Review Article

Indian Pediatrics 2003; 853-860

Environmental Health for Practicing Pediatricians

Children in today’s world are surrounded by a wide array of environmental threats to health. These threats include well-studied exposures to lead, asbestos and ionizing radiation as well as more recently recognized exposures to pesticides, polychlorinated biphenyls (PCBs) and molds. Increasingly, pediatricians are asked about these environ-mental exposures and risks they may pose to children’s health. They are asked about the possible contributions of environmental factors to rising rates of childhood asthma, to the causation of pediatric cancer and to autism.

Pediatric environmental health is concerned with understanding the effects of environmental exposures on children’s health and thus with the etiology, prevention, evaluation and management of conditions in children that are caused or exacerbated by hazardous chemical and physical exposures in the environment(1,2). The field is inherently multidisciplinary with links to numerous specialties including neurology, oncology, and developmental pediatrics. The American Academy of Pediatrics played the key role in launching the field through its development in 1957 of the Committee on Environmental Health. This Committee has authored numerous policy statements and in 1999 produced the first manual for pediatricians on the subject, the Handbook of Pediatric Environmental Health(2). The growth of the field of pediatric environmental health was fostered by a synergistic interaction between advances in scientific understanding of the effects of environmental exposures on children’s health and an exponential increase in concern about the environment that has become a prominent feature of American society. In the United States, catalytic events at the national level were the release in 1993 of a report on pesticides in the diets of infants and children by the National Academy of Sciences declaring that children are fundamentally more sensitive than adults to pesticides(3) and the subsequent development of a federally-supported, national program of research, education and prevention in pediatric environ-mental health.

Unique susceptibility of children

Research in pediatric environmental health has had a broad influence on pediatric practice by elucidating the notion of children’s unique windows of vulnerability(4). Seminal studies, beginning with early work on thalidomide and fetal alcohol syndrome and extending more recently to lead, have reinforced the idea that the fetus and child are exquisitely susceptible to toxicants because of the delicate develop-mental processes that occur so rapidly and are so easily derailed. This research highlights additionally the concept that behavioral development is a risk factor for environmental exposures. All pediatricians learn about the concept during residency training. What the study of pediatric environmental health does is to expand the issue to include consideration of the impact of environmental factors on children’s health and development, thereby offering pediatricians the opportunity to add additional depth to their understanding of pediatrics.

The daily practice of pediatrics is filled with examples of children’s increased exposure and windows of vulnerability.

Increased exposure

Children’s physiologic need for relatively more fluids, calories and oxygen, kilogram per kilogram, as compared to adults results in greater intake of water, food and air and thus greater exposure to environmental contaminants(2). Pediatricians are well aware that children consume more food and water for their body weight than adults, and have a higher resting metabolic rate and rate of oxygen consumption for their body weight than adults(2,9). Relative to body mass, children will uptake more of any contaminants present in water, food and air. For example, children are likely to have greater exposure to carbon monoxide because their greater meta-bolic demands result in increased respiratory minute volume. Increased exposure also results from normal behavioral development. For example, infants and toddlers normally exhibit hand-mouth behavior, increasing potential exposure to lead paint and dust found on the ground and window wells(9).

Windows of vulnerability

Classic examples illustrate the concept of critical windows of susceptibility. Exposure to thalidomide in utero resulted in an epidemic of phocomelia(10). Diethylstilbestrol use in the l940s and 1950s resulted in vaginal adenosis and other malformations including cervical eversion and transverse cervical and vaginal ridges in approximately 80% of women exposed in utero and led to an increased risk of clear cell adenocarcinoma of the vagina in these young women. All of these malforma-tions appear related to disturbance of mullerian duct development in utero(11-14). Tetra-cycline causes discoloration and hypoplasia of tooth enamel when administered to children younger than 8 years of age, which is when tooth enamel is formed. Children older than 8 and adults do not develop discolored teeth.

These examples illustrate that the fetus and infants and children have windows of time during which they are uniquely vulnerable to the adverse effects of drugs and chemical toxicants. The special vulnerability extends beyond drugs to infectious agents. For example, the hemolytic-uremic syndrome is most common in children younger than 4 years of age(15), despite the fact that this is not the age group of children with the highest exposure to E. coli O157:H7 in food and water. It appears that young children are more susceptible to verotoxin, a toxin that is absorbed from the intestines and initiates the endothelial cell injury. Differential localiza-tion in infant versus adult kidneys of the glycolipid receptors in the endothelial cell membrane that bind the toxin is believed to be a reason for the increased risk of hemolytic-uremic syndrome in children(16,17).

Lead exposure

Lead is an environmental toxicant that illustrates with great clarity the concepts of increased exposure and windows of vulner-ability. Lead poisoning in children related to lead based paint was recognized over 100 years ago. At the present time, most high-dose exposure of children comes from leaded paint. Children are particularly susceptible to exposure when they are infants and toddlers. At this time in life, normal toddler activity can result in transfer of lead chips or dust from fingers and hands to mouths. Children may chew on lead-painted window sills-another activity not usually observed in adults.

Children absorb about 40% of ingested lead, while adults absorb 10-15%(18). Lead is absorbed with calcium, which children absorb at high rates because a growing child needs extra calcium to build bones and teeth. Lead at high doses has effects on many organ systems; pediatricians are most concerned about the potentially devastating effects on the nervous system. Unlike the development of the heart, the major structures of the brain continue to develop after birth. Neuronal migration, cell proliferation, and synapse formation are very active from birth through 3 years of age. Selective synaptic pruning and apoptosis is active for several years thereafter(19). Myelination continues into adulthood(20).

