Preventing Lead Poisoning in Young Children: Appendix II.
- Table of Contents
- Chapter 1. Introduction
- Chapter 2. Background
- Chapter 3. Sources and Pathways of Lead Exposure
- Chapter 4. The Role of the Pediatric Health-Care Provider
- Chapter 5. The Role of State and Local Public Agencies
- Chapter 6. Screening
- Chapter 7. Diagnostic Evaluation and Medical Management of Children with Blood Lead Levels > or = to 20 µg/dL
- Chapter 8. Management of Lead Hazards in the Environment of the Individual Child
- Chapter 9. Management of Lead Hazards in the Community
- Appendix I. Capillary Sampling Protocol
- Appendix II. Summary for the Pediatric Health-Care Provider
- Chapters 1 and 2. Introduction and Background
- Chapter 3. Sources and Pathways of Lead Exposure
- Chapter 4. The Role of the Pediatric Health-Care Provider
- Chapter 5. The Role of State and Local Public Agencies
- Chapter 6. Screening
- Chapter 7. Diagnostic Evaluation and Medical Management of Children with Blood Lead Levels > or = to 20 µg/dL
- Chapter 8. Management of Lead Hazards in the Environment of the Individual Child
- Chapter 9. Management of Lead Hazards in the Community
The following material summarizes those parts of the lead statement that are most important for the pediatric health-care provider. It does not include some of the critical information on such topics as primary prevention, sources of lead in the environment, and abatement. More information on all of the topics described herein is included in the complete statement.
Childhood lead poisoning is one of the most common pediatric health problems in the United States today, and it is entirely preventable. Enough is now known about the Sources and Pathways of Lead Exposure and about ways of preventing this exposure to begin the efforts to permanently eradicate this disease. The persistence of lead poisoning in the United States, in light of all that is known, presents a singular and direct challenge to public health authorities, clinicians, regulatory agencies, and society.
Previous lead statements issued by the Centers for Disease Control (CDC) have acknowledged the adverse effects of lead at lower and lower levels. In the most recent previous CDC lead statement, published in 1985, the threshold for action was set at a blood lead level of 25 µg/dL, although it was acknowledged that adverse effects occur below that level. In the past several years, however, the scientific evidence showing that some adverse effects occur at blood lead levels at least as low as 10 µg/dL in children has become so overwhelming and compelling that it must be a major force in determining how we approach childhood lead exposure.
Because 10 µg/dL is the lower level of the range at which effects are now identified, primary prevention activities—communitywide environmental interventions and nutritional and educational campaigns should be directed at reducing children's blood lead levels at least to below 10 µg/dL. Blood lead levels between 10 and 14 µg/dL are in a border zone. While the overall goal is to reduce children's blood lead levels below 10 µg/dL, there are several reasons for not attempting to do interventions directed at individual children to lower blood lead levels of 10-14 µg/dL. First, laboratory measurements of blood lead levels may be variable, so a blood lead level in this range may, in fact, be below 10 µg/dL. Secondly, effective environmental and medical interventions for children with blood lead levels in this range have not yet been identified and evaluated. Finally, the sheer numbers of children in this range would preclude effective case management and would detract from the individualized follow up required by children who have higher blood lead levels.
The single, all-purpose definition of childhood lead poisoning has been replaced with a multi-tier approach. Community prevention activities should be triggered by blood lead levels > or = to 10 µg/dL. Medical evaluation and environmental investigation and remediation should be done for all children with blood lead levels > or = to 20 µg/dL. All children with blood lead levels > or = to 15 µg/dL require individual followup, including nutritional and educational interventions. Furthermore, depending on the availability of resources environmental investigation and remediation should be done for children with blood lead levels of 15-19 µg/dL, if such levels persist. The highest priority should continue to be the children with the highest blood lead levels.
Other differences between the 1985 and 1991 statements are as follows:
Screening test of choice. Because the erythrocyte protoporphyrin level is not sensitive enough to identify children with elevated blood lead levels below about 25 µg/dL, the screening test of choice is now blood lead measurement.
Universal screening. Since virtually all children are at risk for lead poisoning, a phase in of universal screening is recommended, except in communities where large numbers or percentages of children have been screened and found not to have lead poisoning. The full implementation of this will require the ability to measure blood lead levels on capillary samples and the availability of cheaper and easier-to-use methods of blood lead measurement.
Primary prevention. Efforts need to be increasingly focused on preventing lead poisoning before it occurs. This will require communitywide environmental interventions, as well as educational and nutritional campaigns.
Succimer. In January, 1991, the U.S. Food and Drug Administration approved succimer, an oral chelating agent, for chelation of children with blood lead levels over 45 µg/dL.
A child's environment is full of lead. Children are exposed to lead from different sources (such as paint, gasoline, and solder) and through different pathways (such as air, food, water, dust, and soil). Although all U.S. children are exposed to some lead from food, air, dust, and soil, some children are exposed to high dose sources of lead. Lead-based paint is the most widespread and dangerous high-dose source of lead exposure for preschool children.
Lead-based paint (containing up to 50% lead) was in widespread use through the 1940s. Although the use and manufacture of interior lead-based paint declined during the 1950s and thereafter, exterior lead-based paint and lesser amounts of interior lead-based paint continued to be available until the mid-1970s. (Lead-based paint produced after the 1940s tended to have much lower lead concentrations than lead- based paint produced earlier.)
Pica, the repeated ingestion of nonfood substances, has been implicated in cases of lead poisoning; however, a child does not have to eat paint chips to become poisoned. More commonly, children ingest dust and soil contaminated with lead from paint which flaked or chalked as it aged or which has been disturbed during home maintenance and renovation. This lead-contaminated house dust, ingested via normal repetitive hand-to-mouth activity, is now recognized as a major contributor to the total body burden of lead in children. Because of the critical role of dust as an exposure pathway, children living in sub-standard housing and in homes undergoing renovation are at particular risk for lead poisoning.
