探讨孕妇早孕期筛查结果为唐氏综合征(DS)或18-三体综合征高风险、临界风险与低风险的胎儿染色体异常率及其妊娠结局。

选择2017年1至12月，于南方医科大学附属深圳市妇幼保健院接受早孕期筛查，并获得明确妊娠结局的14 598例单胎孕妇为研究对象。对其妊娠结局随访，分别采取查询本院产前诊断中心、深圳市妇幼保健信息管理系统或电话随访受试者本人的方式完成，对其随访截止时间设定为活产儿1岁，或胎儿自然流产/死胎发生时。其中，接受早孕期血清学筛查孕妇为6 825例，接受早孕期血清学联合胎儿超声颈项透明层(NT)筛查为7 773例；早孕期筛查结果为DS或18-三体综合征高风险、临界风险、低风险的孕妇分别为1 082例、1 903例及11 613例；高龄(预产年龄≥35岁)孕妇为2 223例(15.23%，2 223/14 598)。采用回顾性研究方法，收集所有孕妇早孕期筛查与胎儿染色体异常结果及其妊娠结局。对于预产年龄<35岁与≥35岁孕妇的胎儿DS、18-三体综合征筛查阳性率(SPR)比较，早孕期筛查结果为胎儿DS或18-三体综合征高风险、临界风险、低风险的胎儿染色体异常率及不良妊娠结局发生率比较，采用χ²检验。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求。

①高龄孕妇的胎儿DS与18-三体综合征SPR分别为22.22%(494/2 223)与1.30%(29/2 223)，均显著高于预产年龄<35岁孕妇的4.00%(495/12 375)与0.52%(649/12 375)，并且差异均有统计学意义(χ²＝990.737、18.456，P<0.001)。②本研究14 598例孕妇中，经产前诊断确诊为胎儿染色体异常者为49例，经新生儿外周血核型分析确诊为胎儿染色体异常者为2例，胎儿染色体异常率为0.35%(51/14 598)。51例异常染色体胎儿中，26例为DS胎儿。其中，早孕期筛查结果为胎儿DS高风险为22例，临界风险及低风险为4例，DS胎儿检出率为84.62%(22/26)，胎儿DS发生率为0.18%(26/14 598)；胎儿18-三体综合征为3例，早孕期筛查结果均为胎儿18-三体综合征高风险，胎儿18-三体综合征检出率为100.00%(3/3)；胎儿性染色体异常为15例，胎儿性染色体异常率为0.10%(15/14 598)；2例为13-三体综合征胎儿，5例为染色体结构异常胎儿。③早孕期筛查结果为胎儿DS或18-三体综合征高风险、临界风险、低风险孕妇中，确诊胎儿为染色体异常者分别为31例、7例及13例，胎儿染色体异常率分别为2.87%(31/1 082)、0.37%(7/1 903)及0.11%(13/11 613)。在胎儿DS或18-三体综合征临界风险和低风险孕妇中，确诊胎儿为DS或18-三体综合征者共计20例，其中19例经产前诊断确诊，包括17例无创产前检测(NIPT)结果显示异常、1例孕妇为高龄及1例为胎儿NT增厚；1例为产后确诊胎儿染色体异常。④排除51例胎儿染色体异常的孕妇之外，其余14 547例孕妇中，早孕期筛查结果为高风险孕妇，因胎儿超声结构异常而终止妊娠、自然流产/死胎、早产、伴出生缺陷等不良妊娠结局发生率为9.32%(98/1 051)，临界风险孕妇为5.17%(98/1 896)，低风险孕妇为4.19%(486/11 600)，3者比较，差异有统计学意义(χ²＝57.989，P<0.001)。

早孕期筛查对DS和18-三体综合征胎儿具有较高检出率，但是不能检出所有的染色体异常胎儿。在早孕期筛查结果为临界风险、低风险孕妇中，其胎儿仍然存在染色体异常可能，对此类孕妇进一步进行NIPT，有助于检出染色体异常胎儿。早孕期筛查结果为高风险孕妇，除胎儿染色体异常率高外，因胎儿超声结构异常而终止妊娠、自然流产/死胎、早产、伴出生缺陷等不良妊娠结局发生率亦较高。

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.

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.

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).

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.