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December 15, 2004

Free Fetal DNA in Maternal Circulation

Author Affiliations

Letters Section Editor: Robert M. Golub, MD, Senior Editor.

JAMA. 2004;292(23):2835-2836. doi:10.1001/jama.292.23.2835-a

To the Editor: In reading the study by Dr Dhallan and colleagues1 regarding the percentage of fetal DNA recovered from the maternal circulation following formaldehyde treatment, we were concerned that a serial dilution method was used for estimating the fractional concentrations of fetal DNA in maternal plasma, since previous publications in this field have used real-time quantitative polymerase chain reaction (PCR) for this purpose.2,3 One would expect the serial dilution method to be less accurate and less precise than the real-time PCR method. For a given sample that is serially diluted, a test aliquot from the most diluted tube at the end of the series may be positive in one experiment and negative in another, with a frequency described by the Poisson distribution. This would result in a wider confidence interval for the measured fractional concentration of fetal DNA in maternal plasma than would real-time PCR, decreasing the precision of the measurement and increasing the likelihood of inflating the effect, if any, of the formaldehyde treatment.

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