Total cell‐free DNA (β‐globin gene) distribution in maternal plasma at the second trimester: a new prospective for preeclampsia screening

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Abstract
Objectives Levels of cell‐free foetal DNA (f‐DNA) in maternal plasma are higher in those asymptomatic subjects who will eventually develop preeclampsia. f‐DNA is, however, informative only for those women bearing a male foetus, by amplification of Y‐specific sequences and represents a small fraction of total circulating DNA that can be dosed by using ubiquitous genes as well as β‐globin. In this study, we examined the quantitative distribution of total DNA by amplification of β‐globin gene, in asymptomatic women matched with controls to evaluate its possible role in predicting preeclampsia. Methods Forty‐eight low‐risk women (8 asymptomatic cases matched for gestational age at the second trimester with 40 controls) were enrolled in the present study. β‐globin concentrations were converted into multiples of the median of the controls (MoM), in order to assess the possible different distribution of β‐globin MoM in cases and controls. Results MoM values were as follows: controls, 1.00 ± 0.59; asymptomatic cases, 1.99 ± 1.95. After Gaussian conversion of data, at a false‐positive rate (FPR) of 5%, the detection rate (DR) was 46%. Conclusion β‐globin (total DNA) levels are higher in those patients who subsequently developed preeclampsia and can potentially be used in screening for early detection of the disease. These findings represent a step forward in the study of cell‐free DNA in maternal blood as a screening variable, because it overcomes the gender limitations of foetal DNA screening. Copyright © 2004 John Wiley & Sons, Ltd.

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