News Author: Laurie Barclay, MD
CME Author: Bernard M. Sklar, MD, MS

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April 16, 2003 — The Centers for Disease Control and Prevention (CDC) has established 10 µg/dL as the upper limit of acceptable lead levels, mostly because of a lack of studies showing adverse effects of lower levels. Two studies in the April 17 issue of the New England Journal of Medicine provide new evidence for establishing a lower limit. The first demonstrates that an increase from 1 to 10 µg/dL is proportionately associated with cognitive decline, and the second is a cross-sectional study showing delayed puberty for levels of only 3 µg/dL. A recent study reported by Medscape also showed that higher lead levels within the "acceptable" range were linked to increased blood pressure in postmenopausal women.

"More U.S. children may be adversely affected by environmental lead than previously estimated," write Richard L. Canfield, PhD, from Cornell University in Ithaca, New York, and colleagues. "Blood lead concentrations, even those below 10 µg/dl, are inversely associated with children's IQ scores at three and five years of age and associated declines in IQ are greater at these concentrations than at higher concentrations."

Dr. Canfield's group measured blood lead levels in 172 children at 6, 12, 18, 24, 36, 48, and 60 months of age, and IQ at 3 and 5 years using the Stanford-Binet Intelligence Scale, adjusted for potential confounders including maternal IQ and quality of the home environment.

Blood lead levels were inversely correlated with IQ. Each increase of 10 µg/dL in lifetime average blood lead concentration was associated with a 4.6 point decrease in IQ (P = .004). In 101 children with maximal lead concentrations consistently lower than 10 µg/dL, the change in IQ associated with a given change in lead concentration was greater. As lifetime average blood concentration increased from 1 to 10 µg/dL in the full sample of 172 children, IQ declined by 7.4 points.

"Because there is no effective treatment for children with moderately elevated blood lead concentrations, the collective evidence argues for a shift toward primary prevention of lead exposure in contrast to the current, almost exclusive emphasis on the treatment of children with elevated blood lead concentrations," the authors write.

In the second study, from the National Center for Environmental Assessment and the Environmental Protection Agency, blood lead concentration was measured in girls aged 8 to 18 years who were enrolled in the third National Health and Nutrition Examination Survey. This cross-sectional study followed 600 non-Hispanic white girls, 805 non-Hispanic African-American girls, and 781 Mexican-American girls. All three groups had mean lead concentrations less than 3 µg/dL.

Compared with girls who had lead concentrations of 1 µg/dL, those with lead concentrations of 3 µg/dL had decreased height (P < .001), but not body mass index or weight, after adjustment for age, race, and other factors. African-American and Mexican-American girls with lead concentrations of 3 µg/dL had significant delays in breast and pubic-hair development. These delays were most marked in African-American girls, who also had an associated delay in age at menarche of 3.6 months. White girls with lead concentrations of 3 µg/dL had a similar trend in all pubertal measures, but delays were not significant.

"Environmental exposure to lead may delay growth and pubertal development in girls, although confirmation is warranted in prospective studies," write Sherry G. Selevan, PhD, and colleagues. "Delays in pubertal development may be due at least in part to mechanisms independent of effects on growth, conceivably to alterations in endocrine function."

In an accompanying editorial, Walter J. Rogan, MD, from the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina, and James H. Ware, PhD, from the Harvard School of Public Health in Boston, Massachusetts, note that eliminating elevated blood lead concentrations by the end of this decade is already a federal objective. Based on these studies, however, "the job may not be finished even when all children have blood lead concentrations below 10 µg/dl.

"The effects of lead exposure appear to be long-lasting and irreversible," they write. "Prevention is thus the only plausible strategy. Children should not live in housing that exposes them to hazardous amounts of lead, and children who are already exposed need to be identified and their source of exposure interrupted."

N Engl J Med. 2003;348:1515-1516, 1517-1526, 1527-1536

Learning Objectives

Upon completion of this activity, participants will be able to:

• Discuss the results of the study correlating lead levels in young children with results on the Stanford-Binet Intelligence Scale.
• Explain the results of the study correlating lead levels in girls 8 to 18 years of age.

Clinical Context

During the past three decades, epidemiologic studies have demonstrated inverse associations between blood lead concentrations and children's IQs at successively lower lead concentrations.

The CDC has repeatedly lowered its definition of an elevated blood lead concentration, which now stands at 10 µg/dL (0.483 µmol/L). Since the removal of lead from gasoline, the median blood lead concentration in U.S. children has fallen from 15 µg/dL (0.724 µmol/L) in 1978 to 2 µg/dL (0.097 µmol/L) in 1999.

Yet exposure to lead from deteriorating lead paint in older homes continues. Of U.S. homes in which children younger than six years live, 25% contain hazardous lead paint. The CDC has estimated that in 2000, there were still 454,000 children in the U.S. with blood lead concentrations greater than 10 µg/dL.

Environmental lead exposure has been linked to alterations in growth and endocrine function, but it has not been previously known whether such exposure affects pubertal development.

Study Highlights

Two studies are discussed. In the first study, lead levels in young children were correlated with IQ. Blood lead concentrations were measured in 172 children at 6, 12, 18, 24, 36, 48, and 60 months of age. The Stanford-Binet Intelligence Scale was measured at the ages of 3 and 5 years. The relation between IQ and blood lead concentration was estimated and adjusted for maternal IQ, quality of the home environment, and other potential confounders.

Blood lead concentration was inversely and significantly associated with IQ. Each increase of 10 µg/dL in the lifetime average blood lead concentration was associated with a 4.6-point decrease in IQ. For the subsample of 101 children whose maximal lead concentrations remained below 10 µg/dL, the change in IQ associated with a given change in lead concentration was greater. IQ declined by 7.4 points as lifetime average blood lead concentrations increased from 1 to 10 µg/dL.

In the second study, blood lead concentration in girls aged 8 to 18 years were correlated with height, weight, breast, and pubic-hair development and onset of menarche. These girls had been enrolled in the third National Health and Nutrition Examination Survey. Six hundred girls were non-Hispanic white, 805 were non-Hispanic African-American, and 781 were Mexican-American.

Those girls with lead concentrations of 3 µg/dL had decreased height, but not body mass index or weight. African-American and Mexican-American girls with lead concentrations of 3 µg/dL had significant delays in breast and pubic-hair development.

These delays were most marked in African-American girls, who also had an associated delay in age at menarche of 3.6 months. White girls with lead concentrations of 3 µg/dL had a similar trend in all pubertal measures, but delays were not significant.

Pearls for Practice

• Blood lead concentrations, even those below 10 µg/dL, are inversely associated with children's IQ scores at three and five years of age; associated declines in IQ are greater at these concentrations than at higher concentrations. These findings suggest that more U.S. children may be adversely affected by environmental lead than previously estimated.
• Environmental exposure to lead may delay growth and pubertal development in girls. Delays in pubertal development may be due at least in part to mechanisms independent of effects on growth, conceivably to alterations in endocrine function.

Post Test

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