- Email: [email protected]
Lead Toxicity in a Newborn
DEPARTMENT
Case Study—Primary Care
Lead Toxicity in a Newborn Mary Patrice Hildebrand, MSN, RN, CPNP
KEY WORDS Lead toxicity, chelation therapy, geophagy
CHIEF COMPLAINT At 36 weeks gestation, the lead level of a gravida 3 para 2 Hispanic woman was 60 mg/dL. Two weeks later, she delivered a female infant whose lead level was 88 mg/dL. HISTORY OF PRESENT ILLNESS During a routine prenatal visit at 36 weeks gestation, a 34-year-old woman reported that her 2-year-old sonÕs lead level was elevated. As the womanÕs health care provider (HCP) sought more information, the
Section Editors Jo Ann Serota, MSN, RN, CPNP Corresponding Editor Ambler Pediatrics Ambler, Pennsylvania Beverly Giordano, MS, RN, CPNP University of Florida, Gainesville Gainesville, Florida Donna Hallas, PhD, PNP-BC, CPNP New York University New York, New York Mary Patrice Hildebrand, Nurse Practitioner, University of Texas Health Science at Houston, Lyndon B. Johnson Well Baby Nursery, Houston, TX. Conflicts of interest: None to report. Correspondence: Mary Patrice Hildebrand, MSN, RN, CPNP, University of Texas Health Science at Houston, Lyndon B. Johnson Well Baby Nursery, 5656 Kelley St, Houston, Texas 77026-1967; e-mail: [email protected]. J Pediatr Health Care. (2011) 25, 328-331. 0891-5245/$36.00 Copyright Q 2011 by the National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.pedhc.2011.03.008
328
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woman reported that she regularly ingested ground lead pottery. The resultant serum lead test revealed a lead level of 60 mg/dL (reference range < 10 mg/dL). The womanÕs toxic lead level could not be treated by chelation because it would have harmful effects on the fetus (Hale, 2006). The HCP counseled the woman to refrain from eating ground lead pottery and notified the Department of Newborn Services of the impending birth of an infant who could have possible toxic lead levels. MEDICAL AND OBSTETRICAL HISTORY From her initial prenatal examination at 12 weeks gestation, the woman had been compliant in keeping appointments. A prenatal ultrasound showed measurements consistent with the timing of her last menstrual period. Her routine prenatal laboratory tests had been normal, as had the routine screening glucose test (95 mg/dL) at 24 weeks gestation. It was not until her 36th week of gestation when she mentioned that her son had an increased lead level and she ingested ground pottery that concern arose. She also divulged that she had consumed products containing lead in her two previous pregnancies; however, she had never informed her previous HCPs of this practice. Even though the womanÕs lead level was six times the upper limits of normal, she denied having symptoms of lead toxicity. Specifically, she denied having headaches, dizziness, epistaxis, metallic taste, excessive salivation, digestive problems, memory loss, myalgias, or joint pain. She also denied having any acute or chronic health problems. PERSONAL/DEVELOPMENTAL/SOCIAL HISTORY The woman had been married for 10 years, and her husband was the sole income provider. The family lived in a mostly Hispanic neighborhood and attended church regularly. The woman received benefits through both Medicaid and the Special Supplemental Nutrition Program for Women, Infants, and Children. It was not reported how the 2-year-old sonÕs lead level was ascertained, what the result was, or whether he needed treatment. Journal of Pediatric Health Care
LABOR AND DELIVERY Labor began spontaneously when the woman was 38 weeks pregnant. The 5-hour intrapartum period was uncomplicated, with artificial rupture of membranes 20 minutes prior to delivery. A newborn girl cried immediately and had APGAR scores of 8 at 1 minute and 9 at 5 minutes. NEWBORN PHYSICAL EXAMINATION The newbornÕs weight was 3.29 kg, her length was 53.4 cm, her head circumference was 34 cm, and her chest circumference 33.5 cm, all of which made her appropriate for her gestational age of 38+ weeks. Her initial vital signs were age appropriate with a temperature of 36.2 C (98.2 F), heart rate of 160 beats per minute, respiratory rate of 56 per minute, and blood pressure of 64/45 mm Hg. The infant was alert and active. Examination of her head, eyes, nose, and throat revealed a norUnexcreted lead is mocephalic and atrauabsorbed, matic head (i.e., no caput succedaneum, distributed, and cephalohematoma, or exchanged among abrasions). Her antehematologic, soft rior and posterior fontanelles were normal tissue (renal and size. A red reflex was neurologic), and present bilaterally. Mumineralizing tissue cous membranes were moist, and both hard (bones and teeth) and soft palates were compartments. intact. The nose was midline and both nostrils were patent. The ears were symmetrical and appropriately placed on the head. Her neck was supple with
