Analysis of different risk values of Down syndrome or 18 trisomy syndrome in the first trimester screening and fetal chromosomal abnormalities and pregnancy outcomes of pregnant women

doi:10.3877/cma.j.issn.1673-5250.2019.06.007

Objective

To explore high risk, intermediate risk and low risk values of Down syndrome (DS) or 18 trisomy syndrome in first trimester screening in pregnant women and their fetal chromosomal abnormalities and pregnancy outcomes.

Methods

From January to December 2017, a total of 14 598 singleton pregnant women who received first trimester screening in Shenzhen Maternity & Child Healthcare Hospital Affiliated to Southern Medical University and with pregnancy outcomes were selected as research subjects. Their pregnancy outcomes were followed-up by searching information from Prenatal Diagnosis Center of our hospital or Shenzhen Maternal and Child Health Information Management System or telephoning the research subjects. Follow-up of pregnancy outcomes for live births was conducted from 1-12 months after birth or the occurrence of spontaneous abortion/stillbirth or termination of pregnancy. Among them, 6 825 cases received first trimester serological screening only, and 7 773 cases received first trimester serological screening combined with fetal ultrasound nuchal translucency (NT) detection. And 1 082 cases were with high risk of fetal DS or 18 trisomy syndrome in first trimester screening, 1 903 cases were with intermediate risk, and 11 613 cases were with low risk. There were 2 223 cases of pregnant women with advanced age (≥35-year old at parturition), accounting for 15.23% (2 223/14 598). Retrospective research method was used to collect first trimester screening results, fetal chromosomal abnormalities and pregnancy outcomes of all pregnant women. Chi-square test was used to compare screening positive rate (SPR) of fetal DS and 18 trisomy syndrome in pregnant women of different ages (<35-year old and ≥35-year old at parturition), rate of fetal chromosomal abnormalities and incidence of adverse pregnancy outcomes in pregnant women with high risk, intermediate risk and low risk of fetal DS or 18 trisomy syndrome in first trimester screening. The procedures in this study were in line with the requirements of World Medical Association Declaration of Helsinki revised in 2013.

Results

①The SPR of fetal DS and 18 trisomy syndrome of first trimester pregnant women with advanced maternal age were 22.22% (494/2 223) and 1.30% (29/2 223), respectively, which were statistically higher than those 4.00% (495/12 375) and 0.52% (649/12 375) of pregnant women <35-year old, and both the differences were statistically significant (χ²=990.737, 18.456; P<0.001). ②There were 51 cases of fetal chromosomal abnormalities among 14 598 cases of pregnant women, 49 cases were prenatally diagnosed and 2 cases were postnatally diagnosed by neonate peripheral blood karyotype analysis, and the rate of fetal chromosomal abnormalities was 0.35% (51/14 598). Among the 51 cases of fetal chromosomal abnormalities, 26 cases were DS, and 22 case of them were high-risk of DS in first trimester screening, and 4 cases were intermediate and low risk of DS in first trimester screening, the DS detection rate was 84.62% (22/26), the rate of fetal DS was 0.18% (26/14 598); and 3 cases were 18 trisomy syndrome, all of them were high risk of 18 trisomy syndrome in first trimester screening, the detection rate of 18 trisomy syndrome was 100.00% (3/3); and 15 cases were sex chromosome abnormalities, the rate of sex chromosome abnormalities was 0.10% (15/14 598); 2 cases were 13 trisomy syndrome and 5 cases were structural chromosome abnormalities. ③Among pregnant women with high risk, intermediate risk, and low risk of fetal DS or 18 trisomy syndrome in first trimester screening, 31 cases, 7 cases and 13 cases of fetuses respectively were diagnosed as fetal chromosomal abnormalities, and rate of fetal chromosomal abnormalities of them were 2.87% (31/1 082), 0.37% (7/1 903), and 0.11% (13/11 613), respectively. Among pregnant women with intermediate risk and low risk of fetal DS or 18 trisomy syndrome in first trimester screening, 20 cases were diagnosed as fetal chromosomal abnormalities, 19 cases were prenatally diagnosed, including 17 cases with abnormal results in noninvasive prenatal test (NIPT), 1 cases of advanced age and 1 case of NT thickening; and 1 case was postnatally diagnosed. ④Excluding 51 cases of pregnant women with fetal chromosomal abnormalities, among another 14 547 cases of pregnant women with different risks of first trimester screening, the incidences of adverse pregnancy outcomes including termination of pregnancy due to fetal ultrasound abnormality, spontaneous abortion/stillbirth, premature delivery and birth defects of pregnant women with high risk, intermediate risk and low risk of first trimester screening were 9.32% (98/1 051), 5.17% (98/1 896) and 4.19% (486/11 600), respectively, and the difference was statistically significant (χ²=57.989, P<0.001).

