title: Evaluation of cell-free fetal DNA as a second-trimester maternal serum marker of Down syndrome pregnancy.
abstract: BACKGROUND
  Second-trimester cell-free fetal DNA (studied only in pregnancies with male fetuses) is higher in maternal serum samples from women carrying Down syndrome fetuses than in unaffected pregnancies. In this study we evaluated the potential performance of fetal DNA as a screening marker for Down syndrome.
  
  
  METHODS
  Data on maternal serum fetal DNA concentrations and the corresponding concentrations of the quadruple serum markers were available from 15 Down syndrome cases, each matched for gestational age and length of freezer storage, with 5 control samples. Analyte values were expressed as multiple(s) of the control or population median. Screening performance of fetal DNA, both alone and when added to estimates of quadruple marker performance, was determined after modeling using univariate and multivariate gaussian distribution analysis.
  
  
  RESULTS
  The median fetal DNA concentration in Down syndrome cases was 1.7 times higher than in controls. In univariate analysis, fetal DNA gave a 21% detection rate at a 5% false-positive rate. When added to quadruple marker screening, fetal DNA increased the estimated detection rate from 81% to 86% at a 5% false-positive rate.
  
  
  CONCLUSIONS
  Cell-free fetal DNA, measured in maternal serum, can modestly increase screening performance above what is currently available in the second trimester. If and when maternal serum fetal DNA can be measured in pregnancies with both male and female fetuses, the utility and cost-effectiveness of adding it as a Down syndrome screening marker should be assessed.
authors.affiliation: Department of Obstetrics and Gynecology, University of Bologna, Bologna, Italy 40138.
authors.forename: Antonio
authors.initials: A
authors.lastname: Farina
authors.forename: Erik S
authors.initials: ES
authors.lastname: LeShane
authors.forename: Geralyn M
authors.initials: GM
authors.lastname: Lambert-Messerlian
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Canick
authors.forename: Thomas
authors.initials: T
authors.lastname: Lee
authors.forename: Louis M
authors.initials: LM
authors.lastname: Neveux
authors.forename: Glenn E
authors.initials: GE
authors.lastname: Palomaki
authors.forename: Diana W
authors.initials: DW
authors.lastname: Bianchi
mesh_terms: D015415:Biomarkers / Q000032:analysis; D004247:DNA / Q000097:blood*; D004314:Down Syndrome / Q000097:blood / Q000175:diagnosis*; D005260:Female; D005333:Fetus; D006801:Humans; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis / Q000379:methods*
chemical_list: D015415:Biomarkers; D004247:DNA