Lead toxicity continues to be a threat to children in the United States. Sources of lead may not always be obvious. Once ingested, the effects can be irreversible. Toxicity can present with a wide variety of signs and symptoms that may not correlate with serum lead levels. As understanding of the risks has evolved, the Centers for Disease Control and Prevention has progressively lowered the blood lead level of concern to the current threshold of 10 μg/dL. Physicians should screen all pediatric patients to avoid missing asymptomatic cases. Treatment is based on symptoms and/or blood lead level. All symptomatic patients and those with blood lead levels above 70 μg/dL require hospitalization.
For nearly a century, lead has been recognized as a physiologically altering entity, with especially damaging effects on the central nervous and hematopoietic systems of children. In the past, lead was used in many products, virtually ensuring environmental exposure from car exhaust gases, contaminated soil, deteriorating paint, and lead-laced foods and drinking water. Federal regulations have eliminated some lead sources in the United States, most notably the bans on lead-based residential paint, lead solder in food cans and plumbing, and leaded gasoline. Consequently, between 1976 and 2000, average blood lead levels among American children fell from around 15 μg/dL to just over 2 μg/dL.1 Nevertheless, lead poisoning remains a serious threat. About 40% of the nation?s houses contain lead paint, thousands of lead pipes continue to transport water in older cities, and lead particles from past automobile emissions persist in the soil.2
Despite a dramatic decline in the prevalence of lead poisoning, the latest data indicate that approximately 310,000 American children aged 1 to 5 years have blood lead levels of 10 μg/dL or more, which is the level of concern set by the Centers for Disease Control and Prevention (CDC).3
All children are susceptible to lead poisoning. In the United States, the greatest risk is associated with living at or below the poverty line and residing in older housing.4 In one Philadelphia pediatric clinic, 68% of 817 children aged 10 months to 6 years had elevated blood lead levels.5 Black children are about 3 times more likely to have blood lead levels of more than 10 μg/dL than are Hispanic or white children.6 Also at increased risk are children who are recent immigrants, refugees, or international adoptees,7 given the presence of lead products in homes in their native countries.
Lead may be inhaled or ingested from a variety of sources (Table 1). In children, the most common exposure pathways are inhaling or ingesting lead-contaminated dust, ingesting lead-based paint chips, and ingesting lead-contaminated soil. Certain industries and hobbies can directly expose adults to lead, who can then bring home lead dust on their clothes or skin and expose family members.
Pathophysiology: Lead Absorption
Children are vulnerable to lead poisoning because their developing bodies absorb more lead, and they frequently put their hands or contaminated objects into their mouths. Such normal hand-to-mouth behavior renders children aged 12 to 36 months particularly susceptible to lead exposure.
Lead is more easily absorbed when ingested in fine dust on an empty stomach.8 Children and pregnant women tend to have higher absorption rates; children can absorb about 50% of ingested lead, whereas adults absorb about 10%.8
Since calcium and iron compete with lead for binding sites, a deficiency in either may increase lead absorption.7 Almost all inhaled lead is absorbed in the lower respiratory tract.
Lead is deposited in several tissues. Blood is the most significant, since lead can cross the blood-brain barrier. Persisting in bone and teeth for up to 25 years, lead may be released from mineralized tissue, especially during times of calcium stress (eg, pregnancy, lactation, osteoporosis). High bone lead levels can increase blood lead levels even after all external sources are eliminated.
Toxicity occurs in 3 ways. First, lead binds to enzymes in the heme pathway.9 Lead inhibits ferrochelatase, an enzyme that allows protoporphyrin to activate the normal chelation of iron to heme. Consequently, protoporphyrin levels increase. Protoporphyrin levels of 35 μg/dL or more are consistent with lead toxicity, iron deficiency, or recent inflammatory disease.
Second, lead is a competitive inhibitor of calcium. Many sites on the cell surface are activated by calcium but have a greater affinity for lead. For example, lead can adversely affect the release of neurotransmitters, a calcium-dependent process.
Third, lead can interrupt the development of tertiary brain structure.9 Because this development is a timed sequence, interruption can cause permanent disabilities, including poor hand?eye coordination, longer reaction times, hearing or speech impairments, decreased learning and memory, and a lower intelligence quotient (IQ). These disabilities result in low scores on standardized tests, missed school days, and early signs of attention-deficit/hyperactivity disorder.7
Consequences of Lead Toxicity
The medical consequences of lead poisoning vary by the level of toxicity (Table 2). Very high blood lead levels (≥380 μg/dL) can cause convulsions, coma, and death. Encephalopathy occurs with lead levels from 100 to 150 μg/dL and hemolytic anemia with acute poisoning above 70 μg/dL.