Conclusions

The detection rates of fetal DS and 18 trisomy syndrome are high in first trimester screening, but not all fetal chromosomal abnormalities can be detected out. In pregnant women with intermediate risk and low risk of fetal DS or 18 trisomy syndrome in first trimester screening, fetal chromosomal abnormalities still may be found among them, and further NIPT can be helpful to detect fetal chromosomal abnormal in those pregnant women. In pregnant women with high risk of fetal DS or 18 trisomy syndrome in first trimester screening, except for high rate of fetal chromosomal abnormalities, the incidences of other adverse pregnancy outcomes, such as termination of pregnancy due to fetal ultrasound abnormality, spontaneous abortion/stillbirth, premature birth, and birth defects are also relatively high.

Key words: First trimester screening, Risk value, Chromosome aberrations, Down syndrome, Pregnancy outcome, Pregnant women, Fetus

表1 不同年龄孕妇的胎儿DS和18-三体综合征SPR比较[例数(%)]

孕妇	例数	DS	18-三体综合征
预产年龄<35岁	12 375	495(4.00)	64(0.52)
预产年龄≥35岁	2 223	494(22.22)	29(1.30)
χ²值	?	990.737	18.456
P值	?	<0.001	<0.001

表1 不同年龄孕妇的胎儿DS和18-三体综合征SPR比较[例数(%)]

孕妇	例数	DS	18-三体综合征
预产年龄<35岁	12 375	495(4.00)	64(0.52)
预产年龄≥35岁	2 223	494(22.22)	29(1.30)
χ²值	?	990.737	18.456
P值	?	<0.001	<0.001

表2 14 598例孕妇早孕期筛查结果为DS或18-三体综合征不同风险值的胎儿染色体异常情况

早孕期筛查风险值	例数	DS(例)	18-三体综合征(例)	13-三体综合征(例)	性染色体异常(例)	染色体结构异常(例)	合计(例)	胎儿染色体异常率(%)
高风险	1 082	22	3	1	2	3	31	2.87
临界风险	1 903	2	0	0	5	0	7	0.37
低风险	11 613	2	0	1	8	2	13	0.11
合计	14 598	26	3	2	15	5	51	0.35

表2 14 598例孕妇早孕期筛查结果为DS或18-三体综合征不同风险值的胎儿染色体异常情况

早孕期筛查风险值	例数	DS(例)	18-三体综合征(例)	13-三体综合征(例)	性染色体异常(例)	染色体结构异常(例)	合计(例)	胎儿染色体异常率(%)
高风险	1 082	22	3	1	2	3	31	2.87
临界风险	1 903	2	0	0	5	0	7	0.37
低风险	11 613	2	0	1	8	2	13	0.11
合计	14 598	26	3	2	15	5	51	0.35

