Effect of Decreasing Levels of Blood Lead and Cognitive Development
Abstract & Commentary
Synopsis: Long-term follow-up of children exposed in infancy to elevated environmental lead from lead smelteries showed that their lead-related cognitive deficits were only minimally reversed by a subsequent decline in blood lead levels.
Source: Tong S, et al. Declining blood lead levels and changes in cognitive function during childhood. The Port Pirie Cohort Study. JAMA 1998;280:1915-1919.
Port pirie, south australia, is the site of one of the largest lead-smelting facilities in the southern hemisphere. Persons living in this city have been exposed to increased levels of environmental lead for 25 years. The Port Pirie Cohort Study, a long-term study of the effects of lead exposure during early childhood, enrolled approximately 90% of all pregnancies between May 1979 and May 1982. Just more than half (n = 375) of the offspring were followed prospectively until they reached 11-13 years of age. This study attempted to assess the reversibility of deficits in cognitive development caused by exposure to low-moderate lead exposure by examining the possible relationship between individual changes in blood lead concentrations and individual changes in measures of cognitive development during the first 11-13 years of life. The Port Pirie group has previously reported significant inverse associations between blood lead levels and cognitive development at all ages studied. Multiple evaluations were conducted to gather data on a wide range of child, parent, and home environment variables. Blood samples were obtained for lead concentrations at birth, 6, 15, and 24 months of age and annually thereafter until 7 years of age. Another sample was obtained at 11 to 13 years of age. Each child’s developmental status was assessed at 2 years, 4 years, and 7 and 11 to 13 years using age-appropriate psychologic test instruments administered by a single trained research psychologist who was unaware of the child’s exposure and developmental history.
Changes in cognitive development in relation to changes in blood lead concentrations were assessed in each child in the study. It was hypothesized that if the detrimental effects of lead were transient or reversible, cognitive performance might be expected to improve most among those children whose blood lead levels had declined the most. On the other hand, if the effect of lead is permanent and persistent, children’s performance would not be expected to improve as their blood lead concentrations declined.
In this group of children, mean blood levels decreased from a mean of 21.2 g/dL at 2 years of age to 7.9 g/dL at age 11-13 years. However, cognitive scores in the children whose blood lead concentrations declined the most were generally not more improved when compared with children whose blood lead levels declined the least. The cognitive deficits that are associated with exposure to environmental lead in early childhood appear to be only minimally reversed by a subsequent decline in blood levels and appear to be permanent.
Comment by David J. Schonfeld, MD, FAAP
Research on the effects of lead exposure on human cognition and behavior is complex and controversial. Because ethical considerations preclude randomization of children to varying degrees of exposure, research studies cannot use an experimental design and are, therefore, limited in their ability to identify causality. Human intelligence and behavior are highly complex constructs with multiple determinants. Many of these determinants have not been identified or cannot be measured exactly, and so cannot be fully controlled in any analysis. Attempts to measure the permanence of any adverse effects on intelligence are further complicated by developmental aspects of cognition. Intelligence, as measured by a standardized instrument appropriate for a 1-year-old child, may differ significantly from intelligence as measured by a standardized IQ test administered to an 11- to 13-year-old child. In addition, a lack of change in full-scale IQ may obscure significant improvement in more circumscribed areas of intelligence.
In spite of these kinds of reservations, the essentially negative findings reported by Tong and associates are still important and are, in fact, consistent with prior research results. No published study has shown that the cognitive defects attributed to lead poisoning are reversible. A study by Ruff and associates of children 13-87 months of age who had somewhat higher blood lead levels (25-55 g/dL) attempted to find changes in cognitive abilities that could be attributed to the treatment of lead poisoning.1 Although they found that those children who had the greatest decline in blood lead levels were more likely to show relative improvements in cognitive performance, the improvements could not be related to active chelation therapy. The blood lead levels did not decline more rapidly in children who received chelation therapy, and there was no effect of chelation therapy on IQ test results. An alternative explanation, which is consistent with the Port Pirie findings, is that those children who demonstrated a more rapid decline in blood lead levels (and who showed more improvement in cognitive ability) simply had lower total body burdens of lead despite the same blood lead level.
The limited data regarding the efficacy of chelation therapy to decrease blood lead levels for the vast majority of children with lead poisoning (i.e., those with blood lead levels < 45 g/dL), coupled with increasing evidence that the cognitive damage may be in large part irreversible, add to a growing body of evidence of the long-term seriousness of pediatric lead poisoning, even at asymptomatic levels. Furthermore, it underscores the importance of early identification of children with asymptomatic lead poisoning and the importance of screening and secondary prevention. Much more emphasis needs to be given to primary prevention efforts, such as environmental and housing control, for a condition which, after all, should be entirely preventable. (Dr. Schonfeld is Associate Professor of Pediatrics and Child Study Center and Director of the Lead Program at Yale University School of Medicine, New Haven, CT.)
Reference
1. Ruff HA, et al. Declining blood lead levels and cognitive changes in moderately lead-poisoned children. JAMA 1993;269:1641-1646.
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