Walter Rogan, M.D., of NIEHS, and colleagues from the Treatment of Lead-exposed Children Trial (TLC) reported the results in The New England Journal of Medicine (May 10). The TLC study showed that, as expected, drug treatment with succimer lowered blood lead faster than placebo. Treating lead-exposed two-year-olds, however, did not improve scores on psychological, behavioral and IQ tests when the children were followed until age 5 years.

Succimer remains as the only drug given by mouth labeled for treating children with high blood lead levels. But the hope behind the study was that otherwise symptom-free children exposed to just enough lead to have affected their psychological, behavioral and intelligence tests, might be aided.

NIEHS Director Kenneth Olden, Ph.D., said, "For more than twenty years, NIEHS has sponsored much of the research showing that lead at these levels was harmful to children's brain function, and that succimer lowered blood lead. We had hopes that the treatment would prevent or reduce lead-induced damage in these children, who are mostly poor, African-American, and living in deteriorated housing in big cities. The results of the trial show clearly that treatment after the fact does not undo the damage among 5 year olds. We must prevent these children from being exposed in the first place."

TLC was sponsored by NIEHS and the Office of Research on Minority Health, both of the National Institutes of Health, and the Center for Environmental Health of the Centers for Disease Control and Prevention. McNeil Consumer Products, who produced succimer as Chemet when the study began, provided succimer and placebo. Chemet is now owned by Sanofi-Synthelabo, New York, N.Y. TLC was carried out at four urban teaching hospitals:

• The Kennedy Krieger Institute in Baltimore, Md.,

• The University of Cincinnati in Cincinnati, Ohio,

• The University of Medicine and Dentistry of New Jersey, working with children in Newark, and Children's Hospital, Philadelphia, Pa.

The program was managed from NIEHS and the Harvard School of Public Health.

For the study, the Centers for Disease Control and Prevention measured blood lead and the Public Health Service Supply Service Center in Perry Point, Md., provided pharmacy services.

In the early 1990s, when the study was started, it was known that children exposed to more lead had lower scores on IQ tests and that succimer could lower lead levels in blood. It was not known whether using it prevented or reduced the effects of lead on test scores. About 780 children were enrolled between 1994 and 1997. Half were given succimer and half an identical capsule without active drug.

In addition, all the children's homes were cleaned of lead dust, they were given a mineral supplement, and their blood lead was followed. Detailed testing of their cognitive development, neuropsychological function, and behavior was done at three years of follow up. This is a time when the children are old enough to be given sophisticated tests (they were then about 5 years old) and it is the age at which there is the strongest evidence for an effect of lead.

While the children given succimer had more rapid drops in their blood lead, the differences in tests scores were small, inconsistent, and not statistically significant, the investigators said. The study was large enough to have detected an improved IQ score of less than 3 points, and no such improvement was seen.

Side effects were relatively infrequent in both groups, but the children given succimer had an unexpectedly higher rate of injuries, which is so far unexplained.

Based on these data, Rogan said, there is little reason to recommend chelation for children with exposures below the current recommendation of 45 mg/dL. Children generally have no symptoms below that level. Succimer remains the recommended therapy for outpatient treatment of children above that level.

The children who participated in TLC are being followed for an additional two years to see if some benefit emerges. In an Australian study, children whose blood leads fell faster without treatment when they were two years old had better IQ test scores when they were seven years old, and 7 year old children attend school and read and so can be tested more extensively.

Although lead poisoning in the US has declined dramatically since the removal of lead from gasoline, in 1998 about 8% of screened children still had blood lead levels that CDC defined as elevated, and about 1% of screened children had a blood lead level high enough to have been eligible for the TLC trial. Lead poisoning is concentrating now among poor children who are eligible for Medicaid and live in deteriorating, inner city housing.

For more information, see the TLC website at http://dir.niehs.nih.gov/direb/tlc1/home.htm

For general questions about TLC : Dr. Walter Rogan, NIEHS, (919) 541 4578, rogan@niehs.nih.gov

For questions about the specific clinical centers' activities:
Baltimore: Merrill Brophy, Kennedy Krieger Institute (410) 866 0612 brophy@kennedykrieger.org

Cincinnati: Dr. Robert Bornschein, University of Cincinnati (513) 558 0996 robert.bornschein@uc.edu

Or Dr. Kim Dietrich University of Cincinnati (513) 558 5816 dietrikn@uc.edu

Newark: Dr. Richard Wedeen, Veterans' Administration New Jersey Health Care System, (973) 676 1000 x17877 wedeen@umdnj.edu

Or Dr. George Rhoads, UMDNJ Piscataway, (732) 445 0195 rhoads@umdnj.edu

Philadelphia: Dr. Donald Schwarz, Children's Hospital (215) 590 1462 schwarz@email.chop.edu