Effects of Lead on IQ in Children

Referencing: Low-Level Environmental Lead Exposure and Children's Intellectual Function: An International Pooled Analysis

Lanphear et al. (2005) pooled data from seven prospective studies that had been initiated to test the effect of prenatal and early childhood lead exposure. The primary investigators of these studies had planned the studies so that the sequence of data collection might shed light on the question of early causation. At that time, most of us anticipated a strong association of prenatal exposure and developmental deficit related to rapid prenatal central nervous system (CNS) development (Ernhart 1992). Lanphear et al. (2005) pooled our data to report a significant association of cord blood lead (BPb) and IQ (intelligence quotient) and concluded that prevention of lead exposure must occur before pregnancy or childbirth. Their analysis did not include control of the sociodemographic factors known to confound research on the topic; hence, the conclusion is not justified.

In the balance of the report, Lanphear et al. (2005) selected concurrent lead level at 5-6 years of age, as opposed to earlier measures of lead exposure, because it had the highest association with IQ. The closer association for the lead measurement made at or near the time of the IQ test may reflect concomitant factors not well controlled in the analyses. In most studies, parental intelligence and HOME (Home Observation for Measurement of the Environment; a measure of caretaking and parental stimulation) are major predictors of child IQ. These variables are difficult to measure (Kaufman 2001), and undercontrol of confounding is likely. Bias is particularly likely in the data of the Rochester, New York, cohort (Canfield et al. 2003) because the HOME (toddler version) was administered at the age of 2 years, not at 5-6 years of age.

Using available covariate data, Lanphear et al. (2005) did report a deficit of approximately 2 IQ points for the BPb range of 10-20 µg/dL. This replicates previous analyses conducted by Pocock et al. (1994). The latter investigators interpreted the association as possibly due to limited control of confounding, selection biases, and/or reverse causality.

The most problematic portion of the article by Lanphear et al. (2005) concerns very low lead exposure. The authors selected data for the 244 children who had peak, or maximal, BPb levels < 10 µg/dL. The decline in IQ for this group consisted of 6.2 points for the concurrent BPb range of 1-10 µg/dL (β = -0.80, SE = 0.48, p = 0.09). For a more restricted group of 103 children with peak BPb levels < 7.5 µg/dL, the association was stronger (β = -2.94, SE = 1.14, p = 0.012) although the sample size was further truncated. Lanphear et al. (2005) concluded that "lead exposure in children who have maximal BPb levels < 7.5 µg/dL is associated with intellectual deficits." There are major problems with this conclusion.

First, groups selected on the basis of peak lead level < 10 µg/dL and < 7.5 µg/dL differed significantly from the balance of the sample on factors omitted as noncontributing for the full study. Lanphear et al. (2005) ignored race (U.S. cohorts), maternal age, and maternal use of cigarettes and alcohol during pregnancy in the analyses of these groups.

Second, cohort contribution was critical for these groups. Of the 103 children with BPb levels < 7.5 µg/dL (Lanphear et al 2005), 67% were from the Rochester cohort. In addition to the limitation in the HOME data, information regarding this cohort at 3 and 5 years of age reflects peculiar shifts in demographic variables, including race and maternal education (Canfield et al. 2003; Canfield RL, Henderson CR, Lanphear BP, Cory-Schlecta DA, Smith EG, Cox C, unpublished data). This was a prospective study, yet the sample increased from 154 children at 5 years of age to 182 at 6 years of age, and the number with peak lead levels < 10 µg/dL increased from 86 to 103. Canfield et al.'s 6-year data used in the pooled analysis have not been published, and my requests for further information were denied.

Finally, there was no significant association of IQ and three of the four indices of lead exposure--early childhood, peak (or maximal), and lifetime average--for the segments of the sample with peak lead levels < 10 µg/dL or < 7.5 µg/dL. Lanphear et al. (2005) omitted these analyses from their article.

Lanphear et al. (2005) reached conclusions intended to support policies to further reduce the already low level of childhood lead exposure. Although I contributed data [the Cleveland Study (Ernhart et al. 1989)] and participated in planning and review of analyses, I withdrew from authorship because I could not concur with the manuscript, including the inferences drawn.

The author declares she has no competing financial interests.

