Automated processing of serum indices used for interference detection by the laboratory information system.

serum (compared with plasma) was attributable to the release of DNA by hematopoietic cells during the clotting process (11 ). This concentration decreased by 74-fold in formaldehyde-treated serum, highlighting its cell-stabilizing effect. We observed no differences in fetal DNA concentrations in the samples treated or not treated with EDTA and formaldehyde. These results support the notion that use of formaldehyde to inhibit enzymes that destroy DNA, such as deoxyribonucleases, can be eliminated. Moreover, Lo et al. (12 ) previously demonstrated the limited effect of such in vitro DNA degradation. In their study, Dhallan et al. (9 ) had no control group and compared their values with those of Lo et al. (12 ), obtained not only with a different methodology but also at different gestational ages, despite the fact that the absolute amount of fetal DNA increases with gestational age. It is most likely that formaldehyde does not affect DNA stability. Another possible factor is the use of gentle centrifugation. Chiu et al. (10 ) have shown that centrifugation alone is not enough to obtain maternal cell-free plasma and that the number of cells left in plasma after centrifugation is variable. Therefore, in the study of Dhallan et al. (9 ), the role of centrifugation is certainly low when compared with the role of formaldehyde. In our study, although we used similar shipping, handling, and processing conditions, we measured a higher absolute concentration of free fetal DNA (169 vs 66.1 kgeq/L), even taking into account the mean gestational age at sampling. Dhallan et al. (9 ) also addressed the need for a very short time delay between the venipuncture procedure and the addition of formaldehyde. To circumvent this problem, we added the formaldehyde to the sampling tube before venipuncture. As a result, the formaldehyde enrichment effect was shown for all patients in our study, whereas Dhallan et al. (9 ) reported a lack of effect in three cases. We observed, however, a high variability for this enrichment (2to 27-fold for plasma and 21to 138-fold for serum). This variability seems to be unrelated to gestational age (P 0.05) and to the amount of fetal DNA (P 0.05). We speculate that it reflects a variable effect of the formaldehyde or the natural fluctuation in the amount of cell-free maternal DNA present before processing. We conclude that formaldehyde increases the percentage of free fetal DNA in maternal plasma or serum by inhibiting maternal cell lysis. This new simple procedure facilitates study of fetal genetic markers such as single nucleotide mutations, but some issues still need to be addressed, especially the reason for the variability in results. Other strategies are actually under evaluation to achieve this final goal (13, 14) before use of this technique for noninvasive prenatal diagnosis.