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Childhood lead poisoning: Clinical manifestations and diagnosis

Childhood lead poisoning: Clinical manifestations and diagnosis
Author:
Jennifer A Sample, MD
Section Editors:
Michele M Burns, MD, MPH
Jan E Drutz, MD
Deputy Editor:
James F Wiley, II, MD, MPH
Literature review current through: Dec 2022. | This topic last updated: Aug 19, 2022.

INTRODUCTION — The clinical manifestations and diagnosis of lead toxicity will be reviewed here.

Prevention and treatment of lead poisoning are discussed separately. (See "Childhood lead poisoning: Exposure and prevention" and "Childhood lead poisoning: Management".)

EPIDEMIOLOGY — Lead (Pb), a stable metallic element with an atomic number of 82 and atomic weight of 207, was first smelted around 4000 BC as a byproduct of silver processing [1]. The consequences of lead toxicity have been recognized for millennia [2]. Despite this knowledge, lead was included as an ingredient of gasoline in the 1920s and continued to be used in paint in some developed countries until the 1970s [3,4]. In many low-income countries, lead in gasoline and industrialized uses of lead (eg, smelters, mines, or refineries) remain major sources of exposure [1]. About 50 percent of the worldwide burden of lead poisoning occurs in Southeast Asia [5]. In 2021, UNICEF estimated that one in three children, globally, had blood lead levels (BLLs) >5 mcg/dL (0.24 micromol/L) [1,6].

Risk factors, sources, and prevention of childhood lead poisoning include:

Risk factors – Children younger than six years of age (and particularly those younger than 36 months) are more susceptible to the toxic effects of lead than are adults because they have an incomplete blood-brain barrier that permits the entry of lead into the developing nervous system, and because they have a greater prevalence of iron deficiency, which can result from and cause lead poisoning through increased absorption of lead from the gastrointestinal tract [7-9]. In addition, they are at greater risk of exposure to lead dust because of crawling, higher respiratory rates, and hand-to-mouth behavior.

The prevalence of elevated BLLs is highest among urban children who live in deteriorating housing that was built before the 1970s, and children exposed to lead as a result of industrialized use (eg, aerosolized lead from smelters or refineries or lead in water near mining operations) [1,10,11]. Lead poisoning is more common among urban than rural children, low-income than middle-income children, and children who live in older housing [11-16]. While the prevalence of elevated BLLs has decreased over time, disparities in the geometric mean of BLLs continue when assessing for ethnicity and income level. In the United States, Black children continue to have a statistically higher BLL compared with other populations. In addition, the prevalence of lead poisoning is increased among refugee children who have arrived recently in the United States, and among children entering foster care [17,18].

Sources – Children typically are exposed to environmental lead through ingestion or inhalation. Common sources include chips of paint or lead dust from lead-painted surfaces; food or beverages purchased, stored, or served in lead-soldered cans or lead-glazed pottery; water from lead-soldered plumbing; automobile emissions; and lead-using industry (table 1). Although the United States phased out lead-soldered food cans during the 1980s, imported canned goods may still contain lead [10]. Less common sources of lead exposure include herbal and folk medications, imported crayons and other toys, mini blinds, cosmetics, jewelry, and imported cookware [10,16,19]. Parental take-home exposures may also result in elevated BLLs in children [20]. Adolescents may have an increased risk due to hobbies and occupational exposures in firing ranges and lead dust that accumulates in these facilities [21]. (See "Childhood lead poisoning: Exposure and prevention".)

Prevention – Removal of the common sources of lead exposure has resulted in declining BLLs in children. As an example, in the United States, as lead was removed from gasoline and paint, the average BLL in children decreased from 16 mcg/dL (0.77 micromol/L) to less than 3 mcg/dL (0.14 micromol/L) in 1991 [12,22]. This trend in declining BLL in United States children less than five years of age has continued with the estimated geometric mean of 0.67 mcg/dL [23,24] in 2018 [25]. Residual lead from these and other products remains in the environment because elemental lead cannot be degraded. In many resource-limited parts of the world, lead continues to be used in gasoline, pigment (eg, in paint, cosmetics, and crayons), pottery glaze, solder, cooking vessels, jewelry, toys, and even medications [5]. These products occasionally are imported into the United States and are potential sources of lead exposure. Although the incidence and severity of lead poisoning in the United States are decreasing, an estimated 450,000 children in the United States were above the reference value of 3.5 mcg/dL (0.14 micromol/L) in 2021 [26]. (See "Childhood lead poisoning: Exposure and prevention", section on 'Prevention'.)

