A Randomized Trial of Calcium Supplementation for Childhood Lead Poisoning
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A Randomized Trial of Calcium Supplementation for Childhood Lead Poisoning Morri E. Markowitz, MD*; Mark Sinnett, PharmD‡; and John F. Rosen, MD* ABSTRACT. Objective. Lead (Pb) poisoning remains hildhood lead (Pb) poisoning is prevalent a common disease among children despite successful worldwide. In the United States alone, an es- public health efforts that have reduced its prevalence. timated 0.5 million preschool-aged children Treatment options for children with blood Pb levels C Ն 1 have elevated blood Pb levels (BPbs; 10 g/dL). (BPbs) <45 g/dL are limited because chelation therapy The poisoning of this large number of children is, in is generally not indicated. Calcium (Ca) and Pb interac- tions are well documented. Competition for binding to large part, the consequence of the widespread pres- Ca-binding proteins may underlie a mechanism for Pb ence of leaded paint in US residential housing. The absorption. The purpose of this study was to determine National Academy of Sciences estimates that there the role, if any, of supplemental Ca at reducing BPbs in are 3 million tons of leaded paint in housing built moderately poisoned children. primarily before 1960.2 Outside the US, the contin- Methods. Children aged 1 to 6 years with BPbs 10 to ued use of leaded gasoline is associated with ele- 45 g/dL were enrolled in a double-blinded, placebo- vated BPbs in urban populations.3 A study com- controlled trial of the effects of Ca supplementation on pleted recently in India found that average BPbs in 5 BPbs. Children received either a Ca-containing liquid or major cities were comparable to that in the United an indistinguishable placebo. Dosage was adjusted bi- weekly on the basis of responses to a dietary Ca intake States 30 years ago, when leaded gasoline was in questionnaire to reach 1800 mg in the Ca-supplemented common usage; mean BPbs were in the 10 to 20 group. Samples for BPbs and measures to assess safety g/dL range.4 Biochemical and neurodevelopmental were collected before and after 3 months of supplemen- deficits in children have been reported to occur even tation and after an additional 3 months of follow-up. at levels below the current Centers for Disease Con- Bivariate and multiple regression analyses were per- trol and Prevention’s (CDC’s) threshold of concern of formed. 10 g/dL.5,6 Results. A total of 67 of 88 enrolled children with a The main route of Pb entry into children is by mean age of 3.6 years completed 3 months of supplemen- ingestion. As painted surfaces containing Pb deteri- tation. There were no statistically significant differences between groups on hematologic and biochemical mea- orate, leaded chips are released and contaminate sures, including serum and urinary Ca, at any time household dust. Similarly, the use of leaded gasoline points. The average compliance rate was estimated to be contaminates soils and is incorporated into or onto 80% for each group during the 3-month supplementation vegetables. This soil contamination may persist well period. after the elimination of leaded gasoline usage.7 The Conclusions. At enrollment, the average daily Ca in- percentage of ingested Pb that is absorbed from the take in this group of inner-city children was greater than intestine depends on several factors but is estimated the recommended daily intake for age. Although BPbs to approach 50% in children and Ͻ10% in adults.8,9 declined during a 3-month period in both groups, Ca The presence of food in the intestine, especially min- supplementation aimed at providing 1800 mg of Ca/day had no effect on the change in BPbs. Ca supplementa- erals, and the sufficiency in the body’s stores of tion should not be routinely prescribed for mild to nutrients such as iron may reduce these percentag- moderately Pb-poisoned children who are dietarily Ca es.10 sufficient. Pediatrics 2004;113:e34–e39. URL: http://www. In nonintervention studies, an inverse association pediatrics.org/cgi/content/full/113/1/e34; lead, lead poi- between BPbs at age 2 (all Ͻ25 g/dL) and cognitive soning, calcium, calcium supplementation. test scores obtained up to 10 years later was ob- served.11 This suggests that cognitive deficits from ABBREVIATIONS. Pb, lead; BPb, blood lead level; CDC, Centers Pb poisoning are permanent. However, in a previous for Disease Control and Prevention; EP, erythrocyte protoporphy- study of moderately Pb-poisoned children (initial rin; AAS, atomic absorption spectrometry; SD, standard deviation; BPbs: 25–55 g/dL) in which children were treated sCa, serum calcium; uCa, urinary calcium; uCr, urinary creatinine. aggressively to reduce BPbs over a 6-month period, we found that BPbs fell and cognitive test scores improved, especially in iron-sufficient children.12,13 From the *Children’s Hospital at Montefiore, Bronx, New York; and ‡Mon- This could not be attributed to chelation therapy tefiore Medical Center, Bronx, New York. with