表3 20例孕妇早孕期筛查结果为DS或18-三体综合征临界风险和低风险的胎儿染色体异常情况

孕妇编号(No.)	年龄(岁)	孕龄(周)	DS风险值	18-三体综合征	NT厚度(mm)	血清PAPP-A MoM	血清fβ-HCG MoM	产前诊断指征(NIPT结果)	胎儿染色体核型异常情况	妊娠结局
1	31	12^＋2	1/353	低风险	2.2	0.70	1.11	DS高风险	47，XN＋21	终止妊娠
2	42	12^＋6	1/508	低风险	1.4	0.82	1.45	高龄	47，XXY	终止妊娠
3	28	13^＋0	1/577	低风险	1.8	2.48	5.38	无	45，X[4]/46，XY[56]	活产
4	38	12^＋5	1/583	低风险	1.5	0.69	1.89	性染色体数目增多	47，XXX	终止妊娠
5	34	12^＋0	1/625	低风险	1.7	0.34	0.58	DS高风险	47，XN＋21	终止妊娠
6	41	12^＋1	1/777	低风险	1.3	0.74	1.08	性染色体数目增多	47，XXY	终止妊娠
7	44	12^＋1	1/898	低风险	—	1.40	0.48	性染色体数目增多	47，XXY	终止妊娠
8	28	12^＋5	1/1 032	低风险	—	0.37	0.80	性染色体数目减少	45，XO	终止妊娠
9	24	12^＋1	1/1 152	低风险	—	0.63	1.51	DS高风险	47，XN＋21	终止妊娠
10	30	13^＋2	1/1 172	低风险	2.0	0.58	1.46	DS高风险	47，XN＋21	终止妊娠
11	34	12^＋5	1/1 818	低风险	1.4	0.64	1.66	性染色体数目增多	47，XXY	终止妊娠
12	28	10^＋0	1/1 907	低风险	—	1.16	0.65	性染色体数目增多	47，XXX	活产
13	34	12^＋6	1/2 095	低风险	—	0.45	0.42	NT厚度为5.6 mm	47，XN＋13	终止妊娠
14	27	11^＋1	1/2 357	低风险	—	0.51	0.74	性染色体数目增多	47，XXX	终止妊娠
15	37	13^＋4	1/3 193	低风险	—	0.43	1.44	性染色体数目增多	47，XXY	终止妊娠
16	37	11^＋5	1/8 502	低风险	—	0.28	0.96	性染色体数目增多	47，XXX	活产
17	31	11^＋1	1/14 499	低风险	—	1.03	0.67	性染色体数目增多	47，XXY	终止妊娠
18	31	12^＋0	1/30 382	低风险	1.2	0.69	0.42	18号染色体微缺失	染色体结构异常	终止妊娠
19	33	11^＋2	1/14 809	低风险	1.2	0.46	0.42	性染色体数目增多	47，XXY	终止妊娠
20	29	13^＋5	1/21 157	低风险	0.6	0.63	1.40	性染色体减少	染色体微重复、微缺失	终止妊娠

