prevent disease through identifying important environmental triggers and eliminating them from a child's environment. An interesting aspect of these particular children's programs is that there is special emphasis on community involvement, both in identifying important issues of concern and in working with research scientists. We are increasingly finding that engaging the community helps us design better and more relevant studies. Also intervention and prevention strategies have a better chance of success when they are developed with an understanding of what is culturally appropriate and how best to communicate with affected communities. For these reasons community involvement is a cornerstone of the Children's Environmental Health and Disease Prevention Research Centers.
The current activities focus on respiratory diseases and asthma, neurodevelopmental impairment, pesticide poisoning and diseases resulting from exposure to agricultural chemicals. Future plans call for developing more centers devoted to studying the neurodevelopmental and neurobehavioral effects of environmental exposures in children.
Asthma remains a major childhood problem, particularly among minorities. The National Institute of Allergy and Infectious Diseases (NIAID) has an ongoing Inner-City Asthma study in which NIEHS plays a role. NIAID and NIEHS together are evaluating intervention studies aimed at reducing incidence of asthma attacks by reducing levels of airway allergens such as those from cockroach and dust mite. NIAID and NIEHS, together with the EPA, also are evaluating the relationship of indoor and outdoor particulate matter and other pollutants to asthma severity. The NIEHS has also teamed with the Department of Housing and Urban Development (HUD) to do a National Allergen Survey that will identify the most common household allergens in our homes. In addition, the National Heart, Lung, and Blood Institute supports several research activities to identify the causes of asthma in children and potential approaches to prevention by investigating the complex interactions involved in exposure during infancy to respiratory infections and environmental allergens and irritants, lung development, and inherited predispositions to allergy. This information will help guide future research and remediation efforts.
Developmental Problems and Birth Defects
The NIEHS is also teaming with the National Institute of Child Health and Human Development (NICHD) to investigate the biological mechanisms by which normal development is disrupted and structural anomalies, or birth defects, occur. This is an important initiative because birth defects are the leading cause of infant mortality in this country, accounting for one in five infant deaths. Environmental agents are suspected of playing an important role in disrupting normal developmental patterns and research supported by this initiative could help in identifying the mechanisms by which environmentally associated birth defects arise.
Environmental Endocrine Disruptors
An emerging issue of concern is the potential of some environmental agents to be hormonally active in the body and disrupt natural endocrine processes. It is known that at high concentrations in nature some of these agents, particularly chlorinated pollutants, can cause reproductive and developmental disorders in wildlife. What remains to be learned is whether or not the low-level exposures that humans have can translate into adverse health problems. The NIEHS supports a large number of studies investigating if exposure early in life to these compounds can lead to problems in childhood and in later adult life. We have also teamed with CDC to determine the actual exposure levels to environmental endocrine disruptors that occur in this Nation.
FUTURE RESEARCH PRIORITIES
Concerns about the special vulnerability of infants and children have been growing since the National Academy of Sciences released the report on Pesticides in the Diets of Infants and Children in 1993. But, until recently, pediatric environmental health has received little attention in spite of known biological and behavioral differences between children and adults. In response to this need, the NIEHS developed a children's health research agenda to explore the relationship between the timing of exposure, the stage of development, and health outcome. This agenda addresses the fact that children have unique behaviors and physiologies that can render them more vulnerable to adverse environmental effects. Exposures that can have negligible effects in an adult can have potentially devastating effects in an infant or child. Where information is available, it is being incorporated in risk assessment. For example, the recent EPA decision to restrict the use of two widely used organophosphate pesticides (methyl parathion and azinphosmethyl) is based on concerns that children may sustain neurological damage at dose levels that are safe for adults. In fact, surveys have shown that there is a 10-to-40-fold difference in serum levels of the enzyme (paraoxonase) that protects humans against organophosphate pesticide toxicity. Newborns have very low levels of this enzyme, leading to the prediction that very young children are probably significantly more sensitive to these insecticides than adults.
