Philip J. Landrigan, MD, MSc, FAAP and Jordan Slutsky, BA
Children today are surrounded by thousands of synthetic chemicals, most of which have been invented and developed in the past 50 years. Over 85,000 synthetic chemical compounds are now registered for commercial use in EPA's Toxic Substances Control Act (TSCA) inventory, and 2,800 high-production-volume (HPV) chemicals are currently produced in quantities of one million pounds or more per year (1). These HPV chemicals are the most likely to be used in foods and consumer products and to be most widely disseminated in the environment. Many hundreds of HPV chemicals have not been tested for their potential toxicity to humans, and fewer than 20 percent have been examined for their possible developmental toxicity or toxicity to children (1,2). Thus the hazards that these chemicals may pose to children's health and development are still largely unknown (3). Evidence is increasing, however, that chemicals in the environment are contributing to changing patterns of disease in children, the wide prevalence of neurodevelopmental disabilities such as ADHD and autism, increasing rates of asthma and certain childhood cancers, and, possibly, disorders of endocrine function and reproduction.
This commentary reviews current evidence indicating that toxic chemicals in the environment cause or contribute to disease in children. The review also notes several important successes that pediatricians have achieved in reducing children's exposures to environmental threats. It concludes by offering suggestions on how pediatricians and others who care for children can address environmental threats to children's health in offices and clinics, in communities, and in society.
Current Evidence for the Environmental Causation of Pediatric Disease
Diseases of great significance to children in America today and thought, or at least suspected, to be caused or aggravated by chemicals in the environment, including the following:
Neurodevelopmental disorders. Neurodevelopmental disorders, including learning disabilities, dyslexia, mental retardation, attention deficit disorder, and autism are widespread and affect 5 to 10 percent of the four million babies born in the United States each year. Some clinical investigators have reported that prevalence is increasing, but existing data are not of sufficient quality to either sustain or refute that position (4). Causes are largely unknown, but in utero and early life exposures to lead (5,6), mercury (7), PCBs (8), certain pesticides, and other environmental neurotoxicants are known to contribute to causation of these conditions (9,10). A recent report from the National Research Council concluded that 3 percent of developmental disabilities are the direct consequence of neurotoxic environmental exposures and that another 25 percent arise out of the interplay of environmental factors and individual genetic susceptibility (11).
ADHD. Attention deficit/hyperactivity disorder, a learning disorder characterized by hyperactivity, impulsivity, and inattention, is one of the most common childhood behavioral conditions. At least 3 to 5 percent of American children have ADHD, and youth visits to physicians for the disorder have increased 90 percent from 1989 to 1996 (12,13,14,15,16). The use of stimulants such as Ritalin, which are used to treat ADHD, have increased 2.5-fold between 1990 and 1995 for children and 3-fold for preschoolers from 1991 to 1995 (17,18). These increases in doctor visits and stimulant treatment may be explained by one or more of the following factors: an increase in actual incidence of ADHD, greater awareness of the disorder, broadening of the definition of the disorder, and greater acceptance of medication to treat behavioral disorders.
The causes of ADHD are largely unknown. Some studies indicate that genetic factors play a role, while others suggest that substances present in the environment contribute to causation (19,20). Certain toxins are known to reduce attention span in children and thus to interfere with the same aspects of learning that are disrupted in ADHD. Lead is the most well studied environmental toxin that hinders learning. Lead decreases IQ, reduces ability to pay attention, and has been linked to disruptive classroom behavior (21,22,23). Exposure to lead in early life has been correlated with failure to graduate high school, violent tendencies, addictive behaviors, and other behavioral and emotional problems (6,24,25). Due to this wide range of effects on children, researchers are exploring the possibility that lead exposure correlates with a clinical diagnosis of ADHD. Although some studies have shown significant relationships between lead levels and attention-deficit behaviors, the extent to which lead contributes to a clinical diagnosis of ADHD or may interfere with genetic, social, familial and cultural factors is still unclear (26,27).
Polychlorinated biphenyls (PCBs) are another class of toxic chemicals that have been shown to interfere with children's cognitive development including learning and attention (28). PCBs were used as electrical insulators and in other applications by industry until their ban in 1976 in the U.S. PCBs are problematic because of their long persistence in the environment and in human tissue. Children may be exposed to PCBs in utero (as the chemicals can move across the placenta), through breast milk, or by eating fish, shellfish and other fatty foods that contain high concentrations of PCBs.
In the United States, the most common route of exposure to PCBs, eating game fish, has been associated with poorer neurodevelopmental function in infants (29). A Dutch study found that exposure to PCBs can result in decreased intellectual function, and a Michigan study found that such exposures could result in lower full-scale and verbal IQ scores (8,30,31). No human studies examine whether prenatal exposure to PCBs is a risk factor for clinically diagnosed ADHD, although a study of rodents demonstrates a correlation between PCB exposure through mother's milk and hyperactive behavior (32). PCBs quite possibly play a role in the etiology of ADHD because of their documented effects on learning and intelligence.
