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STUDY: Eat your Greens
JOURNAL: Lancet 2003;361:1316
AUTHORS: Dr. Gad Barkai
ABSTRACT: Impaired folate status may increase the risk of Down's syndrome.
COMMENTARY: Mothers of infants with Down's syndrome are believed to have an elevated risk for abnormal folate metabolism that could result in aneuploidy, Dr. Gad Barkai, of Sheba Medical Centre, Tel Hashomer, Israel, and colleagues explain. However, evidence regarding the rate of genetic polymorphisms in mothers with Down's syndrome offspring is inconsistent.
The multinational research team found that Downs' syndrome and neural tube defects (NTD) arise more often in the same families than would be expected from the incidence of each disorder considered separately.
It is on the basis of such an association, and knowledge that folate supplementation reduces the risk of NTD, that they recommend preconception folate supplementation for mothers at risk.
Dr. Barkai's group reviewed the record of 493 families referred to the Sheba Medical Centre between 1971 and 2001 because of prior pregnancies affected by NTD or isolated hydrocephalus. The families included those with at least one sibling in addition to the proband.
Among the 1492 at-risk pregnancies, there were 11 with Down's syndrome. This rate is significantly higher than the 1.87 affected Down's syndrome cases that would be expected among women of the same age in the general population (p < 0.00001), their report indicates.
They also examined data from 516 families who underwent genetic counseling in the Ukraine because of their risk of Down's syndrome. Among 1847 pregnancies, seven families had children affected by NTD. Again, this is a significant increase from the 1.37 cases expected in the general population (p = 0.0005).
Dr. Barkai's team maintains that genomic instability is minimized when maternal plasma folate exceeds 34 nmol/L and homocysteine levels are kept below 7.5 mcg/L. To achieve such levels, folate intake should be no lower than 5 mg/day.