Indications for Testing

• Known lead exposures per CDC recommendations for children

Laboratory Testing

• Whole blood lead is the specimen of choice
  • Elevated lead concentrations in capillary blood specimens should be confirmed with a venous specimen to exclude the potential contribution of external contamination
  • Concentrations ≥5 μg/dL are excessive for children and child-bearing females
  • The Biological Exposure Index (ACGIH guidelines, 2007) for whole blood lead levels in non-pregnant adults is 30 μg/dL
• Urine lead testing may be useful for detecting recent exposures to lead

Imaging Studies

• Non-invasive measurements of lead in bone may be available via K-shell x-ray fluorescence – not widely available except in research settings

Differential Diagnosis

• Porphyria
• Other heavy metal toxicity (eg, arsenic)

• American Academy of Pediatrics recommends screening for all Medicaid children between 1-2 years
  • U.S. Preventive Services Task Force found insufficient evidence for or against screening
• CDC criteria for non-Medicaid children is based on specific localities
• CDC recommends screening in children who meet any of the following criteria
  • Child is suspected by parent or health-care provider to be at risk for lead exposure
  • Child has a sibling or frequent playmate with elevated blood lead level
  • Child is a recent immigrant, refugee, or foreign adoptee
  • Child’s parent or principal caregiver works professionally or recreationally with lead
  • Child has a household member who uses traditional, folk, or ethnic remedies or cosmetics or who routinely eats food imported informally (eg, by a family member) from abroad
  • Child’s family has been designated at increased risk for lead exposure by the health department because the family has local risk factors for lead exposure (eg, residence in a designated high-risk zip code or near a known point source)
• Plasma aminolevulinic acid, whole blood zinc protoporphyrin or free erythrocyte protoporphyrins may be useful for screening in occupational exposures
  • Presence not detected until lead concentrations reach ≥35 μg/dL

• Urine lead – detect acute exposure; monitor chelation therapy

Lead poisoning or lead toxicity generally occurs in two settings – childhood exposure or occupational exposure. The removal of lead from paint and gasoline in the 1970s resulted in lower blood-lead concentrations in the U.S.

Epidemiology

• Prevalence – an estimated >450,000 children in the U.S. have concentrations ≥10 μg/dL (CDC, 2009)
• The Fourth National Report on Human Exposure to Environmental Chemicals (CDC, 2004) identified the 95th percentile for blood-lead concentration for various age groups
  • Children 1-5 years – 5.1 μg/dL
  • Children 6-11 years – 3.3 μg/dL
  • Children 12-19 years – 2.6 μg/dL,
  • Adults 20 years and older – 4.3 μg/dL,

Risk Factors

• Children – main source of exposure is leaded paint
  • Living in older housing, generally inner city areas
  • Low income family
  • Midwest/Northeast residence
• Adults – main source of exposure is occupational
  • Lead smelting, mining, ammunitions, soldering, plumbing, ceramic glazing, construction workers
  • Use of ceramics with lead-based glaze
  • Use of herbal remedies from Asia

Pathophysiology

• Exposure mainly through respiratory and gastrointestinal tracts
  • 30-40% of inhaled lead is absorbed
  • Gut absorption depends on nutritional status and age
    • Absorption is enhanced in children <6 years
    • Absorption may be lessened by adequate intake of iron, calcium, magnesium, alcohol, fat
• Absorbed lead remains bound to erythrocytes for approximately one month and then distributes into soft tissues such as liver, kidney, and brain over 4-6 weeks
• Final storage of absorbed lead
  • Bone
    • Children – 70% of absorbed lead
    • Adults – 80-95% of absorbed lead
  • Soft tissue sites
    • Store remaining absorbed lead 

Clinical Presentation

• Children – clinical symptoms usually present with concentrations ≥60 μg/dL but may occur at much lower concentrations
  • Gastrointestinal – abdominal pain, constipation, colic
  • Central nervous system – clumsiness, gait abnormalities, headache, behavioral changes, seizures
    • IQ declines seen at concentrations ≥10 μg/dL
    • Children who have been exposed to lead may have severe, persistent cognitive and behavioral problems
  • Hematologic – anemia
  • Renal – acute nephropathy
• Adults – whole blood concentrations ≥30 μg/dL indicate significant exposure (WHO)
  • Central nervous system – peripheral neuropathies, motor weakness
  • Renal – chronic renal insufficiency
  • Cardiovascular – systolic hypertension
  • Hematologic – anemia (normochromic/normocytic)
  • Gastrointestinal – abdominal pain, constipation, anorexia, nausea
• Blood lead in children and adults