Autism. Autism spectrum disorder (ASD) consists of a group of developmental disorders that include autistic disorder (commonly referred to as autism), atypical autism, and Asperger's syndrome. Although the exact number of children with ASD is unknown, recent research indicates that as many as two in 1000 children are affected in the U.S. (33). Children affected by autistic disorder or autism have impaired sociability, language, and communication, often coupled with mental retardation.
The reported prevalence of autism has increased globally in recent years, from less than 0.5 per 1000 children in studies before 1970 to a mean rate of about 1 per 1000 children born in or after 1970 (34). Causes for this increase in prevalence are not known but might include change in diagnostic criteria, greater awareness of autism, increased exposure to environmental pollutants, and increased survival of premature infants (34). While prevalence rates of autism do not seem to be increasing in the U.S., an increasing number of autistic patients seem to be using public services (35). In California, the number of autistic patients receiving public services between 1987 and 1998, a time in which the population grew only by 60 percent, increased by 210 percent (35). The population with autism grew faster during that decade than the population with other developmental disabilities (35). The cause of this reported increase is unknown, but could be due to an increased awareness of the disorder and/ or an increased willingness to access public services for the disorder.
Several studies have found that genes may cause autism but genetics does not appear to be the only factor (36,37,38,39,40). Interactions of genes with the environment may also contribute to causation. One potentially important factor is infection: a recent study found that levels of antibody to streptococcus were significantly higher in children with autism than in controls (41). Infection during pregnancy may be correlated with the development of autism. In utero disturbance of neural tube closure may be another important factor. An association between autism and malformations caused by thalidomide was demonstrated in a 1994 study (42): thalidomide is known to act on the embryo during a very specific developmental period (20 to 36 days after conception), and it has been speculated that autism may be caused in children exposed to thalidomide by a disturbance of brain development during that developmental window (43,44).
Few efforts have been made to link autism with specific exposures or exposure levels despite the suggestion of gene-environment interactions in the etiology of the disorder (45). One such project has begun in Brick Township, NJ where residents are concerned with an unusually high number of autistic children (46). Concerned parents suspect a relationship between these cases and a high level of industrial contamination, particularly in the drinking water (46). The CDC and ATSDR have initiated an investigation and found a high rate of autism in the area, but have not to date drawn conclusions about the possible role of environmental contaminants (46).
Asthma. A recent study by the National Center for Health for Health Statistics (NCHS) examined data on self-reports of asthma as well as physician's office and emergency room visits, and hospitalizations for asthma. The study provides strong evidence that striking increases in asthma prevalence in the United States during the past 15 years have occurred, particularly among children (47). These increases are particularly evident among poor, minority children in urban localities. In New York and in other major cities, asthma has become the leading cause of admission of children to hospitals and of school absenteeism (48). Ambient air pollutants, especially ground level ozone and fine particulates of automotive origin, have been shown to be important triggers of epidemic acute asthma. The frequency of asthma attacks increases with pollution and declines when levels of these pollutants drop (49). Indoor air pollution, including insect dust, mites, molds, and environmental tobacco smoke are additional triggers.
Childhood cancer. The incidence of childhood cancer has increased substantially in the United States in the past two decades (50). Although mortality rates are down, as a consequence of early detection and vastly improved treatment, data from the National Cancer Institute show that the reported incidence of acute lymphoblastic leukemia (ALL) increased by 27.4 percent from 1973 to 1990, from 2.8 cases per 100,000 children to 3.5 per 100,000. Since 1990, ALL incidence has declined in boys, but continues to rise in girls. From 1973 to 1994, the incidence of glioma increased by 39.6 percent, with nearly equal increases in boys and girls. In young men, 20 to 39 years of age, incidence of testicular cancer in the years 1973 to 1994 increased by 68 percent (50,51).
While the causes of these rising trends are not known, environmental factors are increasingly suspected to play a role in the genesis of pediatric cancer. Certainly these trends are not due simply to better screening for disease, better diagnostic capabilities, or better reporting (52). Environmental exposures of concern include organic solvents, electromagnetic fields (EMFs) (53) and pesticides (54,55,56,57,58,59).
Endocrine disruption. Endocrine disruptors are chemicals that can interfere with the body's hormonal signaling system (60,61,62). Effects of these chemicals, which have been hypothesized to include cancer, decreased fertility, birth defects of the reproductive organs, altered sex ratios, neurodevelopmental impairment, and immune dysfunction have been observed in cell systems in vitro, experimental posed to specific chemicals in the laboratory, and wildlife populations in several broadly contaminated ecosystems such as the Great Lakes.