no lymphadenopathy. The chest was clear throughout all lung fields. A cardiovascular examination revealed regular S1 and S2 heart sounds with no rub, murmur, or gallop. Capillary refill was 2 seconds and her pulses were equal in all four extremities. Examination of the back revealed a vertebral column with no tufts of hair or sacral dimple. The abdomen was soft with no organomegaly. The umbilical cord had three vessels and had been clamped at delivery. The genitalia examination was consistent with that of a full-term female with a small vaginal tag. Results of Barlow and Ortolani tests were negative. Moro, suck, rooting, palmar grasp, plantar, and stepping reflexes were present and appropriate. A Ballard examination resulted in 35 points, which was consistent with 38+ weeks gestational age. ASSESSMENT AND PLAN Because lead crosses the placental barrier and accumulates in fetal tissue (Riess & Halm, 2007), the perinatal team members knew that the infant was at risk for lead toxicity. Thus a complete blood cell count (CBC) with differential, a basic metabolic profile, and a lead level were obtained. In addition, long-bone radiographs were ordered to assess for evidence of intrauterine lead exposure. LABORATORY AND RADIOLOGIC FINDINGS Results of the CBC with differential and metabolic profile were normal for a person of the infantÕs age. The infantÕs lead level was 88 mg/dL. The long-bone X-rays revealed bands of increased density of the metaphyses of the tubular bones, especially in the proximal fibulas and distal ulnas. Based on these data, the perinatal team diagnosed the infant as having lead toxicity.
CASE STUDY QUESTIONS 1. What is the pathophysiology of lead toxicity, and how does lead toxicity affect body systems? 2. What types of therapy are used to treat lead toxicity in a newborn? What tests are used to monitor response to therapy? 3. What are the potential long-term effects of lead toxicity? 4. What major health care organizations have formulated recommendations for lead screening? CASE STUDY ANSWERS 1. What is the pathophysiology of lead toxicity, and how does lead toxicity affect body systems? Multiple factors (age, nutritional status, and overall health) determine the effects of lead on body systems. Gracia and Snodgrass (2007) report that pregnant women and children are especially vulnerable and may absorb up to 40% to 70% of ingested lead. Newborns are at a higher risk, and their blood lead levels usually exceed maternal levels because of the simple
www.jpedhc.org
diffusion and unidirectional passage of lead across the placenta (Woolf, Goldman, & Bellinger, 2007). LeadÕs primary portals of entry are inhalation, ingestion, and placental transfer. Most lead is excreted through the urinary and gastrointestinal systems. Unexcreted lead is absorbed, distributed, and exchanged among hematologic, soft tissue (renal and neurologic), and mineralizing tissue (bones and teeth) compartments.
September/October 2011
329
Lead has a particular affinity for enzymatic sulfhydryl groups. It interferes with heme synthesis at two sites: ferrochelatase and gamma-aminolevulinic acid dehydratase. Lead causes an accumulation of metabolites such as protoporphyrin, which leads to decreased hemoglobin levels. Microcytic, hypochromic anemia develops because lead binds to sites where iron normally binds within red blood cells. As a result, erythrocyte protoporphyrin levels may be elevated. Lead also interferes with a second pathway of heme synthesis, the formation of porphobilinogen, which is catalyzed by the enzyme delta-aminolevulinic acid dehydratase. If this enzyme is inactivated, it begins to accumulate and causes neurotoxicity (Wong, Hockenberry, Perry, & Lowdermilk, 2006). Lead affects many organ systems, but the most significant effect is on childrenÕs developing nervous systems (Needleman, 2002). Lead cleaves the phosphoribose backbone of transfer ribonucleic acid and binds to brain phosphokinase C more than calcium does. Lead also interferes with neural connectivity and with development of the endogenous opiate system. It interferes with synaptic neurotransmitters (e.g., dopamine and acetylcholine) and their receptors, leading to symptoms of distractibility, impulsivity, coma, and even death. This neurotoxicity disrupts the intercellular junction that seals the capillary endothelium. When this disruption occurs, increased membrane permeability creates a weak blood-brain barrier and leaky capillaries, which eventually leads to increased intracranial fluid accumulation and higher intracranial pressure. Brain tissue ischemia and atrophy are then inevitable (Ibrahim, Froberg, Wolf, & Rusyniak, 2006). Renal function is affected adversely by lead ingestion. An increase in urinary gamma-aminolevulinic acid levels impairs calcium function, which results in glycosuria, proteinuria, ketonuria, and decreased vitamin D synthesis. The proximal tubules of the kidneys, which are important sites in the renin-angiotensin system, are particularly sensitive to lead toxicity. Bone formation is altered with lead ingestion. High levels of serum lead alter the cellular processes in calcium-binding protein synthesis of osteoblastic bone cells. Although chondrogenesis (cartilage formation) is stimulated by lead, the cellular interactions that promote vascularization of new bone and cartilage mineralization are adversely affected. Metaphyseal lead lines are visible on radiographs of the long bones of children with chronic lead exposure (Woolf et al., 2007). 2. What types of therapy are used to treat lead toxicity in a newborn? What laboratory tests are used to monitor response to therapy? Chelation therapy is the treatment of choice to lower lead blood levels. The timing of the initiation of chelation therapy remains controversial, and its use does not reverse cognitive effects. Chelation drugs most commonly used are dimercaprol, edetate calcium 330
