Pediatric Lead Toxicity 

Updated: Dec 12, 2019
Author: Mohamed K Badawy, MD, FAAP; Chief Editor: Stephen L Thornton, MD 

Overview

Practice Essentials

Lead toxicity is a worldwide pediatric problem. Although data continue to demonstrate a decline in the prevalence of elevated blood lead levels (BLLs) in children in the industrialized world, lead remains a common, preventable, environmental health threat. Sequelae of lead intoxication include mental retardation and growth failure. (See Epidemiology and Prognosis.)

The mechanisms of contamination include ingestion, inhalation, prenatal exposure, and dermal exposure, but the most common are ingestion and inhalation. Ingestion is more common in children, while the inhalation is more frequent in occupationally-exposed adults. Deteriorating lead paint in pre-1979 housing remains the most common source of lead exposure in children, accounting for up to 70% of elevated levels.[1]  Other common sources of lead exposure include batteries, putty, cement, imported canned food, cosmetics, jewelry, leaded glass artwork, farm equipment, and illicit intravenous drugs.

Toddlers often place objects in their mouth, resulting in ingestion of dust and soil and, possibly, an increased intake of lead. The physiologic uptake rates of lead in children are higher than those in adults. In addition, children are rapidly growing, and their systems are not fully developed, which renders them more susceptible than adults to the effects of lead exposure.[2]  (See Etiology.)

Lead poisoning in children has been the focus of many researchers. Studies have indicated intellectual impairment in children with BLLs of less than 10 µg/dL.[3, 4]  Behavioral disorders are associated with lead exposure even at detectable blood levels at or below 5 µg/dL The current value of 5 µg/dL is used by clinical and public health care providers to identify children with elevated BLLs.[5]

For patient education information, see Lead Poisoning and Kids and the Lead Poisoning Directory. Because the effects of lead poisoning in children can be irreversible, primary prevention is critical; see the CDC's Prevention Tips.

Pathophysiology

Lead typically enters the body through inhalation or ingestion. Once lead is absorbed into the bloodstream, some of it is cleared from the body by excretion in the urine and bile. The clearance rate is approximately 1-3 mL/min and the half-life of lead in blood is approximately 30 days.[6]

The lead that remains binds to red blood cells and is then distributed to the soft tissues and bone. Lead eventually accumulates in bone, where it has a half-life of 20-30 years. Once lead is deposited in bone, it may be released back into the bloodstream during conditions of rapid bone tissue turnover such as pregnancy, menopause, and lactation.[6]

Lead exerts toxic effects through a variety of mechanisms on many different organ systems. Two systems that are particularly sensitive to lead toxicity are the hematologic system and the developing nervous system.[7, 8]  In the hematologic system, lead destabilizes the red cell membrane, causing oxidative stress and early cell death.[8]  Lead also inhibits the activities of several enzymes involved in heme biosynthesis and may trigger inappropriate production of erythropoietin.[7] These effects contribute to hemolytic anemia.[8]

In the nervous system, lead crosses the blood-brain barrier by displacing calcium ions. Within the brain, it accumulates in astroglial cells and prevents myelin sheath formation. These effects can lead to demyelination and disturbances in neural excitation and memory-related neurotransmitter activity.[8]

Lead has more pronounced adverse effects on the developing brain because it disrupts processes required to establish necessary connections between brain structures, eventually leading to permanent alterations in brain function. These effects can cause irreversible neurobehavioral developmental abnormalities in affected children, even at very low lead levels[9] .[6]

Etiology

Lead toxicity may be caused by inorganic or organic lead. Most cases of lead poisoning are caused by inorganic lead. Lead may enter the body through ingestion, inhalation, or transdermal absorption. Inorganic lead absorption occurs via the mechanisms involved in absorption of essential elements, such as calcium and iron, and depends on the following factors:

  • Solubility - Lead salts are more soluble in acidic media

  • Particle size - Large particles (eg, paint chips) are poorly absorbed, whereas fine dust particles licked from the fingers or other objects may contribute to an increased lead load

  • Nutritional deficiencies -Iron, calcium, zinc, copper, and protein deficiencies result in greater lead absorption

  • Dietary fats and oils - Excess intake results in increased lead absorption

  • Other dietary components - Dietary components such as phytates, found in leafy green vegetables, bind lead particles and increase their elimination

Factors that increase the risk for lead exposure in children include[10] :

  • Living in poverty
  • Member of a racial-ethnic minority group
  • Recent immigrant
  • Living in older, poorly maintained rental property
  • Having parents who are exposed to lead at work.

