M. Kim

Novel Epigenetic Markers on Chromosome 21 for Noninvasive Prenatal Testing of Fetal Trisomy 21

Until now, fetal placenta-specific epigenetic markers for noninvasive prenatal testing of fetal trisomy 21 (T21) have been identified based only on differences in tissue-specific epigenetic characteristics between placenta and maternal blood, but these characteristics have not been validated in T21 placenta. We aimed to discover novel epigenetic markers on chromosome 21 that show a hypermethylated pattern in fetal placenta compared with blood, regardless of the presence of T21. We performed a high-resolution tiling array analysis of chromosome 21 using the methylated-CpG binding domain protein-based method. We identified 93 epigenetic regions that showed fetal placenta-specific differential methylation patterns; among these, three regions showed fetal placenta-specific methylation patterns in T21 placenta samples. The methylation patterns of these three regions in the array were confirmed by bisulfite direct sequencing. The three regions were detectable in first-trimester maternal plasma. Moreover, a combination of their methylation ratio achieved high diagnostic accuracy for noninvasive prenatal testing of fetal T21 by further statistical analysis. These three novel regions with fetal placenta-specific differential methylation patterns on chromosome 21 were identified irrespective of the presence of T21. Our findings suggest that epigenetic characteristics of markers according to the presence or absence of T21 should be considered in the development of noninvasive prenatal testing of fetal T21 using fetal placenta-specific epigenetic markers.

Observed frequency of fetal trisomy between 16 and 24 gestational weeks in pregnant women older than 34 years at delivery

period. It is well known that fetal chromosomal trisomies increase with advanced maternal age [1]. In the 1980s, the risk of mid-trimester trisomy 21 in a 35-years-old woman at delivery was reported to be 1:270. This risk rapidly rises with increasing maternal age over 35 years. The maternal-age-related risk of Observed frequency of fetal trisomy between 16 and 24 gestational weeks in pregnant women older than 34 years at delivery

EP10.18: Whole-exome sequencing for pathogenic gene discovery in prenatally diagnosed dextrotransposition of the great arteries: Electronic Poster Abstracts

Y. Han2, M. Lee1, M. Kim2, D. Lee3, H. Won4, H. Ryu2 1Maternal-Fetal Medicine, Asan Medical Centre, Seoul, Republic of Korea; 2Obstetrics and Gynecology, Cheil General Hospital and Women’s Healthcare Centre, Dankook University College of Medicine, Seoul, Republic of Korea; 3Laboratory of Medicine Genetics, Medical Research Institute, Cheil General Hospital and Women’s Healthcare Centre, Dankook University College of Medicine, Seoul, Republic of Korea; 4Obstetrics and Gynecology, Asan Medical Centre, Seoul, Republic of Korea

OC10.08: *The risk of preterm birth in vanishing twin: a multicentre prospective cohort study

S. Jisu1, S. Lee1, Y. Han2, M. Kim2, J. Shim3, M. Lee3, S. Oh4, J. Lee5, S. Kim6, D. Cha6, G. Cho7, H. Kwon8, B. Kim9, M. Park10, H. Cho11, H. Ko12, C. Park1, J. Park1, J. Jun1, H. Ryu2, S. Lee1 1Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea; 2Obstetrics and Gynecology, Cheil General Hospital and Women’s Healthcare Centre, Dankook University College of Medicine, Seoul, Republic of Korea; 3Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Centre, Seoul, Republic of Korea; 4Obstetrics and Gynecology, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 5Obstetrics and Gynecology, Institute of Women’s Life Medical Science, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Republic of Korea; 6Obstetrics and Gynecology, CHA Gangnam Medical Centre, CHA University, Seoul, Republic of Korea; 7Obstetrics and Gynecology, Korea University College of Medicine, Seoul, Republic of Korea; 8Obstetrics and Gynecology, Konkuk University School of Medicine, Seoul, Republic of Korea; 9Obstetrics and Gynecology, Seoul Metropolitan Government Seoul National University Boramae Medical Centre, Seoul, Republic of Korea; 10Obstetrics and Gynecology, Ewha Woman’s University, Seoul, Republic of Korea; 11Obstetrics and Gynecology, CHA Bundang Medical Centre, CHA University, Sung Nam, Republic of Korea; 12Obstetrics and Gynecology, Catholic University of Korea College of Medicine, Seoul, Republic of Korea

Change in rates of prenatal tests for chromosomal abnormality over a 12-year period in women of advanced maternal age

Objective In 2007, the American College of Obstetricians and Gynecologists (ACOG) recommended that all pregnant women be offered screening or diagnostic tests for chromosomal abnormalities regardless of their age. Noninvasive prenatal testing (NIPT) for common chromosomal aneuploidies was introduced as a screening test in case of high-risk pregnancies. We assessed the rates of prenatal tests in women aged 35 years and older. Methods A retrospective study was conducted to compare the rates of amniocentesis, chorionic villus sampling (CVS), serum screening, and NIPT from January 2005 through March 2017 in women aged 35 years and older. We divided the initial 12 months after NIPT introduction into 4-month intervals, beginning in April 2016 through March 2017. Results The rates of amniocentesis were 56% before the ACOG statement, 38% between the ACOG statement and NIPT introduction, and 10% after NIPT introduction (P=0.001). The rates of CVS during the same periods were 0.5%, 2.1%, and 4.3% (P=0.016), respectively. The rates of serum screening were 44.2%, 61.3%, and 55.1% (P=0.049), respectively. During the 3 quarters after NIPT introduction, the rates of amniocentesis were 16.2%, 12.3%, and 7.3% (P=0.002), respectively; the rates of serum screening were 62%, 54%, and 46% (P=0.03), respectively; and the rates of NIPT were 19.9%, 30.3%, and 39.5% (P=0.007), respectively. The rates of CVS over the same periods were not significantly different. Conclusion The ACOG statement and NIPT introduction significantly decreased the rate of amniocentesis in women of advanced maternal age. NIPT also reduced the rate of serum screening.

First trimester screening for trisomy 18 by a combination of nuchal translucency thickness and epigenetic marker level

with severe disability and compromised survival, with at most 10% of the patients surviving to one year of age. Conventional screening for trisomy 18 has a detection rate of 92% with a false positive rate (FPR) of 2.1% [2]. However, a delay in screening until the second trimester means that decisions about invasive testing or therapeutic abortion of pregnancy must be deferred accordingly. First trimester screening for trisomy 18 by a combination of nuchal translucency thickness and epigenetic marker level