Free fetal DNA in maternal circulation: a potential prognostic marker for chromosomal abnormalities?
OBJECTIVE
Previous studies on the association of fetal cell-free (cf)DNA levels in maternal circulation have produced conflicting results but the sample sizes were small and based on archived material. We aimed to quantify the levels of fetal and total cfDNA on prospectively collected samples, to understand their correlation with other variables and to clarify their diagnostic value.


METHODS
DNA from pre-CVS maternal plasma was extracted from 264 controls, 72 trisomy 21, 24 trisomy 18, 12 trisomy 13, 16 Turner's syndrome and 8 triploidy first-trimester pregnancies and quantified using real-time PCR. beta-globin was used to determine total cfDNA levels and DYS14 and SRY assays to determine fetal cfDNA levels.


RESULTS
Fetal cfDNA levels (DYS14) showed correlation with crown rump length (CRL) (p = 0.004), BMI (p = 0.01) and storage time (p = 0.007) while there was an inverse correlation of total cfDNA levels with nuchal translucency (NT) (p = 0.001). No significant difference was observed between the levels of fetal cfDNA in controls and aneuploidy cases.


CONCLUSIONS
Quantification of fetal and total cfDNA in maternal circulation showed inverse correlation between NT and total cfDNA levels. Our results also suggest that fetal cfDNA is not an ideal prognostic marker for chromosomal abnormalities in first-trimester pregnancies.
Gerovassili
Ageliki
A
Division of Gene and Cell Based Therapy, King's College London School of Medicine, London, UK. ageliki.gerovassili@kcl.ac.uk
Garner
Chad
C
Nicolaides
Kypros H
KH
Thein
Swee Lay
SL
Rees
David C
DC
D015415:Biomarkers / Q000097:blood; D025063:Chromosome Disorders / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D004247:DNA / Q000097:blood*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005315:Fetal Diseases / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D005333:Fetus / Q000737:chemistry*; D006801:Humans; D008297:Male; D008431:Maternal-Fetal Exchange; D016133:Polymerase Chain Reaction / Q000379:methods; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood; D011296:Prenatal Diagnosis / Q000379:methods; D011379:Prognosis; D011446:Prospective Studies; D051876:Sex-Determining Region Y Protein / Q000097:blood / Q000235:genetics
D015415:Biomarkers; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; D004247:DNA