Volume 25 Number 5
disodium, and succimer. Each of these drugs has a common mechanism of action in that they bind lead in soft tissues to increase urinary and biliary excretion (Centers for Disease Control and Prevention [CDC], 2006). Each drug has unique indications. Dimercaprol is used for treating severe symptoms of lead toxicity and encephalopathy. Edetate calcium disodium used in combination with dimercaprol can cause renal toxicity. Succimer, in an oral formulation, is used to treat lead levels greater than 45 mg/dL. Based on these factors, succimer (10 mg/kg/dose) was chosen to treat the infant in this case (Taketomo, Hodding, & Kraus, 2009). The infant remained hospitalized during her therapy. The recommended dosage of succimer was administered every 8 hours for 5 days and then every 12 hours for 14 days. Serial CBC tests with differentials and electrolytes were monitored throughout her stay. Although chelation therapy reduces lead levels, it does not prevent or reverse the known adverse effects of lead toxicity. Woolf, Goldman, and Bellinger (2007) indicate that the primary management of lead toxicity is environmental abatement, with nutritional supplementation and pharmacologic therapy as adjunct therapies, along with parental education. 3. What are the potential long-term effects of lead toxicity? Long-term effects of lead toxicity can include delayed developmental milestone achievement and symptoms of attention-deficit disorder, which can result in poor educational outcomes and antisocial behaviors (Needleman, 2009). One study of more than 4000 children found impaired cognitive function at a blood lead level below 5 mg/dL (Lanphear, Dietrich, Auinger, & Cox, 2000). In addition, lead toxicity can cause growth delays that persist through adolescence (Zuscik et al., 2007) and may be a precursor to hypertension, chronic renal failure, and reproductive problems (Needleman, 2004). 4. What major health care organizations have formulated recommendations for lead screening? The American Academy of Pediatrics (AAP) provides accurate evidence of past and current action for lead screening (AAP, 2005). After conducting an in-depth review of evidence, the AAP now advocates prevention versus screening for lead exposure. The United States Preventive Services Task Force (USPSTF) supports the AAPÕs recommendation and also states that routine screening of children between 1 and 5 years of age is unnecessary unless a risk has been ascertained or the child is enrolled in state Medicaid programs. The USPSTF also concluded that routine screening in asymptomatic pregnant women is not indicated (USPTF, 2006). No national organizations recommend lead screening for pregnant women (Rischitelli, Nygren, Bougatsos, Freeman, & Helfand, 2006). However, a number of cities with high-risk populations have instituted policies for antepartum lead screening (Cleveland, Minter, Cobb, Scott, & German, 2008). Journal of Pediatric Health Care
The CDC and the U.S. Environmental Protection Agency continue to be involved in long-term management of lead toxicity. The CDCÕs current threshold level for lead toxicity in children is 10 mg/dL, which is down from the accepted level of 60 mg/dL in 1960 (Needleman, 2002). The In 1991 the U.S. Department of Health & Human Services (DHHS) issued a publication stating that lead poisoning was entirely preventable by removing lead from dangerous houses (DHHS, 1991). These policy statements do not address cultural practices that place pregnant women, their unborn children, and their young children at risk for lead toxicity. People around the world practice geophagy (i.e., eating dirt or clay) for many reasons. It is a common traditional cultural activity during pregnancy and during religious ceremonies in central Africa and the southern United States. In Africa, pregnant and lactating women consume products that contain lead to satisfy nutritional needs and to prevent nausea (About.com, n.d.). Consumption of imported foods or non-food products is not the only cause of lead toxicity. Lead can be absorbed from cooking utensils, nontraditional medications (e.g., alarcon, alkohl, and rueda), and cosmetics. Although gas and paint are the HCPs need to mostly like sources of consider and be lead toxicity, another source is the lead concognizant of tained in ammunitions. cultural practices Whether lead is inand social and gested, inhaled, or transferred to the plaeconomical risks centa during pregthat cause lead nancy, HCPs need toxicity. to be aware of its toxic effects and the environmental regulations governing its use. In summary, HCPs need to consider and be cognizant of cultural practices and social and economical risks that cause lead toxicity. If lead toxicity is diagnosed, it is imperative for an HCP to ensure prompt removal of the cause and, if indicated, to initiate the most appropriate medical therapy and follow-up care. HCPs also need to remain cognizant of health care laws, public health mandates, and insurance regulations concerning lead testing for at-risk populations.
