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RESEARCH
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Studies & Findings HEALTH EFFECTS OF LEAD IN CHILDREN AND ADULTS Moderator: Dr. R. Reigart; Panel: Dr. H. Needleman, Dr. D. Nag , Dr. P.P. Maiya, Dr. R. Chatterjee, Dr. D.J. Parikh Introduction Before detailing the health effects of lead, it is relevant to understand certain unique properties of lead. Also pertinent is an understanding of the evolution of the disease, research, and several characteristics of lead poisoning. Taken together, this information lays the foundation for the present day physician to make the appropriate diagnosis and take the necessary actions to treat the disease. References to lead’s harmful effects were recorded several thousand years ago by Greek and later Roman physicians. The prevalence of lead exposure during the Roman times is well documented: water pipes, wine urns, wine preventives, and cookware, etc. Throughout the medieval ages, outbreaks of colic could be traced to lead used in wine. During the Industrial Revolution, exposure to lead increased dramatically due to occupational contact. It became clear that the handling of lead by workers would likely result in major health problems, even death. With the hindsight of scientific research, historians knew that people throughout the ages were being exposed to lead and that it resulted in health problems. But at no earlier time did the medical community ever recognize lead poisoning as a disease and establish guidelines for diagnosis, treatment, or prevention. The health of the general population was poor, with infections and other diseases being rampant throughout the periods of lead exposure. In earlier times, if you had lead poisoning symptoms, you would likely be diagnosed with digestive disorders caused by eating rancid meat or other spoiled foods. Even today with our understanding of the most studied toxic metal and all the sophisticated testing technology, clinical features of lead intoxication are nonspecific and often go unrecognized. It is reasonable to conclude that the vast majority of lead poisoned people were never diagnosed or treated, and that is likely true today in most developing countries.
Major event in lead’s evolution: In the early 1890’s the first clinical reports of lead poisoning in children were documented at a children’s hospital in Australia. What is significant is that the source of lead was not a factory but rather, it was found in average homes. The second factor is that the disease centered around children and not adults. The next major era in lead’s history, the 1920’s, was brought on by the introduction of Tetraethyllead (Tel), the lead additive in gasoline. As a result, lead was environmentally dispersed throughout the world. Lead products were also being mass-produced for home use. Research findings change direction of lead poisoning policy: Research was discovering that even without showing symptoms of lead poisoning, one’s health was likely being damaged by elevated lead levels. The research was so compelling that laws were enacted to ban lead from society. It had been known since the early 1900’s that lead intoxication resulted in learning or behavior disorder in children. But what was not fully understood was how little of lead exposure may cause these problems. Finally, during the early 1990’s, the results from several long-term health studies on lead exposure were reported. The results were consistent; that much lower levels of lead exposure caused more severe damage to the nervous system than previously believed. There may be no lower threshold for some of the adverse effects of lead in children. In addition, the harm that lead causes to children increases as their blood lead levels increase. As a result the public health care community became so alarmed that conferences were established and scientific debate commenced. The end result of these conferences, studies, and committees was the United States governmental agency, the Centers for Disease Control, lowered the acceptable standard for lead in the blood from 25 mcg/dl per deciliter to 10 mcg/dl., and called for mandatory lead screening for all pre-school children. What also played a major role in understanding lead poisoning was the advancement of lead testing technology. The equipment made it possible to accurately determine blood lead levels (BLL). The sophistication of the lab equipment resulted in quality research and a much clearer understanding of the impact of low level lead exposure. The development of biologic markers for low lead exposure levels and clinical identification of associated adverse health effects changed forever the way we address lead poisoning. Lead’s Unique Properties Lead is not biodegradable, it never disappears, only accumulates where it is deposited. Lead provides no known biological benefit to humans. Young children absorb lead more readily than adults (42%-48% Vs 8%-10%). Lead may accumulate in the body over decades, and it is stored in the bones and teeth ( half-life is 19 years). There is no such thing as normal or safe levels of lead. More than 95% of retained lead is in bone, acting as a reservoir, where it is in continuous exchange with the soft tissue pools. The half-life of circulating lead in blood is about one month. Troubling characteristics of lead and lead poisoning Lead in the brain interferes with the mechanisms that naturally evolve in a normally developing brain. Brains are often compared to computers but in fact, the brain is a constantly evolving living force, which is affected by and responds to outside stimuli, especially during the first several years of life. Lead does not belong anywhere in the brain and its presence only interferes with maturing processes that promote healthy brain function. It is ironic that very young children play in environments where lead is pervasive, absorb lead quite efficiently during the same time period as their brains are at the height of development! Problem in Developing Countries The theme of the conference is establishing A National lead Prevention Program in Developing Countries. Why is there so much focus on developing countries? Should clinicians be more concerned with children from developing countries? The short answers are: simply because of the need, and yes they should. There are many developing nations with limited funding to properly address all their people’s health needs. With many problems and too few resources, priorities must be set. Often the long-term health consequences resulting from an unsafe environment are not given proper attention. The experts would agree that the question is not whether there is a problem of lead in the environment but the degree to which children are exposed. In most developing countries lead has not yet been banned from gasoline but is in fact in high concentration. The numbers of cars in the larger cities are growing very fast due to the migration of people to the cities looking for work. Most traffic in these larger cities is heavily congested and poorly managed, which compounds the existing problem. Also, lead has not been banned from paint or from plumbing fixtures. The growing population is taxing the existing water systems which are old and leaching lead, and