CaNa2EDTA. A multicenter, placebo-controlled Received for publication Jun 6, 2003; accepted Sep 8, 2003. trial of succimer in Pb-poisoned 2-year-olds (BPbs: Reprint requests to (M.E.M.) Children’s Hospital at Montefiore, 111 E. 210th 20–44 g/dL) also failed to find a benefit of chela- St, Bronx, NY 10467. E-mail: [email protected] 14 PEDIATRICS (ISSN 0031 4005). Copyright © 2004 by the American Acad- tion on cognitive outcomes tested at 4 years of age. emy of Pediatrics. However, change in BPbs over the time period was e34 PEDIATRICS Vol. 113Downloaded No. 1 January from www.aappublications.org/news 2004 http://www.pediatrics.org/cgi/content/full/113/1/ by guest on September 24, 2021 e34 again associated inversely with change in cognitive blinded to assignment group. Children were to receive Ca as Ca scores.15 Thus, in intervention studies, a reversible glubionate, 115 mg of elemental Ca/5 mL, or placebo for 3 months. Both groups were then followed for an additional 3 component of Pb toxicity may have been identified months without supplements. Supplement quantity was adjusted but was not attributable to chelation therapy. on the basis of a 24-hour dietary recall questionnaire that was Currently, the specific treatment of childhood Pb administered biweekly. Specific and quantitative details of Ca- poisoning varies with the degree of intoxication. containing foods (including liquids) consumed during the previ- More than 90% of affected children have mild to ous day were recorded, and the Ca content was calculated using the software Nutribase Professional Nutrition Manager, version moderately elevated BPbs between 10 and 44 g/ 1.0 (Cybersoft Inc, Phoenix, AZ). The responses to the question- 1 dL. The mainstays of therapy consist of the elimi- naire were verified by comparing the answers to the types and nation of all sources of exposure, modifying behav- quantities of food described by the caregiver to the research team iors such as pica to reduce ingestion, and nutritional during scheduled home visits. support.16 Of these approaches, only the effective- The goal of treatment was to provide 1800 mg Ca/day between supplement and diet. This amount was used in our pilot study and ness of eliminating the environmental source of Pb in a published study of Ca supplementation in non–Pb-poisoned 17–19 has been tested in controlled studies. Surprising children.34 It was found to be safe and potentially effective. The is that the contributions of the other 2 components— dose was calculated as follows: daily supplement dosage ϭ 1800 behavior modification and nutritional support—to (mg) Ϫ daily dietary Ca intake by history (mg). the management of childhood Pb poisoning have not The placebo was a Ca-free solution that was comparable in sweetness and color to the Ca supplement. Both supplements been assessed in randomized, controlled trials. Once were given to the parents in graduated, brown, half-liter bottles children have been identified as Pb poisoned and with a dispenser cap. Training on dispensing it and how to deter- these therapeutic efforts have been initiated, BPbs mine the amount remaining in the bottle was given to the care- fall slowly over months in most children.20 giver at the first home visit by the research coordinator. The dose was divided into 3 portions to be given immediately before meals Awareness of a metabolic interaction between cal- to enhance compliance. cium (Ca) and Pb has existed for many years. Pb and The main outcome measure was BPbs measured at enrollment, Ca competition for absorption from the intestine has at 3 months (after 3 months of supplementation), and at 6 months been documented in animal models.21–25 Ca intake (an additional 3 months after completion of supplementation). The and BPbs are inversely related in children.26–29 Ca hypotheses to be tested were that BPbs would be lower at 3 and 6 months in the Ca-supplemented group. intake is well below the daily recommended intake Three home visits were scheduled: within 1 week of enrollment 30 in other countries such as China. However, a ther- and at 3 and 6 months. The main purpose of these visits was 1) to apeutic role of supplemental Ca for the large group determine whether there was Pb in the home and 2) to observe the of children for whom no specific medical treatment is hand-to-mouth behavior of the child. available currently (BPbs: 10–44 g/dL) has not At the first home visit, each child’s caregiver completed a questionnaire that asked about medical, demographic, and envi- been examined. This study tested the hypothesis that ronmental information. The Caldwell Home Scale was used as a Ca supplementation to achieve 1800 mg/day as a sociologic measure of the home.35 component in the treatment of childhood Pb poison- For home Pb assessments, a visual inspection of the surfaces ing (BPbs values of 10–44 g/dL) would result in a was made and the Pb content on painted surfaces was measured greater fall in BPbs over 3 months than those in using x-ray fluorescence instrumentation (XRF).