OAR Box 1126 

Prepped by Ollie Stewart 

Document Number: 

6)11-1-127 

Docket Number: 

A-83-22 

Printed 4/18/2008 9:58:21 AM Sheet 6 of 182 

P.1 
P.2 

Claire B. Ernhart 

October 7, 1983 

Response to Appendix 12-C 

INDEPENDENT PEER-REVIEW OF SELECTED STUDIES CONCERNING 

NEUROBEHAVIORAL EFFECTS OF LEAD EXPOSURES IN NOMINALLY 

ASYMPTOMATIC CHILDREN? 

OFFICIAL REPORT OF FINDINGS AND RECOMMENDATIONS 

OF AN INTERDISCIPLINARY EXPERT REVIEW COMMITTEE 

I'd like first to commend the Committee for the objectivity of 

its analyses and for the care with which it reviewed the materials 

provided. I concur with most of what is included in the report and I 

only wish that I had more and better data with which I could answer 

more definitively the questions posed by the Committee» On only one 

suggestion, discussed below, would I disagree with the recommendations. 

The introduction presented well the more critical of the 

issues relevant to the design of research in this area. The 

weaknesses of cross- sectional designs are well stated. With the 

completion of the very important U.K. studies, we will probably see 

fewer cross-sectional studies. Meanwhile, we are waiting for the 

results and dealing with the difficult problems arising in the 

conduct of the prospective studies. 

The balance of these comments deals with the review of the 

studies by my associates and me. At the time this review was 

written, the Committee did not have my report of further analyses of 

my data. While these were not conducted precisely as suggested by 

the Committee in the report at hand, the major suggestions were 

implemented as well as possible and I feel that further manipulation 

of the data is not warranted. 

Specific Points: 

P.15, first paragraph. All analyses of reading scores had age 

at time of testing entered as the first covariate. Perhaps regressing raw scores for the McCarthy scales on age rather than using 

extrapolated or normed scores would have been better. I'm concerned 

about the regression effects inherent in that approach. It seems 

highly unlikely that this would influence the results in any 

appreciable way. 

P.15, last paragraph. In the reanalyses provided education was 

forced into the covariate set although it was not significantly 

related to the outcome measure in any analysis after entry of parent 

I.Q. I can see the merits of the backward selection procedure in 

this kind of analysis. In this case, I doubt that taking it back out 

would have made any difference. 
P.3 

P.17 (f)o I was unaware that Perino had more high lead cases 

early in the data collection period. His wife set up the data 

collection schedule. Since he was blinded and well trained, I don't 

think the order had an effect, but it was not ideal. 

P.18. I had considered handling the data as a cross-lagged 

panel design as one way of assessing the possiblity that early 

deficits in intelligence could lead to higher levels of lead. As 

noted, the cross correlations were low and not appreciably different 

from each other so I gave up that approacho In some of my present 

work, I'm developing causal models to handle these problems of 

longitudinal relationships. I question, however, whether there is 

much more that can be done in that regard with the set of data under 

review. 

The problems of measuring change are old familiar concerns. A 

simple change score for the intelligence measure was added to the set 

of reanalyses supplied in August. Residuals computed from the 

regression of the later measure on the earlier, as suggested by Dr. 

Jones, would have given a somewhat different resolution of the 

problem, both numerically and in the sense of what the model represents. Aside from all the problems involved in the measurement of 

change, the idea of change in intelligence as a outcome variable 

related to the early exposure index is reasonable. 

One can also put forth a rationale for change in lead level as 

an outcome measure related to early intelligence. (Less intelligent 

children may be more likely to be exposed or more intelligent 

children to stay away from it.) 

In both of the above designs the concern is with the effect of 

the earlier condition on change. What Dr. Jones suggested, however, 

is that both Ister measures be regressed on the corresponding earlier 

measures; this essentially cancels either as a plausible etiological 

factor in the :aodel. The residualization of the lead measure is of 

particular con: -irn both because the more frequently hypothesized 

direction of e;. feet is from lead to deficit and because lead level 

dropped appreciably from the preschool to the schoolage time of 

assessment. If lead levels in the range under consideration do have 

an effect, the earlier higher levels are of much greater concern than 

the later levels. This is particularly so if there is any 

possibility of a threshold of effect within this range. 

The availability of the early lead measure is what makes this 

a longitudinal as opposed to a cross-sectional study and it is 

important. With the full sample of 62 children, the relatively high 

preschool index of exposure was not significantly related to any 

later outcome measure. 

I object to the statement on p.18, 12th line from the bottom: 

"These simple logitudinal analyses provide support for the hypothesis 

that an increase in blood Pb from ages 4-5 to 9-10 yrs, is associated 

with a decrease in IQ ..." While mean IQ changed very little, mean 
P.4 

'-% '. -.' *> 

lead level dropped appreciably and very few children actually 

increased in lead level. The use of residual scores in this situation 

leads to the anomalous situation in which actual decreases in lead 

level are identified as increases in residual score form because they 

do not decrease to the extent predicted by the regression. It's 

interesting to look at the actual paired lead levels for the children 

identified by subject number in Figure 1„ The greatest "decrease" is 

for §58 whose lead level was 10 on both times of sampling. In the 

range to the right of the mean, the same residual score could be 

obtained both by increasing or by decreasing lead level, depending on 

the initial value. This makes sense from what we know about regression, but it is not very sensible from the perspective of the person 

needing to make decisions about the effects of lead. 

Most certainly the fact of the drop in lead level over time 

should be brought into this discussion. The statement quoted above 

can easily be misconstrued by persons not familiar with this fact and 

with the nature of regression analysis. 

With low cross lag correlations, it's hard to make much sense 

out of the correlation between residuals. It could reflect another 

changing condition not included in the covariates, or, perhaps, 

intra-individual lability or stability. 

Once again though, the most important problem with this model 

for analysis of the data is that it statistically extracts the most 

important variable, i.e., the preschool lead index. 

J