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REFERENCES About.com. (n.d.). Geophagy—eating dirt. Retrieved from http:// geography.about.com/cs/culturalgeography/a/geophagy.htm American Academy of Pediatrics Committee on Environmental Health. (2005). Lead exposure in children: Prevention, detection, & management. Pediatrics, 116(4), 1036-1046. Centers for Disease Control and Prevention. (2006). Deaths associated with hypocalcemia from chelation therapy: Texas, Pennsylvania, and Oregon, 2003-2005. Morbidity & Mortality Weekly Report, 55(8), 204-207. Cleveland, L., Minter, M., Cobb, K., Scott, A., & German, V. (2008). Lead hazards for pregnant women and children, part 2. American Journal of Nursing, 108(11), 40-47. Gracia, R., & Snodgrass, W. (2007). Lead toxicity and chelation therapy. American Journal of System Pharmacy, 64, 45-53. Hale, T. (2006). Medications and motherÕs milk (12th ed.). Amarillo, TX: Hale Publishing. Ibrahim, D., Froberg, B., Wolf, A., & Rusyniak, D. (2006). Heavy metal poisoning: Clinical presentations and pathophysiology. Clinics in Laboratory Medicine, 26(1), 67-97. Lanphear, B., Dietrich, K., Auinger, P., & Cox, C. (2000). Cognitive deficits associated with blood lead concentrations <10 microg/dL in US children and adolescents. Public Health Reports, 115(6), 521-529. Needleman, H. (2009). Low level lead exposure: History and discovery. Annals of Epidemiology, 19, 235-238. Needleman, H. (2004). Lead poisoning. Annual Review of Medicine, 55, 209-222. Needleman, H. (2002). Management of lead toxicity. In F. Burg, J. Ingelfinger, R. Polin & A. Gershon (Eds.), Gellis & KaganÕs current pediatric therapy (17th ed., pp. 1051-1052). Philadelphia, PA: W. B. Saunders. Riess, M., & Halm, J. (2007). Lead poisoning in adult: Mobilization by pregnancy? Journal of General Internal Medicine, 6, 1212-1215. Rischitelli, G., Nygren, P., Bougatsos, C., Freeman, M., & Helfand, M. (2006). Screening for elevated lead levels in childhood and pregnancy: An updated summary of evidence for the US Preventive Services Task Force. Pediatrics, 118, e1867-e1895. Taketomo, C., Hodding, J., & Kraus, D. (2009). Pediatric dosage handbook (13th ed.). Hudson, OH: Lexicomp. United States Department of Health & Human Services. (1991). Strategic plan for the elimination of childhood lead poisoning. Atlanta, GA: Centers for Disease Control and Prevention. United States Preventive Services Task Force. (2006). Screening for elevated lead levels in childhood and pregnancy. Pediatrics, 118, 2514-2518. Wong, D., Hockenberry, M., Perry, S., & Lowdermilk, D. (2006). Maternal child nursing care (3rd ed.). St. Louis, MO: Mosby. Woolf, A., Goldman, R., & Bellinger, D. (2007). Update on the clinical management of childhood lead poisoning. Pediatric Clinics of North America, 54, 271-294. Zuscik, M., Ma, L., Buckley, T., Puzas, E., Drissi, H., Schwarz, M., & OÕKeef, R. (2007). Lead induces chondrogenesis and alters transforming growth factor-beta and bone morphogenetic protein signaling in mesenchymal cell populations. Environmental Health Perspectives, 115(9), 1276-1282.
