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Preventing Lead Poisoning in Young Children: Chapter 6


Chapter 6. Screening

Summary

Screening is important both to ensure that poisoned children are identified and to generate data to target primary prevention activities.

Virtually all children should be screened for lead poisoning. Screening children with high probability of exposure to high-dose sources is the highest priority.

Screening should be done using a blood lead test.

Children at greatest risk for high-dose lead exposure should be screened more frequently.

Analytical considerations affect interpretation of blood lead test results, particularly at low levels.

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.


Suggested Priorities for Screening

Virtually all U.S. children are at risk for lead poisoning.

Children at highest risk should be given the highest priority for screening.

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 (ATSDR, 1988). Furthermore, about 74% of occupied, privately owned housing built before 1980 contains lead-based paint (defined as > or = to 1 milligram per square centimeter (mg/cm2)) (HUD, 1990). 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.

* The health departments need to take lead role in assessing whether or not a community has a childhood lead poisoning problem.


Screening Method

Screening should be done using a blood lead test.

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 (McElvaine et al., 1991), 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 (see Appendix I for a capillary sampling protocol). 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.

Programs will need to increase their capacity to perform blood lead testing. During the transition to the use of the blood lead test as the primary screening method, some programs will temporarily continue to use EP as a screening test. In addition, some nutrition programs (for example, the Supplemental Food Program for Women, Infants, and Children (WIC)) use the EP test to identify children with iron deficiency.

For a discussion of the units used to report EP results (Erythrocyte Protoporphyrin). All EP test results of > or = to 35 µg/dL if standardized using 241 L cm-1 mmol-1, > or = to 28 µg/dL if standardized using 297 L cm-1 mmol-1, or > or = to 70 µmol ZnPP/mol heme, if the hematofluorometer reports in these units, must be followed by a blood lead test (preferably venous) and an evaluation for iron deficiency (Iron Status and Special Tests). Work on developing easy-to-use, cheap, portable instruments for blood lead testing is ongoing.


Anticipatory Guidance and Assessing Risk

Anticipatory guidance helps prevent lead poisoning by educating parents on ways to reduce lead exposure.

Questions about housing and other factors are used to identify which children are at greatest risk for high-dose lead exposure.

Anticipatory guidance and assessment of risk should be tailored to important Sources and Pathways of Lead Exposure in the child's community.

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 more 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.


Screening Schedule

The Screening Schedule

The screening schedule is based on the fact that children's blood lead levels increase most rapidly at 6-12 months and peak at 18-24 months.

Anticipatory guidance on preventing lead poisoning and assessing the risk for high-dose lead exposure should be part of routine pediatric care.

The urgency and type of followup depends on the screening blood lead test result.

Background

The rationale for the screening schedule is based on data such as those shown in Figure 6-1. Those data were collected in a prospective study in Cincinnati (Clark et al., 1985). Blood lead levels were measured every 3 months from birth onward, and illustrate the trends in blood lead concentration in relation to the child's age and housing age and condition. Blood lead concentrations increase steadily up to at least 18 months of age. The most rapid rate of increase occurs between 6 and 12 months of age. The highest blood lead levels occur in children living in deteriorated older housing.

Assessment of Risk

Table 6-2 has sample questions. 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.

Using Questionnaire Results

If answers to the questionnaire indicate that the child is not at high risk for high-dose lead exposure, the child should be screened at 12 months of age, and, if resources allow, at 24 months of age.

If answers to the questionnaire indicate that the child is at risk for high-dose lead exposure, the child should be screened starting at 6 months of age.

For children previously at low risk, any history suggesting that exposure to lead has increased should be followed up with 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.

Example: A pediatrician in southern California almost exclusively serves communities built after 1988. She is aware, however, that some of her patients' families store juice and punch in pottery imported from Mexico. In her guidance to parents, she warns them that lead can leach from improperly fired pottery. At every routine visit, she asks parents about the use of this pottery and screens any children whose parents use this pottery. In her anticipatory guidance and assessment of her patients' risks of lead poisoning, she emphasizes sources of exposure that are common in the community she serves.