In 1997, the White House issued an Executive Order (#13045), Protection of Children from Environmental Health Risks and Safety Risks , which directed federal agencies to identify and assess environmental health and safety risks that may disproportionately affect children. This initiative is led by the DHHS and the EPA. Issues of concern to the NIEHS that are being discussed by the President's Task Force on Environmental Health Risks and Safety Risks to Children pertain to all aspects of the risk assessment process that affect children's health. Do current models of hazard identification capture the agents of concern to children? Is there adequate data on in utero, perinatal, and childhood exposure? Are exposure studies appropriate for modeling exposure of children based on their biology, behavior, and activities? Do we have adequate knowledge of dose-response and mechanisms to assess risk in infants and children? Do we have adequate information on timing of exposure; that is, do exposures earlier in life have the same health consequences as exposures later in life?
I. High-throughput Technology and Testing Needs
As we know, only a subset of the 70,000 commercially useful compounds have been tested and, of these, most of the studies were done in adult animals. It is imperative that we have quick, reliable screens for the toxic potential of these compounds, particularly their toxic effects during critical periods of development. By exploiting recent advances in human genetics and recombinant DNA technology, we are optimistic that we can develop animal models and in vitro test systems to identify carcinogens and toxicants in a matter of days or weeks rather than years, with considerable savings in terms of money and animal use.
Children, as we know, are more susceptible than adults to adverse effects of many common contaminants. Although this is in part due to their smaller body mass, mouthing behaviors, and crawling, all of which optimize exposures to environmental contaminants, basic physiology is also involved. Children's organ systems, immune systems, and metabolic systems are still developing. The profiles of critical enzymes, such as paraoxanase which detoxifies organophosphate pesticides and P-450 enzymes that degrade ingested chlorinated compounds, are much less active in newborns than in adults. Thus, not only are children more vulnerable because of their developmental stage, their biological protective mechanisms are also immature or inefficient.
In order to better understand the risks of very early exposures on later disease endpoints, the NIEHS is conducting rodent studies on several important pesticides. Rodents are exposed early in life and followed into adulthood where tests are made on potential adverse effects to the neurological, reproductive, and immunological systems.
Another major project being discussed by NIEHS and others on the President's Task Force on Environmental Health Risks and Safety Risks to Children is the creation of a national birth cohort to look at genetic and environmental components of children's health. We envision that, through the efforts of the National Institute of Child Health and Human Development (NICHD), the NIEHS, the CDC, and the EPA, a large cohort of pregnant women could be recruited and their offspring followed through birth and childhood. Planning is now underway and potential end points that could be investigated include low birth weight, asthma, juvenile diabetes, learning disorders, and birth defects. This would be an ambitious undertaking, but it represents the type of investment that we could make to define better the important contributors to childhood disease.
Much research needs to be done to assess human exposure. We would like to learn more about the effect of environmental agents, particularly hormonally active agents, on growth and development. We would all benefit if these research efforts were guided by the knowledge of what the actual, real world, exposures are. Unfortunately such data are usually lacking. We might know what is in the environment, but we do not usually know the extent to which these environmental agents are absorbed and retained in the body. To address this knowledge gap, the NIEHS has established an exposure assessment project. In partnership with CDC, we are currently focusing on defining which environmental endocrine disrupting compounds can be found in a representative section of the American population. This information will help tremendously in guiding the ongoing research on the ability of these compounds to affect health, particularly when the exposures occur early in life.
In summary, research on children's health is urgently needed. To realize the public health and economic potential of environmental health research, we plan to invest in several critical areas. The first of these is to address the information gaps that create uncertainties in current risk assessments. This work will require developing high-throughput technologies as well as establishing a mechanistic understanding of toxicity in order to better extrapolate from rodent studies to human risks and to predict toxic responses to unknown factors having similar chemical, physical, and biological properties. The second strategic investment is to incorporate individual susceptibility into risk assessments. This ability will evolve as we define better the genetic basis of individual responses to toxicants, define important gender differences, define the unique vulnerabilities of children, and define the impact of poverty, race/ethnicity, and cultural factors on environmentally associated diseases. The third strategic investment is to strengthen the scientific basis for testing and regulatory decision making. This investment would generate knowledge about the actual, real-world exposures of the American public, the important environmental triggers identified by ongoing population-based cohort studies, and an understanding of multiple, complex exposures rather than the single-compound studies upon which current risk assessments are based.
