Fetal sex determination using circulating cell-free fetal DNA (ccffDNA) at 11 to 13 weeks of gestation.
OBJECTIVE
To examine the performance of a mass spectrometry-based detection platform using three Y-chromosome sequences for fetal sex determination from circulating cell-free fetal DNA (ccffDNA) in maternal blood in the first trimester of pregnancy.


METHODS
We extracted ccffDNA for the determination of fetal sex from stored maternal plasma obtained at 11 to 13 weeks' gestation from singleton pregnancies with documented fetal gender. Mass spectrometry was used to examine 236 specimens for the presence of three Y-chromosome sequences (SRY, DBY and TTTY2). The sample was classified as male, female or inconclusive depending on the detection of three, one/none and two sequences, respectively.


RESULTS
Three (1.3%) of the 236 cases were classified as invalid due to the absence of a well-defined spectral peak for TGIF and 22 (9.3%) were reported as inconclusive. In the 211 cases with a valid result, the fetal sex was correctly identified in 90 of 91 male babies and 119 of 120 female babies giving an accuracy of 99.1% and sensitivity and specificity for prediction of male fetuses of 98.9 and 99.2%, respectively.


CONCLUSIONS
Fetal sex determination can be accurately determined from maternal ccffDNA in the first trimester of pregnancy using mass spectrometry analysis.
Akolekar
Ranjit
R
Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
Farkas
Daniel H
DH
VanAgtmael
Anna L
AL
Bombard
Allan T
AT
Nicolaides
Kypros H
KH
D000328:Adult; D041322:Chromosomes, Human, Y; D053487:DEAD-box RNA Helicases / Q000032:analysis / Q000235:genetics; D004247:DNA / Q000097:blood* / Q000737:chemistry; D005260:Female; D005865:Gestational Age; D006801:Humans; D008297:Male; D008431:Maternal-Fetal Exchange; D015778:Minor Histocompatibility Antigens; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood*; D011506:Proteins / Q000032:analysis / Q000235:genetics; D015203:Reproducibility of Results; D029589:Seminal Plasma Proteins; D012732:Sex Determination Analysis / Q000379:methods*; D051876:Sex-Determining Region Y Protein / Q000032:analysis / Q000235:genetics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D015778:Minor Histocompatibility Antigens; D011506:Proteins; C497745:SRY protein, human; D029589:Seminal Plasma Proteins; D051876:Sex-Determining Region Y Protein; C497750:TTTY2 protein, human; D004247:DNA; C492034:DDX3Y protein, human; D053487:DEAD-box RNA Helicases