表3 20例孕妇早孕期筛查结果为DS或18-三体综合征临界风险和低风险的胎儿染色体异常情况

孕妇编号(No.)	年龄(岁)	孕龄(周)	DS风险值	18-三体综合征	NT厚度(mm)	血清PAPP-A MoM	血清fβ-HCG MoM	产前诊断指征(NIPT结果)	胎儿染色体核型异常情况	妊娠结局
1	31	12^＋2	1/353	低风险	2.2	0.70	1.11	DS高风险	47，XN＋21	终止妊娠
2	42	12^＋6	1/508	低风险	1.4	0.82	1.45	高龄	47，XXY	终止妊娠
3	28	13^＋0	1/577	低风险	1.8	2.48	5.38	无	45，X[4]/46，XY[56]	活产
4	38	12^＋5	1/583	低风险	1.5	0.69	1.89	性染色体数目增多	47，XXX	终止妊娠
5	34	12^＋0	1/625	低风险	1.7	0.34	0.58	DS高风险	47，XN＋21	终止妊娠
6	41	12^＋1	1/777	低风险	1.3	0.74	1.08	性染色体数目增多	47，XXY	终止妊娠
7	44	12^＋1	1/898	低风险	—	1.40	0.48	性染色体数目增多	47，XXY	终止妊娠
8	28	12^＋5	1/1 032	低风险	—	0.37	0.80	性染色体数目减少	45，XO	终止妊娠
9	24	12^＋1	1/1 152	低风险	—	0.63	1.51	DS高风险	47，XN＋21	终止妊娠
10	30	13^＋2	1/1 172	低风险	2.0	0.58	1.46	DS高风险	47，XN＋21	终止妊娠
11	34	12^＋5	1/1 818	低风险	1.4	0.64	1.66	性染色体数目增多	47，XXY	终止妊娠
12	28	10^＋0	1/1 907	低风险	—	1.16	0.65	性染色体数目增多	47，XXX	活产
13	34	12^＋6	1/2 095	低风险	—	0.45	0.42	NT厚度为5.6 mm	47，XN＋13	终止妊娠
14	27	11^＋1	1/2 357	低风险	—	0.51	0.74	性染色体数目增多	47，XXX	终止妊娠
15	37	13^＋4	1/3 193	低风险	—	0.43	1.44	性染色体数目增多	47，XXY	终止妊娠
16	37	11^＋5	1/8 502	低风险	—	0.28	0.96	性染色体数目增多	47，XXX	活产
17	31	11^＋1	1/14 499	低风险	—	1.03	0.67	性染色体数目增多	47，XXY	终止妊娠
18	31	12^＋0	1/30 382	低风险	1.2	0.69	0.42	18号染色体微缺失	染色体结构异常	终止妊娠
19	33	11^＋2	1/14 809	低风险	1.2	0.46	0.42	性染色体数目增多	47，XXY	终止妊娠
20	29	13^＋5	1/21 157	低风险	0.6	0.63	1.40	性染色体减少	染色体微重复、微缺失	终止妊娠

表4 14 547例孕妇(排除51例胎儿染色体异常孕妇)早孕期筛查结果为DS或18-三体综合征不同风险值的不良妊娠结局比较

早孕期筛查风险值	例数	因胎儿超声结构异常而终止妊娠^a(例)	自然流产/死胎(例)	早产(例)	伴出生缺陷(例)	合计(例)	不良妊娠结局发生率(%)
高风险	1 051	20	24	22	32	98	9.32
临界风险	1 896	9	21	25	43	98	5.17
低风险	11 600	57	67	123	239	486	4.19
合计	14 547	86	112	170	314	682	4.69

表4 14 547例孕妇(排除51例胎儿染色体异常孕妇)早孕期筛查结果为DS或18-三体综合征不同风险值的不良妊娠结局比较

早孕期筛查风险值	例数	因胎儿超声结构异常而终止妊娠^a(例)	自然流产/死胎(例)	早产(例)	伴出生缺陷(例)	合计(例)	不良妊娠结局发生率(%)
高风险	1 051	20	24	22	32	98	9.32
临界风险	1 896	9	21	25	43	98	5.17
低风险	11 600	57	67	123	239	486	4.19
合计	14 547	86	112	170	314	682	4.69

