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NEJM: Pb IQ effects not reversible

Gary Greenberg Gary.Greenberg at Duke.edu
Thu May 10 06:02:52 EST 2001

The New England Journal of Medicine -- May 10, 2001 -- Vol. 344, No.


The Effect of Chelation Therapy with Succimer on Neuropsychological
Development in Children Exposed to Lead

Walter J. Rogan, Kim N. Dietrich, James H. Ware, Douglas W. Dockery,
Mikhail Salganik, Jerilynn Radcliffe, Robert L. Jones, N. Beth Ragan,
J. Julian Chisolm, Jr., George G. Rhoads, for the Treatment of
Lead-Exposed Children Trial Group 


Background. Thousands of children, especially poor children living in
deteriorated urban housing, are exposed to enough lead to produce
cognitive impairment. It is not known whether treatment to reduce
blood lead levels prevents or reduces such impairment. 

Methods. We enrolled 780 children with blood lead levels of 20 to 44
µg per deciliter (1.0 to 2.1 µmol per liter) in a randomized,
placebo-controlled, double-blind trial of up to three 26-day courses
of treatment with succimer, a lead chelator that is administered
orally. The children lived in deteriorating inner-city housing and
were 12 to 33 months of age at enrollment; 77 percent were black, and
5 percent were Hispanic. Follow-up included tests of cognitive, motor,
behavioral, and neuropsychological function over a period of 36

Results. During the first six months of the trial, the mean blood lead
level in the children given succimer was 4.5 µg per deciliter (0.2
µmol per liter) lower than the mean level in the children given
placebo (95 percent confidence interval, 3.7 to 5.3 µg per deciliter
[0.2 to 0.3 µmol per liter]). At 36 months of follow-up, the mean IQ
score of children given succimer was 1 point lower than that of
children given placebo, and the behavior of children given succimer
was slightly worse as rated by a parent. However, the children given
succimer scored slightly better on the Developmental
Neuropsychological Assessment, a battery of tests designed to measure
neuropsychological deficits thought to interfere with learning. All
these differences were small, and none were statistically significant. 

Conclusions. Treatment with succimer lowered blood lead levels but did
not improve scores on tests of cognition, behavior, or
neuropsychological function in children with blood lead levels below
45 µg per deciliter. Since succimer is as effective as any lead
chelator currently available, chelation therapy is not indicated for
children with these blood lead levels. (N Engl J Med 2001;344:1421-6.) 

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[Please visit the website for this whole article. - Mod]


Primary Prevention of Childhood Lead Poisoning -- The Only Solution

Lead poisoning in children was first recognized in its severe acute
form, known as lead encephalopathy. (1) This condition is
characterized by seizures, coma, and -- not infrequently -- death, and
it is associated with severe neurologic sequelae in survivors.
Although lead encephalopathy has become rare in the past 15 to 20
years, the dangers of clinically asymptomatic lead poisoning in
children have become increasingly clear. Longitudinal studies of
development from birth to adolescence show that irreversible cognitive
damage can occur with blood lead levels considerably lower than those
typically associated with overt symptoms. (2,3) Recognition of this
problem has led to routine screening programs and clear guidelines for
the management of severe lead poisoning (defined by whole-blood lead
levels of 45 µg per deciliter or more). In contrast, the appropriate
management of moderate lead poisoning (defined by whole-blood lead
levels of 20 to 44 µg per deciliter) remains uncertain. 


Chelation therapy is now used routinely in children who have blood
lead levels of 45 µg per deciliter or more, with the goal of
preventing neurologic deterioration, lead encephalopathy, and death.
However, there have been no clear guidelines from the Centers for
Disease Control and Prevention or other advisory bodies regarding
therapy for children with blood lead levels of 20 to 44 µg per
deciliter, (6,7) who were represented by the participants in the
present study. (4) 


The lack of efficacy of succimer for the prevention of neurotoxic harm
due to moderate blood lead levels in the children in the study by
Rogan et al. and the limited efficacy of chelation therapy in cases of
severe lead poisoning clearly cast doubt on the value of public health
programs that rely primarily on treatment after lead poisoning has
occurred. Rogan et al. emphasize the importance of the primary
prevention of lead poisoning, which is the only satisfactory solution
to this devastating problem. The predominant source of toxic exposure
to lead for children in urban areas is lead paint, (10) although some
incremental but far less substantial toxicity may be due to other
sources, such as tap water contaminated by lead pipes. 

For the primary prevention of lead poisoning from paint, we recommend
permanent abatement -- that is, the complete removal or replacement of
lead paint before a child lives in a home. (11,12) In contrast,
"interim" measures, which were introduced for the short-term reduction
of hazards associated with lead paint (11,13) and which involve
scraping and painting over deteriorated surfaces and controlling
household dust, have been claimed by some to save substantial cost;
however, there is no evidence of savings in terms of net benefit over
cost in the long-term prevention of childhood lead poisoning.
Lead-painted surfaces in good condition rarely remain so. What was
once intact lead-based paint is the source of all lead-bearing dust
and paint chips. Therefore, it is the presence of lead paint on
surfaces that defines the hazard, not the condition of surfaces
containing lead paint. 


John F. Rosen, M.D. Paul Mushak, Ph.D. Children's Hospital at
Montefiore Bronx, NY 10467 

Sent to me for broadcast by "Rui Carvalho" <medi at mail.telepac.pt>
- Thanks!

Gary N. Greenberg, MD MPH    Sysop / Moderator Occ-Env-Med-L MailList
gary.greenberg at duke.edu     Duke Occupat, Environ, Int & Fam Medicine
OEM-L Maillist Website:                      http://occhealthnews.net


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