Fetal sex determination from maternal plasma in pregnancies at risk for congenital adrenal hyperplasia.
OBJECTIVE
To determine first-trimester fetal sex by isolating free fetal DNA from maternal plasma.


METHODS
The index case was a pregnant woman who previously delivered a girl with congenital adrenal hyperplasia. The SRY gene as a marker for the fetal Y chromosome was detected in maternal serum and plasma by quantitative polymerase chain reaction analysis. Simultaneously, we performed the same test in 25 and 19 women in the first and second trimester, respectively, and compared plasma results with fetal gender as assessed by prenatal karyotyping or as seen at ultrasound or birth.


RESULTS
In 44 of 45 patients at gestational ages ranging from 8 3/7 to 17 3/7 weeks, we correctly predicted fetal sex using quantitative polymerase chain reaction analysis of the SRY gene in maternal plasma. In one case, the test result was inconclusive. Overall, fetal sex was correctly predicted in 97.8% of cases (95% confidence interval 88.2%, 99.9%).


CONCLUSIONS
Amplification of free fetal DNA in maternal plasma is a valid technique for predicting fetal sex in early pregnancy. In case of pregnancies at risk for congenital adrenal hyperplasia, the technique allows restriction of dexamethasone treatment to female fetuses resulting in a substantial decrease of unnecessary treatment and invasive diagnostic tests.
Rijnders
R J
RJ
Division of Obstetrics, Neonatology, and Gynecology, University Medical Center Utrecht, Utrecht, The Netherlands.
van der Schoot
C E
CE
Bossers
B
B
de Vroede
M A
MA
Christiaens
G C
GC
D000312:Adrenal Hyperplasia, Congenital; D000328:Adult; D020732:Cytogenetic Analysis; D004247:DNA / Q000032:analysis; D004268:DNA-Binding Proteins / Q000097:blood; D005260:Female; D006801:Humans; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction / Q000379:methods*; D011237:Predictive Value of Tests; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D012732:Sex Determination Analysis / Q000379:methods*; D019849:Sex Determination Processes; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors; D004247:DNA