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Case Study—Primary Care
Lead Toxicity in a Newborn Mary Patrice Hildebrand, MSN, RN, CPNP
KEY WORDS Lead toxicity, chelation therapy, geophagy
CHIEF COMPLAINT At 36 weeks gestation, the lead level of a gravida 3 para 2 Hispanic woman was 60 mg/dL. Two weeks later, she delivered a female infant whose lead level was 88 mg/dL. HISTORY OF PRESENT ILLNESS During a routine prenatal visit at 36 weeks gestation, a 34-year-old woman reported that her 2-year-old sonÕs lead level was elevated. As the womanÕs health care provider (HCP) sought more information, the
Section Editors Jo Ann Serota, MSN, RN, CPNP Corresponding Editor Ambler Pediatrics Ambler, Pennsylvania Beverly Giordano, MS, RN, CPNP University of Florida, Gainesville Gainesville, Florida Donna Hallas, PhD, PNP-BC, CPNP New York University New York, New York Mary Patrice Hildebrand, Nurse Practitioner, University of Texas Health Science at Houston, Lyndon B. Johnson Well Baby Nursery, Houston, TX. Conflicts of interest: None to report. Correspondence: Mary Patrice Hildebrand, MSN, RN, CPNP, University of Texas Health Science at Houston, Lyndon B. Johnson Well Baby Nursery, 5656 Kelley St, Houston, Texas 77026-1967; e-mail: [email protected]. J Pediatr Health Care. (2011) 25, 328-331. 0891-5245/$36.00 Copyright Q 2011 by the National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.pedhc.2011.03.008
328
Volume 25 Number 5
woman reported that she regularly ingested ground lead pottery. The resultant serum lead test revealed a lead level of 60 mg/dL (reference range < 10 mg/dL). The womanÕs toxic lead level could not be treated by chelation because it would have harmful effects on the fetus (Hale, 2006). The HCP counseled the woman to refrain from eating ground lead pottery and notified the Department of Newborn Services of the impending birth of an infant who could have possible toxic lead levels. MEDICAL AND OBSTETRICAL HISTORY From her initial prenatal examination at 12 weeks gestation, the woman had been compliant in keeping appointments. A prenatal ultrasound showed measurements consistent with the timing of her last menstrual period. Her routine prenatal laboratory tests had been normal, as had the routine screening glucose test (95 mg/dL) at 24 weeks gestation. It was not until her 36th week of gestation when she mentioned that her son had an increased lead level and she ingested ground pottery that concern arose. She also divulged that she had consumed products containing lead in her two previous pregnancies; however, she had never informed her previous HCPs of this practice. Even though the womanÕs lead level was six times the upper limits of normal, she denied having symptoms of lead toxicity. Specifically, she denied having headaches, dizziness, epistaxis, metallic taste, excessive salivation, digestive problems, memory loss, myalgias, or joint pain. She also denied having any acute or chronic health problems. PERSONAL/DEVELOPMENTAL/SOCIAL HISTORY The woman had been married for 10 years, and her husband was the sole income provider. The family lived in a mostly Hispanic neighborhood and attended church regularly. The woman received benefits through both Medicaid and the Special Supplemental Nutrition Program for Women, Infants, and Children. It was not reported how the 2-year-old sonÕs lead level was ascertained, what the result was, or whether he needed treatment. Journal of Pediatric Health Care
LABOR AND DELIVERY Labor began spontaneously when the woman was 38 weeks pregnant. The 5-hour intrapartum period was uncomplicated, with artificial rupture of membranes 20 minutes prior to delivery. A newborn girl cried immediately and had APGAR scores of 8 at 1 minute and 9 at 5 minutes. NEWBORN PHYSICAL EXAMINATION The newbornÕs weight was 3.29 kg, her length was 53.4 cm, her head circumference was 34 cm, and her chest circumference 33.5 cm, all of which made her appropriate for her gestational age of 38+ weeks. Her initial vital signs were age appropriate with a temperature of 36.2 C (98.2 F), heart rate of 160 beats per minute, respiratory rate of 56 per minute, and blood pressure of 64/45 mm Hg. The infant was alert and active. Examination of her head, eyes, nose, and throat revealed a norUnexcreted lead is mocephalic and atrauabsorbed, matic head (i.e., no caput succedaneum, distributed, and cephalohematoma, or exchanged among abrasions). Her antehematologic, soft rior and posterior fontanelles were normal tissue (renal and size. A red reflex was neurologic), and present bilaterally. Mumineralizing tissue cous membranes were moist, and both hard (bones and teeth) and soft palates were compartments. intact. The nose was midline and both nostrils were patent. The ears were symmetrical and appropriately placed on the head. Her neck was supple with