Many cases of childhood lead poisoning that result from renovation or remodeling of homes have been reported. Before older homes undergo any renovation that may generate dust, they should be tested for the presence of lead-based paint. If such paint is found, contractors experienced in working with lead-based paint should do the renovations.
Other potentially important Sources and Pathways of Lead Exposure include soil and dust, water, "take home" exposures from parental occupations and hobbies, water, and food. Very high-dose exposure may occasionally result from sources other than lead-based paint in specific situations.
Pediatric health-care providers, working as part of the public health team, must play a critical role in the prevention and management of childhood lead poisoning. Their roles include: 1) educating parents about key causes of childhood lead poisoning; 2) screening children and interpreting blood lead test results; 3) working with appropriate groups in the public and private sectors to make sure that poisoned children receive appropriate medical, environmental, and social service followup; and 4) coordinating with public health officials and others involved in lead-poisoning prevention activities.
Along with educating parents about nutrition and developmental stages, providers should discuss the potential hazards of lead. They should focus on the major likely preventable sources of high-dose lead poisoning in their communities. Parents should be told of the potential dangers of peeling lead-based paint, the potential hazards of renovating older homes, and the need for good work practices if their occupations or hobbies expose them to lead. In some communities parents should be warned about the potential for lead exposure from improperly fired ceramicware and imported pottery. In others, where water lead levels are a concern, parents could be advised to use only fully-flushed water (that is, water that has not been standing in pipes for a prolonged time) from the cold-water tap for drinking, cooking, or preparing infant formula.
Pediatric health-care providers should provide information about simple ways parents can reduce exposure to lead. Some examples of these are discussed below.
Housekeeping interventions. Particularly in older homes, which may have been painted with lead-based paint, interventions to reduce exposure to dust may help reduce blood lead levels. These include:
- Make sure your child does not have access to peeling paint. Pay special attention to windows and window sills and wells.
- If the house was built before about 1960 and has hard surface floors, wet mop them at least once a week with a high phosphate solution (for example, 6-8% phosphates). (The phosphate content of automatic dishwashing detergents and other cleaning substances is often listed on the label and may be high enough for this purpose. Otherwise, Trisodium Phosphate can be purchased in hardware stores.) Other hard surfaces (such as window sills and baseboards) should also be wiped with a similar solution. Do not vacuum hard surface floors or window sills or wells, since this will disperse dust. Vacuum cleaners with agitators remove dust from rugs more effectively than vacuum cleaners with suction only.
- Wash your child's hands and face before he/she eats.
- Wash toys and pacifiers frequently.
Other interventions to reduce exposure to lead.
- If soil around the home is or is likely to be contaminated with lead (for example, if the home was built before 1960 or the house is near a major highway), plant grass or other ground cover. Since the highest concentrations of lead in a yard tend to be near surfaces that were once painted with lead paint, like exterior walls, if exterior lead paint was likely to be used, plant bushes around the outside of your house so your child cannot play there.
- In areas where the lead content of water exceeds the drinking water standard, use only fully-flushed water from the cold-water tap for drinking, cooking, and making formula. In communities where water conservation is a concern, use first-flush water for other purposes.
- Do not store food in open cans, particularly if the cans are imported.
- Do not use pottery or ceramicware that was improperly fired or is meant for decorative use for food storage or service.
- Make sure that take-home exposures are not occurring from parental occupations or hobbies (Chapter 3).
Not all aspects of a poisoned child's followup will be managed by the pediatric health-care provider, although the provider is an important part of the team. Through his or her interactions with the child and family and the responsible public health agency, the provider should make sure that any appropriate interventions are occurring. If the child needs a medical evaluation (for a blood lead level > or = to 20 µg/dL) or pharmacologic treatment (Chapter 7), either the provider should do it or should refer the child to a place that treats large numbers of poisoned children. The provider should make sure that the child receives an appropriate environmental investigation and remediation with the help of the public health agencies. Particularly if the child is developmentally delayed, the provider should refer the child to an appropriate infant stimulation or child development program. In many cases, lead-poisoned children and their families will also benefit from social services followup.
A variety of local, state and federal agencies play a role in preventing childhood lead poisoning. Pediatric health care providers and parents should know about what these agencies do so that they can use these resources effectively. In turn, these agencies must coordinate their activities to ensure that all aspects of childhood lead poisoning prevention—health, housing, and environment—are being addressed, and to provide the most comprehensive and cost-effective services to at-risk children, their parents, and their health-care providers.
Traditionally, the main purpose of a childhood lead poisoning screening program has been to identify asymptomatic lead-poisoned children and to intervene as quickly as possible to reduce their blood lead levels. An additional benefit of screening programs is that abatement of lead sources for poisoned children results in prevention of lead poisoning for children who would have been exposed to those sources in the future. As the focus in lead poisoning prevention turns more to primary prevention, an additional benefit of screening is that data generated can be used in targeting interventions to places with children at high risk for lead poisoning.
In 1984, the last year for which estimates are available, it is believed that between 3 and 4 million children younger than age 6 years (17% of all U.S. children in this age group) had blood lead levels above 15 µg/dL. Furthermore, about 74% of occupied, privately owned housing built before 1980 contains lead-based paint (defined as > or = 1 mg/cm2). Because almost all U.S. children are at risk for lead poisoning (although some children are at higher risk than others), our goal is that all children should be screened, unless it can be shown that the community in which these children live does not have a childhood lead poisoning problem. (Deciding that no problem exists requires that a large number or percentage of children be tested.) The full implementation of this will require the ability to measure blood lead levels on capillary samples and the availability of cheaper and easier-to-use methods of blood lead measurement. Children at highest risk for lead poisoning are the highest priority for screening. Table 6-1 provides guidance on the groups for which repeated screening is most strongly indicated.
