Maternal Age-Specific Rates of Fetal Chromosomal Abnormalities in Korean Pregnant Women of Advanced Maternal
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Original Article Obstet Gynecol Sci 2013;56(3):160-166 http://dx.doi.org/10.5468/ogs.2013.56.3.160 pISSN 2287-8572 · eISSN 2287-8580 Maternal age-specific rates of fetal chromosomal abnormalities in Korean pregnant women of advanced maternal age Young Joo Kim, Jee Eun Lee, Soo Hyun Kim, Sung Shin Shim, Dong Hyun Cha Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University, Seoul, Korea Objective To evaluate the association of maternal age with occurrence of fetal chromosomal abnormalities in Korean pregnant women of advanced maternal age (AMA). Methods A retrospective review of the amniocentesis or chorionic villous sampling (CVS) database at Gangnam and Bundang CHA Medical Centers, between January 2001 and February 2012, was conducted. This study analyzed the incidence of fetal chromosomal abnormalities according to maternal age and the correlation between maternal age and fetal chromosomal abnormalities in Korean pregnant women ≥35 years of age. In addition, we compared the prevalence of fetal chromosomal abnormalities between women of AMA only and the others as the indication for amniocentesis or CVS. Results A total of 15,381 pregnant women were selected for this study. The incidence of aneuploidies increased exponentially with maternal age (P<0.0001). In particular, the risk of trisomy 21 (standard error [SE], 0.0378; odds ratio, 1.177; P<0.001) and trisomy 18 (SE, 0.0583; odds ratio, 1.182; P=0.0040) showed significant correlation with maternal age. Comparison between women of AMA only and the others as the indication for amniocentesis or CVS showed a significantly lower rate of fetal chromosomal abnormalities only in the AMA group, compared with the others (P<0.0001). Conclusion This study demonstrates that AMA is no longer used as a threshold for determination of who is offered prenatal diagnosis, but is a common risk factor for fetal chromosomal abnormalities. Keywords: Fetal chromosome aberrations; Maternal age; Prenatal diagnosis Introduction Received: 2012.12.16. Revised: 2013.2.8. Accepted: 2013.2.18. Pregnancy in advanced age is defined as childbirth at the age Corresponding author: Sung Shin Shim Department of Obstetrics and Gynecology, CHA Gangnam of 35 years or order regardless of whether the childbirth is Medical Center, CHA University, 566 Nonhyeon-ro, Gangnam-gu, the first or not. Recently, the percentages of pregnancies in Seoul 135-913, Korea advanced age have shown a gradual increase as women have Tel: +82-2-3468-3000 Fax: +82-2-558-1119 E-mail: [email protected] entered the workforce in increasing numbers. In South Korea, the percentages of pregnancies in women of advanced age Articles published in Obstet Gynecol Sci are open-access, distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons. have more than doubled, increasing from 6.2% in 1999 to org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, 15.4% in 2009 [1]. and reproduction in any medium, provided the original work is properly cited. Fetal chromosomal abnormalities may be caused by a non- Copyright © 2013 Korean Society of Obstetrics and Gynecology 160 www.ogscience.org Young Joo Kim, et al. The effect of advanced maternal age on fetal chromosomal abnormalities disjunction phenomenon that occurs in the period of meiosis cording to autosomal and sex chromosomal abnormalities. In during maternal oogenesis, which has been reported to have regard to structural chromosomal abnormalities, normal varia- a direct association with maternal age. Therefore, pregnancy tions such as heterochromatin, satellite chromosomes and in advanced age is a critical risk factor for fetal chromosomal pericentric inversion of chromosome 9 were excluded from abnormalities [2-4]. the abnormal category. Currently, fetal chromosomal abnormalities due to maternal For analysis of maternal age-specific rates of fetal chro- age have been reported to include trisomy 21, trisomy 18, mosomal abnormalities in pregnant women of advanced trisomy 13, triple X syndrome, and Klinefelter’s syndrome [5]. maternal age (AMA), maternal age beyond 35 years was As the percentages of pregnancies in women of advanced segmented with a one-year interval. In addition to, among age have increased, there has been increasing demand for women ≥35 years of age, when only AMA was considered as prenatal genetic counseling that helps to predict the risk of indication of amniocentesis or CVS was performed, analysis fetal chromosomal abnormalities depending on age. Most was also performed to determine whether there was any dif- of the data were obtained from studies of women in North ference in incidence rate of fetal chromosomal abnormalities America or Europe. However, rare data from study of fetal compared to cases where other indications