  Blood Lead in Children and Adults*
  Lead Total	Comment
  5.0-9.9 μg/dL	Adverse health effects are possible, particularly in children <6 years and pregnant women. Discuss health risks associated with continued lead exposure. For children and women who are or may become pregnant, reduce lead exposure.
  10.0-19.9 μg/dL	Reduced lead exposure and increased biological monitoring are recommended.
  20.0-69.9 μg/dL	Removal from lead exposure and prompt medical evaluation are recommended. Consider chelation therapy when concentrations >50 μg/dL and symptoms of lead toxicity are present.
  >69.9 μg/dL	Critical. Immediate medical evaluation is recommended. Consider chelation therapy when symptoms of lead toxicity are present.
  * Sources of reference interval and interpretive comments include the CDC Guidelines for Screening Children for Blood Lead (1997) and the Recommendations for Medical Management of Adult Lead Exposure, Environmental Health Perspectives (2007). Thresholds and time intervals for retesting, medical evaluation, and response vary by state and regulatory body. Contact your State Department of Health and/or applicable regulatory agency for specific guidance on medical management recommendations. Elevated results may be due to skin or collection-related contamination. Elevated levels of blood lead should be confirmed with a venous specimen collected in a lead-free tube.

Treatment

• Chelation has been mainstay of treatment
  • Indicated in patients with concentrations ≥50 μg/dL
  • Chelation in patients with concentrations <50 μg/dL has not been proven to alter neurotoxicity
• Remove source of lead exposure

Tests generally appear in the order most useful for common clinical situations

Guidelines

• Department of Health and Human Services Centers for Disease Control and Prevention. Fourth National Report on Human Exposure to Environmental Chemicals. [Accessed: 15 Oct 2010] 
• Kosnett MJ, Wedeen RP, Rothenberg SJ, Hipkins KL, Materna BL, Schwartz BS, Hu H, Woolf A. Recommendations for medical management of adult lead exposure. Environ Health Perspect. 2007; 115 (3) :463-471.PubMed
• Rischitelli G, Nygren P, Bougatsos C, Freeman M, Helfand M. Screening for elevated lead levels in childhood and pregnancy: an updated summary of evidence for the US Preventive Services Task Force. Pediatrics. 2006; 118 (6) :e1867-e1895.PubMed
• Screening for elevated blood lead levels in children and pregnant women: recommendation statement. United States Preventive Services Task Force - Independent Expert Panel. 1996 (Revised 2006). NGC:005433
• Wengrovitz AM, Brown MJ. Recommendations for blood lead screening of Medicaid-eligible children aged 1-5 years: an updated approach to targeting a group at high risk. MMWR Recomm Rep. 2009; 58 (RR-9) :1-11.PubMed

General

• Brodkin E, Copes R, Mattman A, Kennedy J, Kling R, Yassi A. Lead and mercury exposures: interpretation and action. CMAJ. 2007; 176 (1) :59-63.PubMed
• Hu H, Shih R, Rothenberg S, Schwartz BS. The epidemiology of lead toxicity in adults: measuring dose and consideration of other methodologic issues. Environ Health Perspect. 2007; 115 (3) :455-462.PubMed
• Mudipalli A. Lead hepatotoxicity & potential health effects. Indian J Med Res. 2007; 126 (6) :518-527.PubMed
• Patrick L. Lead toxicity, a review of the literature. Part 1: Exposure, evaluation, and treatment. Altern Med Rev. 2006; 11 (1) :2-22.PubMed
• Rusyniak DE, Arroyo A, Acciani J, Froberg B, Kao L, Furbee B. Heavy metal poisoning: management of intoxication and antidotes. EXS. 2010; 100 :365-396.PubMed
• Schwartz BS, Stewart WF. Lead and cognitive function in adults: a questions and answers approach to a review of the evidence for cause, treatment, and prevention. Int Rev Psychiatry. 2007; 19 (6) :671-692.PubMed
• Warniment C, Tsang K, Galazka SS. Lead poisoning in children. Am Fam Physician. 2010; 81 (6) :751-757.PubMed
• Woolf AD, Goldman R, Bellinger DC. Update on the clinical management of childhood lead poisoning. Pediatr Clin North Am. 2007; 54 (2) :271-94, viii.PubMed

ARUP Institute for Clinical and Experimental Pathology®

• Bornhorst JA, Hunt JW, Urry FM, McMillin GA. Comparison of sample preservation methods for clinical trace element analysis by inductively coupled plasma mass spectrometry. Am J Clin Pathol. 2005; 123 (4) :578-583.PubMed

Developmental Delay (DD) or Intellectual Disability (ID) Testing
Porphyrias