OBJECTIVE: To determine the diagnostic accuracy of noninvasive fetal sex determination in maternal plasma.
METHODS: All consecutive patients for whom fetal sex determination in maternal plasma was performed in our laboratory from 2003 up to 2009 were included in the study. Real-time polymerase chain reaction was performed for the SRY gene and multicopy DYS14 marker sequence. A stringent diagnostic algorithm was applied. In the case of a positive result for both Y chromosome–specific assays, a male-bearing pregnancy was reported. In the case of a negative result, the presence of fetal DNA was ascertained through the use of 24 biallelic insertion/deletion polymorphisms or paternally inherited blood group antigens. Only if the presence of fetal DNA was confirmed was a female-bearing pregnancy reported. Results were compared with the pregnancy outcomes.
RESULTS: A total of 201 women were tested. The median gestational age was 9 0/7 weeks (interquartile range 8 0/7 to 10 0/7 weeks). In 189 of 201 cases (94%), a test result was issued; in 10 cases, the presence of fetal DNA could not be confirmed; in two cases, an early miscarriage was observed. Pregnancy outcome was obtained in 197 cases, including 105 male-bearing and 81 female-bearing pregnancies and 11 miscarriages. Sensitivity and specificity of the test were 100% (95% confidence intervals 96.6–100% and 95.6–100%, respectively). In all 10 cases in which the presence of fetal DNA could not be confirmed, a female was born.
CONCLUSION: Noninvasive fetal sex determination in maternal plasma is highly reliable and clinically applicable.
LEVEL OF EVIDENCE: III
Noninvasive fetal sex determination is highly accurate and applicable in a clinical diagnostic setting.
From the Division of Perinatology and Gynaecology, University Medical Center Utrecht, The Netherlands; The Department of Experimental Immunohaematology, Sanquin Research Amsterdam and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands; The Department of Immunohaematology Diagnostics, Sanquin Diagnostic Services, Amsterdam, The Netherlands; and The Department of Human Genetics, Radboud University Nijmegen Medical Center, The Netherlands.
The development and validation of the polymerase chain reaction protocols were performed within the European Commission for Special Noninvasive Advances in Fetal and Neonatal Evaluation (SAFE) Network of Excellence (LSHB-CT-2004–503243).
The authors thank Lutgarde Govaerts, clinical geneticist (Erasmus Medical Center, Rotterdam), Eva Pajkrt, gynecologist (Academic Medical Center, Amsterdam), Maaike Vreeburg, clinical geneticist (Maastricht University Medical Center, Maastricht), Jiddeke van de Kamp, clinical geneticist (VU University Medical Center, Amsterdam), Nicolette den Hollander, clinical geneticist, and Jennie Verdoes, research nurse (Leiden University Medical Center, Leiden), and Katelijne Bouman, clinical geneticist (University Medical Center Groningen, Groningen), for the clinical implementation of the protocol.
Presented in abstract form at the 6th International Conference of Circulation Nucleic Acids in Plasma and Serum (CNAPS-IV), November 9–11, 2009, Hong Kong.
Corresponding author: Peter G. Scheffer, MD, Sanquin Research Amsterdam, PO Box 9190, 1006 AD Amsterdam, The Netherlands; e-mail: firstname.lastname@example.org.
Financial Disclosure: The authors did not report any potential conflicts of interest.