were considered. chromosomal abnormalities depending on age targeting Ko- Logistic regression analysis was performed in order to inves- rean women have been reported [6]. tigate correlation between increase in maternal age and fetal Against this background, the intention of this study was to chromosomal abnormalities. In addition, SPSS ver. 16.0 (SPSS examine the incidence rate of fetal chromosomal abnormali- Inc., Chicago, IL, USA) was used for statistical analysis of the ties depending on maternal age and to investigate correlation study results. Significance probability of less than 0.05 was between fetal chromosomal abnormalities and maternal age, considered to show statistical significance. which targeted Korean pregnant women who underwent am- niocentesis or chorionic villous sampling (CVS). In addition, this study examined if there was any meaningful difference in the Results incidence rate of fetal chromosomal abnormalities between cases where only advanced age of pregnant women was con- Among pregnant women who underwent amniocentesis or sidered as an indication for amniocentesis or CVS and cases CVS during the study period 15,381 persons were selected for where other indications were considered for such examinations. inclusion in this study. Age of the cases ranged from 19 years to 52 years. Average age was 34.0 years (±4.3); age distribu- tion of the entire group of study subjects is shown in Fig. 1. Materials and methods According to the results of fetal chromosomal examination, 14,818 cases (96.34%) were found to have normal fetus This study targeted 15,454 pregnant women who underwent chromosomes while 563 cases (3.66%) were found to have amniocentesis or CVS in Gangnam and Bundang CHA Medi- abnormal fetus chromosomes. Among the abnormal cases cal Centers during the period from January 2001 to February (3.66%), 357 cases (2.32%) had numeric chromosomal ab- 2012 and was approved by Institutional Review Board in CHA normalities, while 206 cases (1.34%) had structural chromo- Medical Center. This study was conducted as a retrospective somal abnormalities. With respect to numeric chromosomal study based on genetic information and inpatient and out- abnormalities, trisomy 21 was found in 181 cases (1.18%), patient charts. However, 71 persons whose age could not be which was the highest frequency. Then, trisomy 18 was found determined and 2 persons whose indication for amniocentesis in 72 cases (0.47%), Turner’s syndrome in 41 cases (0.27%), or CVS could not be confirmed were excluded from this study. Klinefelter’s syndrome in 28 cases (0.18%), trisomy 13 and As a result, the cases of 15,381 pregnant women were in- triple X syndrome in 14 cases for each (0.09%), and XYY syn- cluded. Age of the cases was the age at the time of delivery. drome in 7 cases (0.05%), in this order. Fetal chromosomal abnormalities were classified according Tables 1, 2 show the analyses of the incidence rate of nu- to numeric and structural chromosomal abnormalities. The meric and structural chromosomal abnormalities when age numeric chromosomal abnormalities were divided again ac- was increased by a one-year interval among women older www.ogscience.org 161 Vol. 56, No. 3, 2013 1,400 1,311 1,800 1,587 1,600 1,532 1,200 1,048 1004 1,026 1,400 1,000 942 1,248 1,200 767 1,035 800 1,000 631 772 600 800 Number Number 466 584 600 400 268 400 329 207 200 150 237 200 134 51 27 10 7 8 0 0 <25 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 Maternal age (yr) Maternal age (yr) Fig. 1. Age distribution in the study group. Table 1. Incidences of numeric chromosomal abnormalities found in amniocentesis or chorionic villus sampling Maternal No. of Numeric chromosomal abnormalities a) age (yr) fetuses All 47,+21 47,+18 47,+13 45,X 47,XXX 47,XXY 47,XYY 35 1,587 31 (19.53) 18 (11.34) 3 (1.89) 0 (0) 2 (1.26) 3 (1.89) 3 (1.89) 2 (1.26) 36 1,532 21 (13.71) 9 (5.87) 6 (3.92) 1 (0.65) 2 (1.31) 1 (0.65) 2 (1.31) 0 (0) 37 1,248 24 (19.23) 8 (6.41) 10 (8.01) 0 (0) 3 (2.4) 0 (0) 3 (2.4) 0 (0) 38 1,035 31 (29.95) 14 (13.53) 5 (4.83) 1 (0.97) 6 (5.8) 3 (2.9) 2 (1.93) 0 (0) 39 772 21 (27.2) 14 (18.13) 1 (1.3) 1 (1.3) 1 (1.3) 2 (2.59) 2 (2.59) 0 (0) 40 584 13 (22.26) 9 (15.41) 3 (5.14) 0 (0) 0 (0) 0 (0) 1 (1.71) 0 (0) 41 329 15 (45.59) 7 (21.28) 2 (6.08) 1 (3.04) 3 (9.12) 1 (3.04) 1 (3.04) 0 (0) 42 237 12 (50.63) 6 (25.32) 4 (16.88) 1 (4.22) 0 (0) 0 (0) 1 (4.22) 0 (0) 43 134 7 (52.24) 5 (37.31) 2 (14.93) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 44 51 5 (98.04) 3 (58.82) 1 (19.61) 0 (0) 0 (0) 0 (0) 1 (19.61) 0 (0) 45 27 2 (74.07) 1 (37.04) 1 (37.04) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 46 10 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 47 15 1 (66.67) 0 (0) 0 (0) 0 (0) 0 (0) 1 (66.67) 0 (0) 0 (0) Total 7,561 183 (24.2) 94 (12.43) 38 (5.03) 5 (0.66) 17 (2.25) 11 (1.45) 16 (2.12) 2 (0.26) Values are presented as number (incidences per 1,000).