The projects I have mentioned are a small sampling of the many federal programs devoted to children's environmental health. The attachment provided gives a more complete listing of the NIEHS research portfolio and our collaborations with public and private groups. I appreciate the opportunity to speak with you today and would welcome any questions you might have.
NIEHS' CONTRIBUTION TO RESEARCH ON CHILDREN'S ENVIRONMENTAL HEALTH AND SAFETY
I. Children's Environmental Health and Disease Prevention Research Centers
The first Federal research program devoted exclusively to children's environmental health and disease prevention was created in 1998. This joint effort by the NIEHS, the Environmental Protection Agency (EPA), and the Centers for Disease Control and Prevention (CDC) uses the expertise and resources of nonprofit institutions across the Nation. This program also incorporates the concept that research is made more meaningful when the public has input and access to scientists. Public outreach is a cornerstone of the program, with community participation and information exchange between researchers and local citizens a requirement of each center. At present there are eight centers, with individual focuses on asthma and developmental effects. Future plans call for developing more centers devoted to studying the neurodevelopmental and neurobehavioral effects of environmental exposures in children. The current activities focus on respiratory diseases and asthma, neurodevelopmental impairment, pesticide poisoning and diseases resulting from exposure to agricultural chemicals.
II. Asthma and Other Respiratory Diseases.
Inner-city disadvantaged and minority children appear to be at greater risk of respiratory illness, especially asthma. An ongoing study, the Five-Cities Study, is assessing the degree to which minority and/or economically-disadvantaged children are at increased risk for adverse respiratory health effects of air pollutants such as ozone, acid aerosols, and particulate air pollution. It is expected that results from this research will complement those from previous NIEHS-supported studies (the Six-and Twenty-Four Cities Studies) that demonstrated increased respiratory illness and reduced lung function associated with air pollution among children in suburban and rural communities. Preliminary data from the Five-Cities Study indicate that there are differences in sensitivity among the specific groups examined. Children living in the inner city demonstrated a greater response to the same exposure than did children in the suburbs. Greater responses were also found in African-American children compared to whites; girls compared to boys; and children with hay fever compared to those without allergies. All these differences suggest that genetic, socioeconomic, and/or housing characteristics may contribute to increased sensitivity to air pollution.
National Allergen Survey
Cumulative exposure to indoor allergens can increase risk for developing allergic disease and asthma. For this reason the NIEHS has teamed with the Department of Housing and Urban Development (HUD) to conduct a National Allergen Survey. This study is assessing the magnitude of the American public's exposure to household indoor allergens, including those implicated in development and exacerbation of asthma. Specifically this study will: (1) estimate indoor allergen exposures of the general population, (2) assess the magnitude of levels of indoor allergens in the U. S. housing stock, and (3) evaluate the differences in population exposure to allergens based on factors such as region/ geography, ethnicity, socioeconomic status, and housing type. This is the first survey of its kind and represents a unique collaboration between a health agency and a housing agency. The ultimate benefit derived from this study will be in providing an assessment of the actual allergen exposures in American homes; this information can help guide future research characterizing the role of indoor allergens in asthma.
Inner-City Asthma Study and Other Intervention Programs
The NIEHS and the National Institute of Allergy and Infectious Diseases (NIAID) are collaborating on the Inner-City Asthma Study. This multi-center study is an intervention trial that evaluates the effectiveness of modifying environmental factors, such as cockroach allergens and tobacco smoke, in reducing asthma morbidity in inner-city children. In addition to this study, the NIEHS is evaluating a number of other asthma prevention and intervention schemes. Collectively, these programs focus on assessing how childhood asthma can be reduced or eliminated through controlling exposures to known indoor allergens. Most of these studies target individuals from low-income residences and are designed to be culturally appropriate, comprehensive, and cost-effective.