[1]	Nicolaides KH, Azar G, Byrne D, et al. Fetal nuchal translucency: ultrasound screening for chromosomal defects in first trimester of pregnancy[J]. BMJ, 1992, 304(6831): 867-869.
[2]	Snijders RJ, Noble P, Sebire N, et al. UK multicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal-translucency thickness at 10-14 weeks of gestation. Fetal Medicine Foundation First Trimester Screening Group[J]. Lancet, 1998, 352(9125): 343-346.
[3]	Schaelike M, Kossakiewicz M, Kossakiewicz A, et al. Examination of a first-trimester Down syndrome screening concept on a mix of 11, 107 high-and low-risk patients at a private center for prenatal medicine in Germany[J]. Eur J Obstet Gynecol Reprod Biol, 2009, 144(2): 140-145.
[4]	Morgan S, Delbarre A, Ward P. Impact of introducing a national policy for prenatal Down syndrome screening on the diagnostic invasive procedure rate in England[J]. Ultrasound Obstet Gynecol, 2013, 41(5): 526-529.
[5]	谢幸，孔北华，段涛. 妇产科学[M]. 9版. 北京：人民卫生出版社，2018: 64-65.
[6]	Santorum M, Wright D, Syngelaki A, et al. Accuracy of first-trimester combined test in screening for trisomies 21, 18 and 13[J]. Ultrasound Obstet Gynecol, 2017, 49(6): 714-720.
[7]	许遵鹏，李蓓，廖灿，等. 广州市早孕期产前筛查胎儿染色体异常的结果分析[J]. 中华医学遗传学杂志，2014, 31(5): 632-635.
[8]	何天文，陈柯艺，唐斌，等. 20 323例孕早期一站式唐氏筛查结果分析[J]. 国际检验医学杂志，2016, 37(1): 35-36, 39.
[9]	葛婷婷，孙庆梅，吴菊，等. 12 807例孕早期唐氏筛查的临床应用现状分析[J]. 中国优生与遗传杂志，2018, 26(6): 54-55.
[10]	何法霖，赵彦，王薇，等. 2014年早孕期母血清产前筛查检验项目室内质控结果调查与分析[J]. 中国妇幼保健杂志，2015, 30(8): 1235-1236.
[11]	郑文吉，陈志央，余颀，等. 早孕期唐氏综合征筛查指标中位数本地化的研究[J]. 中华围产医学杂志，2016, 19(10): 785-788.
[12]	涂新枝，段纯，李玉哲，等. 无创胎儿DNA检测在2 949例传统唐氏筛查临界风险孕妇中的应用[J]. 天津医药杂志，2017, 5(2): 180-183.
[13]	孔京慧，李娴，赵鼎，等. 郑州地区628例先天畸形新生儿的细胞遗传学分析[J]. 中华医学遗传学杂志，2018, 35(6): 926-927.
[14]	宋春林，郭晓玲，陈淑芬，等. 无创产前检测在胎儿性染色体检测中的应用价值[J]. 中国优生与遗传杂志，2018, 26(5): 36-37.
[15]	罗艳梅，胡华梅，徐聚春，等. 无创产前基因检测在胎儿染色体非整倍体筛查中的应用研究[J]. 实用妇产科杂志，2018, 34(6): 464-467.
[16]	Kornman L, Palma-Dias R, Nisbet D, et al. Non-invasive prenatal testing for sex chromosome aneuploidy in routine clinical practice[J]. Fetal Diagn Ther, 2018, 44(2): 85-90.
[17]	Gregg AR, Skotko BG, Benkendorf JL, et al. Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics[J]. Genet Med, 2016, 18(10): 1056-1065.?
[18]	苏杭，刘之英，赖怡，等. 高龄孕妇产前诊断结果及其首选无创产前筛查局限性的大样本分析[J/CD]. 中华妇幼临床医学杂志(电子版), 2018, 14(6): 719-723.
[19]	侯亚萍，杨洁霞，郭芳芳，等. 无创DNA产前检测在胎儿染色体非整倍体疾病筛查中的应用[J]. 检验医学与临床，2018, 15(11): 1542-1544, 1548.
[20]	张敏，梅瑾，张闻，等. 唐氏综合征产前筛查高风险与不良妊娠结局的相关性探讨[J]. 现代实用医学，2016, 28(9): 1206-1208.
[21]	潘敏，孙茜，陈儒香，等. 唐氏综合征产前筛查结果为极高风险孕妇的妊娠结局分析[J/CD]. 中华妇幼临床医学杂志(电子版), 2019, 15(2): 157-163.