Children ages 6 to 72 months who live in or are frequent visitors to deteriorated old buildings, including day care centers, make up the highest priority group. Because the highest concentrations of lead in paint were used in the early 1900s, homes built before about 1960 are of greatest concern. Children whose homes are being renovated are also at extremely high risk. Since siblings, housemates, visitors, and playmates of children with confirmed lead poisoning may have similar exposures to lead, they also should be promptly screened. In communities with a high prevalence of lead poisoning, health departments should consider door-to-door screening, since many children with lead poisoning may be missed by fixed-site screening.
Children with parents whose work or hobbies involve lead may also risk lead exposure (Chapter 3). Also, children living near lead smelters or other industries where lead is processed may be at increased risk for lead poisoning.
In general, screening and assessment for lead poisoning should focus on children younger than 72 months of age, particularly on children younger than 36 months of age. Young children engage in the most hand-to-mouth activity (and therefore are at highest risk for lead exposure) and have the most rapidly developing nervous systems, making them more vulnerable to the effects of lead. Children with developmental delays, who may exhibit pica or have more extensive hand-to-mouth activity than other children, would be expected to be at increased risk for lead poisoning even if they are 72 months of age and older. These children may have to be screened more often during early infancy, and may require screening into their school years.
Children who have unexplained seizures, neurological symptoms, abdominal pain, or other symptoms that are consistent with lead poisoning should also have their blood lead levels measured. In addition, the possibility of lead poisoning should be considered in any child with growth failure, developmental delay, hyperactivity, behavior disorders, hearing loss, anemia, etc.
Since erythrocyte protoporphyrin (EP) is not sensitive enough to identify more than a small percentage of children with blood lead levels between 10 and 25 µg/dL and misses many children with blood lead levels > or = to 25 µg/dL, measurement of blood lead levels should replace the EP test as the primary screening method. Unless contamination of capillary blood samples can be prevented, lead levels should be measured on venous samples. Obtaining capillary specimens is more feasible at many screening sites. Contamination of capillary specimens obtained by finger prick can be minimized if trained personnel follow proper technique. Elevated blood lead results obtained on capillary specimens should be considered presumptive and must be confirmed using venous blood. At the present time, not all laboratories will measure lead levels on capillary specimens.
Anticipatory Guidance and Assessing Risk
Guidance on childhood lead poisoning prevention and assessment of the risk of lead poisoning should be part of routine pediatric care. Anticipatory guidance is discussed in detail in Chapter 4. The guidance and risk assessment should emphasize the sources and exposures that are of greatest concern in the child's community (Chapter 3). Because lead-based paint has been used in housing throughout the United States, in most communities it will be necessary to focus on this source.
Table 6-2 has sample questions for assessing a child's risk for high-dose lead exposure. Starting at 6 months of age and at each regular office visit thereafter, pediatric health-care providers should discuss childhood lead poisoning and assess the child's risk for high-dose exposure. The questions asked should be tailored to the likely sources of exposure in the community. The questions are not a substitute for a blood lead test.
On the basis of responses to questions such as those in Table 6-2, children can be categorized as low or high risk for high-dose lead exposure. If the answers to all questions are negative, the child is at low risk for high-dose lead exposure and should be screened by a blood lead test at 12 months and again, if possible, at 24 months (since blood lead levels often peak at ages greater than 12 months). If the answer to any question is positive, the child is potentially at high risk for high-dose lead exposure, and a blood lead test should be obtained. For children previously at low risk, any history suggesting that exposure to lead has increased should be followed up with a blood lead test.
The following sections provide a minimum screening schedule for children aged 6 up to 36 and 36 to 72 months. The schedule is not rigid. Rather, it is a guide for pediatric health-care providers and screening programs to use in conjunction with other pertinent information in determining when an individual child should be tested. Programs and pediatric health-care providers may choose to screen more frequently than described below.
Children 6 up to 36 months of age:
A questionnaire should be used at each routine office visit to assess the potential for high-dose lead exposure and, therefore, the appropriate frequency of screening.
Schedule if the
child is at low risk for high dose lead exposure by questionnaire:
A child at low risk for exposure to high-dose lead sources by questionnaire should have an initial blood lead test at 12 months of age.
If the 12-month blood lead result is < 10 µg/dL, the child should be retested at 24 months if possible, since that is when blood lead levels peak.
If a blood lead test result is 10-14 µg/dL, the child should be retested every 3 to 4 months. After 2 consecutive measurements are < 10 µg/dL or three are < 15 µg/dL, the child should be retested in a year.
If any blood lead test result is > 15 µg/dL, the child needs individual case management and should be retested at least every 3 to 4 months.
Schedule if the child is at high risk for high dose lead exposure by questionnaire:
A child at high risk for exposure to high-dose lead sources by questionnaire should have an initial blood lead test at 6 months of age.
If the initial blood lead result is < 10 µg/dL, the child should be rescreened every 6 months. After 2 subsequent consecutive measurements are < 10 µg/dL or three are < 15 µg/dL, testing frequency can be decreased to once a year.
If a blood lead test result is 10-14 µg/dL, the child should be screened every 3 to 4 months. Once 2 subsequent consecutive measurements are < 10 µg/dL or three are < 15 µg/dL, testing frequency can be decreased to once a year.
If any blood lead test result is > or = to 15 µg/dL, the child needs individual case management and should be retested at least every 3 to 4 months.
