Council on Environmental Health
Article Review

Prepared by: Robert O. Wright, MD, MPH
February 2008

TITLE
Associations between cognitive function, blood lead concentration, and nutrition among children in the central Philippines

AUTHORS
Solon O, Riddell TJ, Quimbo SA, Butrick E, Aylward GP, Lou Bacate M, Peabody JW

SOURCE
Journal of Pediatrics 2008;152(2):237-43

OBJECTIVE
Because little is known about its effects on cognitive function among children in less-developed countries, we determined the impact of lead exposure from other nutritional determinants of cognitive ability.

STUDY DESIGN
Data were from a cross-sectional population-based stratified random sample of 877 children (age 6 months-5 years) participating in the Quality Improvement Demonstration Study we are conducting in the Philippines. With data from validated psychometric instruments, venous blood samples, and comprehensive survey instruments, we developed multi-stage models to account for endogenous determinants of blood lead levels (BLLs) and exogenous confounders of the association between BLLs and cognitive function.

STUDY RESULTS
A 1 microg/dL increase in BLL was associated with a 3.32 point decline in cognitive functioning in children aged 6 months to 3 years and a 2.47 point decline in children aged 3 to 5 years old. BLL was inversely associated with hemoglobin and folate levels. Higher folate levels mitigated the negative association between BLL and cognitive function.

STUDY CONCLUSIONS
These population-based data suggest greater lead toxicity on cognitive function than previously reported. Our findings also suggest that folate and iron deficient children are more susceptible to the negative cognitive effects of lead. Folate supplementation may offer some protective effects against lead exposure

OVERVIEW
This studied determine the dose response curve for blood lead levels and infant development in a developing country, where nutritional status is likely to differ from a developed country. The authors hypothesized that nutritional status would likely alter the relationship between lead exposure and development, i.e. that poor nutrition would synergistically make lead more toxic. While minerals/elements (Fe, Zn, Ca) have been studied with respect to lead poisoning, this is the first study to address the vitamin folate and lead. Folate is critical for multiple cellular functions, and has been the subject of intense research recently for its role in regulating gene expression through the process of DNA methylation.

CONTEXT
The authors sought to determine if lower serum folate made lead synergistically more toxic.

WHAT DID THEY DO?
This was a cross-sectional study of over 800 children living in the Philippines. Children were on average 2 years of age at testing(Bayley Scale of Infant Development).

WHAT DID THEY FIND?
The author’s report a 2% to 3% decrease in cognitive test scores for every 1 ug/dL increase in blood lead level. This differs from other studies in Western Countries which typically report a 1% decrease for every 1 ug/dL increase in blood lead level. Furthermore, they found that serum folate levels modified this effect. The association between blood lead level and Bayley Mental Developmental Index score was less steep among children with higher serum folate levels.

WHAT DOES IT MEAN?
This suggests that higher serum folate may be protective against the toxic effects. As this is an observational study, the findings should be seen as an association and might not be due to cause and effect. There may be overall better nutrition in the children with higher serum folate, and serum folate may simply be a marker of this better nutrition. Nevertheless, the study illustrates another nutritional factor that might help children overcome the toxic effects of lead. Iron, Zinc deficiency and Calcium have also been studied as risk factors for lead poisoning. While folate does not interact with lead metabolism the way these elements do, it does play a vital role in regulating gene expression. There is evidence from animal studies that metals interfere with gene expression via changes in DNA methylation, a process for which folate is critical. There is also an accompanying editorial: Wright RO. Neurotoxicology: what can context teach us?. Journal of Pediatrics. 152(2):155-7, 2008.

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