Pocket Pediatrics: The Massachusetts General Hospital for Children Handbook of Pediatrics (Pocket Notebook Series), 2 Ed.

LEAD SCREENING AND TOXICITY

(Pediatr Rev 2010;31:399; Pediatrics 2005;116:1036; NEJM 2003;348:1517; Environ Health Perspect 2005;113:894; Pediatrics 2007;120:e1285; Pediatr Clin North Am 2007;54:271)

Sources of Lead

• Lead paint (banned in US in 1977) chips or dust, contaminated soil or household dust (from exterior paint or prior use of leaded gasoline from nearby traffic)

• Air: Historically important until leaded gas phased out 1973–1986 with >96% reduction in lead levels 1980–2005, now most comes from industrial emissions, esp lead smelters

• Water from lead pipes and solder, also brass fittings; worse if standing/stagnant or hot

• Imported or antique toys, cookware, ceramics

• Imported folk/ethnic/herbal remedies, cosmetics, foods, and spices

• Occupational: Ceramic/glass work, auto/ship repair, plumbing, painting, mining, soldering

• Transplacental (infant lead levels approximate maternal levels)

Lead Screening

• Most at risk: African-American children, pts on Medicaid, lower SES or urban areas, recent immigrants, developmental delays, and repetitive oral behaviors, those w/ siblings with elev lead levels

• Begin 6 mo, assess pt risk (pre-1950 home w/ peeling paint; pre-1978 w/ renovating; sibling or friend w/ toxicity; household adult in high-risk occupation; high-risk home location)

• Children w/ gov assistance (Medicaid, WIC) screen btw 9–12 mo and again at 24 mo

• Non-Medicaid eligible pts, selective screening according to state recs. Screen at age 3 to 6 yo if not screened previously

• Immigrants, refugees, and international adoptees screened upon arrival to US

• Consider screening in all pts w/ PDD, pica, or those who are neglected or abused

Pathogenesis

• Toxic to CNS and PNS, hematopoiesis, kidneys, liver, and endocrine systems; children at inc risk b/c immature blood–brain barrier. Lead interferes with neurotransmission and disrupts cell migration during brain development

• Inhibits enzymes in heme synthesis δ-aminolevulinic acid dehydratase (ALA) and ferrochelatase (resulting in ↑ protoporphyrin levels)

• Inhibits pyrimidine 5’ nucleotidase (results in basophilic stippling [BS])

Clinical Symptoms

• Neuro: Dev delay, cogn deficits, ADHD, aggression, delinquency, hearing loss, periph neuropathy, encephalopathy (Δ MS, szr, ataxia, papilledema/cerebral edema, coma)

• IQ decline of 3.9 for levels 2.4–10 mcg/dL, by 1.9 for levels 10–20 mcg/dL, and by 1.1 for levels of 20–30 mcg/dL (Environ Health Perspect 2005;113:894)

• Relationship nonlinear 2/2 differential lead saturation pathways (highest <10 mcg/dL)

• Heme: Microcytic hypochromic anemia, hemolysis (↓ RBC lifespan), BS, inhibits T-cell fxn

• Renal: Proximal tubular dysfunction (aminoaciduria, glycosuria, hyperphosphaturia/hypophosphatemia), ↑ risk for adult-onset HTN and CKD

• GI: Abd colic, anorexia, vomiting, constipation, lead lines at interface teeth and gingiva

• Endocrine: Delayed puberty, growth failure, vitamin D deficiency/osteopenia

• Ortho: Lead lines on long-bone radiographs, dental caries, spontaneous abortion, impairs cartilage mineralization

Diagnostic Studies

• Venous lead level (VLL) >10 mcg/dL = + (if capillary >10 mcg/dL need venous confirmation)

• If lead level is elevated, screen all siblings, housemates, and friends

• Blood lead levels peak at 18–30 mo, then gradually decline

• Free erythrocyte protoporphyrin or zinc-chelated protoporphyrin: ↑ w/ iron def & lead poisoning (VLLs >30 mcg/dL), may help assess chronicity & response to rxs

• CBC, retic count, iron level, TIBC, ferritin level; if hx ingestion/pica, obtain KUB

• For chelation, check Chem20 and U/A; if w/ dimercaprol or succimer, check G6PD

Management

• No RCTs that chelation improves neurocognitive outcomes; protocols based on clinical judgment and experience

• Pharmacologic therapy

• Calcium disodium ethylenediaminetetraacetate (EDTA)

• Indication: VLL 45 mcg/dL or encephalopathy

• Side effects: Renal dysfunction, hypokalemia; monitoring: For hydration Chem10, UA, and telemetry

• Contraindications: Anuria

• If encephalopathic, separate infusion of EDTA and BAL by >4 hr

• Succimer (DMSA); indication: VLL 45–69 mcg/dL

• Side effects: Hypersensitivity reactions, GI sx, transient transaminitis, ↓ hemoglobin, reversible neutropenia; monitoring: LFTs and CBC

• Dimercaprol (BAL = “British anti-Lewisite”): Indication: VLL 70 mcg/dL or lead enceophalopathy

• Side effects: Pain, hemolysis in G6PD, toxic complexes if given w/ iron, HTN, N/V, fever, lacrimation, paresthesia, renal dysfunction, zinc depletion, headache, leucopenia, tachycardia, hyperpyrexia

• Contraindications: G6PD, hepatic disease, peanut allergy

• Monitoring: CV and mental status; alkalinize urine during tx