A blood lead level (BLL) threshold of > 10 mcg/dL has been in-use for over the past 20 years; however, with accruing evidence that low amounts of lead can cause deleterious effects in children, the Advisory Committee on Childhood Lead Poisoning Prevention (ACCLPP) concluded that there is no safe childhood BLL underscoring the critical importance of primary prevention strategy (1). The ACCLPP recommended discontinuing the blood lead ‘level of concern’ term and in its place use of a reference value based on the 97.5th percentile blood lead level distribution in children 1-5 years old per data acquired through the National Health and Nutrition Examination Survey (NHANES). The most recent NHANES data show the 97.5th percentile to be a BLL of 5 mcg/dL. In May 2012, the Center for Disease Control (CDC) announced that they are on-board with these recommendations (2); subsequently, there has been rapid rollout of the new lead reference value by many state regulatory agencies and laboratories.
With the change in blood lead reference value from < 10 mcg/dL to < 5 mcg/dL, will the technical performance of laboratory lead assays, particularly point-of-care (POC), measure up to the challenge? Federal regulations currently require BLL testing to operate with a total allowable error of ± 4 mcg/dL or ± 10 %, whichever is greater (Evaluation criteria noted in 2012 College of American Pathologists BL-C survey). However, with a new lead action level of 5 mcg/dL, the acceptable error limit of ± 4 mcg/dL is exceedingly broad raising interest in the issues of what level of testing accuracy is needed for reliable and effective lead screening/diagnosis, as well as what improvements in assay methodologies and/or quality assurance practices may be required to meet the tightened error limits. The ACCLPP has engaged a workgroup to continue assessing these issues though reiterated a previous recommendation to the Centers for Medicare & Medicaid Services that the total allowable error be reduced from ± 4 mcg/dL to ± 2 mcg/dL for BLL < 20 mcg/dL. Meeting the proposed tightened criteria may be challenging with current POC lead testing devices.
A few years ago a study was performed in theUMass Memorial Medical Center Clinical ToxicologyLaboratory that compared BLL results measured using a CLIA-waived POC portable lead testing analyzer versus an inductively-coupled plasma mass spectrometry (ICP/MS) reference method. Overall, POC BLL compared well with ICP/MS with an overall concordance of 99.6%, only 2 false negative results were observed with POC testing using < 10 mcg/dL reference value. This study was limited however in the number of lead positive specimens ≥ 10 mcg/dL (13 true positive by ICP/MS out of 531 specimens; (3)). Retrospective analyses of these data using the recommended < 5 mcg/dL lead reference value indicated that the number of lead positive results increased nearly 5 fold (13 to 61 true positive). Moreover, the clinical sensitivity of POC lead testing plunged to 65.6% (32 false negative) and decreased the overall concordance of POC lead results with corresponding ICP/MS results to 93.0%.
It is likely that improvements in assay methodologies will be required to maintain quality assurance with continued lowering of lead reference values. Given the available evidence, I believe that the current use of available CLIA-waived POC testing for blood lead screening in children has limited utility (if confirmation testing is readily available) as it offsets the benefit of lowering the blood lead reference value to better identify children at risk for adverse health and development effects of lead exposure. Do you agree or disagree? What do you feel should be required of POC lead testing devices for use in routine lead screening programs for children?
1. Advisory Committee on Childhood Lead Poisoning Prevention. Low level lead exposure harms children: A renewed call for primary prevention. Atlanta, GA: US Department of Health and Human Services, CDC, Advisory Committee on Childhood Lead Poisoning Prevention; 2012. Available at http://www.cdc.gov/nceh/lead/ACCLPP/Final_Document_030712.pdf (Accessed November 2012).
2. CDC. CDC response to Advisory Committee on Childhood Lead Poisoning Prevention recommendations in “Low level lead exposure harms children: a renewed call for primary prevention.” Atlanta, GA: US Department of Health and Human Services, CDC; 2012. Available at http://www.cdc.gov/nceh/lead/acclpp/cdc_response_lead_exposure_recs.pdf (Accessed November 2012).
3. Korpi-Steiner NL, Jenkins AJ. Comparative analysis of lead quantitation via inductively-coupled plasma mass spectrometry and point-of-care LeadCare® II system. Clin Chem 2012; 58(10): A166.