title: Cell-free fetal DNA (SRY locus) concentration in maternal plasma is directly correlated to the time elapsed from the onset of preeclampsia to the collection of blood.
abstract: OBJECTIVE
  To determine (1) if fetal DNA (fDNA) in the maternal circulation in women affected by preeclampsia correlates with the time elapsed from the onset of symptoms to the time of blood collection, and (2) if the inclusion of this variable improves the discrimination between affected and unaffected patients by using fDNA distributions.
  
  
  METHODS
  Plasma were collected from 34 women at 33.7 +/- 3.9 weeks' gestation, affected by preeclampsia, and bearing a single male fetus. fDNA was extracted from 1.5-mL plasma samples, and the SRY and beta-globin gene were analyzed by real-time quantitative PCR. MoMs (multiple of the control median) were calculated by using a log equation of 102 normal cases. Log MoMs were then plotted against the time elapsed from onset of symptoms to blood collection (expressed in days) by means of a log-linear regression. Adjusted MoMs were then calculated. ROC curves were used to test the discrimination obtained by using adjusted MoMs.
  
  
  RESULTS
  The median MoMs of controls and preeclamptic patients were 1.00 +/- 1.53 and 2.62 +/- 2.70 respectively. By plotting log MoM fDNA against the time elapsed from onset of symptoms to blood collection, we found a significant positive correlation, (p-value < 0.001, R2 = 0.55, F = 38.97, from 1 to 50 days). The adjusted median fDNA MoM was 2.66 +/- 2.50. Areas under the curves, as estimated by ROC curves, were 76.7 for unadjusted and 85.5 for adjusted MoMs respectively (p-value = 0.02).
  
  
  CONCLUSIONS
  The effect of a further covariate showed that (1) fDNA passage from trophoblasts to maternal circulation for unit of time is proportional to the duration of the damage and that (2) increased discrimination can be obtained in comparison to normal subjects.
authors.affiliation: Institute of Medical Embryology, University of Bologna, Bologna, Italy. antonio.farina@unibo.it
authors.forename: Antonio
authors.initials: A
authors.lastname: Farina
authors.forename: Akihiko
authors.initials: A
authors.lastname: Sekizawa
authors.forename: Nicola
authors.initials: N
authors.lastname: Rizzo
authors.forename: Manuela
authors.initials: M
authors.lastname: Concu
authors.forename: Irina
authors.initials: I
authors.lastname: Banzola
authors.forename: Paolo
authors.initials: P
authors.lastname: Carinci
authors.forename: Giuliana
authors.initials: G
authors.lastname: Simonazzi
authors.forename: Takashi
authors.initials: T
authors.lastname: Okai
mesh_terms: D019540:Area Under Curve; D001800:Blood Specimen Collection; D004247:DNA / Q000097:blood*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005333:Fetus / Q000737:chemistry*; D005865:Gestational Age; D006801:Humans; D009687:Nuclear Proteins; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051876:Sex-Determining Region Y Protein; D013997:Time Factors; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors; D004247:DNA