TOXICOLOGY — The key aspects determining toxicity are based upon blood lead levels (BLLs), the disposition of lead once it enters the body (toxicokinetics), and molecular toxicology as follows:

Toxic level – The American Academy of Pediatrics and the Centers for Disease Control and Prevention (CDC) state that no safe or "nontoxic" BLL exists. In the United States, a reference level corresponding to the 97.5th percentile of BLLs in children in the United States (3.5 mcg/dL [0.14 micromol/L] as of 2021) has been adopted [26]. The reference level should not be mistaken for an "action" level as this terminology has changed based on the science that has shown lead to be more toxic than previously thought. Between 1970 and 2012, the toxic level or "action" level was gradually decreased from 60 mcg/dL (2.9 micromol/L) to 10 mcg/dL (0.48 micromol/L). In 2012, the CDC, recognizing that no safe blood level existed, established a reference level at the 97.5th percentile of BLLs in children in the United States (3.5 mcg/dL [0.14 micromol/L] as of 2021) (table 2). The decrease in 1991 was prompted by evidence of cognitive and behavioral effects of low-level lead toxicity [27,28]. Changes in the definition of the toxic level have been accompanied by changes in policies for screening, treatment, and prevention [29]. (See "Screening tests in children and adolescents", section on 'Lead poisoning' and "Childhood lead poisoning: Management".)

Toxicokinetics – Inorganic lead is not metabolized but is directly absorbed, distributed, and excreted. The absorption of lead depends upon the route of exposure and the age and nutritional status of the exposed individual [10]. Inhaled lead may either be cleared by cilia, resulting in ingestion, or retained by the lung (30 to 50 percent) for rapid and complete absorption [30]. Children absorb a greater proportion of lead from the gastrointestinal tract than do adults (up to 70 versus 20 percent) [31,32]. Fasting, iron deficiency, and calcium deficiency also may increase the gastrointestinal absorption of lead [10,33,34].

Lead that is absorbed from the gastrointestinal or respiratory tracts is distributed by a three-compartment model to the blood, soft tissues, and bone (trabecular and cortical). The half-life of lead varies depending upon the body compartment and the age of the child [10,30,35-38].

On average, the half-life in each compartment is:

Blood – 28 to 36 days

Soft tissue – 40 days

Mineralizing tissues – Greater than 25 years

Lead that is not retained in the tissues is excreted by the kidneys or through biliary clearance into the gastrointestinal tract. Children younger than two years of age retain approximately one-half of absorbed lead, whereas adults ultimately retain only 1 percent [10]. More than 70 percent of the total body burden of lead in children is contained in the mineralized tissues [10,39]. Thus, the BLL is not a good reflection of the total body lead burden. In general, the concentration of lead in other organs is comparable to that found in blood. Approximately 99 percent of the lead in blood is bound to red blood cells. The remaining 1 percent (ie, plasma lead) serves as an intermediate in transporting lead from the erythrocytes to other body compartments.

The lead in mineralizing tissues accumulates in two subcompartments: a labile compartment that readily exchanges lead with the blood, and an inert pool [38]. The inert pool of lead can be mobilized during periods of physiologic stress (eg, pregnancy, lactation, fractures, chronic disease) and represents an endogenous source of lead that can maintain an elevated BLL long after the exogenous exposure source has been removed [10]. Because the body accumulates lead over a lifetime and releases it slowly, lead toxicity may occur without a major acute exposure.

Molecular toxicology – Lead is a potent toxic substance with no apparent threshold [40]. Lead interferes with the interactions of divalent cations and sulfhydryl groups. It has widespread physiologic effects because most biochemical reactions are regulated by these agents [41,42]. In vitro, many of the reactions in which lead serves as a competitive inhibitor are reversible. However, in vivo, downstream events lead to cell death and irreversible damage at the cellular level, particularly in the central nervous system [43-45].

