Treatment of Maternal Blood Samples with Formaldehyde Does Not Alter the Proportion of Circulatory Fetal Nucleic Acids (DNA and mRNA) in Maternal Plasma

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Abstract
Cell-free fetal DNA and fetal mRNA can be found in maternal plasma and used for noninvasive prenatal diagnosis and, potentially, for monitoring and prognosis of certain pregnancy-related clinical conditions (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). The excess of maternal DNA in these samples, however, complicates the detection of fetal genetic traits that are similar to those in the maternal genome (e.g., point mutations) (1)(13)(14). In normal pregnancies, fetal DNA represents only ∼3–6% of the total DNA in maternal plasma (15). Thus, technical challenges lie in either developing methods permitting the reliable differentiation of fetal genetic loci or in reducing the amount of circulatory maternal DNA. Dhallan et al. (16) have recently reported that the addition of formaldehyde to maternal blood samples increases the proportion of cell-free fetal DNA in maternal plasma by decreasing the concentration of maternal DNA. This effect was proposed to reflect an ability of formaldehyde to stabilize the maternal blood cells, thereby preventing the release of DNA from these cells should they die during sample collection and processing. We have sought to verify this report and have investigated whether the addition of formaldehyde to maternal blood samples does indeed significantly alter the proportion of fetal DNA in maternal plasma samples. We also examined whether such treatment would improve the yield of fetal RNA. The rationale for this additional analysis was provided by the recent observation that circulating fetal hematopoietic cells may contribute to the pool of mRNA molecules in plasma (17) and the view that formaldehyde treatment may inhibit the activity of any ribonucleases in the sample. We also examined whether the effect mediated by formaldehyde described by Dhallan et al. (16) was specific for the …