Methods to increase the percentage of free fetal DNA recovered from the maternal circulation

Present invasive methods for detecting fetal chromosomal abnormalities, although quite reliable, carry a risk of pregnancy loss. Many candidates for such testing reject it for this reason. An alternative is to recover fetal cells and fetal DNA from the maternal circulation, as has been done to determine fetal gender. In the hope of increasing the recovery of free fetal DNA, the investigators determined whether inhibiting cell lysis at all stages with formaldehyde would increase the proportion of free fetal DNA in maternal blood samples. Initially, 2 blood samples were taken from each of 10 pregnant women to compare the percentage of free fetal DNA in treated and untreated samples. Treated samples were exposed to 4% weight per volume of formaldehyde. In a second phase, free fetal DNA was measured in 69 formaldehyde-treated maternal blood samples collected from 27 clinical sites in 16 states. In the initial phase of the study, untreated and formaldehyde-treated maternal blood samples contained a mean of 7.7% and 20.2%, respectively, of free fetal DNA. In several untreated samples, DNA levels were substantially below the median. In the second phase, a median of 25% free fetal DNA was detected in the treated maternal blood samples. Only 16% of samples contained less than 10% fetal DNA, whereas 27.5% had 50% or more. Inhibiting cell lysis by treating maternal blood samples with formaldehyde clearly increases the relative percentage of free fetal DNA recovered. Hopefully this work will help in developing a noninvasive prenatal diagnostic test for detecting fetal chromosomal abnormalities.