In children, elevated blood lead levels are most commonly caused by inhalation or ingestion of lead dust and chips of deteriorating lead-based paint. Other sources of exposure include the following[11] :

  • Imported or antique toys painted with lead paint
  • Imported cookware
  • Toy jewelry made of lead
  • Contaminated tap water
  • Ingested foreign bodies
  • Dietary supplements

Transcutaneous absorption of inorganic lead is minimal. However, organic lead, such as tetraethyl lead, may enter through the skin. Tetraethyl lead, the main organic compound in leaded gasoline, is converted in the body to triethyl lead and inorganic lead. While inorganic lead does not readily enter the body through the skin, it can enter the body through accidental ingestion (eating, drinking, and smoking) via contaminated hands, clothing, and surfaces.[9]

Adults are mainly exposed to lead by breathing in lead-containing dust and fumes at work, or from hobbies that involve lead.[9]  Toxic lead exposures have also resulted from retained bullets or shrapnel fragments.[12]  Intraarticular bullets can fragment and dissolve in synovial fluid, leading to lead absorption and delayed symptomatic lead poisoning.[13]

Inhalation of lead can also occur with exposure to tobacco smoke. Blood lead levels high enough to suggest possible adverse cognitive outcomes have been measured in youths with secondhand smoke exposure.[14]

Several environmental factors expose children to lead hazards, among which are dust, soil, paint chips, folk remedies, and the use of old ceramic cookware. Several parental occupations place children at risk, including lead mining, glass making, printing, welding, and electronic scrap recycling.[1, 9]  Workers should be instructed to change their working clothes at work.

Epidemiology

At least 4 million households in the United States have children living in them that are being exposed to high levels of lead. There are approximately half a million children ages 1-5 with blood lead levels above 5 µg/dL, the reference level at which CDC recommends public health actions be initiated.Children who belong to minority populations or low-income families or who live in older homes are particularly at risk.[10]

In 2017, the American Association of Poison Control Centers (AAPCC) reported 2219 single exposures to lead: 1099 were in children under the age of 6 years, 179 in children 6 to 12 years old, and 97 in patients 13 to 19 years old; there were four major outcomes and one death.[15]

According to the Centers for Disease Control and Prevention (CDC), in 2014 the incidence rate of blood lead levels (BLLs) ≥10 µg/dL in US children younger than 5 years old, was 50.66 per 100,000 for children ages 1-5 years and 19.90 for children less than a year old; and, the incidence rate of blood lead levels (BLLs) between 5 and 9 µg/dL in US children younger than 5 years old, was 444.49 per 100,000 for children ages 1-5 years and 148.51 for children less than a year old.[5]  

The CDC also reported that 36% of new cases of elevated BLL in 2014 were identified during August–October, more than any other consecutive 3-month period. In warm weather, windows possibly painted with lead-based paint are opened and closed, creating lead dust in the air and on the ground. Repainting and renovation activities also are more common in warmer months. Increased presence and activity of children in and around the home might lead to children having more contact with contaminated dust, surfaces, and soil which can account for the higher BLLs in the late summer and early fall.[5]

Retained bullet fragments (RBFs) are an infrequently reported, but important, cause of severe lead toxicity. During 2003–2012, elevated BLLs associated with RBFs constituted 0.3% of all elevated BLLs and 4.9% of BLLs ≥80 μg/dL. Elevated BLLs associated with RBFs occurred predominantly among males aged 16–24 years in nonoccupational settings.[12]

Lead continues to be a significant public health problem in developing countries. In Africa, children, especially those living in the vicinity of industrial areas, are exposed to the highest levels of lead from different sources, such as heavy exposure to automobile exhaust (in countries where leaded gasoline is still sold), lead released by burning of paper products, discarded rubber, battery casings, and painted wood for cooking and heating.[16]  In addition, children exposed to lead-based paint, or home-industry manufacture of batteries, ceramics, or painted artifacts have high lead burdens.[17, 18] Children living in rural areas who are not engaged in manufacturing pursuits do not usually have high lead burdens.

Prognosis

Prognosis depends on the blood lead level (BLL) and whether the patient was symptomatic on presentation. Asymptomatic patients tend to have a better prognosis, and studies demonstrate some improvement in intellectual functions following lowering of the BLL. Severe neurologic damage may follow lead encephalopathy.