Screening Schedule

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.

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 > or = to 15 µg/dL, the child needs individual case management, which includes retesting the child 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, which includes retesting the child at least every 3 to 4 months.

Children > or = to 36 months and less than 72 months 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 developmentally delayed child with pica). Children should also be rescreened any time history suggests exposure has increased. Children with blood lead levels > or = to 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 15-19 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

Venous blood is preferred for blood lead measurement.

Analytical variation in the laboratory can affect blood lead results.

Laboratories measuring blood lead levels should participate successfully in a blood lead proficiency testing program.

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 finger stick, 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 (DeSilva and Donnan, 1977; Mitchell et al., 1974).

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. At the present time, not all laboratories will accept capillary samples for blood lead analysis.

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.

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.

Several analytical techniques available can be used to make accurate blood lead measurements at levels <25 µg/dL. These techniques are electrochemical techniques, usually anodic stripping voltammetry (ASV), and atomic absorption spectroscopy (AAS). Either of these techniques is capable of achieving detection limits <2 to 5 µg/dL. Success by these methods, however, requires careful and meticulous attention to the details of the analysis.

The reliability of a set of blood lead measurements is greatly enhanced by the use of high quality lead standard solution for instrument calibration. In the United States, the National Institute of Science and Technology has made such a material (SRM 3121) available. In addition, a set of whole blood reference materials (SRM 955A, Lead in Blood) provides a useful set of control materials over a wide range of concentrations—about 6 to 70 µg/dL.

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 should 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.

Analytical variability must be considered when interpreting blood lead results. Changes in successive blood lead measurements on an individual can be considered significant only if the net difference of results exceeds the limit of analytic variance that the laboratory allows. As a general rule, trends should not be considered significant unless the magnitude of the change is > or = to 5 µg/dL.

The degree of analytical variability between laboratories that employ different analytic methods usually exceeds that within a single laboratory. Therefore, a single laboratory using one analytical method should be used to best compare multiple blood lead results from an individual or a population.


Erythrocyte Protoporphyrin (EP)

EP is not a sensitive test for identifying children with blood lead levels below about 25 µg/dL.

An EP level is elevated if it 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. All elevated EP results should be followed by a venous blood lead test.

Laboratories measuring EP levels should be successful participants in an EP proficiency testing program.

Interpreting EP Results and Following Up on Children with High EP Levels

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. Generally, EP is measured using a two-step extraction process followed by direct fluorometric measurement or by front-surface fluorometry (hematofluorometry). Most protoporphyrin in erythrocytes (about 90%) exists as zinc protoporphyrin (ZnPP) (Smith et al., 1980; Gotelli et al., 1980). This fraction is preferentially measured by hematofluorometers. Extraction methods measure all the protoporphyrin present, but strip the zinc from the ZnPP during the extraction process. For this reason, extraction results are sometimes referred to as [zinc] free erythrocyte protoporphyrin (FEP). Although the chemical forms measured by the two methods differ slightly, on a weight basis they are roughly equivalent, so results reported as EP, ZnPP, or FEP all reflect essentially the same analyte (Stanton et al., 1989).

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-1 (Gunter et al., 1989). 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 responbile for the elevation. Elevated concentrations of EP also result from several health conditions other than lead intoxication, particularly iron deficiency (Reeves et al., 1984; Yip et al., 1983; Thomas et al., 1977). 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 (Stanton et al., 1989).

Analytic Considerations

Only fresh blood is suitable for analysis by hematofluorometer (Blumberg et al., 1977). 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.