Children > or = to 36 months and < 72 months of age:
As for younger children, a questionnaire should be used at each routine office visit of children from 36 to 72 months of age. Any child at high risk by questionnaire who has not previously had a blood lead test should be tested. All children who have had venous blood lead tests > or = to 15 µg/dL or who are at high risk by questionnaire should be screened at least once a year until their sixth birthday (age 72 months) or later, if indicated (for example, a retarded child with pica). Children should also be re-screened any time history suggests exposure has increased. Children with blood lead levels > or = 15 µg/dL should receive followup as described below.
Followup of children with blood lead levels > or = to 15 µg/dL
Followup of children with blood lead levels > or = to 15 µg/dL is discussed in more detail in later Chapters and is briefly summarized below. In general, such children should receive blood lead tests at least every 3 to 4 months.
If the blood lead level is 16-19 µg/dL, the child should be screened every 3-4 months, the family should be given education and nutritional counseling as described in Chapter 4, and a detailed environmental history should be taken to identify any obvious sources or pathways of lead exposure. When the venous blood lead level is in this range in two consecutive tests 3-4 months apart, environmental investigation and abatement should be conducted, if resources permit.
If the blood lead level is > or = to 20 µg/dL, the child should be given a repeat test for confirmation. If the venous blood lead level is confirmed to be > or = to 20 µg/dL, the child should be referred for medical evaluation and followup as described in Chapter 7. Such children should continue to receive blood lead tests every 3-4 months or more often if indicated. Children with blood lead levels > or = to 45 µg/dL must receive urgent medical and environmental followup, preferably at a clinic with a staff experienced in dealing with this disease. Symptomatic lead poisoning or a venous blood lead concentration > or = to 70 µg/dL is a medical emergency, requiring immediate inpatient chelation therapy, as described in Chapter 7.
Classification on the Basis of Screening Test Results
On the basis of screening test results, children can be classified into categories according to their risk for adverse effects of lead. The urgency and type of followup are based on these risk classes. These classes are shown in Table 6-3.
Measurement of Blood Lead Levels
Several factors can influence the quality of blood lead measurements. The ubiquity of lead in the environment makes contamination of specimens during collection a major source of error. Analytical variation in the laboratory can affect results. Accuracy and precision of blood lead measurements, particularly at low concentrations, can be assured by the use of appropriate analytical standards, maintenance of equipment, training of personnel, and participation in external proficiency testing programs.
Since blood collected by venipuncture has a low likelihood of contamination compared to blood collected by fingerstick, venous blood is the preferred specimen for analysis and should be used for lead measurement whenever practicable. In addition, venous specimens provide a larger volume for analysis and are less prone to clotting and other problems that can be encountered with capillary specimens. At the present time, not all laboratories will accept capillary samples for lead analysis.
Fingerstick specimens are acceptable for blood lead screening, provided that special collection procedures are followed to minimize the risk of contamination. Personnel must be thoroughly trained in collection procedures. A procedure for collecting finger stick specimens is described in Appendix I.
Elevated blood lead results obtained on capillary specimens are presumptive and must be confirmed using venous blood. In general, children who have blood lead levels > or = to 15 µg/dL on capillary samples should have these levels confirmed on venous samples, according to the timetable in Table 6-4. A child with a blood lead level > or = to 70 µg/dL or with symptoms of lead poisoning should be treated immediately while the results of an immediate confirmatory test are awaited.
Blood Lead Levels—Additional Analytical Considerations
Blood lead levels can be determined by several analytic methods. The method used can affect the specimen volume required, the choice of anticoagulant (usually heparin or ethylenediaminetetraacetic acid (EDTA)), and other aspects related to specimen suitability. Specimen collection procedures and equipment must be checked for compatibility with laboratory requirements. Special lead-free evacuated tubes are available for blood collection, but standard tubes containing EDTA or heparin (lavender or green caps) can be acceptable after screening each lot to determine the lead content of the containers, needles, etc. Though reports of unsuitable levels of background lead in other collection materials are infrequent, all materials used should be determined to be lead-free before use.
Laboratories where blood is tested for lead levels should be successful participants in a blood lead proficiency testing program, such as the program conducted jointly by CDC, the Health Resources and Services Administration, and the University of Wisconsin. In interpreting laboratory results, it should be recognized that a "proficient" laboratory need only measure blood lead levels to within several µg/dL of the true value (for example, within 4 or 6 µg/dL of a target value). The blood lead level reported by a laboratory, therefore, may be several µg/dL higher or lower than the actual blood lead level.
Erythrocyte Protoporphyrin (EP)
EP is not a sensitive test to identify children with blood lead levels below about 25 µg/dL, and therefore it is no longer the screening test of choice. In some programs, however, it will continue to be used until the transition to blood lead measurements is complete.
Only fresh blood is suitable for analysis by hematofluorometer. Complete oxygenation of sample hemoglobin is necessary to prevent low results in some instruments. The hemoglobin concentration in the sample can also affect hematofluorometer EP readings. Results obtained by extraction methods are not affected by these factors and can be used to confirm hematofluorometer EP results.
In the past, an absorptivity of 241 L cm-1 mmol-1 has been used to determine EP levels. Recently, however, the correct absorptivity has been determined to be 297 L cm-1 mmol-l. Use of the correct absorptivity will result in EP values about 19% lower than those standardized using 241 L cm-1 mmol-1. Standardization of EP levels that are based on the correct absorptivity is expected to be widely adopted in 1992. Use of the correct standardization requires a change in calibration and is not simply a reduction of the screening cutoff value. Standardization criteria should also be considered when reviewing data in the literature.
