Non-invasive prenatal determination of fetal gender using QF-PCR analysis of cell-free fetal DNA in maternal plasma

BackgroundDetection of cell-free fetal DNA (cffDNA) in maternal plasma has given rise to the possibility of new non-invasive approaches for early prenatal diagnoses. We evaluated the feasibility and accuracy of non-invasive fetal gender determination using quantitative fluorescent-polymerase chain reaction (QF-PCR) analysis of circulating cffDNA in the first-trimester maternal plasma.MethodsPlasma samples were prospectively collected from 202 singleton pregnancies at 4 to 13 weeks of gestation. Fetal gender was determined by QF-PCR with the sex-determining region Y (SRY) and amelogenin X/Y (AMELX/Y) genes. The result was confirmed by fetal karyotyping or phenotype at birth.ResultsOf the 202 pregnancies, 162 had pregnancy outcomes available and could be included in our evaluation. The accuracies of AMELX/Y, SRY, and combined AMELX/Y + SRY analysis for fetal gender determination were 83.3%, 82.1%, and 97.5%, respectively, compared with those of the invasive approach and the fetal gender outcome at birth (82 males and 80 females). Combined AMELX/Y + SRY analysis had the highest sensitivity (98.8%) for fetal gender determination with a specificity of 96.3%. Moreover, fetal gender detection by the combined AMELX/Y + SRY analysis at 11 to 13 weeks of gestation was 100% correct.ConclusionFetal gender determination could be accurately determined from maternal cffDNA in the first-trimester using QF-PCR analysis of combined AMELX/Y + SRY.

► Early detection of fetal sex is required for fetuses at risk of X-linked diseases. ► We determined fetal sex in the first-trimester using cffDNA in maternal plasma. ► QF-PCR analysis of combined AMELX/Y + SRY can accurately detect fetal sex. ► It could reduce invasive procedure in pregnancies carrying X-linked diseases or CAH.