no lymphadenopathy. The chest was clear throughout all lung fields. A cardiovascular examination revealed regular S1 and S2 heart sounds with no rub, murmur, or gallop. Capillary refill was 2 seconds and her pulses were equal in all four extremities. Examination of the back revealed a vertebral column with no tufts of hair or sacral dimple. The abdomen was soft with no organomegaly. The umbilical cord had three vessels and had been clamped at delivery. The genitalia examination was consistent with that of a full-term female with a small vaginal tag. Results of Barlow and Ortolani tests were negative. Moro, suck, rooting, palmar grasp, plantar, and stepping reflexes were present and appropriate. A Ballard examination resulted in 35 points, which was consistent with 38+ weeks gestational age. ASSESSMENT AND PLAN Because lead crosses the placental barrier and accumulates in fetal tissue (Riess & Halm, 2007), the perinatal team members knew that the infant was at risk for lead toxicity. Thus a complete blood cell count (CBC) with differential, a basic metabolic profile, and a lead level were obtained. In addition, long-bone radiographs were ordered to assess for evidence of intrauterine lead exposure. LABORATORY AND RADIOLOGIC FINDINGS Results of the CBC with differential and metabolic profile were normal for a person of the infantÕs age. The infantÕs lead level was 88 mg/dL. The long-bone X-rays revealed bands of increased density of the metaphyses of the tubular bones, especially in the proximal fibulas and distal ulnas. Based on these data, the perinatal team diagnosed the infant as having lead toxicity.
CASE STUDY QUESTIONS 1. What is the pathophysiology of lead toxicity, and how does lead toxicity affect body systems? 2. What types of therapy are used to treat lead toxicity in a newborn? What tests are used to monitor response to therapy? 3. What are the potential long-term effects of lead toxicity? 4. What major health care organizations have formulated recommendations for lead screening? CASE STUDY ANSWERS 1. What is the pathophysiology of lead toxicity, and how does lead toxicity affect body systems? Multiple factors (age, nutritional status, and overall health) determine the effects of lead on body systems. Gracia and Snodgrass (2007) report that pregnant women and children are especially vulnerable and may absorb up to 40% to 70% of ingested lead. Newborns are at a higher risk, and their blood lead levels usually exceed maternal levels because of the simple
www.jpedhc.org
diffusion and unidirectional passage of lead across the placenta (Woolf, Goldman, & Bellinger, 2007). LeadÕs primary portals of entry are inhalation, ingestion, and placental transfer. Most lead is excreted through the urinary and gastrointestinal systems. Unexcreted lead is absorbed, distributed, and exchanged among hematologic, soft tissue (renal and neurologic), and mineralizing tissue (bones and teeth) compartments.
September/October 2011
329
Lead has a particular affinity for enzymatic sulfhydryl groups. It interferes with heme synthesis at two sites: ferrochelatase and gamma-aminolevulinic acid dehydratase. Lead causes an accumulation of metabolites such as protoporphyrin, which leads to decreased hemoglobin levels. Microcytic, hypochromic anemia develops because lead binds to sites where iron normally binds within red blood cells. As a result, erythrocyte protoporphyrin levels may be elevated. Lead also interferes with a second pathway of heme synthesis, the formation of porphobilinogen, which is catalyzed by the enzyme delta-aminolevulinic acid dehydratase. If this enzyme is inactivated, it begins to accumulate and causes neurotoxicity (Wong, Hockenberry, Perry, & Lowdermilk, 2006). Lead affects many organ systems, but the most significant effect is on childrenÕs developing nervous systems (Needleman, 2002). Lead cleaves the phosphoribose backbone of transfer ribonucleic acid and binds to brain phosphokinase C more than calcium does. Lead also interferes with neural connectivity and with development of the endogenous opiate system. It interferes with synaptic neurotransmitters (e.g., dopamine and acetylcholine) and their receptors, leading to symptoms of distractibility, impulsivity, coma, and even death. This neurotoxicity disrupts the intercellular junction that seals the capillary endothelium. When this disruption occurs, increased membrane permeability creates a weak blood-brain barrier and leaky capillaries, which eventually leads to increased intracranial fluid accumulation and higher intracranial pressure. Brain tissue ischemia and atrophy are then inevitable (Ibrahim, Froberg, Wolf, & Rusyniak, 2006). Renal function is affected adversely by lead ingestion. An increase in urinary gamma-aminolevulinic acid levels impairs calcium function, which results in glycosuria, proteinuria, ketonuria, and decreased vitamin D synthesis. The proximal tubules of the kidneys, which are important sites in the renin-angiotensin system, are particularly sensitive to lead toxicity. Bone formation is altered with lead ingestion. High levels of serum lead alter the cellular processes in calcium-binding protein synthesis of osteoblastic bone cells. Although chondrogenesis (cartilage formation) is stimulated by lead, the cellular interactions that promote vascularization of new bone and cartilage mineralization are adversely affected. Metaphyseal lead lines are visible on radiographs of the long bones of children with chronic lead exposure (Woolf et al., 2007). 2. What types of therapy are used to treat lead toxicity in a newborn? What laboratory tests are used to monitor response to therapy? Chelation therapy is the treatment of choice to lower lead blood levels. The timing of the initiation of chelation therapy remains controversial, and its use does not reverse cognitive effects. Chelation drugs most commonly used are dimercaprol, edetate calcium 330