A number of other studies are underway that further our understanding of how a broad spectrum of potential allergens affect asthma in children. One study, for example, is testing the hypothesis that carefully quantitated indoor allergen exposures (including house dust mite, dog, cat and, cockroach antigen, and fungi) and air contaminant exposures (environmental tobacco smoke, nitrogen dioxide, nitrous acid, ozone, fine particle mass, fine particle composition and pollen) are associated with the increased incidence and severity of asthma.
Five of the eight Children's Environmental Health and Disease Prevention Research Programs emphasize research on asthma and other respiratory disorders.
Community-Based Prevention/ Intervention Research (CBPIR)
The NIEHS CBPIR program supports a number of asthma studies in urban, socioeconomically- disadvantaged populations. One study is evaluating whether nurse management and peer counseling help to reduce severe episodes of asthma. Another study focuses on methods to help control and prevent asthma with interventions such as case management and environmental control of asthma. A third is evaluating the relationship between cockroach and dust allergens on asthma. These studies will develop and implement culturally- appropriate methods and materials for communicating the study findings to the community involved.
There is a marked geographical variation in rates of childhood asthma. Identification of factors that could cause asthma can result from studies that compare high-and low-incidence populations. For example, if exposure to a factor believed to be related to asthma (such as cockroach allergens) is common in both low and high-incidence populations, it is important to understand why the risk varies. Explanations can include: (1) that the factor is actually a marker for some other exposure that is related to asthma development, or (2) that another, as yet unidentified, co-factor alters the risk due to exposure. Such co-factors can include genetic susceptibility where marked ethnic variations exist, dietary patterns, physical activity and time spent outdoors, and early life exposure to infectious or environmental agents. This type of information will be critical for devising and choosing appropriate interventions and prevention strategies. The NIEHS is supporting studies of genetic susceptibility to childhood asthma among residents in Southern California, Mexico City and Wuhan, China. Wuhan has a low rate of asthma (1- 2.5 percent), Mexico City has a moderate rate (~ 4 percent), and Southern California has a high rate (~ 10 percent). Both the Wuhan and Mexico City populations are exposed to high levels of particulates and other ambient air pollutants, as well as to antigens such as those from cockroach that are believed to be asthma risk factors. The Southern California sites represent contrasting exposure to air pollutants such as ozone, particulates, and nitrogen oxides.
Role of Endotoxin
The NIEHS is examining the role of exposure to endotoxin in a longitudinal cohort study of infants at high risk of developing asthma. Endotoxins are compounds found in the outer membrane of some common bacteria that can initiate an allergic response. It is an established factor associated with occupational asthma in adults and may play an important role in childhood asthma. Levels of endotoxin as high as those in occupational settings have been reported in home air samples. Thus, exposure to endotoxin early in life may play an important role in development of airways inflammation, wheeze, allergy and asthma before age five. Results from this work will better define what role endotoxin plays in childhood asthma.
Ozone as a Risk Factor
Recent data suggest that persons with asthma have an enhanced inflammatory response to short- term inhalation of the common air pollutant, ozone. One NIEHS-sponsored study will test the hypothesis that there is a progression of ozone-induced respiratory tract inflammation in asthmatic subjects with repeated short-term exposure to ozone, such as would happen during smog episodes. This study will also validate the current use of sputum induction as a marker for air pollution effects and will evaluate if the increased emergency room and hospital utilization for asthma during high smog times is due to a measurable increase in airway inflammation. Another study seeks to examine the hypothesis that pre- existing oxidant burden is a risk factor in the exacerbation of allergic asthma by ozone. This study's overall goal is to determine whether the baseline oxidative state is a useful marker of risk for asthma exacerbation by oxidant pollutants, such as ozone.
