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.

Measurement of 20-Hydroxyeicosatetraenoic Acid in Human Urine by Gas Chromatography–Mass Spectrometry

“…Recently, Skoog et al (11 ) identified a C/A exchange at position Ϫ863 of the TNF-␣ gene promoter and found higher transcriptional activity of the C allele in reporter gene assays. This polymorphic site was found to be associated with thyroid-associated ophthalmopathy (12 ), Crohn disease (13 ), juvenile rheumatoid arthritis (14 ), and the lumbar spine area (15 ).…”

Noninvasive Prenatal Detection of Fetal Trisomy 18 by Epigenetic Allelic Ratio Analysis in Maternal Plasma: Theoretical and Empirical Considerations

“…In addition, quantitative aberrations of circulating fetal DNA have been reported in preeclampsia (10,11 ), preterm labor (12 ), and certain fetal chromosomal aneuploidies (13 ). Despite in-creased circulating fetal DNA concentrations in trisomy 21 pregnancies, there is a large overlap in fetal DNA concentrations between healthy and aneuploid pregnancies (13,14 ). Moreover, these applications are based on the detection of paternally inherited variations or Y chromosomal sequences and thus are useful for only a fraction of all pregnancies unless a large panel of polymorphic markers is used.…”

Accurate and Robust Quantification of Circulating Fetal and Total DNA in Maternal Plasma from 5 to 41 Weeks of Gestation

“…The ultimate goal in this field is to develop reliable noninvasive tests for clinical prenatal diagnosis. Current applications center on detection of common paternally inherited traits such as sex (3 ) or Rh status (4 ), but recent reports have described methods to screen for or diagnose diseases in the fetus (5)(6)(7)(8)(9)(10)(11)(12)(13)(14).…”