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.

Conclusion: Fetal sex determination can be accurately determined from maternal ccffDNA in the first trimester of pregnancy using mass spectrometry analysis.