III. Birth Defects
Norwegian Birth Cohort
Studying the adverse effects of low-dose exposures during fetal development is significantly complicated by the fact that many of these effects do not appear until much later in life. The best way to detect these effects in humans is through long-term epidemiologic studies that follow a child through its mother's pregnancy and into the later years of a child's life. Such studies are expensive and can be difficult to monitor. One cost-effective approach is in collaborating on existing studies in countries where this type of monitoring is done. The NIEHS is investigating the possibility of such a collaboration with Norway, which has an excellent infrastructure for human health studies. The Norwegian government plans, beginning in 2000, to establish a cohort of 100,000 pregnant women and their children to be followed for the rest of their lives. Questionnaires will be administered periodically throughout the mothers' pregnancy and the babies' childhood. Study participants will also be followed through the various Norwegian national medical registries. NIEHS is exploring the feasibility of collecting blood and urine of all mothers during pregnancy . If such a collaboration is feasible, then NIEHS would store these biological samples and use them later to determine maternal and fetal exposure to environmental agents such as pesticides, plasticizers, and heavy metals. Important health outcomes that could be monitored if NIEHS is able to do this study would include birth defects, preterm delivery, preeclampsia, childhood development, diseases of childhood, and diseases of adulthood.
A common and particularly disfiguring birth defect is that of cleft lip and palate. This condition is obvious at birth and results from miscues during fetal development of facial structures. Reasons for these miscues may include in utero exposures to environmental toxicants and possibly the interaction of these toxicants with genetic variants within the genome of the mother or fetus that make the baby more susceptible to toxicant action. To examine this hypothesis, NIEHS researchers are conducting a large study in Norway. Norway has one of the highest reported rates of facial clefts in the world and also has a highly organized birth registry that records these defects. Both genetic material and environmental exposure information is being collected on the mothers of these infants. Due to be completed in 2001, this study will provide the largest and most complete collection of data ever obtained on the genetic and environmental components of this all-too-common birth defect.
The effect of pesticides and other agricultural compounds on the developing organism is another area of concern. Many of the pesticides applied to crops are present in foods, including foods that children eat. The National Research Council released a report in 1993, Pesticides in the Diets of Infants and Children, that revealed the paucity of data on possible adverse effects from these exposures. In response, the NIEHS initiated animal studies to investigate the ability of common pesticides to affect the neurological, immunological, and reproductive systems when exposure occurs early in life. NIEHS works closely with the EPA to ensure that the pesticides studied are those with greatest relevance to childhood exposures.
In collaboration with the National Cancer Institute (NCI), the NIEHS is engaged in a large epidemiologic study to assess the effect of agricultural exposures on a variety of health endpoints in children as well as adults. Increased risk of birth defects from agricultural exposures is one endpoint being evaluated. Exposures to agricultural chemicals will include those from contaminated groundwater, soil deposition, home track-in, wind dispersion and occupational exposure.
The NIEHS has expanded this study to assay well-water for the presence of nitrates as a possible risk factor in developing juvenile diabetes. In a study from the United Kingdom, the incidence of childhood diabetes was found to be higher in rural areas where nitrate levels in water were up to four times higher than in urban locations. This intriguing but preliminary result may be pursued in a more rigorous prospective study within the Agricultural Health Study.
IV. Learning and Behavioral Disorders
Lead is an common environmental contaminant found in household dusts and soil, pipe solder, old paint, and some ceramics. It has long been known to cause health problems at high doses. What was unappreciated were the effects of low lead exposures early in life. NIEHS-supported researchers have shown that levels of lead in blood previously thought to be safe were, in fact, associated with subtle neurologic and behavioral problems in children. These problems included lowered IQ scores, impaired coordination, and increased aggression. Based on these findings the CDC revised its guidelines for acceptable blood lead levels in children to a lower value.
