Using maternal serum to do fetal screening

There may soon be a viable, noninvasive way to screen fetuses for chromosomal abnormalities using nothing more than a sample of maternal blood. While such determination has been hindered by the inability to distinguish fetal from maternal DNA, a preliminary study finds single nucleotide polymorphisms (SNPs) can be used to both distinguish DNA and determine the number of fetal chromosomes.

Researchers gathered formaldehyde-treated blood samples from 60 pregnant women and the stated biologic fathers and then employed the novel method of quantifying and comparing allele ratios for multiple SNP sites on chromosomes 13 and 21 after fetal DNA enrichment in maternal plasma.

By doing so, they predicted that three of the women carried a fetus affected by trisomy 21 and that the rest were chromosomally normal. Amniocentesis and newborn reports confirmed that 58 of their 60 predictions were correct. With one false-positive and one false-negative result, researchers calculated a sensitivity and positive predictive value for the method of 66.7% (95% CI; 12.5–98.2) and a specificity and negative predictive value of 98.2% (95% CI; 89.4–99.9).

The authors of an accompanying editorial point out that one of the problems with the method is that a large number of SNPs are needed for the technique to work. When too few SNPs are analyzed in a sample with a low percentage of free fetal DNA, the possibility of a false-positive result increases. And the optimum number of SNPs needed to provide a highly accurate answer is as yet unknown.

While the findings undoubtedly require replication in a large-scale, multicenter setting, the method could prove particularly useful in light of the American College of Obstetricians and Gynecologists' (and several European countries') recent recommendation that all pregnant women, regardless of age, be offered fetal genetic screening.

Dhallan R, Guo X, Emche S, et al. A non-invasive test for prenatal diagnosis based on fetal DNA present in maternal blood: a preliminary study. Lancet. 2007;369:474-481.

Benachi A, Costa JM. Non-invasive prenatal diagnosis of fetal aneuploidies. Lancet. 2007;369:440-442.