Research has demonstrated that cognitive defects may occur at levels below the currently accepted BLL of 10 μg/dL.[3] Lanphear et al found an inverse relationship between blood-lead concentration and all cognitive function scores; this result was observed in math and reading scores for concentrations as low as 2.5 μg/dL.[19]

Lead-related deaths have become extremely rare since the advent of lead screening measures and decreased use of lead. Presently, death from lead encephalopathy is rarely encountered because of the aggressive approach to using chelating agents. However, complications may arise from the chelated lead complex. Therefore, careful monitoring of mental status, cardiovascular function, and renal and hepatic functions are essential parts of the ongoing evaluation.

 

Presentation

History

The clinical picture associated with lead poisoning is vague. Symptoms are not specific enough to alarm the physician about lead toxicity. Most cases are currently identified through effective screening of the population at risk. However, patients with lead poisoning frequently have constipation, abdominal pain, and/or anorexia.

Gastrointestinal (GI) symptoms of lead poisoning include the following:

  • Anorexia

  • Vomiting

  • Constipation

  • Abdominal pain

Neurobehavioral changes observed in lead poisoning include the following:

  • Inattentiveness

  • Distractibility

  • Impulsiveness

  • Learning problems

Peripheral nervous system effects (rare in children) associated with lead poisoning include the following:

  • Weakness

  • Peripheral palsies

Physical Examination

No specific physical signs for lead poisoning are recognized, but patients may exhibit pallor (due to associated anemia) and hyperactivity.

Signs of increased intracranial pressure can include the following:

  • Impaired consciousness

  • Bradycardia

  • Hypertension

  • Respiratory depression

  • Papilledema

  • Coma

 

DDx

 

Workup

Approach Considerations

Perform a rapid bedside glucose determination in children who present with altered mental status. Obtain serum pH and electrolyte levels, including calcium, magnesium, and phosphorus. Check for anion gap acidosis (see the Anion Gap calculator) that may be present in co-ingestions. A complete blood count (CBC) may reveal hypochromic microcytic anemia. Basophilic stippling of the erythrocytes, which is characteristic of lead poisoning, is uncommon in children.

Perform urinalysis. Children may appear mildly dehydrated, with concentrated urine and poor appetite. This can signal the beginning of the development of inappropriate secretion of antidiuretic hormone.

Except for rare circumstances, there is little or no value in measuring lead in urine or hair. Because of the pharmacokinetics of lead clearance, urine lead changes more rapidly and may vary independently of BLL. Urine lead is less validated than BLL as a biomarker of external exposure, or as a predictor of health effects. Lead in hair may be a reflection of external contamination rather than internal lead dose and laboratory analysis is not standardized.[9]

Whole blood lead level

Whole blood lead level (BLL) is the criterion standard for confirming the diagnosis of lead poisoning. For convenience, a fingerstick capillary lead level has been used for screening. Properly collected capillary samples have a 10% false-positive rate. Once an elevated lead level is detected, a venous lead level is assessed for confirmation.

Currently, the CDC recommends 5 μg/dL as a threshold for identifying children who have been exposed to lead and prompting measures to reduce the child’s future exposure to lead.[10]

Erythrocyte protoporphyrin

Erythrocyte protoporphyrin (EP) may be obtained in selected patients. Lead toxicity affects heme synthesis at several steps; this includes interference with the enzyme ferrochelatase, leading to the accumulation of EP. EP is easily detected because it fluoresces easily. EP is an adjunct for the diagnosis in the presence of elevated lead levels of 55 mcg and higher. At lead levels below that, EP is not a very sensitive measure, and its positivity declines. Therefore, EP is not used as a primary screening tool.

Imaging Studies

Abdominal radiography

Presence of radiopaque flakes is a clear indicator of pica.

Long-bone radiography

Radiodensity may be detected at the distal metaphyseal area. These indications, known as lead lines, are true growth arrest lines and, although not pathognomonic, are associated with chronic lead exposure.

Chest radiography

This study is indicated in patients with lead encephalopathy to confirm the position of the endotracheal tube. Although radiographic findings of suspected aspirations may be initially absent, an initial radiograph is often helpful.

CT scanning

Head computed tomography (CT) scanning may be needed in patients who present with altered mental status to exclude cerebral edema and structural lesions.