Current NIEHS research on lead is focused on three important areas. The first is the conduct of a large multicenter clinical trial to establish the efficacy of the chelating compound, Succimer, to treat low blood lead levels and to reverse its neurological effects. The second is an ongoing investigation into the health and behavioral consequences of low- lead exposures, including basic research efforts that define the cellular and molecular pathways of toxicity and epidemiologic studies that assess its role in neurobehavioral problems such as attention-deficit/hyperactivity disorder and aggression. The third is defining the role of maternal lead stores in contributing to lead exposures of the fetus and neonate. Results from these latter studies are revealing that maternal bone lead stores are a source of early exposure for the child. This is an important finding, because it offers a way to reduce early exposures by treating the mother. In fact, an NIEHS-supported study has preliminary evidence that dietary calcium might reduce mobilization of maternal bone lead in pregnant women, significantly reducing its transplacental and lactational transmission. If further work verifies this finding, it offers a significant, and inexpensive, clinical prevention technique for reducing early lead exposures in infants and the subsequent neurobehavioral and cognitive deficits arising from these exposures.
Methylmercury is a common environmental contaminant that gets into water where it is subsequently concentrated in food sources such as fish and other aquatic organisms. Methylmercury is neurotoxic and can be transported across the placenta to the developing child. Thus, it is important to understand at what exposure levels methylmercury can cause neurological problems for the developing fetus and child. The NIEHS is supporting two, long- term epidemiologic studies to determine the effect of early exposure to methylmercury on the subsequent neurodevelopment of children.
The first study is in a fish-eating population in the Seychelles Islands and involves a cohort of children followed prenatally to the current age of 66 months. This study established that the amount of methylmercury found in a mother's hair during pregnancy correlated well with the level in prenatal brain of her child. This fact was determined by autopsy of the brains of 22 stillborn children. A battery of tests designed to detect mental deficiencies has, thus far, found no measureable detrimental effects by age 5.5 years that correlate with low-level methylmercury exposures (0.5 - 27 ppm in the study population).
The second long-term epidemiologic study is being done in the Faeroe Islands in a seafood-eating population that is exposed to both methylmercury and polychlorinated biphenyls (PCBs). The children are now seven years old; the range of exposures is 0.2 - 40 ppm. Although some of the evaluative tests are the same as in the Seychelles Islands cohort, other tests have also been used that give a better measure of neurocognitive defects, as opposed to mental deficiencies. Most test scores are within the normal range, except one C those for long-term recall measurements are reduced as a function of methylmercury levels detected in cord blood at birth. This study has also shown that PCB exposures correlated to adverse performance on the Boston Naming Test. Because of these results, the Seychelles Islands study will be extended to age seven and some of the same tests that were used in the Faroe Islands will be administered.
Polychlorinated Biphenyls (PCBs)
Reduced intelligence is an unfortunate legacy of early exposure to a common group of environmental contaminants, the PCBs. These compounds are widely distributed in the environment due to previous uses in electric transformers, paper recycling, and other commercial processes. NIEHS-supported scientists have shown that when the child is exposed to PCBs while in its mother's womb, serious neurological problems can develop. These problems translate later in life into lower I.Q. scores, poor reading comprehension, memory problems, and difficulty in concentration. Although PCBs have long been banned, partly in response to earlier NIEHS study results, they still contaminate water and soil in many communities. Caution should be exercised in eating fish from PCB-contaminated waters. Women of childbearing age and children under 15 are especially vulnerable.
Many rural, low-income communities rely on fishing as a major source of their diet. An NIEHS grantee has been following a population of children born to mothers who consumed large amounts of fish contaminated with PCBs, methylmercury, lead, cadmium, and organochlorine pesticides. The relationship between these exposures and a variety of developmental outcomes are being studied, including measures of infant size, infant behavior and neurologic function. This study will measure PCB levels in umbilical cord blood and maternal blood and milk samples and correlate these values with the children's behavior, achievement and performance on reading mastery tests.
Breast Milk Contaminants
NIEHS-supported studies have shown that breast milk can be a significant source of early exposures to PCBs, DDT and other organochlorine pesticides. In the 1970s, NIEHS researchers identified 900 children in North Carolina and tracked them through puberty. They made two interesting findings. The first was that, in the case of PCBs, transplacental exposure appeared to be more important than lactational exposure, producing small but persistent delays in motor development from birth to age two. The second finding was that high levels of the DDT metabolite, DDE, were associated with earlier weaning. This finding was replicated in subsequent studies in Mexico. It appears that exposure to DDE interferes with lactation itself, thus shortening the lactational period and necessitating an earlier weaning. This early weaning can have a significant effect on a child's health since a mother's milk provides protective antibodies during this developmental period when a child's own immune system is still immature.