Evidence of the effects of endocrine disruptors on human health is relatively scant, but most investigations are still in their early stages (60). Some data link precocious puberty with PBB among girls exposed during gestation and breast-feeding. Based on animal studies, the embryo and fetus appear to be at particularly high risk of adverse consequences following exposure to endocrine disruptors, because early exposures to them can alter anatomic structures and may influence the subsequent course of endocrine functioning, neurological development, and sexual development (63,64). Through the Food Quality Protection Act, Congress mandated extensive screening of chemical compounds to assess their potential for endocrine disruption (65).
The Concept of Subclinical Toxicity
A critically important step in the development of understanding children's special vulnerability to chemicals in the environment was the recognition that environmental toxicants can exert a range of adverse effects in children -- some of these effects are very severe and clinically evident, but others can be discerned only through special testing and are not evident through standard clinical examination: hence the term "subclinical toxicity." The underlying concept is the existence of a dose-dependent continuum of toxic effects in which clinically obvious effects have subclinical counterparts (66).
The concept of subclinical toxicity traces its origins to pioneering studies by Herbert Needleman and his colleagues of lead toxicity in clinically asymptomatic children (21). Needleman et al. showed that children's exposure to lead could cause decreases in intelligence and alteration of behavior even in the absence of clinically visible symptoms of lead toxicity (21). The subclinical toxicity of lead in children has subsequently been confirmed in prospective epidemiologic studies (5). Similar subclinical neurotoxic effects have been documented in children exposed in uteroto polychlorinated biphenyls (PCBs) (8) and to methyl mercury (67).
Subclinical toxicity can have major implications for the health and productivity of a population: for instance, a five-point drop in population mean IQ reduces by half the number of gifted children (IQ above 120) and increases by half the number with borderline IQ (IQ below 80) (68). These effects are permanent and irreversible. Thus, the concept of subclinical toxicity focuses importantly on the protection of populations of children from subtle, but persistent toxicities.
Costs of Pediatric Disease of Environmental Origin
Diseases of toxic environmental origin make an important economic contribution to total health care costs among children in the United States. It is estimated that the direct medical plus indirect costs attributable to these diseases currently amount to $54.9 billion annually: $43.4 billion for lead poisoning, $2.0 billion for asthma, $0.3 billion for childhood cancer, and $9.2 billion for neurobehavioral disorders (69). This sum represents approximately 2.8 percent of the total annual cost of illness in the United States (70). By comparison, the total annual health care costs attributable to motor vehicle accidents are $80.6 billion, and those due to stroke are $51.5 billion (70). The annual costs of military weapons research are $35 billion, and the costs of veterans' benefits are $39 billion (71). The costs of pediatric disease of environmental origin are large in comparison to the relatively meager amount of money spent on all research related to children, which in 1995 was only about $2 billion, a sum less than 3 percent of the total research enterprise of the federal government (72).
The burden of illness and economic costs due to pediatric disease of environmental origin may be anticipated to become yet greater in the years ahead if children's exposures to inadequately tested chemicals are permitted to continue. Increased investment is required in toxicity testing of chemicals, disease tracking and surveillance, basic studies of disease mechanisms, and prevention oriented epidemiologic research. Most importantly, increased investment is needed in pollution prevention.
Success Stories in Children's Environmental Health
Pediatricians in the United States and around the world have made major contributions to reducing children's exposures to environmental health threats. These successes underscore the very great influence that pediatricians and others who care for children's health can have over public policy, particularly when they join their obvious concern for children's health with a strong base of scientific evidence and a well-constructed strategy for child advocacy.
Removal of Lead from Gasoline. The quantity of lead used in the twentieth century far surpasses the total consumed in all previous eras. This heavy recent use reflects industrial applications as well as the consumption of vast quantities of lead as an anti-knock agent in gasoline. In the United States alone, nearly 200,000 tons of lead were consumed annually as a gasoline additive in the mid-1970s, the period of peak usage, and hundreds of thousands of tons continue to be used worldwide (73). Virtually all lead in gasoline is emitted into the environment through vehicle exhaust in finely particulate form, causing contamination of air, dust, and soil, locally and worldwide. Traces of automotive lead contamination have been detected as far from centers of population as the polar ice caps (74).