Lead can disrupt signal transduction cascades by activating protein kinase C, competing with magnesium and inhibiting cyclic nucleotide hydrolysis by phosphodiesterases, or inhibiting function at the N-methyl-D-aspartate-type glutamate receptor [46-49]. Lead also can uncouple mitochondrial oxidative phosphorylation in the central nervous system [45,50].

Magnetic resonance spectroscopy (MRS) in individuals with elevated BLLs demonstrates reduction in the N-acetylaspartate/creatine and phosphocreatine ratios in the frontal gray matter, suggesting that lead poisoning affects metabolism in the brain [51,52].

Lead competes with calcium for entry into synaptosomes [53] and interacts with numerous receptor-activated and voltage-gated cation channels [54,55]. In addition, lead increases the infidelity of DNA and RNA polymerase, leading to somatic and germline mutations [56,57]. Lead-exposed rodents have an increased incidence of cancer [58-63]. However, this association has not been found in humans [64-66].

Hematologic complications of lead toxicity result from the ability of lead to directly inhibit delta-aminolevulinic acid dehydratase (ALAD), enzymes necessary for heme biosynthesis, and ferrochelatase, a mitochondrial sulfhydryl enzyme causing increased urinary delta-aminolevulinic acid (ALA), urinary coproporphyrin, and erythrocyte zinc protoporphyrin [67-70]. The enzymatic blocks responsible are partial. While anemia may not be seen until blood lead concentrations are markedly elevated, the effect on hemoglobin synthesis occurs at lower levels [10]:

ALA dehydratase is inhibited at very low BLLs with no threshold yet apparent.

Elevation of erythrocyte protoporphyrin occurs at levels of 30 mcg/dL (1.48 micromol/L).

Reduced hemoglobin synthesis is found in children at levels of 40 (1.93 micromol/L) and in adults at levels of 50 mcg/dL (2.41 micromol/L), respectively.

The basophilic stippling of red cells is due to the presence of aggregated ribosomes, which may also include mitochondrial fragments. Conditions, such as lead poisoning, can result in altered ribosomes to have a higher propensity to aggregate. With staining, this appears as increased basophilic granulation (picture 1) [71].

CLINICAL MANIFESTATIONS — Lead affects at least three major organ systems (see 'Toxicology' above):

Central and peripheral nervous systems

Heme biosynthetic pathway

Renal system with injury to the renal and cardiovascular systems closely related

In the child, the most serious symptoms are found in the central nervous system with subtle effects (eg, decreased intelligence quotient [IQ] and cognitive effects) occurring at lower levels and severe effects (eg, seizures, encephalopathy) occurring at higher levels. The majority of children with elevated blood lead concentrations will be asymptomatic from overt clinical manifestations of lead poisoning. Symptoms will vary depending upon the acuity of the lead exposure and the age of the exposed individual (table 3) [10].

The clinical manifestations of lead poisoning in adults are discussed separately. (See "Lead exposure, toxicity, and poisoning in adults", section on 'Clinical manifestations'.)

Neurologic — Neurologic effects of lead poisoning in children include:

Neurobehavioral deficits – Detectable blood lead levels (BLLs) are associated with neurocognitive deficits, and a lower limit for these effects has not been established in population studies. While blood lead tests may result below 5 mcg/dL (0.24 micromol/L), there is no safe lead level, and none should be considered "normal." Low-level lead poisoning may lead to permanent central nervous system injury in young children [72]. Population-based studies consistently have shown that BLLs greater than 10 mcg/dL (0.48 micromol/L) affect the cognitive and behavioral development of children [27,28,73-81]. However, neurocognitive effects also have been demonstrated at even lower BLLs, and no threshold is known to exist [82-86]. Data suggests environmental lead exposure in children at blood lead concentrations <7.5 mcg/dL (0.36 micromol/L) is associated with cognitive deficits. Furthermore, studies suggest that a permanent pattern of cognitive dysfunction may result from lead poisoning in the first several years of life [87], and in-utero lead exposure may adversely affect infant neurodevelopment (measured at 24 months) independent of postnatal BLL [88,89].