Chronic lead exposure at levels above 60 μg/dL may diminish proximal tubular function,10 leading to aminoaciduria, glycosuria, and hyperphosphaturia.11 Levels above 40 μg/dL can decrease hemoglobin synthesis. At levels above 20 μg/dL, delayed nerve conduction is possible.
Even at levels below 20 μg/dL, lead poisoning takes a tremendous toll. Maternal blood lead levels of 10 to 15 μg/dL may increase risk for premature birth and low birth weight, and since lead readily crosses the placenta, fetal viability can be endangered.8,12 Levels as low as 10 μg/dL slow a child?s cognitive and behavioral development, manifested as reading disabilities and deficits in vocabulary, fine motor skills, and reaction time.13
Some effects may persist into adolescence, even if blood lead levels decline.14 Peripheral neuropathy has been demonstrated in children with lead toxicity, particularly those with concomitant sickle-cell anemia. In addition, low-level lead poisoning can stunt bone growth as a consequence of decreased vitamin D metabolism. Exposure to lead may also result in delayed puberty in girls, particularly in black and Mexican-American girls.15
The CDC has progressively lowered the recommended blood lead level of concern from 60 μg/dL in 1970 to the current threshold of 10 μg/dL. Recent investigations, however, question whether this threshold is low enough, since serum levels below 10 μg/dL are inversely associated with IQ scores in children.16
A pooled analysis of 7 studies involving 1333 children showed an inverse relationship between blood lead levels below 10 μg/dL and IQ scores. This observational study cannot show causality, but it does suggest that IQ declines intensify at blood lead concentrations below 7.5 μg/dL. Thus even more children may be at risk for the irreversible effects of lead toxicity.16
Screening venous blood lead levels is the most common way to detect lead poisoning. The Food and Drug Administration recently announced that it was broadening the availability of the portable, easy-to-perform LeadCare II Blood Lead Test System to include more than 115,000 certified point-of-care locations, which should simplify screening for children and adults.17
The American Academy of Pediatrics (AAP) and the CDC recommend universal screening for all Medicaid-eligible children.7 Medicaid reimburses for 1 screening at age 1 year and another at age 2. Medicare no longer covers lead screening tests.7
Recommendations for at-risk children who are not eligible for Medicaid vary by state, and sometimes by municipality; thus physicians should check with their state and city health departments.7 (CDC-funded programs can be found at www.cdc.gov/nceh/lead/grants/contacts/CLPP%Map.htm.)
However, because children with levels above the current threshold of 10 μg/dL may be asymptomatic, all children should be screened.
The history helps identify those who are at risk for lead poisoning (Table 3). If a child presents with symptoms, document the onset of symptoms, dietary intake of iron and calcium, occurrence of pica (repeated ingestion of nonfood substances), and any family history of lead poisoning.7 Since identifying the lead source is critical to preventing reexposure, information should be obtained about the child?s home, areas of play and daycare, nearby industrial or waste sites, water supply, and use of glazed ceramics.7 If the source is not obvious, obtain a detailed history of the parents? occupations and hobbies.
In the physical examination, focus on neurologic signs and symptoms, such as lethargy, speech delay, hearing loss, and behavioral problems. At higher blood lead levels, the child might have seizures and mental retardation.
If you suspect lead poisoning, obtain a venous blood sample, since capillary samples can be falsely elevated.18 If encephalopathy is the presenting symptom and lead is the suspected etiology, do not wait for test results: start treatment immediately. If you suspect exposure through ingestion, abdominal films may confirm the presence of a source (eg, fishing weights). The AAP does not recommend long bone films at any blood lead level.7
In children with serum lead levels of 45 μg/dL or more, it can be helpful to determine the erythrocyte protoporphyrin level, which increases when blood lead levels exceed 30 μg/dL, indicating impairment of the heme biosynthetic pathway. Therefore, children with elevated levels should be tested for iron deficiency; the zinc protoporphyrin test can also be used to evaluate iron status.19 Furthermore, because erythrocyte protoporphyrin levels lag behind blood lead levels by several weeks, periodically monitor the erythrocyte protoporphyrin level to gauge the effectiveness of medical and environmental interventions.
Table 4 outlines management guidelines based on blood lead level. For asymptomatic children with levels between 10 and 19 μg/dL, focus on parental education.11 If the blood lead level is borderline, repeat testing is indicated, since results may vary by as much as ?4 μg/dL between laboratories.
