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Hum. Reprod. Advance Access originally published online on April 7, 2007
Human Reproduction 2007 22(6):1736-1743; doi:10.1093/humrep/dem058
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Correlation of maternal plasma total cell-free DNA and fetal DNA levels with short term outcome of first-trimester vaginal bleeding

Aihua Yin1,2, E.H.Y. Ng3, Xiangzhong Zhang4, Yunshao He1,5, Jing Wu2 and K.Y. Leung3,6

1 Department of Anatomy, Zhongshan School of medicine, Sun Yat-sen University, Guangzhou, Guangdong 510089, People's Republic of China 2 Prenatal Diagnostic Center, Maternal and Children Hospital of Guangdong Province, Guangzhou 510010, Guangdong, People's Republic of China 3 Department of Obstetrics and Gynaecology, Queen Mary Hospital, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China 4 Department of Hematology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong, People's Republic of China 5 DaAn Gene Diagnostic Center, Zhongshan School of medicine, Sun Yat-sen University, Guangzhou 510089, Guangdong, People's Republic of China

6 Correspondence address. Department of Obstetrics and Gynaecology, Queen Mary Hospital, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. E-mail: leungky1{at}ha.org.hk

BACKGROUND: The current methods using sonographic parameters and/or maternal serum beta-HCG levels to predict spontaneous abortion are not satisfactory. The aim of this study was to determine whether maternal plasma fetal DNA and total DNA levels could be used to predict spontaneous abortion.

METHODS: We prospectively studied pregnant women who presented with vaginal bleeding in the first trimester of pregnancy, and those who had no vaginal bleeding (controls). DYS14 and the beta-globin gene were used to measure the maternal plasma levels of fetal and total DNA, respectively, by real-time PCR. RESULTS: A total of 1114 women were studied. Both maternal plasma fetal and total DNA concentrations increased with gestation from 6 to 11.6 weeks in the controls. The multiple of medians (MoMs) of fetal and total DNA concentration in those who miscarried were significantly greater (P < 0.001) than in the normal controls by about 5- and 4-fold respectively. Using a cut-off value of 1.6 MoMs for total DNA to predict spontaneous abortion, the sensitivity was 98.2% and false positive rate was 4.7%. However, using a cut-off value of 1.8 MoMs for fetal DNA, the corresponding figures were 97% and 44.3%, respectively.

CONCLUSIONS: Both maternal plasma fetal and total DNA concentrations increased throughout the first trimester. Significantly high levels of fetal and total DNA were found in those who miscarried.

Key words: fetal DNA/maternal plasma/spontaneous abortion/total DNA

Submitted on January 21, 2007; resubmitted on February 8, 2007; accepted on February 13, 2007.


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