An EP result of > or = to 35 µg/dL standardized using 241 L cm-1 mmol-1 or > or = to 28 µg/dL standardized using 297 L cm-1 mmol-1 is considered elevated. All elevated EP results should be followed with a venous blood lead test to determine if lead poisoning is responsible for the elevation. Elevated concentrations of EP also result from several health conditions other than lead intoxication, particularly iron deficiency. The iron status of children with elevated EP levels should always be determined, especially since iron deficiency and lead poisoning often coexist. In such cases, the EP may be disproportionately elevated in comparison to the blood lead level.
Some hematofluorometers report EP levels as µmol ZnPP/mol heme. For instruments that give results in these units, EP values > or = to 70 µmol/mol should be considered elevated and should be promptly investigated.
Children with blood lead levels between 10 µg/dL and 19 µg/dL and their siblings need followup and repeat screening as described in previous Chapters. They do not, however, need medical evaluation as described in this Chapter.
The cornerstones of clinical management are careful clinical and laboratory surveillance of the child, medical treatment when indicated, and eradication of controllable sources of environmental lead. The most important factor in case management is to drastically reduce the child's exposure to lead.
All children with confirmed venous blood lead levels > or = to 20 µg/dL require medical evaluation. The urgency of further medical evaluation depends on the blood lead level and whether symptoms are present.
The decision to institute medical management should virtually always be made on the basis of a venous blood lead measurement. No other screening test can be considered diagnostic. If the first evaluation was made on capillary blood, a confirmatory venous blood lead level must be done. Even if the first diagnostic measurement was on venous blood, it is preferable to retest before starting chelation therapy. For children with blood lead levels > or = to 70 µg/dL or clinical symptoms of lead poisoning, chelation should not be postponed while awaiting results of the repeat test.
Symptoms of Lead Poisoning
Symptoms of lead poisoning in a child with an elevated blood lead level constitute a medical emergency, and the child should be hospitalized. Symptoms, which can mimic several other pediatric disorders, must be looked for so they are not missed.
Acute lead encephalopathy is characterized by some or all of these symptoms: coma, seizures, bizarre behavior, ataxia, apathy, incoordination, vomiting, alteration in the state of consciousness, and subtle loss of recently acquired skills. Any one or a mixture of these symptoms, associated with an elevated blood lead level, is an acute medical emergency. Lead encephalopathy is almost always associated with a blood lead level exceeding 100 µg/dL, although, occasionally, it has been reported at blood lead levels as low as 70 µg/dL. Even when identified and promptly treated, severe and permanent brain damage may result in 70%-80% of children with lead encephalopathy. Children with symptomatic lead poisoning with or without encephalopathy represent an acute medical emergency. The possibility of lead encephalopathy should be considered in the differential diagnosis of children presenting with coma and convulsions of unknown etiology.
Except for coma and seizures, symptomatic lead poisoning without encephalopathy is characterized by symptoms similar to those of lead encephalopathy. Symptomatic lead poisoning without encephalopathy is characterized by one or a combination of these symptoms: decrease in play activity, lethargy, anorexia, sporadic vomiting, intermittent abdominal pain, and constipation. These symptoms are usually associated with a blood lead levels of at least 70 µg/dL, although occasionally cases have been associated with levels as low as 50 µg/dL. If the blood lead level is below 50 µg/dL, other causes of the symptoms should be sought. Since acute lead encephalopathy may develop in any symptomatic child, treatment and supportive measures must be started immediately on an emergency basis.
Evaluation of the Child with a Blood Lead Level > or = to 20 µg/dL
A child with a blood lead level > or = to 20 µg/dL should have a pediatric evaluation, whether or not symptoms are present.
Special attention should be given to:
- A detailed history, including the presence or absence of clinical symptoms, child's mouthing activities, the existence of pica, nutritional status (especially iron and calcium intake), dietary habits, family history of lead poisoning, potential sources of lead exposure (including exposure due to home renovation), and previous blood lead measurements.
- Detailed environmental and occupational histories of adults in the household or other places the child spends a lot of time.
- The physical examination, with particular attention to the neurologic examination and psychosocial and language development. A neurobehavioral assessment may be useful in children receiving chelation therapy both at the time of diagnosis and as the child approaches school age. Findings of language delay or other problems can prompt referral to appropriate programs.
- Evaluation of iron status using measurement of iron and total iron binding capacity or of ferritin.
Tests for iron deficiency. Because iron deficiency can enhance lead absorption and toxicity and often coexists with it, all children with blood lead levels > or = to 20 µg/dL should be tested for iron deficiency. Measurements of hemoglobin, hematocrit, and reticulocytes are not adequately sensitive, and erythrocyte Protoporphyrin (EP) is not specific enough to diagnose iron deficiency (although EP can be used to screen for iron deficiency).
Serum iron and iron binding capacity (transferrin saturation) and ferritin are the most sensitive indicators of iron status. An abnormally low ratio of serum iron to iron binding capacity (transferrin saturation) of 0.2 is consistent with iron deficiency. The serum ferritin level, however, is the most definitive and accurate indication of overall iron status, although it is an acute phase reactant and may be falsely elevated in sick children; a value > or = to 12 µg/dL indicates iron deficiency. Although all iron deficient children should receive treatment for this condition, the treatment should not be started until after chelation is completed in children receiving dimercaprol (BAL).
EP level. An elevated EP level indicates impairment of the heme biosynthetic pathway. EP levels are sensitive screening tests for iron deficiency, and iron status should be assessed in any child with an elevated EP level (that is, > or = to 35 µg/dL when standardized using 241 L cm-1 mmol-1, > or = to 28 µg/dL when standardized using 297 L cm-1 mmol-1, or > or = to 70 µmol/mol when measured in µmol/mol units).
Because EP levels take about 2 weeks to increase, EP levels may provide an indication of the duration of lead exposure. Similarly, monitoring the EP level after medical and environmental interventions for poisoned children may be useful. If exposure to lead has ceased, EP values elevated because of lead poisoning decline slowly over several weeks or months. A progressive decline in EP concentrations indicates that combined medical and environmental case management is proceeding efficaciously.
