The effect of chelation therapy with succimer on neuropsychological development in children exposed to lead.

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 microg per deciliter (1.0 to 2.1 micromol 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 months. RESULTS: During the first six months of the trial, the mean blood lead level in the children given succimer was 4.5 microg per deciliter (0.2 micromol per liter) lower than the mean level in the children given placebo (95 percent confidence interval, 3.7 to 5.3 microg per deciliter [0.2 to 0.3 micromol 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 microg 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.

Menstruation and reproduction in women with polychlorinated biphenyl (PCB) poisoning: long-term follow-up interviews of the women from the Taiwan Yucheng cohort.

BACKGROUND: In 1979 in Taiwan, about 2000 people were poisoned by cooking oil contaminated with heat-degraded polychlorinated biphenyls (PCBs). Victims developed chloracne and other symptoms; the illness is called Yucheng (oil disease). The chemicals persist in the victims' bodies and some are toxic to the female reproductive system in experimental animals. METHODS: In 1993-1994, we identified the living Yucheng women and neighbourhood controls and interviewed them about their reproductive experience. Of the 596 living Yucheng women aged 30-59 years, we found 368, and interviewed 356. We identified 329 controls, and interviewed 312. RESULTS: Of the Yucheng women, 16% reported abnormal menstrual bleeding compared to 8% (P < 0.05) of control women; 4.2% versus 1.7% reported a stillbirth since 1979 (P = 0.068). Other characteristics of the menses, fertility, frequency of intercourse, and age at menopause appeared unaffected. More of the Yucheng women reported that one of their offspring had died during childhood (10.2% versus 6.1%, P < 0. 05), and that they had decided to limit childbearing because of health problems (7% versus 2%, P = 0.01). CONCLUSIONS: These findings suggest that high level PCB/polychlorinated dibenzofuran (PCDF) exposure has some effect on female endocrine and reproductive function.

Recall of a lead-contaminated vitamin and mineral supplement in a clinical trial.

PURPOSE: The Treatment of Lead-exposed Children (TLC) trial tested whether developmental outcome differed between children treated for lead poisoning with succimer or placebo. On 7 July 1997, TLC was informed that the vitamin and mineral supplements it gave to all children were contaminated with about 35 microg of lead per tablet. METHODS: TLC recalled the contaminated supplements and measured the children's exposure. RESULTS: The families of 96% of the children were contacted with 30 days. Among the 571 children to whom the contaminated supplements were dispensed, the mean increase in blood lead was 0.06+/-0.01 micromol/L (1.2+/-0.2 microg/dL); among 78 children to whom they were not, it was 0.09+/-0.03 micromol/L (1.8+/-0.7 microg/dL). There was no evidence of a dose-response relation between estimated supplement consumption and increase in blood lead concentration. CONCLUSIONS: The children's blood lead concentrations were not detectably affected by the contamination. Since the association of cognitive delay with lead exposure is best described for blood lead, we believe that the trial's inference about the effect of drug therapy on lead induced cognitive delay should be unaffected.

Increased mortality from chronic liver disease and cirrhosis 13 years after the Taiwan "yucheng" ("oil disease") incident.

In 1979, a mass poisoning involving some 2,000 persons occurred in central Taiwan from cooking oil contaminated by polychlorinated biphenyls (PCBs) and their heat-degraded byproducts, including polychlorinated dibenzofurans (PCDFs). The responsible health department registered cases for clinical purposes between 1979 and 1983. The exposed persons are referred to as the "yucheng" (oil disease) cohort. PCBs and PCDFs are toxic chemicals widely dispersed in the environment and in human tissue, which persist long after exposure. The consequences of exposure to these agents are not well understood. We traced the cohort through December 31, 1991, and compared overall and cause-specific mortality of 1,837 "yucheng" subjects with age, gender, and calendar time-specific mortality rates for the Taiwan general population. Eighty-three deaths were identified from 23,404 observed person-years. Even though the overall standardized mortality ratio (SMR) was 0.8 (95% confidence interval (CI) 0.7-1.0), there was a substantial elevation in the mortality rate for chronic liver disease and cirrhosis (10 deaths, SMR = 2.7, 95% CI = 1.3-4.9). Mortality from malignant neoplasms and other causes was not significantly different from that of the Taiwan population. PCB/PCDF exposure appears to promote the development of severe liver disease, perhaps in combination with known risk factors such as infection with hepatitis B virus. Further follow-up of this young cohort is necessary to see if the consequences include hepatic cancer.

Cognitive development of Yu-Cheng ("oil disease") children prenatally exposed to heat-degraded PCBs.

OBJECTIVE: To compare the cognitive development in Taiwanese children who had been exposed prenatally to high levels of heat-degraded polychlorinated biphenyls (PCBs) with control children who were exposed to background levels. The disorder was called Yu-Cheng, "oil disease," in Taiwan. DESIGN: Matched-pair cohort study. SETTING: Communities in central Taiwan in which there had been a cooking-oil contamination and mass poisoning by heat-degraded PCBs in 1978 through 1979. PARTICIPANTS: One hundred eighteen children born between June 1978 and March 1985 during or after their mothers' consumption of contaminated rice oil; 118 children matched for age, sex, neighborhood, maternal age, and parental education and occupational class; and 15 older siblings of exposed children, born before the poisoning. MAIN OUTCOME MEASURES: Cognitive development measured from 1985 through 1990 using the Chinese versions of the Stanford-Binet test and the Wechsler Intelligence Scale for Children, Revised, RESULTS: The exposed children scored approximately 5 points lower on the Stanford-Binet test at the ages of 4 and 5 years and approximately 5 points lower on the Wechsler Intelligence Scale for Children, Revised, at the ages of 6 and 7 years. Children born up to 6 years after their mothers' exposure were as affected as children born within a year or two after exposure when examined at 6 and 7 years of age. Older siblings resembled the control children. CONCLUSION: Children prenatally exposed to heat-degraded PCBs had poorer cognitive development than their matched controls. The effect persisted in the children up to the age of 7 years, and children born long after the exposure were still affected.

Polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) in human milk: effects of maternal factors and previous lactation.

The authors measured polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) in maternal serum, cord blood, placenta, and serial samples of breast milk from 868 women. Almost all samples of breast milk showed detectable levels of both chemicals. Overall, values for DDE in this study are within the range of those found previously, whereas those for PCBs are somewhat higher. Possible causes of variation in levels were investigated. For DDE, older women, Black women, cigarette smokers, and women who consumed sport fish during pregnancy had higher levels; only age and race showed large effects. For PCBs, older women, women who regularly drink alcohol, and primiparae had higher levels. In addition, both chemicals showed modest variation across occupational groupings. Casual exposure to a PCB spill did not result in chemical levels different from background. In general, women have higher levels in their first lactation and in the earlier samples of a given lactation, and levels decline both with time spent breast-feeding and with number of children nursed. These striking declines are presumably a measure of exposure to the child.