in some communities the people are forced to share the same water used by industry who use the water for disposal of toxic materials. Most industries are small and not regulated and are located within or close to where families live. Many cottage industries are located in homes or close to homes and use lead in many forms. The very nature of lead and its many uses guarantees problems. Lead is not biodegradable, it never disappears, only accumulates where it is deposited. Considering these realities, experts would conclude that the children who play and live in the larger cities of developing countries are being exposed to excessive lead levels in their environments and thus develop unacceptable elevated blood lead levels. Doctors Have to Become Detectives When It Comes to Lead Poisoning It is vital that physicians understand the many pathways of lead into the children’s environment. Eliminating the source of lead is vital for effective treatment. In fact, to give some treatments, such as chelation therapy, while the child is still being exposed to lead, may cause more absorption of the lead into the body. For adults, the problem of discovering the lead source is usually simple and occupational in nature. Every country in the world has lead in its environment, in both rich and poor neighborhoods. Every community has it’s own lead profile. To get an accurate picture of just how much lead is in an environment, one has to analyze each separate lead pathway in every community and even every home if need be. When taken together: numerous pathways of lead, biological characteristics, cumulative nature, asymptomatic, low level impact on the health of young children, etc., lead poisoning is a very complex disease to diagnose and treat.
Health Effects in Children Lead is a pervasive environmental poison that affects virtually every system in the body. It can damage the kidneys, the nervous system, the reproductive system, and cause high blood pressure. It is especially harmful to the developing brains of fetuses and young children. Lead poisoning is the number one environmental problem for most children. Lead exposure in young children is of particular concern because children absorb lead more readily than adults, and children's developing nervous systems are particularly vulnerable to lead's effects. Blood lead levels (BLL) as low as 10 micrograms/deciliter (ug/dL) are associated with harmful effects on children's learning and behavior. Elevated BLL in children are a major preventable health problem that affects children's mental and physical health. The higher a child's BLL and the longer it persists, the greater the chance that the child will be affected. Elevated BLLs can result in: Learning disabilities. Behavioral problems. Mental retardation. At extremely high levels (70 ug/dL or higher), seizures, coma, and even death. Amounts of lead that don’t appear to harm an adult can slow down the normal mental and physical development of children. Lead levels that were once thought to be safe (25 ug/dL.) are associated with lower cognitive function, learning disabilities, shorter stature, hearing loss, and behavior problems in children. At lower BLL, lead poisoning is likely to produce few or no symptoms. What makes lead poisoning so devastating is that at lower BLL there may be no distinctive clinical symptoms but the effects of childhood lead poisoning on intellectual and neurobehavioral functioning are measurable and may persist for life. Diagnosis and Treatment The onset of clinical lead intoxication is usually insidious and is associated with moderately elevated BLLS over 20 ug/dL. It begins with lethargy, malaise, irritability, and sometimes, abdominal pain. It may progress to complaints of severe stomachaches, constipation, sporadic vomiting, loss of balance, sleepiness, stupor, and headaches. Further advanced poisoning results in repeatedly vomiting, extreme abdominal pains, seizures ending with coma and death. Frequently, there may be a rapid progression through all stages of lead poisoning. Even at relatively low lead levels there can be subtle effects on a child’s development and intellectual capacity. In some children the best signs of lead toxicity are in behavior changes, not necessarily physical changes. Children sometimes become more irritable, aggressive, show signs of attention deficits. Some children lose coordination and may seem " wobbly" when they walk. Other children may demonstrate delayed motor function, open eyes when stimulated but not be able to speak. Some children may show signs of losing recently learned skills and abilities. Depending on the severity of a child's BLL, follow-up actions and treatment can include:
Elevated BLL can result in anemia, lead in the body can interfere with the manufacturing of Hemoglobin, (Lead interferes with heme pathway enzymes which are found in all cells). Therefore, all testing results with BLL >10mcg/dL should also be checked for anemia. Children with symptoms and elevated BLL > 45 mcg/dL should be treated as an emergency. All children with elevated BLL should be removed from the toxic source immediately. Children at Higher Risk All children ages 6 months to 72 months are considered at risk and should be screened Children considered to be at higher risk include those in low-income families, living in older housing stock, near areas busy with traffic, industrial parks, renovations, and demolished buildings. In the US, children from low-income families were four times more likely to have elevated levels of lead in their blood than children from high-income families. Very young children are more at risk because of the hand -to-mouth activity. Additional risk factors include parents who work with lead at their job or as a hobby. Lead is the number one pollutant in most major cities of developing countries. The good news is that lead poisoning is the most preventable disease in children!! It is important that prevention takes place by removing the lead from the environment before it enters the child’s body. In the USA, the findings from the National Health and Nutrition Examination Surveys (NHANES) show declines in BLLs in every segment of the U.S. population. Whereas in 1976-1980 the average BLL in children was 15ug/dL, in 1991-1994, the average was 2.7ug/dL. This is believed to be the result of removal of lead from gasoline as well as from other sources such as household paint, food and drink cans and plumbing systems. However, BLLs remain higher among children in low-income families, especially those living in older housing where leaded paints may have been used. Race is a factor as well, though the mechanism is unknown. According to a national survey, from 1991-1994, 21.9% of black children ages 1 to 5 who were living in older housing had elevated blood lead levels (10ug/dL or higher). To reach children still at risk, USA CDC has issued lead screening guidelines to be used by state and local health officials. In particular, the guidelines recommend targeted screening at children who live in older homes and children from low-income families. For developing countries, an assessment of the pathways of lead needs to be evaluated first and then appropriate protocols can be established to address each community’s screening procedures.