Edetate disodium calcium (CaNa2EDTA) provocative chelation test. The mobilization test is used to determine whether a child with an initial confirmatory blood lead level of 25 to 44 µg/dL will respond to chelation therapy with a brisk lead diuresis. Because of the cost and staff time needed for quantitative urine collection, this test is used only in selected medical centers where large numbers of lead-poisoned children are treated. Children whose blood lead levels are > or = to 45 µg/dL should not receive a provocative chelation test; they should be referred for appropriate chelation therapy immediately.
The outcome of the provocative chelation test is determined not by a decrease in the blood lead level but by the amount of lead excreted per dose of CaNa2EDTA given. This ratio correlates well with blood lead levels. In one study, almost all children with blood lead levels 45 µg/dL had positive provocative tests, 76% of the children with blood lead levels 35 to 44 µg/dL had positive test results, and 35% of the children with blood lead levels 25 to 34 µg/dL had positive test results. This test should not be done until the child is iron replete, since iron status may affect the outcome of the test. Details on how to conduct and interpret a provocative chelation test are in Chapter 7.
Radiologic examination of the abdomen. Radiologic examination of the abdomen (flat plate) may show radiopaque foreign material if the material has been ingested during the preceding 24 to 36 hours. Neither negative nor positive x-ray results are diagnostic or definitive. A flat plate of the abdomen may, however, provide information about the source of lead if paint chips or other lead objects are found.
Radiologic examination of the long bones. Xrays of the long bones are unreliable for diagnosing acute lead poisoning, and they should not be obtained on a routine basis. They may provide some indication of whether lead poisoning has occurred in the past or has been ongoing for a length of time, and this may occasionally be important. Lines of increased density in the metaphyseal plate of the distal femur, proximal tibia, and fibula may be caused by lead which has disrupted the metabolism of bone matrix. Although these lines are sometimes called lead lines, they are areas of increased mineralization or calcification and not xray shadows of deposited lead.
The following tests are NOT indicated for the diagnosis or clinical management of lead poisoning:
- Microscopic examination of red cells for basophilic stippling. Since basophilic stippling is not always found in severe lead poisoning and is insensitive to lesser degrees of lead poisoning, it is not useful in diagnosis.
- Tests of hair and fingernails for lead levels. The levels of lead in hair or fingernails do not correlate well with blood lead levels, except in extreme cases of symptomatic lead poisoning; therefore, these tests are not useful in diagnosis. Children should never receive chelating agents on the basis of analyses of lead levels in hair or fingernails.
Pharmacology of Chelating Agents
Several drugs are used in the treatment of lead poisoning. These drugs, capable of binding or chelating lead, deplete the soft and hard (skeletal) tissues of lead and thus reduce its acute toxicity. All drugs have potential side effects and must be used with caution. The basic pharmacologic characteristics of the various drugs are described below.
Mechanism of action. Two molecules of dimercaprol (BAL) combine with one atom of heavy metal to form a stable complex. BAL enhances fecal and urinary excretion of lead and diffuses well into erythrocytes. Because it is predominantly excreted in bile, BAL can be administered in the presence of renal impairment.
Route of administration and dosage. BAL is available only in peanut oil for intramuscular administration. It is usually given every 4 hours, although it may be given every 8 hours; dosages are discussed below.
Precautions and toxicity. For patients with glucose-6-phosphate dehydrogenase deficiency (G-6-PD), some clinicians recommend that BAL should be used only in life-threatening situations because it may induce hemolysis. Medicinal iron should never be administered during BAL therapy, because the combination of iron and BAL has been implicated in serious reactions. If iron deficiency coexists, it should not be treated until after BAL therapy has been completed. In cases of extreme anemia, blood transfusions are preferable.
Between 30% and 50% of patients who receive BAL will experience side effects. Mild febrile reactions and transient elevations of hepatic transaminases may be observed. Other minor adverse effects include, in order of frequency, nausea and occasional vomiting, headache, mild conjunctivitis, lacrimation, rhinorrhea, and salivation. Most side effects are transient and rapidly subside as the drug is metabolized and excreted. Intravenous hydration coupled with restricting oral intake can circumvent, in large part, gastrointestinal distress. BAL should not be used for children who are allergic to peanuts or peanut products.
Only CaNa2EDTA can be used for treating children with lead poisoning. Na2edta (disodium edetate) should never be used for treating children with lead poisoning because it will induce tetany and possibly fatal hypocalcemia.
Mechanism of action. CaNa2EDTA increases urinary lead excretion twentyfold to fiftyfold. CaNa2EDTA removes lead from the extracellular compartment only, because it does not enter cells.
Route of administration and dosage. The preferred route for administration of CaNa2EDTA is intravenous. CaNa2EDTA must be diluted to a concentration < 0.5% in dextrose and water or in 0.9% saline solution. It can be given as a continuous infusion or it can be given in two divided doses a day through a heparin lock over 30 to 60 minutes. CaNa2EDTA causes extreme pain when administered intramuscularly; therefore, when given by this route, it should be mixed with procaine so that the final concentration of procaine is 0.5%. CaNa2EDTA should never be given orally because it enhances absorption of lead from the gastrointestinal tract.
Dosages vary by situation and are detailed in Chapter 7. Individual courses should be limited to 5 days and repeated courses should be given at a minimum of 2- to 5-day intervals. Particularly when CaNa2EDTA is given on an outpatient basis, some clinicians use sequential 3-day courses of treatment.