Volume 25 Number 5
disodium, and succimer. Each of these drugs has a common mechanism of action in that they bind lead in soft tissues to increase urinary and biliary excretion (Centers for Disease Control and Prevention [CDC], 2006). Each drug has unique indications. Dimercaprol is used for treating severe symptoms of lead toxicity and encephalopathy. Edetate calcium disodium used in combination with dimercaprol can cause renal toxicity. Succimer, in an oral formulation, is used to treat lead levels greater than 45 mg/dL. Based on these factors, succimer (10 mg/kg/dose) was chosen to treat the infant in this case (Taketomo, Hodding, & Kraus, 2009). The infant remained hospitalized during her therapy. The recommended dosage of succimer was administered every 8 hours for 5 days and then every 12 hours for 14 days. Serial CBC tests with differentials and electrolytes were monitored throughout her stay. Although chelation therapy reduces lead levels, it does not prevent or reverse the known adverse effects of lead toxicity. Woolf, Goldman, and Bellinger (2007) indicate that the primary management of lead toxicity is environmental abatement, with nutritional supplementation and pharmacologic therapy as adjunct therapies, along with parental education. 3. What are the potential long-term effects of lead toxicity? Long-term effects of lead toxicity can include delayed developmental milestone achievement and symptoms of attention-deficit disorder, which can result in poor educational outcomes and antisocial behaviors (Needleman, 2009). One study of more than 4000 children found impaired cognitive function at a blood lead level below 5 mg/dL (Lanphear, Dietrich, Auinger, & Cox, 2000). In addition, lead toxicity can cause growth delays that persist through adolescence (Zuscik et al., 2007) and may be a precursor to hypertension, chronic renal failure, and reproductive problems (Needleman, 2004). 4. What major health care organizations have formulated recommendations for lead screening? The American Academy of Pediatrics (AAP) provides accurate evidence of past and current action for lead screening (AAP, 2005). After conducting an in-depth review of evidence, the AAP now advocates prevention versus screening for lead exposure. The United States Preventive Services Task Force (USPSTF) supports the AAPÕs recommendation and also states that routine screening of children between 1 and 5 years of age is unnecessary unless a risk has been ascertained or the child is enrolled in state Medicaid programs. The USPSTF also concluded that routine screening in asymptomatic pregnant women is not indicated (USPTF, 2006). No national organizations recommend lead screening for pregnant women (Rischitelli, Nygren, Bougatsos, Freeman, & Helfand, 2006). However, a number of cities with high-risk populations have instituted policies for antepartum lead screening (Cleveland, Minter, Cobb, Scott, & German, 2008). Journal of Pediatric Health Care
The CDC and the U.S. Environmental Protection Agency continue to be involved in long-term management of lead toxicity. The CDCÕs current threshold level for lead toxicity in children is 10 mg/dL, which is down from the accepted level of 60 mg/dL in 1960 (Needleman, 2002). The In 1991 the U.S. Department of Health & Human Services (DHHS) issued a publication stating that lead poisoning was entirely preventable by removing lead from dangerous houses (DHHS, 1991). These policy statements do not address cultural practices that place pregnant women, their unborn children, and their young children at risk for lead toxicity. People around the world practice geophagy (i.e., eating dirt or clay) for many reasons. It is a common traditional cultural activity during pregnancy and during religious ceremonies in central Africa and the southern United States. In Africa, pregnant and lactating women consume products that contain lead to satisfy nutritional needs and to prevent nausea (About.com, n.d.). Consumption of imported foods or non-food products is not the only cause of lead toxicity. Lead can be absorbed from cooking utensils, nontraditional medications (e.g., alarcon, alkohl, and rueda), and cosmetics. Although gas and paint are the HCPs need to mostly like sources of consider and be lead toxicity, another source is the lead concognizant of tained in ammunitions. cultural practices Whether lead is inand social and gested, inhaled, or transferred to the plaeconomical risks centa during pregthat cause lead nancy, HCPs need toxicity. to be aware of its toxic effects and the environmental regulations governing its use. In summary, HCPs need to consider and be cognizant of cultural practices and social and economical risks that cause lead toxicity. If lead toxicity is diagnosed, it is imperative for an HCP to ensure prompt removal of the cause and, if indicated, to initiate the most appropriate medical therapy and follow-up care. HCPs also need to remain cognizant of health care laws, public health mandates, and insurance regulations concerning lead testing for at-risk populations.