The neurobehavioral effects of lead poisoning appear to persist, at least in part, into adolescence and adulthood, despite a decline in BLL [28,75,90-96]. As an example, in a longitudinal cohort study of over 1000 patients, lead exposure, based upon BLL at eleven years of age (mean BLL 11 mcg/dL [0.53 micromol/L]), was associated in a dose-dependent fashion with lower IQ and lower socioeconomic status at age 38 years despite adjustment for maternal IQ, child IQ, and childhood socioeconomic status [97,98]. These studies are contradicted, however, by others that state the magnitude of these effects are small and cannot be interpreted at the individual child [95,99,100]. Although studies cannot predict performance in an individual child with elevated BLL [101], it is clear that primary prevention of lead exposures can prevent the adverse neurotoxic effects of lead.

However, evidence also identifies other important variables besides elevated BLLs when assessing intelligence that may better explain the decline of intellectual abilities, such as parental and social environments [95,100].

Acute encephalopathy – Acute encephalopathy occurs at BLLs greater than 100 to 150 mcg/dL (4.8 to 7.2 micromol/L) and is indicated by persistent vomiting, altered or fluctuating state of consciousness, ataxia, seizures, or coma. Cerebral edema is a variable finding, more often present in younger than older children. Children with lead encephalopathy may develop inappropriate antidiuretic hormone secretion [102], partial heart block [103], and marked decrease in renal function. (See 'Renal' below.)

Hearing loss – The hearing loss occurs primarily in the higher frequencies and may contribute to learning and behavior problems [10,104]. (See "Hearing loss in children: Screening and evaluation".)

Peripheral neuropathy – Peripheral neuropathy, rare in children with isolated lead poisoning, is more common in children with concomitant sickle cell anemia [105-108]. Decreased nerve conduction velocity occurs at BLLs as low as 20 mcg/dL (1 micromol/L) [109,110].

Renal — In the child, lead appears to have an effect on renal function even at levels below 10 mcg/dL (0.48 micromol/L). This is especially true if the lead exposure occurs over a sustained period of time. Subtle abnormalities in renal tubular function, associated with aminoaciduria, glycosuria, and increased excretion of low-molecular weight proteins can occur [111]. Lead nephropathy, which is characterized histologically by chronic interstitial nephritis, is a potential complication of prolonged high-level lead exposure. In addition, current levels of lead exposure have the potential for lead-related nephrotoxicity, primarily in adults with diabetes, hypertension, or underlying chronic kidney disease. These issues, including the long-term renal outcomes of childhood lead poisoning, are discussed in detail separately. (See "Lead nephropathy and lead-related nephrotoxicity", section on 'Pediatric populations'.)

Gastrointestinal — Lead colic, which includes sporadic vomiting, intermittent abdominal pain, and constipation, may occur [105].

Endocrine — BLLs and vitamin D levels are inversely related as lead interferes in the formation of active vitamin D, which has an important role in its influence on calcium metabolism. Calcium is under tight homeostatic control in all cells [10,112]. Vitamin D metabolism is decreased at BLLs of 30 mcg/dL (1.45 micromol/L) [112]. The effects of lead toxicity on cell growth and maturation and tooth and bone development probably are mediated through the effects on vitamin D [10]. Likewise, because of the similar biochemical nature between lead and calcium, increased absorption of lead can occur, especially in children who have decreased calcium intake.

Hematologic — Lead poisoning in children rarely results in anemia [10]. The two major mechanisms are decreased hemoglobin synthesis and hemolysis. Decreased hemoglobin synthesis has been well documented at BLLs of 40 mcg/dL (1.9 micromol/L) [113] and is caused by the interference of lead with several enzymatic steps in the heme pathway. With prolonged exposure to high levels of lead, red blood cell survival is diminished. Acute, high-level lead poisoning (BLL >70 mcg/dL [3.4 micromol/L]) has been associated with hemolytic anemia [10]. Increased erythrocyte destruction is more marked in adults than in children. Increased red cell fragility and decreased osmotic resistance may be observed. The degree of hemolysis is insufficient to produce jaundice. (See 'Toxicology' above and "Approach to the child with anemia".)

Anemia in children with lead poisoning may in fact be caused by iron deficiency because lead poisoning and iron deficiency have similar risk factors [114,115]. Anemia secondary to lead toxicity usually is mild, hemolytic, and normocytic. In contrast, anemia secondary to iron deficiency is hypochromic, microcytic, and reticulocytopenic [116,117]. (See "Iron deficiency in infants and children <12 years: Screening, prevention, clinical manifestations, and diagnosis".)