Precautions and toxicity. During chelation therapy with CaNa2EDTA, urine output, urine sediment, blood urea nitrogen (BUN), serum creatinine, and hepatocellular enzyme levels must be carefully monitored. The appearance of protein and formed elements in urinary sediment, and rising BUN and serum creatinine values reflect impending renal failure the serious toxicity associated with inappropriately excessive or prolonged administration of CaNa2EDTA. Liver transanimases may increase by the fifth day of therapy, but return to pretreatment levels within a week after treatment has ended.
When CaNa2EDTA is used alone without concomitant BAL therapy, it may aggravate symptoms in patients with very high blood lead levels. Therefore, it should be used in conjunction with BAL when the blood lead level is > or = to 70 µg/dL or overt clinical symptoms of lead poisoning are present. In such cases, the first dose of BAL should always precede the first dose of CaNa2EDTA by at least 4 hours.
The kidney is the principal site of potential toxicity. Renal toxicity is dose related, reversible, and rarely (if ever) occurs at doses < 1500 mg/m2 when the patient is adequately hydrated. CaNa2EDTA must never be given in the absence of an adequate urine flow.
The Food and Drug Administration (FDA) has approved D-penicillamine for the treatment of Wilson's disease, cystinuria, and severe, active rheumatoid arthritis. Although not approved for this use, it is used in some centers for treating lead poisoning. Until the recent approval of succimer, it was the only commercially available oral chelating agent. It can be given over a long period (weeks to months). D-penicillamine has been used mainly for children with blood lead levels < 45 µg/dL.
Mechanism of acton. D-penicillamine enhances urinary excretion of lead, although not as effectively as CaNa2EDTA. Its specific mechanism and site of action are not well understood.
Route of administration and dosage. D-penicillamine is administered orally. It is available in capsules or tablets (125 mg and 250 mg). These capsules can be opened and suspended in liquid, if necessary. The usual dose is 25 to 35 mg/kg/day in divided doses. Side effects can be minimized, to an extent, by starting with a small dose and increasing it gradually, monitoring all the time for side effects. For example, 25% of the desired final dose could be given in week 1, 50% in week 2, and the full dose by week 3.
Precautions and toxicity. Toxic side effects (albeit minor in most cases) occur in as many as 33% of patients given the drug. The main side effects of D-penicillamine are reactions resembling those of penicillin sensitivity, including rashes, leukopenia, thrombocytopenia, hematuria, proteinuria and hepatocellular enzyme elevations, and eosinophilia. Anorexia, nausea, and vomiting are infrequent. Of most concern, however, are isolated reports of nephrotoxicity, possibly from hypersensitivity reactions. For these reasons, patients should be carefully and frequently monitored for clinically obvious side effects, and frequent blood counts, urinalyses, and renal function tests should be performed. In particular, blood counts and urinalyses should be done on day 1, day 14, day 28, and monthly thereafter. If the absolute neutrophil count falls to < 1500/µL, the count should be rechecked immediately, and treatment should be stopped if it falls to < 1200/µL. D-penicillamine should not be given on an outpatient basis if exposure to lead is continuing or the physician has doubts about compliance with the therapeutic regimen. D-penicillamine should not be administered to patients with known penicillin allergy.
The FDA approved succimer in January, 1991 for treating children with blood lead levels > 45 µg/dL. Succimer appears to be an effective oral chelating agent. Its selectivity for lead is high, whereas its ability to chelate essential trace metals is low. Although its use to date has been limited, succimer appears to have promising potential, and a broader range of clinical research studies in children are being undertaken.
Succimer is chemically similar to BAL but is more water soluble, has a high therapeutic index, and is absorbed from the gastrointestinal tract. It is effective when given orally and produces a lead diuresis comparable to that produced by CaNa2EDTA. This diuresis lowers blood lead levels and reverses the biochemical toxicity of lead, as indicated by normalization of circulating aminolevulinic acid dehydrase levels. Succimer is not indicated for prophylaxis of lead poisoning in a lead-containing environment. As with all chelating agents, succimer should only be given to children who reside in environments free of lead during and after treatment.
Mechanism of action. Succimer appears to be more specific for lead than the most commonly used chelating agent, CaNa2EDTA; the urinary loss of essential trace elements (for example, zinc) appears to be considerably less with succimer than with CaNa2EDTA. The site of lead chelation by succimer is not known.
Route of administration and dosage. Succimer is administered orally. It is available in 100 mg capsules. The recommended initial dose is 350 mg/m2 (10 mg/kg) every 8 hours for 5 days, followed by 350 mg/m2 (10 mg/kg) every 12 hours for 14 days. A course of treatment, therefore, lasts 19 days. If more courses are needed, a minimum of 2 weeks between courses is preferred, unless blood lead levels indicate the need for immediate retreatment. These doses may be modified as more experience is gained in using succimer.
Patients who have received therapeutic courses of CaNa2EDTA with or without BAL may use succimer for subsequent treatment after an interval of 4 weeks. Data on the concomitant use of succimer and CaNa2EDTA with or without BAL are not available, and such use is not recommended.
If young children cannot swallow capsules, succimer can be administered by separating the capsule and sprinkling the medicated beads on a small amount of soft food or by putting them on a spoon and following with a fruit drink. Data are not available on how stable succimer is when it is suspended in soft foods for prolonged periods of time; succimer should be mixed with soft foods immediately before being given to the child.
Precautions and toxicity. To date, toxicity due to succimer (transient elevations in hepatic enzyme activities) appears to be minimal. The most common adverse effects reported in clinical trials in children and adults were primarily gastrointestinal and included nausea, vomiting, diarrhea, and appetite loss. Rashes, some necessitating discontinuation of therapy, have been reported for about 4% of patients. Though succimer holds considerable promise for the outpatient management of lead poisoning, clinical experience with succimer is limited. Consequently, the full spectrum and incidence of adverse reactions, including the possibility of hypersensitivity or idiosyncratic reactions, have not been determined. Other precautions that need to be taken with succimer are discussed in the full statement.