 

Treatment

Approach Considerations

Treatment of lead toxicity involves the prevention of further lead exposure, decontamination, chelation, and supportive therapy.

Outpatient treatment seems to be a good option for asymptomatic children with blood lead levels (BLLs) in the range of 45-69 μg/dL. However, be absolutely sure that the environment in which the child is placed is safe and lead free. If this is impossible to ensure, inpatient treatment is needed until the environmental situation is investigated in collaboration with social services and the local health department.

For patients with a BLL 70 μg/dL or higher, hospitalize the patient, obtain a confirmatory venous BLL, and initiate chelation with dimercaprol and calcium disodium edetate (EDTA). Because calcium EDTA does not cross the blood-brain barrier, its use as the only agent in this situation is not recommended because of the possibility of lead redistribution from the soft tissues to the central nervous system (CNS). Pretreatment with dimercaprol (which crosses the blood-brain barrier) is recommended.

When children have lead encephalopathy, the best approach is to transfer them to a children's hospital where pediatric intensivists and other resources are available.

All children being treated for lead poisoning need close follow-up care. Monitoring their BLLs is important. Closely monitor cardiovascular and mental status in patients with lead poisoning, maintain an adequate urine output, and assess renal and hepatic functions.

Decontamination

Decontamination may be performed in patients with acute lead ingestion in whom lead paint chips are identified on plain abdominal radiographs.

Gastric lavage may be performed. Secure the airway before the initiation of gastric lavage in an obtunded child with acute lead ingestion. The use of gastric lavage is controversial because lead paint chips, being large in size, are believed to be poorly absorbed and mainly excreted in stools. In 1997, the American Academy of Clinical Toxicology (AACT) stated that no evidence indicates that gastric lavage use improves clinical outcomes.

Although whole-bowel irrigation (WBI) may be performed to decrease the bioavailability of paint chips, it remains a theoretical option for lead ingestion because insufficient data support or exclude its use. Charcoal binds poorly to lead, and no evidence supports its use in acute lead ingestion.

Chelation

Use of chelating agents is recommended for children with venous lead levels of 45 μg/dL or higher. These include oral succimer and parenteral  calcium disodium edetate (calcium EDTA) and British antilewisite (BAL; dimercaprol).

Significant intravascular hemolysis may occur in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency who are receiving BAL as a chelating agent. Iron supplementation should be avoided in patients receiving BAL chelation therapy because BAL forms a complex with iron, leading to toxicity. Diphenhydramine may help to alleviate the adverse effects of British antilewisite (BAL).

Supportive Therapy

Most children with lead poisoning are asymptomatic and are identified by screening. However, certain children may develop acute lead encephalopathy. In such circumstances, protection of the airway via endotracheal intubation may be necessary.

In the event of seizures, benzodiazepines are indicated. Maintenance of seizure control with phenobarbital may be needed. If seizures are difficult to control, presume the presence of increased intracranial pressure and pursue measures to decrease it (eg, hyperventilation, mannitol, steroids).

Maintain an adequate urinary flow to promote excretion of the lead-chelated complex. Once urinary flow is established, restrict fluids to maintenance and losses to prevent cerebral edema.

Prevention

The key to preventing lead toxicity in children is identification and elimination of the major sources of lead exposure. The 2020 Healthy People objective to eliminate childhood lead poisoning can be achieved through primary prevention. Pediatricians and family practitioners provide a fundamental role with anticipatory guidance about potential sources of lead exposure and its hazards for the development of children.

A successful primary prevention plan should focus on the two main exposure sources for children in the United States: (1) lead in housing and (2) nonessential uses of lead in certain products, such as imported and domestically manufactured toys, eating and drinking utensils, cosmetics, and traditional medicines.

Age of the housing is a major determinant of lead paint hazards. For housing built from 1978 to 1998, 2.7% contained one or more lead paint hazards, whereas the prevalence of residential hazards increased to 11.4% of housing built from 1960 to 1977, 39% of housing built from 1940 to 1959, and 67% of housing units built before 1940. In addition, the primary sources of lead in water is lead service lines, lead solder, and brass fittings that contain high concentrations of lead. Plumbing installed before 1986 (the year a federal ban was enacted), is likely to contain higher concentrations of lead.[20]

Lead-based paint is the major source of lead, but ingestions of lead-contaminated house dust and residential soil are the major pathways for exposure. House dust can be contaminated by small particles of lead-based paint or lead-contaminated soil can be tracked indoors leaving children who live in older, poorly maintained housing vulnerable to exposure. Ingestions of lead-contaminated house dust and soil are also the primary pathways of exposure for children who live in homes that were recently abated or renovated.[20]

Parents should be educated about sources of lead, the common behavior involved (ie, pica), and the hazards associated with lead exposure on children's development.[10, 21]

Nutritional assessment is of particular importance because lead absorption is enhanced by improper dietary intake, especially in the presence of high fat intake and/or deficiency of certain elements, such as calcium and iron.