DIAGNOSIS — Lead poisoning is diagnosed by an elevated venous blood lead level (BLL). Specific interventions for lead poisoning start at BLLs ≥3.5 mcg/dL (0.14 micromol/L), the current reference level as designated by the Centers for Disease Control and Prevention (CDC). (See 'Lead levels' below.)

Specific treatment of childhood lead poisoning depends upon the degree of the blood lead elevation, the presence of symptoms, and local resources available for lead abatement. (See "Childhood lead poisoning: Management".)

Asymptomatic patients — The diagnosis of lead toxicity usually is made through a lead screening program because most children with lead toxicity do not have overt clinical symptoms although neurobehavioral abnormalities may be present. (See "Screening tests in children and adolescents", section on 'Lead poisoning'.)

Symptomatic patients — The symptoms of lead toxicity by level of exposure are shown in the table (table 3). They include cognitive impairment, language delay, and behavior problems at low concentrations and progress to vomiting, colicky abdominal pain, fatigue, renal insufficiency, and encephalopathy at higher concentrations. Lead poisoning should be included in the differential diagnosis for children with any of these complaints or conditions [118].

Encephalopathy — When a patient presents with an acute onset of persistent vomiting, alteration of mental status, and/or seizures consistent with lead encephalopathy and a BLL cannot be obtained emergently, one or more of the following clinical findings constitute strong supportive evidence for a diagnosis of lead poisoning and permit emergency initiation of chelation therapy pending confirmation by blood lead testing [119,120]:

Age one to five years

Prodrome of gastrointestinal symptoms with progression from lethargy to encephalopathy

History of pica, prior increased lead levels, or other history of lead exposure

Strongly positive qualitative urine coproporphyrin

Elevated erythrocyte protoporphyrin

Basophilic stippling of peripheral red blood cells or erythroblasts in the bone marrow (picture 1)

Hypophosphatemia

Glycosuria

Lead flecks on abdominal radiograph (image 1)

Lead lines on long-bone radiographs (image 2)

Children with lead encephalopathy almost always have elevated blood erythrocyte protoporphyrin (EP) or zinc protoporphyrin (ZPP) concentrations (>35 mcg/dL) [121]. Both are precursors of heme and become elevated as lead inhibits heme synthesis [122]. Thus, elevated EP or ZPP concentrations can be used as a rapid confirmatory test in most hospitals. However, it should be noted that elevated ZPP is usually not seen until the BLL is above 30 mcg/dL and may not be elevated in acute exposures given the delay from lead's effect on heme synthesis. (See 'Erythrocyte protoporphyrin' below.)

Emergency treatment should begin if encephalopathy secondary to severe lead toxicity is suspected. A BLL should be obtained to confirm the diagnosis, but treatment should not be delayed while awaiting the result. (See "Childhood lead poisoning: Management", section on 'Symptomatic lead poisoning'.)

EVALUATION

History — A careful history should be obtained from the families of all children suspected of toxic lead exposure (table 4). The history should include:

Onset and severity of symptoms of toxicity (table 3)

Nutritional history with particular attention to intake of iron and calcium

History of pica

Family history of lead poisoning

Foreign birthplace and recent foreign residence with attention to refugee status [123-126]

Assessment of potential sources of lead exposure: work history of the parents/primary caregivers and other significant caregivers, hobbies, age of the home and history of home renovations, source of water supply, location and condition of play areas, use of imported or glazed ceramics, imported jewelry and cosmetics, and proximity to industrial facilities or hazardous waste sites (table 1)

Physical examination — There are few specific findings on physical examination that can help identify the presence of lead poisoning:

Delayed language development and neurobehavioral dysfunction are important features and should raise concern for lead poisoning when present.

Lethargy is particularly concerning because it indicates encephalopathy.

Lead lines, at the junction of the teeth and gums, are rarely seen. If present, they usually indicate severe and prolonged lead exposure (picture 2) [10].