Consumption of lead has decreased sharply in the industrially developed nations in the past two decades. This reduction reflects the phase-out of leaded gasoline as well as decreases in industrial uses of lead and major reductions in human exposure and population blood lead levels have resulted (75). In the U.S., for instance, a 90 percent decline in population blood lead levels occurred between 1976 and 1997, and this decline closely paralleled the decline in use of leaded gasoline (76). Total cost savings resulting from the removal of lead from gasoline are estimated to exceed $50 billion each year with most of the gain resulting from increases in intelligence and thus in economic productivity over the entire lifespan of children whose exposure was prevented. Schwartz, et al. emphasize that in addition to these economic benefits, reduction in exposure to lead almost certainly produces large but poorly quantified social benefits that result from reductions in criminality, drug abuse, and incarceration (77,78). By contrast, in nations undergoing transition to industrialization, lead use in gasoline as well as in industry is only beginning to decline, environmental contamination may be intense, and blood lead levels in workers as well as in children living in communities near polluting industries have been reported to be dangerously elevated (79,80,81). These findings underscore the concept that, in the information age, the wealth of a nation is directly correlated with developmental health and aggregate intelligence.
Control of Children's Exposures to Toxic Pesticides. In the late 1980s, in the face of rising concern about the possible hazards of children's exposures to carcinogenic and other toxic pesticides, the U.S. Congress directed the National Research Council (NRC) to form a committee to examine these issues. This Committee on Pesticides in the Diets of Infants and Children was chaired by a pediatrician and included three other pediatricians as well as an obstetrician among its 14 members. The report of this committee raised concern on a broad national level about children's special vulnerabilities to pesticides and other environmental agents, making it clear that children are highly vulnerable to pesticides and other toxic chemicals and that protection of the health of vulnerable populations would require a new approach to risk assessment (82). The NRC report recommended an approach that moved beyond consideration of "average" exposures based primarily on adult characteristics to one that accounted for the heterogeneity of exposures and potential differential sensitivities at various life stages, particularly during prenatal development, infancy and childhood. Infants and children were identified in the NRC reports as groups within the population who require special consideration in risk assessment because of (1) their unique patterns of exposures to environmental hazards, and (2) special vulnerabilities.
The NRC report noted that "children are not little adults." It called for the development of new risk assessment methods that would incorporate better data on children's exposures to chemicals, along with improved information on the potentially harmful effects of chemicals during fetal development, infancy, and childhood.
The NRC Committee concluded that "in the absence of data to the contrary, there should be a presumption of greater risk to infants and children." To validate this presumption, the Committee recommended that "the sensitivity of mature and immature individuals should be studied systematically to expand the current limited database as to relative sensitivity."
To provide added protection to children during vulnerable periods of early development, the NRC Committee recommended that a child-protective uncertainty factor up to 10-fold be considered in risk assessment "when there is evidence of developmental toxicity and when data from toxicity testing relative to children are incomplete."
This series of steps will substantially reduce children's exposures to neurotoxic, endocrine disrupting, and carcinogenic pesticides.
Steps Pediatricians Can Take to Reduce Environmental Threats to Children's Health
In the Office and Clinic
Ask each family about the age of their house or apartment. Buildings constructed before 1970 are more likely than newer houses to contain lead paint, and the risk is greatest in houses built before 1950. Warn families against do-it-yourself lead paint removal. Be aggressive in screening blood lead levels among children.
Ask each family whether there are any smokers in the house. Seize the "teachable moment" to warn against the hazards of smoking. If parents must smoke, urge them to smoke outside.
Ask each family whether there is a gun in the house. Whenever possible, urge against gun possession. If relinquishing possession is not an option, urge responsible gun safety.
Warn each family against unnecessary use of pesticides. Encourage non-chemical options for pest control such as sealing cracks and crevices against cockroaches (in cities) and learning to live with dandelions (in the suburbs).
Take courses and obtain Continuing Medical Education (CME) credits in children's environmental health.
In The Community
Pediatricians enjoy enormous respect in their communities as physician-advocates for children. A few of many possible avenues by which pediatricians may turn that respect into good action are:
Join the school board and warn against lead, asbestos, and pesticide hazards in local schools.
Join the local board of health and ensure that the protection of children's health is a high priority of the health department.
Join the state chapter or district Committee on Environmental Health of the American Academy of Pediatricians.
In the Broader Society
Join the National Committee on Environmental Health of the American Academy of Pediatrics.
Run for political office, and use your elected position to educate for children's health generally, and for children's environmental health generally. America's children could certainly use a few more pediatricians in county and state legislatures as well as the U.S. Congress.
Toxic chemicals in the environment are a serious and still insufficiently recognized threat to children's health. The unique patterns of children's exposures to these chemicals and their physiologically based sensitivities unparalleled in adult life make children particularly vulnerable to toxic chemicals.
Pediatricians are in a unique position to reduce children's exposures to toxic chemicals in the environment. Indeed, pediatricians have made major gains already. The challenge is to build further upon those successes to further reduce environmental threats to children's health.
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Phillip J. Landrigan, MD, MSc, FAAP, Mount Sinai Hospital, New York, NY.