Fetal sex determination from maternal plasma in pregnancies at risk for congenital adrenal hyperplasia

• Published in: Obstetrics and gynecology (New York. 1953) Vol. 98; no. 3; pp. 374 - 378
• Main Authors: Rijnders, Robbert J.P, van der Schoot, C.Ellen, Bossers, Bernadette, de Vroede, Monique A.M.J, Christiaens, Godelieve C.M.L
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.09.2001; by The American College of Obstetricians and Gynecologists; Elsevier Science
• Subjects: Adrenal Hyperplasia, Congenital; Adult; Biological and medical sciences; Cytogenetic Analysis; DNA - analysis; DNA-Binding Proteins - blood; Female; Gynecology. Andrology. Obstetrics; Humans; Management. Prenatal diagnosis; Medical sciences; Nuclear Proteins; Polymerase Chain Reaction - methods; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, First; Pregnancy. Fetus. Placenta; Sex Determination Analysis - methods; Sex Determination Processes; Sex-Determining Region Y Protein; Transcription Factors; Endocrinopathy; Human; Adrenal cortex diseases; Male; First trimester; Hyperadrenocorticism; Y-Chromosome; Enzymopathy; Blood plasma; Pregnancy; Congenital adrenal hyperplasia syndrome; Prenatal; Polymerase chain reaction; Sensitivity; Mother; Sex determination; DNA; Adrenal gland diseases; Cytogenetics; Female; Fetus; Diagnosis; Molecular biology; Karyotype
• ISSN: 0029-7844; 1873-233X
• DOI: 10.1016/S0029-7844(01)01480-6

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%). CONCLUSION: 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.