[1]	Xining Wu, Yunshu Ouyang, Yixiu Zhang, Hua Meng, Zhonghui Xu, Peipei Zhang, Ke Lyu. Application of fetal echocardiography in prenatal management of fetuses with positive maternal anti-SSA/Ro-SSB/La antibodies[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(10): 1056-1060.
[2]	Shuihua Yang, Guidan He, Guican Qin, Mengfeng Liang, Yanhe Luo, Xueqin Li, Juansong Tang. Echocardioimagedata characteristics of fetal isolated total anomalous pulmonary venous connection and application of high definition flow imaging and spatio-temporal image correlation[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(10): 1061-1067.
[3]	Jingjing Zhang, Bowen Zhao, Mei Pan, Xiaohui Peng, Yankai Mao, Chenke Pan, Lingyan Zhu, Linlin Zhu, Qiuye Lan. Evaluation of fetal pulmonary development using McGoon index measured by fetal echocardiography[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(08): 860-865.
[4]	Peng Xu, Jun Li, Weilun Gao, Zheng Wang, Shen Pang, Chunni Li, Ting Zhu. Application of fast rotary scanning method in fetal echocardiography[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(07): 761-766.
[5]	Gang Luo, Silin Pan, Taotao Chen, Qian Xu, Zhixian Ji, Sibao Wang, Lingyu Sun. Application of echocardiography in fetal cardiac intervention of pulmonary atresia with intact ventricular septum[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(06): 605-609.
[6]	Jia Huang, Hua Shi, Yuguo Zhang, Jiaqi Hu, Qian Chen. Ultrasonographic features of normal and abnormal fetal left brachiocephalic vein and their clinical significance[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(06): 610-617.
[7]	Ze Yuan, Li Zhuang. Value of ultrasound detection of fetal umbilical artery and middle cerebral artery blood flow in diagnosis of fetal intrauterine distress[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(06): 618-621.
[8]	Haoyuan Yang, Jie Gong, Qingwei Zou, Hang Ruan. Current research status on adverse pregnancy outcomes of maternal and infant in pregnant women with asthma[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(05): 522-529.
[9]	Tiantian Chen, Xiaodong Wang, Haiyan Yu. Pregnancy outcome of twin pregnancy with Gitelman syndrome: a case report and literature review[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(05): 559-568.
[10]	Xiaoqing Ju, Yunjie Jin, Xiaoyan Wang. Influencing factors of uterine rupture during vaginal delivery in patients with scarred uterus after cesarean section[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(05): 575-581.
[11]	Juan Gu, Qingqing Sun, Fangfang Hu, Yijuan Cao, Yujuan Qi. Clinical application of endometrial receptivity array to improve pregnancy outcomes in women with repeated embryo implantation failure[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(05): 582-587.
[12]	Beibei Wang, Qixiu Dong, Hongyan Xi, Qingyun Yu, Lijun Zhang, Guang Shi. Analysis of influencing factors of medical abortion failure of pregnant women in early pregnancy and construction of related prediction model and its predictive value for medical abortion success[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(05): 588-594.
[13]	Xu Chen, Yuru Zhan, Chunhua Wang. Clinical value of ABO blood group combined with thyroid function in prediction of gestational diabetes mellitus[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(05): 604-610.
[14]	Mengling Zhou, Zhiwei Xue, Shu Zhou. Changes in size of uterine myoma during pregnancy and its association with adverse pregnancy outcomes[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(05): 611-615.
[15]	Yuyan Zhang, Bin Hu, Weihong Zhang, Mei Xu, Hui Zhu, Xinyue Yang, Hailing Liu. Relationship between echocardiography parameters and liver function during the second trimester of pregnancy and their predictive value for adverse pregnancy outcomes[J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2023, 13(06): 499-504.

Viewed

Full text

Abstract

Please choose a citation manager

Content to export