As with lead data, analytical variance must be considered when EP data are being interpreted. If trends in EP data are to be assessed correctly, analyses should preferably be performed by a single laboratory, and the variance of the method should be known when interpreting data. As with blood lead levels, interlaboratory variance usually exceeds intralaboratory variance. The observed variance for EP is wider than that for blood lead, underscoring the importance of analytical variance in the evaluation of EP data. In addition, because of substantial intermethod differences, extraction and hematofluorometer results should not be compared when assessing trends (Mitchell and Doran, 1985; Kaul et al., 1983; Peter et al., 1978). Laboratories that test patient specimens for EP levels should be participants in one or more external proficiency testing programs.


References

ATSDR (Agency for Toxic Substances and Disease Registry). The nature and extent of lead poisoning in children in the United States: a report to Congress. Atlanta: ATSDR, 1988.

Blumberg WE, Eisinger J, Lamola AA, Zuckerman DM. The hematofluorometer. Clin Chem 1977; 23:270-4.

Clark CS, Bornschein RL, Succop P, Que Hee SS, Hammond PB, Peace B. Condition and type of housing as an indicator of potential environmental lead exposure and pediatric blood lead levels. Environ Research 1985:38:46-53.

DeSilva PE, Donnan MB. Petrol venders, capillary blood lead levels, and contamination. Med J Aust 1977;1:794-5.

Gotelli GR, Wall JH, Kabra PM, Morton LJ. Simultaneous liquid-chromotagraphic determination of zinc protoporphyrin IX, protoporphyrin IX, and coproporphyrin in whole blood. Clin Chem 1980;26:205-8.

Gunter EW, Turner WE, Huff DL. Investigation of protoporphyrin IX standard materials used in acid-extraction methods, and a proposed correction for the millimolar absorptivity of protoporphyrin IX. Clin Chem 1989;35:1601-8.

HUD (U.S. Department of Housing and Urban Development). HUD Interim Guidelines on Lead-Based Paint. Washington (DC): HUD, 1990.

Kaul B, Slavin G, Davidow B. Free erythrocyte protoporphyrin and zinc protoporphyrin measurements compared as primary screening methods for detection of lead poisoning. Clin Chem 1983;29:1467-70.

McElvaine MD, Orbach HG, Binder S, Blanksma LA, Maes EF, Krieg RM. Evaluation of the erythrocyte protoporphyrin test as a screen for elevated blood lead levels, Chicago, Illinois, 1988-1989. J Pediatr (in press) 1991.

Mitchell DG, Aldous KM, Ryan FJ. Mass screening for lead poisoning: capillary blood sampling and automated Delves-cup atomic-absorption analysis. N Y State J Med 1974;74:1599-1603.

Mitchell DG, Doran D. Effect of bias in hematofluorometer measurements of protoporphyrin in screening programs for lead poisoning. Clin Chem 1985;31:38 I 90.

Peter F, Growcock G, Strunc G. Fluorometric determination of erythrocyte protoporphyrin in blood, a comparison between direct (hematofluorometric) and indirect (extraction) methods. Clin Chem 1978; 24:1515-57.

Reeves JD, Yip R, Kiley VA, Dallman PR. Iron deficiency in infants: the influence of mild antecedent infection. J Pediatr 1984:105:874-9.

Smith RM, Doran D, Mazur M, Bush B. High performance liquid chromatographic determination of protoporphyrin and zinc protoporphyrin in blood. J Chrom 1980;181:319-27.

Stanton NV, Gunter EW, Parsons PJ, Field PH. Empirically determined lead-poisoning screening cutoff for the protofluor-Z hematofluorometer. Clin Chem 1989;35:2104-7.

Thomas WJ, Koenig HM, Lightsey AL Jr, Green R. Free erythrocyte porphyrin: hemoglobin ratios, serum ferritin, and transferring saturation levels during treatment of infants with iron-deficiency anemia. Blood 1977; 49:455-62.

Yip R, Schwartz S, Deinard AS. Screening for iron deficiency with the erythrocyte protoporphyrin test. Pediatrics 1983:72:214-9.


    
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