Claire B. Ernhart
Case Western Reserve University
Strongsville, Ohio
E-mail: cxe@po.cwru.edu

References

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Lead and IQ in Children: Lanphear et al. Respond

As described in our original article (Lanphear et al. 2005), we decided a priori to focus our analyses on the blood lead (BPb) variable that had the strongest association with IQ (intelligence quotient) scores. This decision was made to limit the number of analyses and to minimize problems with multiple comparisons. There was a clear consensus among the co-investigators--which originally included Ernhart--to use this strategy. Because concurrent BPb concentration was the strongest predictor of intellectual functioning, we focused most of our analyses on this variable.

There are now several studies indicating that concurrent or lifetime average BPb concentration are better predictors of children's IQ scores than measures taken in early childhood (Baghurst et al. 1992; Canfield et al. 2003; Chen et al. 2005; Dietrich et al. 1993; Tong et al. 1996; Wasserman et al. 2003). Thus, existing evidence indicates that interpretation of this literature should rely on concurrent or lifetime measures of BPb concentration.

Ernhart is concerned that we found no significant association of IQ and three of the four indices of lead exposure at peak BPb levels < 10 µg/dL or < 7.5 µg/dL (Lanphear et al. 2005). In addition to a significant inverse association of concurrent BPb concentration and IQ score for children with maximal BPb levels < 7.5 µg/dL, we found a consistent inverse association for lifetime average BPb concentration (β = -3.13, p = 0.054). As we reported, the relationship of peak BPb concentration and early childhood BPb concentration was not as predictive of children's IQ scores.

Ernhart is particularly concerned about our analyses for children with "very low" lead exposure (Lanphear et al. 2005). The results of our parsimonious analysis for children who had maximal BPb concentrations < 10 µg/dL and < 7.5 µg/dL were entirely consistent with the fully adjusted model. When we included all of the additional covariates, for concurrent BPb concentration changed by < 5%, and it remained statistically significant (β = -2.99, p = 0.019) for the children with maximal BPb levels < 7.5 µg/dL. When we further restricted the analysis to U.S. cohorts and introduced race as a covariate, race was clearly not a significant factor, and the pattern remained similar. These secondary analyses support our original conclusion that there is an inverse relationship of lead exposure and intellectual function, with greater decrements at lower BPb concentrations (Lanphear et al. 2005).

We agree that using an early measure of the HOME (Home Observation for Measurement of the Environment) inventory (Caldwell and Bradley 1984) in the Rochester cohort was a potential limitation. Still, when we excluded the Rochester cohort from the pooled analysis, the coefficient changed by < 3% and remained statistically significant (Lanphear et al. 2005). Thus, this limitation did not alter the conclusions of the study.

Ernhart is critical about the "peculiar" increase in sample size and shifts in demographic variables in the Rochester Study. Although some families became "too busy" to participate when their children were toddlers, we routinely invited them to participate in subsequent visits. A larger number of families were willing to return for an evaluation as their children aged.

We conducted a secondary analysis of studies that included prenatal BPb concentration. Contrary to Ernhart's comment, prenatal lead exposure was not significantly associated with children's IQ scores in adjusted analyses (Lanphear et al. 2005). We concluded that "prevention of lead exposure must occur before pregnancy or a child's birth" (Lanphear et al. 2005) because children are particularly vulnerable to lead intake and absorption during the first 2-3 years of life (Clark et al. 1985; Lanphear et al. 2002; Ziegler et al. 1978).

Ernhart argues that her request for further information about the 6-year data from the Rochester Study "was denied." The earlier measures of intellectual function in the Rochester children (i.e., at 3 and 5 years of age) were measured using the Stanford Binet test (Canfield et al. 2003). The IQ test at 6 years of age, which was measured using the Wechsler Preschool and Primary Scales of Intelligence, was done specifically for the pooled analysis. We believed that it was in the best interest of public health to confirm the findings of the original Rochester study with the larger pooled analysis rather than await publication of the follow-up 6-year IQ tests.

Numerous studies have found evidence for adverse consequences of childhood lead exposure at BPb levels < 10 µg/dL (Bellinger and Needleman 2003; Chiodo et al. 2004; Fulton et al. 1987; Lanphear 2000; Sood et al. 2001; Walkowiak et al. 1998; Wasserman et al. 2000). These studies provide sufficient evidence that childhood lead exposure should be reduced even more by banning all nonessential uses of lead and further reducing the allowable levels of lead in air emissions, house dust, soil, water, and consumer products.

The authors declare they have no competing financial interests.

Bruce P. Lanphear
Richard Hornung
Jane Khoury
Kimberly Yolton
Kim N. Dietrich
Departments of Pediatrics and of Environmental Health
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio
E-mail: bruce.lanphear@chmcc.org

References