Attention Deficit/Hyperactivity Disorder
Diagnoses of Attention Deficit/ Hyperactivity Disorder (ADHD) among children are increasing, although no one knows why. The NIEHS, in an attempt to bring scientific rigor to this issue, has instituted a study of all elementary school-age children in Johnston County, NC. The study screens for ADHD in all Johnston County school children for whom parental permission was obtained, and will look at preventive risk factors for this disorder. NIEHS is also working with the schools to set up a mobile clinic to evaluate children identified by the study, bring social service agencies in the county together to address issues around ADHD, and train health professionals, teachers and parents so they have the tools to more effectively work with children who have ADHD. Preliminary results have surprisingly shown that the prevalence of ADHD was higher in this group than indicated by clinical studies. The study also has found that a large proportion of the children being treated with stimulant medication still continue to show many ADHD symptoms, suggesting there may be gaps in followup and communication between health providers, schools, and parents. The study is now examining possible environmental components of this disorder, with initial emphasis on premature birth and maternal smoking and alcohol consumption.
V. Developmental Disorders
Pesticide Residues in Food
Understanding of health effects of exposure to pesticides early in life is important because infants and children consume more food and water by body mass than do adults and are at an extremely vulnerable stage in their development. Unfortunately, exposure standards have been typically set based on studies in adults and on estimated adult intakes. NIEHS is conducting rodent studies to examine how exposure to pesticides early in life can impair the function of the adult reproductive, immune, and nervous systems. Pesticides under study are methxoychlor, carbaryl, tebuconazole, and heptachlor. The NIEHS is working with EPA to identify other pesticides for study.
Endocrine disruptors comprise a large class of diverse compounds that have the ability to disrupt endocrine function through estrogenic, androgenic, or other hormonal pathways. Suspected endocrine-disrupting compounds include PCBs, chlorinated pesticides such as DDT, dioxin, and some plasticizing compounds. In tissue samples taken from the U.S. population, over 95% had detectable concentrations of some endocrine-disrupting compounds.
NIEHS supports numerous research on the effects of endocrine-disrupting compounds on the developing fetus and neonate. Studies being done in rodents include (1) the effect of bisphenol A on female genital tract development and function, (2) three-generation studies of the effects of nonylphenol, methoxychlor, genistein, and ethinylestradiol exposures on numerous health endpoints, including reproductive, behavioral, and immune function, (3) the effect of fetal exposure to tamoxifen and genistein, (4) the effects of anti-androgenic plasticizers on the development of normal reproductive function, (5) the effect of juvenile exposure to methoxychlor on subsequent adult reproductive function, (6) the ability of organochlorines such as PCBs and dioxin to alter development of the inner ear through interfering with thyroid hormone receptors and retinoic acid receptors, and (7) the detection of early genomic changes after exposure to endocrine-disrupting chemicals and their link to modified function in the adult animal.
In addition to laboratory studies, NIEHS sponsors a number of studies in human populations. These include (1) a retrospective epidemiologic study on the affect of prenatal exposure to specific PCB-related compounds to subsequent cognitive development, hearing, and speech articulation, (2) a study of infants in the Inuit community of Northern Quebec to verify earlier findings in North Carolina and Michigan that prenatal exposure to PCBs translates into delayed gross motor development in infancy and deficits in physical growth and cognitive function in childhood, (3) a study assessing the effect of maternal levels of DDE and PCBs during pregnancy on subsequent neurologic and developmental measures in children, and (4) a study examining the effect of early life exposure to DDT on subsequent abnormal development of genitalia in males.