Laboratory evaluation

Lead levels — The laboratory evaluation of the child with lead poisoning should include a repeat venous blood lead level (BLL) to confirm the diagnosis. BLLs should also be obtained in the patient's siblings, housemates, and/or playmates. Parents/primary caregivers may also require testing, especially if the child is an infant who is not crawling or is breastfeeding. All family members should be tested if the source is not found to be from peeling paint chips or soil because household items (eg, cosmetics, jewelry, pottery, or spices) are shared by everyone in the home. Confirmatory samples should be obtained through venous sampling and processed in lead-free collection tubes. The phlebotomy site should be carefully cleaned with an alcohol wipe to remove any lead from the skin surface.

Capillary blood sampling is simpler than venous blood sampling for lead screening and is a valid collection method if it is performed properly [127]. However, capillary samples are subject to contamination with exogenous lead and can yield false-positive results. Common causes of falsely elevated BLLs from capillary lead sampling include [128]:

Inadequate use of gloves by phlebotomists

Use of alcohol wipes contaminated with lead-based ink

Inadequate cleansing of the child's finger

Failure to wipe off the first drop of blood

The limit of detection of point-of-care tests are such that lead levels below 5 mcg/dL (0.24 micromol/L) may not be accurate [129]. Despite the reference level set by the Centers for Disease Control and Prevention (CDC; 3.5 mcg/dL [0.14 micromol/L]), the response to an elevated BLL should remain the same and is dependent on the resources available to local and state health departments. Despite potential inaccuracy, point-of-care tests are still our preferred method of lead screening because their use is associated with much higher screening rates [130].

All patients who have elevated BLLs on capillary samples must have confirmatory venous blood testing. However, an elevated capillary blood lead result may indicate lead in the environment and proceeding with anticipatory guidance for reducing lead risk is appropriate pending confirmation.

Magellan Diagnostics, Inc and the US Food and Drug Administration (FDA) issued a recall of certain lots of capillary point-of-care blood lead testing kits (LeadCare II, LeadCare Plus, and LeadCare Ultra) distributed after October 27, 2020 because of a significant risk of falsely low results [131,132]. As of March 30, 2022, distribution of the LeadCare II product has resumed [133,134].

Provider recommendations regarding test kits identified in the recall include:

Discontinue use and quarantine inventory of all affected test kit lots.

Retest all children and individuals who are pregnant or breastfeeding with either capillary or venous blood lead samples by higher-complexity testing (eg, inductively coupled plasma mass spectrometry [ICP-MS] or graphite furnace atomic absorption spectrometry [GFAAS]) if they had test results <3.5 mcg/dL (0.14 micromol/L) using a recalled test kit or if the initial test kit lot is unknown and the test was performed after October 27, 2020.

Prioritize retesting of children with concern for symptoms or development problems potentially related to lead exposure, populations at higher risk of elevated BLLs, and pregnant or breastfeeding individuals.

Federal regulations in the United States permit laboratories that perform BLL testing to operate with an allowable error of ±4 mcg/dL (0.19 micromol/L) or 10 percent, whichever is greater [135,136]. As an example, a laboratory that meets proficiency standards may report an actual BLL of 8 mcg/dL (0.38 micromol/L) as any value ranging from 4 to 12 mcg/dL (0.19 to 0.58 micromol/L).

Bone and dentine lead levels, measured by K x-ray fluorescence spectroscopy or atomic absorption spectroscopy, respectively, are better indicators of the child's total lead burden than BLLs [38,73,90]. However, these tests are not routinely available and are not recommended by the CDC [137]. BLLs remain the gold standard for the diagnosis of lead poisoning in children. (See 'Diagnosis' above.)

Erythrocyte protoporphyrin — Erythrocyte protoporphyrin (EP), typically assayed as zinc protoporphyrin (ZPP), is elevated (greater than 35 mcg/dL) in iron deficiency, lead poisoning, many erythrocyte disorders, and porphyria. Thus, it is not diagnostic for lead poisoning. EP levels usually are not elevated until lead levels are greater than 30 mcg/dL (1.45 micromol/L) [10,138,139]. Thus, EP is not a good screening test for mild lead toxicity and is not recommended for screening for pediatric lead poisoning.

  • EP can be helpful to diagnose moderate to severe lead poisoning and determine the acuity of the exposure as follows:

An EP ≥250 mcg/dL (4.44 micromol/L) in a patient with findings suggestive of lead encephalopathy supports the initiation of emergency chelation in situations where the results of a venous BLL are not rapidly available [140-142]. (See "Childhood lead poisoning: Management", section on 'Symptomatic lead poisoning'.)