For School Children Several studies have examined the effects of lead on school aged children.
Special Care for Pregnant Women and Infants Lead accumulates and can be stored for decades in bone. This presents a special problem for pregnant women with past lead exposure. Lead can be released from the bone whenever there is a demand for Calcium, such as during pregnancy and lactation. Lead crosses the placenta and can be detected in breast milk.. It is quite conceivable that some mothers may be the major source of lead for their babies. Even for mothers living in relatively lead- free societies, they may be transferring lead which accumulated in their bodies in other environments in earlier times. If the stored lead in the bones is released into the developing baby it may likely wreak neurological havoc.
In Adults Lead poisoning continues to be one of the most prevalent occupational and environmental illnesses affecting adults. Adults at highest risk are those who are exposed to lead at work: such as painters, printers, plumbers, in industrial centers, renovation work, jewelers, and smelters, etc. Therefore, a trained clinician needs to do a good environmental and occupational history of a patient who shows any signs of possible lead poisoning. Clinical diagnosis of lead poisoning in the adult is often complicated by the lack of any clear symptoms and signs. Awareness of the sources of lead exposure by the physician may be the best chance for a patient to be properly diagnosed for the disease. Adults do not absorb lead as easily as children, 10% range Vs 40% for children. Chronic exposure with elevated BLLs are associated with hypertension, headaches, confusion, irritability, focal motor dysfunction, and insomnia. Higher levels cause drowsiness, loss of muscular coordination, kidney damage, fatigue, apathy, and susceptibility to infection, gouty arthritis conditions, and anemia. Renal Effects: Acute renal effects include reversible loss of renal function--damage to the proximal tubules, which produces a Fanconi Syndrome manifested by aminoaciduria, glucosuria, and phosphaturia. Continuous prolonged high lead exposure results in chronic and nonreversible effects associated with progressive interstitial fibrosis, which may lead to renal damage characterized by interstitial fibrosis, sclerosis of vessels, glomerular atrophy, reduced glomerular filtration, and azotemia. Gastrointestinal Effects: Colic is a consistent early symptom in occupationally exposed cases or in cases of acute intoxication. Initial nonspecific symptoms appear at blood lead levels of approximately 80 mcg/dl, and include dyspepsia, anorexia, postprandial epigastritis, constipation, cramps, and nausea. Gastrointestinal symptoms are aggravated when blood lead levels reach 100 mcg/dl or higher and can include severe abdominal colic and constipation. Severe symptoms occur at blood lead levels of 150 mcg/dl or higher and can include "lead colic" (severe abdominal spasms that resemble acute abdominal pain requiring surgery) and liver damage. More research is needed to determine the full health impact lead poisoning has on adults. Future Suggestions on the Direction of Research Lead poisoning should be included in the differential diagnosis of unexplained convulsions in children. In the light of the multi-centric study in India, with such a high percentage of children having dangerously elevated levels of lead, it is relevant to consider lead poisoning as a major cause of convulsions in the pediatric population in the clinical setting, of course, after ruling out the major commoner and established causes. Again, unexplained convulsions in the newborn could reflect maternal lead toxicity. Emphasis is to be placed on studies to determine the extent of lead transfer to the fetus in the last trimester of pregnancy due to mobilization from the bones. It would be relevant to determine cord lead levels with greater frequency in the Indian settings. Hence, the need for easy availability of the lead estimation systems. The interactive session also threw up various points on neuropsychiatric manifestations of lead poisoning, which were expertly discussed by the panelists. The importance of more extensive and detailed studies to correlate Alzheimer’s Disease and possibly Parkinson’s disease, with increased mobilization of lead from bones in old age was well brought out. Members of the audience also raised several important issues pertaining to environment and public health policies. Interesting observation of concomitant tea consumption and cigarette smoking contributing to increased blood lead levels was highlighted by Dr. Nag in her study, which has relevance in our subcontinent.
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