Air Quality Criteria for Lead Volume II of II - (NEPIS)(EPA) - US ...

AX6-27
Table AX6-2.10. Reversibility of Lead-related Deficits in Children
Reference, Study
Location, and Period Study Description Pb Measurement Findings, Interpretation
United States
Ruff et al. (1993)
U.S.
Rogan et al. (2001);
Dietrich et al. (2004)
U.S.
Design: Intervention study, non-randomized.
126 children with complete data age 13 to 87 mos
and with blood Pb levels between 25 and 55 µg/dL
were given chelation with ETDA and/or therapeutic
iron where indicated. At baseline and follow-up,
patients were evaluated with the Bayley Scales of
Infant Development, Mental Development Index,
or Stanford Binet Scales of Intelligence depending
upon age.
Design: Double blind, placebo-controlled
randomized clinical trial. The Treatment of Pb-
Exposed Children (TLC) clinical trial of 780
children in 4 centers was designed to determine if
children with moderately elevated blood Pb
concentrations given succimer would have better
neuropsychological outcomes than children given
placebo. Children between 12 and 33 mos of age
were evaluated 3 yrs following treatments and
again at 7 and 7.5 yrs of age. A wide range of
neurological, neuropsychological, and behavioral
tests was administered. Assessment of potentially
confounding factors included sociodemographics
and parental IQ.
Blood Pb at time of
treatment
Blood Pb 31.2 (SD 6.5)
µg/dL
Blood Pb
Baseline blood Pb 26
(SD 26.5) µg/dL in both
drug and placebo groups
Without respect to treatment regimen, changes in
performance on cognitive measures after 6 mos were
significantly related to changes in blood Pb levels after
control for confounding factors. Standardized scores on tests
increased 1 point for every 3 µg/dL decrement in blood Pb.
Succimer was effective in lowering blood Pb levels in
subjects on active drug during the first 6 mos of the trial.
However, after 1 yr differences in the blood Pb levels of
succimer and placebo groups had virtually disappears.
3 yrs following treatment, no statistically significant
differences between active drug and placebo groups were
observed for IQ or other more focused neuropsychological
and behavioral measures. When evaluated at 7 and 7.5 yrs of
age, TLC could demonstrate no benefits of earlier treatment
on an extensive battery of cognitive, neurological, behavioral
and neuromotor endpoints. Authors conclude that the TLC
regimen of chelation therapy is not associated with
neurodevelopmental benefits in children with blood Pb levels
between 20 and 44 µg/dL and that these results emphasize
the importance of taking environmental measures to prevent
exposure to Pb in light of the apparent irreversibility of Pbassociated
neurodevelopmental deficits.