The CDC and the AAP recommend consulting an expert in the management of lead chemotherapy before starting chelation therapy for blood levels between 20 and 44 μg/dL. Also, there is disagreement about the use of chelation therapy for children with blood lead levels of less than 45 μg/dL. Results of a study by the Treatment of Lead-Exposed Children Clinical Trial Group showed that chelation therapy with succimer (Chemet) did not benefit children with blood lead levels of 20 to 44 μg/dL.20 This led investigators to recommend against chelation therapy when blood lead levels are from 20 to 44 μg/dL.
For asymptomatic children with blood lead levels of 45 to 69 μg/dL, begin chelation therapy immediately with edetate calcium disodium (EDTA; Calcium Disodium Versenate) at a dose of 1000 mg/m2 over a 24-hour period or over 5 days, for 20 to 30 minutes at a time. The intravenous route is preferred, as the intramuscular injection is painful; however, the treatment route will depend on the patient?s age, the need for inpatient therapy, and the likelihood of compliance. Be aware that calcium EDTA binds to zinc, allowing the accumulation of gamma-aminolevulinic acid, which is neurotoxic and can potentiate seizures. Using dimercaprol (BAL in Oil) before administering calcium EDTA decreases the chances of adverse neurologic events.
Oral succimer is an alternative treatment. The AAP recommends treatment with succimer when the blood lead concentration is greater than 45 μg/dL and the child?s exposure to lead has been controlled.7
The dose is 350 mg/m2 every 8 hours for 5 days, followed by the same dose every 12 hours for 14 days. If needed, treatment may be repeated to reduce blood lead levels to less than 20 μg/dL. Succimer is usually well tolerated, with only mild side effects.21 However, because it can increase intestinal lead absorption, succimer should not be given when lead is present in the gut. Another oral chelating agent, penicillamine (Cuprimine, Depen), is not approved for the treatment of lead toxicity in children; the AAP regards it as a third-line treatment.22
All symptomatic patients and those with blood lead levels above 70μg/dL require hospitalization. The standard treatment is a 5-day course, beginning with dimercaprol at 75 mg/m2 every 4 hours for the first day, followed by EDTA at 1000 to 1500 mg/m2 every 24 hours for the next 4 days. When blood lead levels drop below 60 μg/dL, discontinue the dimercaprol. Note that dimercaprol is contraindicated in patients with peanut allergies or hepatic or renal insufficiency.
Prevention, Parent Education
Because the detrimental effects of lead exposure are generally irreversible, it is imperative to prevent exposure and identify and eliminate lead source(s) whenever poisoning is detected.7 Education is key (see Box). Help parents understand the importance of avoiding exposure to lead and the role of proper nutrition in ameliorating its harmful effects. Dietary intake of calcium, for example, may help prevent absorption of lead in the intestines and lessen the likelihood of pica.7 Finally, notify the public health department, and screen other children who may have had similar exposures.
Lead has been used by humans for more than 6000 years. This metal is toxic to humans, and its detrimental effects are worse in children, who can have irreversible neurologic effects. Physicians play a key role in educating parents about the dangers of lead toxicity. Screening recommendations differ by state and municipality, but physicians are urged to screen all children, since lead poisoning is often asymptomatic.
The authors would like to thank Dr Omer Berger, Director of the Lead Clinic at Cincinnati Children?s Hospital Medical Center, for his assistance and guidance.
1. Which of these functions is NOT typically impaired in children with lead toxicity?
2. All the following statements about lead toxicity are true, except:
A. Children absorb 5 times as much ingested lead as adults
B. Calcium deficiency can increase lead absorption
C. Lead poisoning can cause delayed puberty in girls
D. Intellectual abilities are not impaired until blood lead levels reach 10 μg/dL
3. Which of the following signs/symptoms is most characteristic of severe lead toxicity?
4. What is the recommended follow up for a child with a blood lead level of 17 μg/dL?
A. No confirmatory test; follow-up test in 3 months
B. Confirm within 1 week; follow-up test in 2 months
C. Confirm within 1 month; follow-up test in 2 months
D. Confirm within 24 hours; follow-up test in 1 month
5. The correct management of lead toxicity includes all these strategies, except:
A. A child with a blood lead level of 19 μg/dL does not require chelation therapy
B. A serum level of 65 μg/dL mandates hospitalization
C. A child whose blood lead level is 50 μg/dL should be treated with chelation therapy within 48 hours
D. A child with a level of 100 μg/dL should be treated with parenteral EDTA therapy
(Answers at end of reference list)
1. Centers for Disease Control and Prevention. Children?s blood lead levels in the United States. Available at www.cdc.gov/nceh/lead/research/kidsbll.htm.