EP can also help identify the acuity of lead exposure when measured along with a venous BLL. If the BLL is markedly elevated but the EP is normal, then lead exposure is acute [143]. However, if both the BLL and EP are elevated, then the exposure is likely chronic [144]. Thus an EP is suggested for all children with a BLL that warrants chelation (>45 mcg/dL [2.17 micromol/L]) (table 5). However, if the results of EP testing are not rapidly available, chelation should proceed based upon the BLL.

The pattern of decline in EP in lead poisoned patients who have received chelation provides information regarding the level of body burden of lead. However, there is a delay in the decrease in EP after chelation due to delayed recovery of the heme synthesis pathway when it has been inhibited by elevated lead levels.

Additional tests — In patients with elevated BLLs, screening for iron deficiency anemia should also occur (eg, complete blood count, ferritin, and C-reactive protein) [137]. (See "Iron deficiency in infants and children <12 years: Screening, prevention, clinical manifestations, and diagnosis", section on 'Laboratory screening'.)

Additional tests are necessary for children who require chelation therapy (see "Childhood lead poisoning: Management", section on 'Initial evaluation' and "Childhood lead poisoning: Management", section on 'Pharmacologic agents for chelation'):

Serum electrolytes

Blood urea nitrogen and creatinine

Serum calcium and magnesium

Alanine and aspartate aminotransferases

Urinalysis

In addition, screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency should be performed in patients who will be treated with dimercaprol or succimer and who have risk factors or findings consistent with the disease. (See "Childhood lead poisoning: Management" and "Diagnosis and management of glucose-6-phosphate dehydrogenase (G6PD) deficiency".)

Diagnostic imaging — A plain abdominal radiograph should be obtained in symptomatic children or those with a history of pica or acute ingestion of lead-containing objects (eg, fishing weights) to identify leaded objects (eg, lead toys, leaded paint chip, or lead flecks in the stool).

Radio-opaque lead flecks in the intestinal tract suggesting recent ingestion are found inconsistently (image 1). However, their presence may have implications for treatment at the time of diagnosis [119]. (See "Childhood lead poisoning: Management".)

The CDC does not recommend obtaining long-bone radiographs in the evaluation of children with lead exposure [137]. Lead lines at the end of growing long bones (image 2) are found only in children with BLLs greater than 45 mcg/dL (2.2 micromol/L). Thus, long-bone radiographs are not useful as part of the diagnostic evaluation of children with lower BLLs and are not used as a diagnostic tool, routinely, in children with lead levels greater than 45 mcg/dL.

Computed tomography of the head should be obtained in children with signs of lead encephalopathy to assess for findings of increased intracranial pressure.

Magnetic resonance imaging in adults with chronic elevated BLLs has shown decreased myelination and white matter loss [145].

MANAGEMENT — The management of childhood lead poisoning is discussed separately. (See "Childhood lead poisoning: Management".)

ADDITIONAL RESOURCES

Lead poisoning management resources — To identify a physician and other clinicians with expertise in managing childhood lead poisoning, contact the regional health department, regional poison control center, or, in the United States, a Pediatric Environmental Health Specialty Unit.

In the United States, additional sources for information for the general public and professionals include the Centers for Disease Control and Prevention (CDC; 1-800-CDC-INFO [800-232-4636]), Pediatric Environmental Health Specialty Units, and the National Lead Information Center (1-800-424-LEAD [5323]).

Regional poison control centers — Regional poison control centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison control centers".)

Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Lead and other heavy metal poisoning".)

SUMMARY AND RECOMMENDATIONS

Clinical manifestations – In children, the most serious symptoms of lead poisoning affect the central nervous system with subtle effects (eg, decreased intelligence quotient [IQ] and cognitive effects) occurring at lower levels and severe effects (eg, seizures, encephalopathy) occurring at higher levels. The majority of children with elevated blood lead concentrations will be asymptomatic from overt clinical manifestations of lead poisoning. If present, symptoms will vary depending upon the acuity of the lead exposure and the age of the exposed individual (table 3). (See 'Clinical manifestations' above.)