 

Guidelines

Guidelines Summary

Guidelines and recommendations on screening for elevated BLL are available from the following organizations:

  • American Academy of Pediatrics (AAP) [22, 20]
  • Centers for Disease Control and Prevention (CDC) [23, 24]
  • United States Preventive Services Task Force (USPSTF)​ [25]

In May 2012, the CDC recommended that a reference value based on the 97.5th percentile of the National Health and Nutrition Examination Survey (NHANES) generated BLL distribution in children 1-5 years old (currently 5 μg/dL) be used to identify children with elevated BLL.[26]  

The USPSTF concluded that evidence is insufficient to recommend for or against routine screening for elevated blood lead levels in asymptomatic children aged 1 to 5 who are at increased risk for lead exposure. Routine screening for elevated blood lead levels in asymptomatic children aged 1 to 5 years who are at average risk is recommended against.[25]

The CDC guidelines require lead testing for the following children[26] :

  • At 12 and 24months for all Medicaid‐enrolled children, regardless of known lead‐exposure risk.
  • Children < 72 months who missed the recommendedscreening at a younger age 
  • All immigrant, refugee, and internationally adopted children when they arrive in the United States 
  • Neonates and infants born to women with lead exposure during pregnancy and lactation.

Universal screening is recommended by both the CDC and AAP in areas where at least 27% of houses were built before 1950 and in places where the prevalence of elevated blood levels in children aged 1-2 years is 12%.[22, 20, 26]

Targeted screening is recommended in all other areas in which a positive response is received to one or more of the following screening questionnaire items issued by the CDC:

  • Does your child live in or regularly visit a house that was built before 1950?
  • Does your child live in or regularly visit a house that was built before 1978 with recent or ongoing renovations or remodeling (within the past 6 mo)?
  • Does your child have a sibling or a playmate that has or did have lead poisoning?

The AAP also recommends that states and cities formulate their own lead screening recommendations on the basis of local data because of the wide variation in lead exposure.[20]

 

 

 

 

Medication

Medication Summary

In patients with lead toxicity, the use of chelating agents is recommended for blood lead levels (BLLs) of 45 μg/dL or higher. Chelation can be started with oral succimer, or, if the patient is hospitalized, calcium disodium edetate (calcium EDTA) can be used. These agents have potential toxicities, and monitoring of the complete blood cell count, electrolytes, and liver function test results is necessary.

Chelating Agents

Class Summary

Chelating agents are the criterion standard for the treatment of patients with lead poisoning according to the blood lead levels (BLLs) discussed above. These agents bind to lead and promote its excretion. Patients receiving chelation therapy must be closely monitored because of the agents' potential toxicities.

Dimercaprol (BAL in oil)

Dimercaprol was first developed as an antidote for lewisite toxicity. It is water soluble and rapidly crosses the blood-brain barrier. Dimercaprol forms a nonpolar compound with lead that is excreted in bile and urine. It is the drug of choice in patients with acute lead encephalopathy, in whom the first dose is given and then the second dose is given combined with calcium EDTA after a 4-hour interval.

Edetate calcium disodium (Calcium Disodium Versenate)

This agent decreases blood lead concentration, reverses the hematologic effects of lead, and enhances the excretion of lead in urine.

Succimer (Chemet)

Dimercaptosuccinic acid (DMSA) is a water-soluble analog of dimercaprol. It causes a rapid decline in lead level and replenishes many of the sulfhydryl-dependent enzymes. In the absence of encephalopathy, patients may be treated with DMSA.

D-penicillamine (Cuprimine, Depen)

D-penicillamine is also known as D-dimethyl cysteine. It offers an alternative for oral treatment of lead poisoning. This agent is not approved by the US Food and Drug Administration (FDA) for use in lead poisoning, but has nonetheless been in use for more than 20 years.