Cognitive development after the Fontan operation.

BACKGROUND: Patients with a single ventricle have multiple risk factors for central nervous system injury, both before and after the Fontan procedure. METHODS AND RESULTS: A geographically selected cohort was invited to undergo standardized testing, including age-appropriate measures of intelligence quotient (IQ) and achievement tests. Historical information was obtained by chart review and patient questionnaires. Of the 222 eligible patients, 133 (59.9%) participated. Median age at testing was 11.1 years (range, 3. 7 to 41.0 years), 6.0 years (range, 1.6 to 19.6 years) after surgery. Mean full-scale IQ was 95.7+/-17.4 (P<0.006 versus normal); 10 patients (7.8%) had full-scale IQ scores <70 (P=0.001). After adjustment for socioeconomic status, lower IQ was associated with the use of circulatory arrest before the Fontan operation (P=0.002), the anatomic diagnoses of hypoplastic left heart syndrome (P<0.001) and "other complex" (P=0.05), and prior placement of a pulmonary artery band (P=0.04). Mean composite achievement score was 91.6+/-15. 4 (P<0.001 versus normal); 14 patients (10.8%) scored <70 (P<0.001). After adjustment for socioeconomic status, independent risk factors for low achievement scores included the diagnoses of hypoplastic left heart syndrome (P=0.004) and "other complex" (P=0.003) or prior use of circulatory arrest (P=0.03), as well as a reoperation with cardiopulmonary bypass within 30 days of the Fontan (P=0.01). CONCLUSIONS: Most individual patients palliated with the Fontan procedure in the 1970s and 1980s have cognitive outcome and academic function within the normal range, but the performance of the cohort is lower than that of the general population.

Epidemiologic approaches to assessing the developmental toxicity of lead.

A variety of designs have been employed in epidemiologic studies of the developmental morbidity associated with low-level lead exposure. Historically, cross-sectional and retrospective cohort designs have been used most frequently. Despite improvements in their methodological rigor, however, certain design features constrain the inferences such studies can support. These limitations stem from the substantial risk that children's exposure status may be misclassified due to reliance on indices with short averaging times, and an inability to identify either age-related changes in vulnerability or time-dependent aspects of the expression of toxicity (e.g., reversibility). In response to these limitations, several studies were initiated involving repeated measurements of children's lead exposure and development over periods as long as a decade. Although these prospective studies are characterized by an unusual degree of coordination among the investigators, there are differences among them as well, most notably in terms of sample characteristics and patterns of exposure. As a result, the studies should be viewed as complementary rather than simply as replicates of one another. Moreover, like all epidemiologic approaches the prospective design has its own limitations. These include the need to maintain follow-up over a long period of time, as well as the attendant risk of bias in sample attrition, and the need to distinguish developmental effects of lead from psychometric artifacts. The Boston prospective study is used to illustrate both the strengths and weaknesses of the prospective design.

Neuropsychological correlates of low-level lead exposure in school-age children: a prospective study.

The neuropsychological underpinnings of lead-associated deficits in general cognitive abilities and academic achievement were investigated in a cohort of 148 middle and upper-middle class 10 year-olds. Scores on a battery of neuropsychological tests were examined in relation to blood lead levels measured at birth and ages 6, 12, 18, 24, 57 months, and 10 years. Although numerous indices of the level, nature, and variability to children's performance on the WISC-R were associated with blood lead level measured at 24 months of age (pb24), relatively few significant associations were noted between specific measures of neuropsychological functions and pb24 (or other blood lead measurements). Some evidence was found for an association between recently measured lead levels and qualitative aspects of a child's performance (e.g. perseveration). The presence of more significant lead effects on broad-based measures of functioning than on neuropsychological tests may be attributable to the use of insensitive measures of neuropsychologic function, limitations in coverage provided by the tests, the nature of lead's CNS impact, or individual differences in biologic vulnerability to lead.

Low-level lead exposure, intelligence and academic achievement: a long-term follow-up study.

The implications of low-level lead exposure for children's intellectual and academic performance at school age are uncertain. This issue was investigated in a prospective study of middle-class and upper-middle-class children with low lifetime exposures to lead. A battery of neuropsychological tests was administered at age 10 years to 148 children whose lead exposure and cognitive function had been previously assessed at ages 6, 12, 18, 24, and 57 months. Primary endpoints were Wechsler Intelligence Scale for Children-Revised (WISC-R) and the Kaufman Test of Educational Achievement (K-TEA). Higher levels of blood lead at age 24 months, but not at other ages, were significantly associated with lower global scores on both the WISC-R and the K-TEA after adjustment for potential confounders. Over the range of approximately 0 to 25 micrograms/dL, a 0.48-mumol/L (10 micrograms/dL) increase in blood lead at 24 months was associated with a 5.8-point decline in WISC-R Full-Scale IQ (95% confidence interval: 1.7 to 9.9, P = .007) and an 8.9-point decline in K-TEA Battery Composite score (95% confidence interval: 4.2 to 13.6, P = .0003). Mean blood lead level at age 24 months was 0.31 mumol/L (6.5 micrograms/dL; SD: 4.9, 90% percentile: 12.5). Slightly elevated blood lead levels around the age of 24 months are associated with intellectual and academic performance deficits at age 10 years.