Diagnosis – The diagnosis and evaluation of lead poisoning depends upon whether or not symptoms of lead poisoning are present:

Symptomatic patients – Lead poisoning can cause diverse and nonspecific symptoms such as vomiting, cognitive impairment, language delay, hearing loss, and behavior problems at low concentrations and colicky abdominal pain, anemia, intellectual disability, seizures, renal insufficiency, and encephalopathy at higher concentrations (table 3). Lead poisoning should be included in the differential diagnosis for children with any of these complaints or conditions. (See 'Symptomatic patients' above.)

Symptomatic lead intoxication is a medical emergency warranting an emergency repeat venous blood lead level (BLL) for confirmation, emergency evaluation, hospitalization, and chelation. The laboratory evaluation for these patients is described separately. (See "Childhood lead poisoning: Management", section on 'Initial evaluation'.)

When a patient presents with an acute onset of persistent vomiting, alteration of mental status, and/or seizures consistent with lead encephalopathy and a stat BLL is not available, one or more of the following clinical findings constitutes strong supportive evidence for a diagnosis of lead poisoning and permits emergency initiation of chelation therapy pending confirmation by blood lead testing (see 'Encephalopathy' above and "Childhood lead poisoning: Management", section on 'Symptomatic lead poisoning'):

-Age one to five years

-Prodrome of gastrointestinal symptoms with progression from lethargy to encephalopathy

-History of pica, prior increased lead levels, or other history of lead exposure

-Strongly positive qualitative urine coproporphyrin

-Elevated erythrocyte or zinc protoporphyrin

-Basophilic stippling of peripheral red blood cells or erythroblasts in the bone marrow (picture 1)

-Hypophosphatemia

-Glycosuria

-Lead flecks on abdominal radiograph (image 1)

-Lead lines on long-bone radiographs (image 2)

Asymptomatic patients – The diagnosis of lead poisoning in asymptomatic patients usually is made through measurement of an elevated BLL during routine blood lead screening. False-positive elevation caused by contamination of the fingertip can occur if capillary samples are obtained. (See 'Asymptomatic patients' above.)

All patients who have elevated BLLs on capillary samples must have confirmatory venous blood testing that are collected in lead-free tubes. Management decisions should only be based upon venous blood lead results (table 6). (See 'Lead levels' above and "Childhood lead poisoning: Management".)

The limit of detection of point-of-care tests are such that lead levels below 5 mcg/dL (0.24 micromol/L) may not be accurate. Despite the reference level set by the Centers for Disease Control and Prevention (CDC; 3.5 mcg/dL [0.14 micromol/L]), the response to an elevated BLL should remain the same and is dependent on the resources available to local and state health departments.

Evaluation of asymptomatic patients – In asymptomatic patients with elevated BLLs, additional evaluation includes (see 'Evaluation' above):

Careful history (table 4) and physical examination to assess for subtle signs of lead poisoning. (See 'History' above and 'Physical examination' above.)

Screening for iron deficiency anemia (eg, complete blood count, ferritin, and C-reactive protein). (See 'Additional tests' above and "Iron deficiency in infants and children <12 years: Screening, prevention, clinical manifestations, and diagnosis", section on 'Laboratory screening'.)

Additional studies for asymptomatic children who require chelation therapy (see 'Additional tests' above and "Childhood lead poisoning: Management"):

-Serum electrolytes

-Blood urea nitrogen and creatinine

-Serum calcium and magnesium

-Alanine and aspartate aminotransferases

-Urinalysis

-Screening for glucose-5-phosphate dehydrogenase (G6PD) deficiency in patients who will be treated with dimercaprol or succimer and who have risk factors or findings consistent with the disease (see "Childhood lead poisoning: Management", section on 'Pharmacologic agents for chelation')

A plain abdominal radiograph should be obtained in asymptomatic children with a history of pica or acute ingestion of lead-containing objects (eg, curtain or fishing weights). (See 'Diagnostic imaging' above.)

ACKNOWLEDGMENT

The editorial staff at UpToDate acknowledge both Richard L Hurwitz, MD and Dean A Lee, MD, PhD, who contributed to earlier versions of this topic review.

The UpToDate editorial staff acknowledges extensive contributions of Donald H Mahoney, Jr, MD to earlier versions of this topic review.

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Topic 6491 Version 37.0

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