"Subclinical" toxicity

A critically important step in the development of understanding of 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 clinically evident, but others can be discerned only through special testing and are not evident on the standard clinical examination, hence the term "subclinical toxicity." The underlying concept is that there exists a dose-dependent continuum of toxic effects, in which clinically obvious effects have their subclinical counterparts(21).

The concept of subclinical toxicity traces its origins to pioneering studies of lead toxicity in clinically asymptomatic children under-taken by a number of investigators including Byers and Lord in the 1940s(22) and Needleman and his colleagues in the 1970s and 1980s(23). Prior to that work, it was thought that children who were lead poisoned but who did not die would not suffer adverse effects(24). When subsequent work revealed that children who recovered from an acute episode had a high likelihood of having behavioral and learning problems, it was believed that only children with symptoms later developed sequelae(22). Needleman and his colleagues 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(23). The subclinical toxicity of lead in children has subsequently been confirmed in prospective epidemiologic studies(25). Similar subclinical neurotoxic effects have been documented in children exposed in utero to polychlorinated biphenyls (26) and to methyl mercury(27).

Effects of other toxic chemicals in the environment

Children of the world are surrounded by thousands of synthetic chemicals, most of which have been invented and developed only in the past 50 years. Over 85,000 synthetic chemical compounds are now registered for commercial use in the U.S. Environmental Protection Agency’s Toxic Substances Control Act inventory, and 2,800 high-production-volume chemicals are currently produced in quantities of one million pounds or more per year(28). These high-production-volume chemicals are most likely to be used extensively in foods and consumer products and to be most widely disseminated in the environment. Fewer than half of high-production-volume chemicals have been tested for their potential toxicity to humans, and fewer than 10% for their developmental toxicity or toxicity to children(28,29). The hazards that these chemicals may pose to children’s health and development are still largely unknown(30). There is speculation that chemicals in the environment may be associated with changing patterns of disease in children – increasing rates of asthma, increas-ing incidence of certain childhood cancers, and the wide prevalence of neurodevelopmental disabilities.

Asthma

During the past 15 years asthma has increased in prevalence in the United States, particularly among children(31). This increase is 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 the leading cause of school absenteeism(32). Indoor air pollution, includ-ing environmental tobacco smoke, mites, molds, and insect parts is an important trigger. Ambient air pollutants, especially ground-level ozone and fine particulates of automotive origin, have also been associated with increased asthma visits(33).

Childhood cancer

The incidence of childhood cancer has also increased in the United States in the past two decades(34). Although mortality rates have decreased as a consequence of early detection and vastly improved treatment, the reported incidence of acute lymphoblastic leukemia (ALL) increased by 27.4% 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 1973-1994, the incidence of glioma increased by 39.6%, with nearly equal increases in boys and girls. In young men, 20-39 years incidence of testicular cancer in the years 1973-1994 increased by 68%(35,36).

These trends are not thought to be due simply to better screening for disease, better diagnostic capabilities or better reporting(37). The causes of these rising trends are not known; investigations are attempting to evaluate what role, if any, environmental factors such as organic solvents and pesticides(38-42) may play.

Neurodevelopmental disorders

Neurodevelopmental disorders, including learning disabilities, dyslexia, mental retarda-tion, attention deficit disorder and autism affect 5-10% 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(43). Causes are largely unknown; studies are evaluating the role of in utero and early life exposures to lead(25,44), mercury(45), PCBs(26), certain pesticides and other environmental neurotoxicants(46-48). A recent report from the National Research Council (NRC) concluded that 3% of developmental disabilities are the direct consequence of neurotoxic environmental exposures and that another 25% arise out of the interplay of environmental factors and individual genetic susceptibility(49).

Positive steps already taken

Pediatricians in the United States and in nations 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 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. The removal of lead from gasoline represents a major public health success story. 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(50). Virtually, all of the lead in gasoline is emitted into the environment through vehicle exhaust in finely particulate form. It causes 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(51).

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(52). Major reductions in human exposure and in population blood lead levels have resulted. In the US, for instance, there occurred an 80% decline in population blood lead levels between 1976 and 1997(53), and this decline paralleled closely the decline in use of leaded gasoline. In children, average lead levels dropped dramatically as a result of these measures: From 1976 to 1980, before the regulations had their full impact, 1 to 5 year-old US children had a median blood lead level of 15 µg/dL; in 1988-91, the median was 3.6 µg/dL; in 1999, the median was 2.0 µg/dL(54-56).

The control of children’s exposures to pesticides has been a legislative success story in the US, although the implementation of the legislation has been less successful. 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 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 fourteen members.

The NRC report elevated concern on a broad national level about children’s special vulnerabilities to pesticides(3). It made clear that children are highly vulnerable to pesticides and other toxic chemicals and that protection of the health of vulnerable popula-tions would require a new approach to risk assessment. 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 for 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 pesticides, 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 incor-porate better data on children’s exposures to pesticides along with improved information on the potentially harmful effects of pesticides during fetal development, infancy and childhood. The NRC Committee concluded "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 of 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 could substantially reduce children’s exposures to pesticides.

Conclusion

The unique patterns of children’s exposures to environmental contaminants and their physiologically-based sensitivities that are unparalleled in adult life make children particularly vulnerable.

Pediatricians are in a unique position to reduce children’s exposures to contaminants in the environment. Indeed, pediatricians have made major gains already. The challenge is for pediatricians to work with policy makers to build upon those successes to further reduce environmental threats to children’s health.

References