Treatment Guidelines for Children with Blood Lead Levels > or = to 20 µg/dL
The single most important factor in managing of childhood lead poisoning is the reducing the child's exposure to lead; some children, however, will benefit from chelation therapy. Sample regimens for treating children with lead poisoning are described in Chapter 7.
Medical Management of Symptomatic Lead Poisoning (with or without Encephalopathy)
Children with symptomatic lead poisoning (with or without encephalopathy) must be treated only at a pediatric center that has an intensive care unit. They should be managed by a multi disciplinary team that includes, as needed, critical care, toxicology, neurology, and neurosurgery. The child's neurological status and fluid balance must be carefully monitored.
Medical Management of Asymptomatic Lead Poisoning
Blood lead level > or = to 45 µg/dL. Children with blood lead levels > or = to 45 µg/dL (with or without symptoms) should undergo chelation therapy. A blood lead level > or = to 70 µg/dL is a medical emergency.
Blood lead level 25 to 44 µg/dL. For this blood lead range, the effectiveness of chelation therapy in decreasing the adverse effects of lead on children's intelligence has not been shown. Treatment regimens vary from clinic to clinic. Some practitioners treat children with lead levels in this range pharmacologicly, some use D-penicillamine. The minimum medical management for children with these blood lead levels is to decrease exposure to all sources of lead, to correct any iron deficiency and maintain an adequate calcium intake, and to test frequently to ensure that the child's blood lead levels are decreasing. Many experienced practitioners decide whether to use chelation therapy on the basis of the results of carefully performed CaNa2EDTA mobilization tests.
Blood lead level 20 to 24 µg/dL. Only very minimal data exists about chelating children with blood lead levels below 25 µg/dL, and such children should not be chelated except in the context of approved clinical trials. A child with a confirmed blood lead level of 20 to 24 µg/dL will require individual case management by a pediatric health-care provider. The child should have an evaluation with special attention to nutritional and iron status. The parents should be taught about 1) the causes and effects of lead poisoning, 2) the need for more routine blood lead testing, 3) possible sources of lead intake and how to reduce them, 4) the importance of adequate nutrition and of foods high in iron and calcium, and 5) resources for further information. (This is described in more detail in Chapter 4.) Sequential measurements of blood lead levels along with review of the child's clinical status should be done at least every 3 months. Iron deficiency should be treated promptly. Children with blood lead levels in this range should be referred for environmental investigation and management. Identifying and eradicating all sources of excessive lead exposure is the most important intervention for decreasing blood lead levels (Chapter 8).
At the end of each treatment cycle, the blood lead concentration usually declines to < 25 µg/dL. Within a few days, however, reequilibration among body lead compartments takes place and may result in a rebound; thus, The blood lead level must be rechecked 7 to 21 days after treatment to determine whether retreatment is necessary.
Children who undergo chelation treatment require long-term follow up preferably from pediatric health-care providers, nutritionists, environmental specialists, and community out-reach workers. Community outreach workers provide a critical bridge between hospital-based or clinic-based (outpatient) medical care, health advocacy education, and environmental remediation outside the hospital. Children should never be discharged from the hospital until they can go to a lead-free environment. Lead-free safe housing (with friends, relatives, or in designated transitional housing), in which a treated child can live during the entire abatement process through the post-abatement clean-up, must be arranged. With appropriately carried-out public health measures, complete and safe abatement should be achieved during the treatment period.
Once a child is discharged to a safe environment, frequent follow up is mandatory. In general, depending on the initial blood lead value, most children who require chelation therapy must be followed closely for at least one year or more. All children undergoing chelation treatment should be seen every other week for 6-8 weeks, then once a month for 4-6 months. A child treated with BAL and CaNa2EDTA should be followed more closely: weekly for 4 to 6 weeks, then monthly for 12 months.
Eradicating childhood lead poisoning requires a long-term active program of primary lead-poisoning prevention, including abatement of lead-based paint hazards in homes, day-care centers, and other places where young children play and live. For the child who is lead poisoned, however, efficient and effective interventions are needed as quickly as possible. Abatement means making the source of lead inaccessible to the child.
Each situation in which a child gets poisoned is unique and must be evaluated by a person or team of persons skilled and knowledgeable about lead poisoning, hazard identification, and interventions to reduce lead exposure, including abatement of lead-based paint in housing. Childhood lead poisoning prevention programs need to work closely with other relevant agencies (for example, housing and environmental agencies) to ensure that the quickest and most effective approach is taken to remediating the environments of poisoned children.
Environmental case management includes a number of actions prescribed for a child with lead poisoning. Ideally, environmental case management should be conducted by a team of professionals in public health, environmental activities, medical management, and social management. A team approach to intervention will help ensure that follow up is timely and effective. The management team may need to solve many related problems, such as whether to investigate supplemental addresses, where to find temporary alternative housing, and how to use community resources to assist the family in dealing with the lead-poisoned child.
In theory, primary prevention has always been the goal of childhood lead poisoning prevention programs. In practice, however, most programs focus exclusively on secondary prevention, dealing with children who have already been poisoned. As programs shift the emphasis to primary prevention, their efforts must be designed to systematically identify and remediate environmental sources of lead, including, most importantly, dwellings containing old lead paint.
The shift from case management to community-level intervention will require a fundamental shift in perspective. The focus must shift from the individual child to the population of children at risk and the environment in which they live. The purpose of community-level intervention is to identify and respond to sources, not cases, of lead poisoning. The responsibility for addressing lead poisoning will have to be expanded beyond health agencies to include a variety of housing, environmental and social service agencies at the local, county state and national level.