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REFERENCES About.com. (n.d.). Geophagy—eating dirt. Retrieved from http:// geography.about.com/cs/culturalgeography/a/geophagy.htm American Academy of Pediatrics Committee on Environmental Health. (2005). Lead exposure in children: Prevention, detection, & management. Pediatrics, 116(4), 1036-1046. Centers for Disease Control and Prevention. (2006). Deaths associated with hypocalcemia from chelation therapy: Texas, Pennsylvania, and Oregon, 2003-2005. Morbidity & Mortality Weekly Report, 55(8), 204-207. Cleveland, L., Minter, M., Cobb, K., Scott, A., & German, V. (2008). Lead hazards for pregnant women and children, part 2. American Journal of Nursing, 108(11), 40-47. Gracia, R., & Snodgrass, W. (2007). Lead toxicity and chelation therapy. American Journal of System Pharmacy, 64, 45-53. Hale, T. (2006). Medications and motherÕs milk (12th ed.). Amarillo, TX: Hale Publishing. Ibrahim, D., Froberg, B., Wolf, A., & Rusyniak, D. (2006). Heavy metal poisoning: Clinical presentations and pathophysiology. Clinics in Laboratory Medicine, 26(1), 67-97. Lanphear, B., Dietrich, K., Auinger, P., & Cox, C. (2000). Cognitive deficits associated with blood lead concentrations <10 microg/dL in US children and adolescents. Public Health Reports, 115(6), 521-529. Needleman, H. (2009). Low level lead exposure: History and discovery. Annals of Epidemiology, 19, 235-238. Needleman, H. (2004). Lead poisoning. Annual Review of Medicine, 55, 209-222. Needleman, H. (2002). Management of lead toxicity. In F. Burg, J. Ingelfinger, R. Polin & A. Gershon (Eds.), Gellis & KaganÕs current pediatric therapy (17th ed., pp. 1051-1052). Philadelphia, PA: W. B. Saunders. Riess, M., & Halm, J. (2007). Lead poisoning in adult: Mobilization by pregnancy? Journal of General Internal Medicine, 6, 1212-1215. Rischitelli, G., Nygren, P., Bougatsos, C., Freeman, M., & Helfand, M. (2006). Screening for elevated lead levels in childhood and pregnancy: An updated summary of evidence for the US Preventive Services Task Force. Pediatrics, 118, e1867-e1895. Taketomo, C., Hodding, J., & Kraus, D. (2009). Pediatric dosage handbook (13th ed.). Hudson, OH: Lexicomp. United States Department of Health & Human Services. (1991). Strategic plan for the elimination of childhood lead poisoning. Atlanta, GA: Centers for Disease Control and Prevention. United States Preventive Services Task Force. (2006). Screening for elevated lead levels in childhood and pregnancy. Pediatrics, 118, 2514-2518. Wong, D., Hockenberry, M., Perry, S., & Lowdermilk, D. (2006). Maternal child nursing care (3rd ed.). St. Louis, MO: Mosby. Woolf, A., Goldman, R., & Bellinger, D. (2007). Update on the clinical management of childhood lead poisoning. Pediatric Clinics of North America, 54, 271-294. Zuscik, M., Ma, L., Buckley, T., Puzas, E., Drissi, H., Schwarz, M., & OÕKeef, R. (2007). Lead induces chondrogenesis and alters transforming growth factor-beta and bone morphogenetic protein signaling in mesenchymal cell populations. Environmental Health Perspectives, 115(9), 1276-1282.
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