Center for the Evaluation of Risks to Human Reproduction
The NIEHS has established a unique center that provides the public an expert assessment of the potential of a compound, or class of compounds, to cause developmental effects in offspring. The assessment is made by a panel of scientists who review all known information on a chemical, provide an evaluation of the probable effect on reproduction and development, and identify areas where more research needs to be done. Panel meetings are open to the public and provide opportunity for public comment. The first review will be done on seven phthalate compounds. Phthalates are used commercially as plasticizers in such products as shower curtains, medical tubing and intravenous administration bags, upholstery, raincoats, balls, and soft squeeze toys. They have the ability to migrate out of plastic and be absorbed into the body; thus, low-level exposure to these compounds is suspected to be widespread.
DES is a synthetic estrogen once used by physicians to prevent miscarriage. Female offspring (DES daughters) who were exposed in utero developed a rare vaginal cancer, clear cell adenocarcinoma, and reproductive abnormalities later in life. To date, DES sons have shown no increased cancer risk although reproductive abnormalities have been reported.
NIEHS took an early lead in DES research by developing a mouse model that mimicked human effects from this drug, generated results quickly and could be used to guide about how to monitor DES daughters. For example, early results in mice showed an increase in ovarian cysts, a finding that was verified in follow-up studies in DES daughters. More recently, NIEHS-supported mouse studies have shown that adverse effects of DES exposure can appear in DES granddaughters, even though this group had no direct exposure to DES. In a multigenerational mouse study, DES granddaughters had a much higher cancer susceptibility than controls. Reproductive effects, however, were not transmitted across generations. These findings provide an early warning to physicians and health officials that they need to monitor DES granddaughters to improve their chances of a healthy life. Studies on these effects continue, with efforts concentrating on identifying the molecular mechanisms that may be associated with the increased tumor susceptibility transferred to DES-lineage mice.
VI. Environmental Components of Other Important Diseases
Low birthweight is associated with a number of adverse health outcomes, including reduced growth, lower cognitive performance, and greater morbidity and mortality. Low birthweight is more prevalent among infants in low-income families. A new NIEHS-supported study measured pregnant women's bone lead levels and found that the higher the level, the greater the possibility her child was born with a low birthweight. This finding identifies a controllable environmental component to this important public health problem.
The NIEHS has also joined with the National Institute of Nursing Research, the National Institute of Dental and Craniofacial Research, and the National Institute of Child Health and Human Development to support research on low birthweight in minority populations. This program seeks to encourage research to develop innovative strategies to prevent low birthweight in minority populations and to expand our understanding of how psychosocial and environmental factors affect or interact with the biologic mechanisms that influence pregnancy outcomes.
VII. TRAINING RESOURCES
NIEHS Kid's Page
The NIEHS proves that science can be fun in the NIEHS Kid's Page at www.niehs.nih.gov/kids/home.htm. The Kid's Page is environmental science education in an entertaining and humorous format. It includes games, jokes, coloring books, word puzzles, and Environmental Diseases from A to Z, as well as links to other on-line resources for kids.
K-12 Environmental Health Science Education
In 1992, the NIEHS began development of an environmental health sciences education program at the K-12 grade levels. The objective of this program is to improve the understanding of environmental health issues by all students and to expand career awareness for those interested in pursuing research and service occupations in environmental health sciences. Initiatives within this grant program support development of instructional materials for use in grades K-12 and teacher enhancement and development activities.
The Institute's journal, Environmental Health Perspectives (EHP), represents a venue for educating the American public, pediatricians, and research scientists. Each year it devotes an entire issue to children's environmental health topics. Two important symposia concerning children and their environments were featured in the June, 1998 issue of the EHP Supplements. These publications have proven particularly useful in providing a forum for exchange of ideas on current research efforts in children's environmental health sciences.
IX. Collaborations with the Children's Environmental Health Network and the Children's Health Environmental Coalition
NIEHS is proud of its long-standing partnerships with the Children's Environmental Health Network and the Children's Health Environmental Coalition (CHEC). The input and advice of both groups has been important in the development of the Institute's research agenda on children's health. We have co-sponsored conferences with both organizations and published the proceedings in the Institute's journal, Environmental Health Perspectives. Presently NIEHS is co-sponsoring the "National Environmental Child Proofing Campaign" developed by CHEC.