2. National Safety Council. Lead poisoning happens more than you think. Available at www.nsc.org/issues/lead.
3. Centers for Disease Control and Prevention. Blood lead levels?United States, 1999-2002. Morb Mortal Wkly Rep. 2005; 54:513-516.
4. Centers for Disease Control and Prevention. Screening Young Children for Lead Poisoning: Guidance for State and Local Public Health Officials. 1997. Available at www.cdc.gov/nceh/lead/guide/guide97.htm. Accessed October 6, 2006.
5. Melman ST, Nimeh JW, Anbar RD. Prevalence of elevated blood lead levels in an inner-city pediatric clinic population. Environ Health Perspect. 1998; 106:655-657.
6. Bernard SM, McGeehin MA. Prevalence of blood lead levels ≥5 μg/dL among US children 1 to 5 years of age and socioeconomic and demographic factors associated with blood of lead levels 5 to 10 μg/dL, Third National Health and Nutrition Examination Survey, 1988-1994. Pediatrics. 2003; 112:1308-1313.
7. American Academy of Pediatrics Committee on Environmental Health. Lead exposure in children: prevention, detection, and management. Pediatrics. 2005; 116:1036-1046.
8. Agency for Toxic Substances and Disease Registry. Toxicological Profile for Lead (Draft). Atlanta, Ga: ATSDR; September 2005. Available at www.atsdr.cdc.gov/toxprofiles/tp13.html. Accessed October 3, 2006.
9. Piomelli S. Lead poisoning. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson?s Textbook of Pediatrics. 16th ed. Philadelphia, Pa: WB Saunders; 2000: 2156-2159.
10. Loghman-Adham M. Renal effects of environmental and occupational lead exposure. Environ Health Perspect. 1997; 105: 928-939.
11. Centers for Disease Control and Prevention. Managing Elevated Blood Lead Levels Among Young Children: Recommendations From the Advisory Committee on Childhood Lead Poisoning Prevention. 2002. Available at www.cdc.gov/nceh/lead/CaseManagement/caseManage_main.htm. Accessed October 2, 2006.
12. Centers for Disease Control and Prevention. Childhood Lead Poisoning Prevention Program. Available at www.cdc.gov/nceh/lead/about/program.htm.
13. Mendelsohn AL, Dreyer BP, Fierman AH, et al. Low-level lead exposure and behavior in early childhood. Pediatrics. 1998; 101:E10.
14. Bellinger D, Sloman J, Leviton A, et al. Low-level lead exposure and children?s cognitive function in the preschool years [published correction appears in Pediatrics. 1994;93:A28]. Pediatrics. 1991; 87:219-227.
15. Selevan SG, Rice DC, Hogan KA, et al. Blood lead concentration and delayed puberty in girls. N Engl J Med. 2003;348: 1527-1536.
16. Lanphear BP, Hornung R, Khoury J, et al. Low-level environmental lead exposure and children?s intellectual function: an international pooled analysis. Environ Health Perspect. 2005; 113:894-899.
17. FDA broadens access to lead screening test that gives immediate results [press release]. Rockville, Md: US Food and Drug Administration; September 18, 2006.
18. Sargent JD, Dalton M, Klein RZ. Diagnostic testing unwarranted for children with blood lead 10 to 14 μg/dL. Pediatrics. 1999;103:e51.
19. Centers for Disease Control and Prevention. Preventing Lead Poisoning in Young Children. Atlanta, Ga: Centers for Disease Control and Prevention; 2005. Available at www.cdc.gov/nceh/lead/Publications/books/plpyc/contents.htm. Accessed October 2, 2006.
20. Dietrich KN, Ware JH, Salganik M, et al, for the Treatment of Lead-Exposed Children Clinical Trial Group. Effect of chelation therapy on the neuropsychological and behavioral development of lead-exposed children after school entry. Pediatrics. 2004; 114:19-26.
21. Treatment of Lead-Exposed Children (TLC) Trial Group. Safety and efficacy of succimer in toddlers with blood lead levels of 20-44 μg/dL. Pediatr Res. 2000; 48:593-599.
22. American Academy of Pediatrics Committee on Drugs. Treatment guidelines for lead exposure in children. Pediatrics. 1995; 96:155-160.
Answers: 1. A; 2. D; 3. B; 4. C; 5. B.