孕11～13周＋6胎儿多个超声指标联合母血清学指标在筛查染色体异常胎儿中的价值

Study on several ultrasound markers combined maternal serum biochemical markers to screen fetal chromosomal aneuploidy at 11 to 13＋6 weeks of gestation

目的 探讨孕11 ～13周＋6胎儿多个超声指标联合母血清学指标在筛查染色体异常胎儿中的临床效果.方法 选择2010年1月1日至2011年12月31日天津市中心妇产科医院进行联合筛查的单胎孕妇5000例（筛查孕周为11 ～13周＋6）.采用超声仪对胎儿颈项透明层（NT）厚度,鼻骨缺失与否,静脉导管a波血流反向及三尖瓣反流情况进行检测;同时检测孕妇血清妊娠相关蛋白A（PAPP-A）和游离β绒毛膜促性腺激素（β-hCG）水平.将NT值和β-hCG及PAPP-A水平输入计算机,计算风险值（≥1∶270）.联合筛查的5000例孕妇中筛查出高风险204例,对这204例孕妇进行绒毛组织活检,检测胎儿染色体核型,对染色体异常胎儿的超声特征进行分析.结果 （1） 5000例单胎孕妇中,正常染色体核型胎儿4983例,活产儿4938例,62例胎儿因各种原因于孕中期引产,其中40例染色体核型正常但伴先天性心脏病,17例为染色体异常（其中21三体9例、18三体2例、13 三体1例、45X 4例）,2例脊柱裂,2例消化道梗阻,1例巨膀胱.染色体核型异常胎儿中有1例联合筛查为低风险,年龄高风险（孕妇年龄均≥40岁）,后经产前诊断证实胎儿为21三体综合征.（2）9例21 三体胎儿中有5例为鼻骨缺失（5/9）、5例有三尖瓣反流（5/9）、4例为静脉导管a波反向（4/9）、3例胎儿鼻骨缺失伴有三尖瓣反流及静脉导管a波血流反向（3/9）.2例18 三体胎儿中有l例鼻骨缺失、2例均为三尖瓣反流及静脉导管a波血流反向.4例45X胎儿中有2例为静脉导管a波血流反向.4983例正常核型胎儿中有8例鼻骨缺失（0.16％）、48例三尖瓣反流（0.96％）以及44例静脉导管a波血流反向（0.88％）.40例先天性心脏病胎儿中有32例为三尖瓣反流（80％）,30例静脉导管a波血流反向（75％）.8例孕早期发现的鼻骨缺失的正常核型胎儿,于孕20周时超声检测均发现鼻骨.结论 孕11 ～13周＋6胎儿联合筛查检出率高,假阳性率低;异常核型胎儿往往伴有三尖瓣反流、静脉导管的a波反向及鼻骨缺失,增加超声标记有提高异常胎儿检出率的作用;孕11 ～13周＋6超声标记物异常可能与胎儿先天性心脏病有关.

Objective To evaluate the efficiency of combined screening for chromosomal abnormalities in the first trimester and the ultrasound characteristics of these fetuses.Methods Retrospective study for 5000 singleton pregnancies by combined screening of trisomies 21,18,13 and Turner syndrome.Risk algorithms were developed for calculation of patient-specific risks for each of the three trisomies based on maternal age,fetal nuchal translucency,free β human chorionic gonadotropin and serum pregnancy associated plasma protein A at 11 to 13 ＋6 weeks of pregnant.The value of nuchal translucency （NT） and β-hCG and pregnancy-associated plasma protein A （PAPP-A） level were inputted computer,and calculate the risk value （≥ 1 ∶ 270） by automatic analysis software.Two hundred and four cases with high risk were performed transabdominal chorionic villus biopsy to detect the fetal chromosomal karyotypes.Meanwhile,other ultrasonic characteristics of fetal were elevated.Results （1） Five thousand cases of pregnant women were detected,including 4983 normal cases,62 cases were induced labor for a variety of reasons in the second trimester,including 40 cases with normal karyotype but with congenital heart disease,17 cases of chromosome abnormalities （9 cases trisomy 21,2 cases trisomy 18,1 cases trisomy 13,4 cases 45X）,2 cases spina bifida,2 cases digestive tract obstruction,1 cases giant bladder.One case with low risk of fetal chromosomal abnormalities in combined screening,but high risk of age （maternal age were over 40 years old）,it was 21 trisomy syndrome after the prenatal diagnosis.（2） Five cases of nasal bone loss in 9 cases of trisomy 21 （5/9）,5 cases with three tricuspid regurgitation （5/9）,4 cases of venous ductus a wave flow reverse （4/9）,3 cases of fetal nasal bone loss accompanied by tricuspid regurgitation and venous ductus a wave flow reverse （3/9）.One case of nasal bone loss in 2 cases of trisomy 18,2 cases were tricuspid regurgitation and venous ductus a wave flow reverse.Two cases in 4 cases of 45X had venous ductus a wave flow reverse.There were 8 cases （0.16％） nasal bone absence in 4983 cases of normal karyotype fetus,48 cases （0.96％） of tricuspid regurgitation and 44 cases （0.88％） of venous ductus a wave flow reverse.Thirty-two cases in 40 cases （80％） of fetal congenital heart disease were tricuspid regurgitation,30 cases of venous ductus a wave flow reverse （75％）.Eight cases of nasal bone absence normal karyotype fetus were found the nasal bone at 20 weeks gestation.Conclusion Combination screening of nuchal translucency with serum markers in the first trimester were high detection rate and low false positive rate; a wave reversion and fetal nasal bone absence accompanied by tricuspid regurgitation can improve the detection rate of abnormal karyotype; abnormalities ultrasound marker may be associated with fetal congenital heart disease at 11-13 ＋6 weeks of pregnancy.