孕11⁺⁰至13⁺⁶周时，通过胎儿三尖瓣反流、颈部透明带以及母体血清游离β-人绒毛膜促性腺激素和妊娠相关血浆蛋白-A筛查21三体综合征。

Screening for trisomy 21 by fetal tricuspid regurgitation, nuchal translucency and maternal serum free beta-hCG and PAPP-A at 11 + 0 to 13 + 6 weeks.

作者信息

Falcon O, Auer M, Gerovassili A, Spencer K, Nicolaides K H

机构信息

Harris Birthright Research Centre for Fetal Medicine, King's College Hospital Medical School, London, UK.

出版信息

Ultrasound Obstet Gynecol. 2006 Feb;27(2):151-5. doi: 10.1002/uog.2699.

DOI:10.1002/uog.2699

PMID:16388509

Abstract

OBJECTIVE

To examine whether in pregnancies with fetal trisomy 21 the level of maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 to 13 + 6 weeks' gestation is independent of the presence or absence of tricuspid regurgitation and to estimate the performance of a screening test that combines tricuspid regurgitation with fetal nuchal translucency (NT) thickness and serum free beta-hCG and PAPP-A.

METHODS

The study population comprised 77 trisomy 21 and 232 chromosomally normal fetuses from singleton pregnancies at 11 + 0 to 13 + 6 weeks of gestation. In all cases the fetal karyotype was determined by chorionic villus sampling (CVS), which was carried out at the request of the parents after first-trimester screening for trisomy 21 by fetal NT and maternal serum free beta-hCG and PAPP-A. Immediately before chorionic villus sampling, fetal echocardiography was performed and the presence or absence of tricuspid regurgitation was determined by pulsed wave Doppler ultrasonography. The distribution of fetal NT, maternal serum free beta-hCG and PAPP-A in trisomy 21 fetuses with absent and present tricuspid regurgitation was examined. We examined two screening strategies: first, integrated first-trimester screening in all patients and second, first-stage screening of all patients using fetal NT and maternal serum free beta-hCG and PAPP-A followed by second-stage assessment of tricuspid regurgitation only in those with an intermediate risk of 1 in 101 to 1 in 1000 after the first stage.

RESULTS

Tricuspid regurgitation was observed in 57 (74.0%) of the trisomy 21 fetuses and in 16 (6.9%) of the chromosomally normal fetuses. There were no significant differences in median maternal age, median gestational age, free beta-hCG multiples of the median (MoM) and PAPP-A MoM in trisomy 21 fetuses with and without tricuspid regurgitation. The modeled detection rates of trisomy 21 for fixed false positive rates of 1%, 2% and 5% in screening by maternal age, fetal NT thickness and maternal serum free beta-hCG and PAPP-A and assessment of tricuspid flow in all cases were 87%, 90% and 95%. In the two-stage approach, the estimated detection rate was 91% and the false positive rate was 2.6%.

CONCLUSIONS

There is no relationship between tricuspid regurgitation and the levels of maternal serum free beta-hCG and PAPP-A in cases with trisomy 21. An integrated sonographic and biochemical test at 11 + 0 to 13 + 6 weeks can potentially identify about 90% of trisomy 21 fetuses for a false-positive rate of 2-3%.

摘要

目的

研究孕11⁺⁰至13⁺⁶周时，胎儿21-三体妊娠中母体血清游离β-人绒毛膜促性腺激素（β-hCG）和妊娠相关血浆蛋白-A（PAPP-A）水平是否独立于三尖瓣反流的存在与否，并评估一项将三尖瓣反流与胎儿颈部透明带（NT）厚度以及血清游离β-hCG和PAPP-A相结合的筛查试验的性能。

方法

研究对象包括77例孕11⁺⁰至13⁺⁶周单胎妊娠的21-三体胎儿和232例染色体正常的胎儿。所有病例均通过绒毛取样（CVS）确定胎儿核型，CVS是在孕早期通过胎儿NT及母体血清游离β-hCG和PAPP-A进行21-三体筛查后，应父母要求进行的。在绒毛取样前，立即进行胎儿超声心动图检查，并通过脉冲波多普勒超声确定三尖瓣反流的存在与否。检查了三尖瓣反流不存在和存在的21-三体胎儿中胎儿NT、母体血清游离β-hCG和PAPP-A的分布情况。我们研究了两种筛查策略：第一种是对所有患者进行孕早期综合筛查；第二种是对所有患者先使用胎儿NT、母体血清游离β-hCG和PAPP-A进行第一阶段筛查，然后仅对第一阶段后风险处于1/101至1/1000之间的中度风险患者进行三尖瓣反流的第二阶段评估。

结果

在21-三体胎儿中，57例（74.0%）观察到三尖瓣反流，在染色体正常的胎儿中，16例（6.9%）观察到三尖瓣反流。有三尖瓣反流和无三尖瓣反流的21-三体胎儿在母体年龄中位数、孕周中位数、游离β-hCG中位数倍数（MoM）和PAPP-A MoM方面无显著差异。在所有病例中，通过母体年龄、胎儿NT厚度、母体血清游离β-hCG和PAPP-A筛查以及三尖瓣血流评估，对于1%、2%和5%的固定假阳性率，21-三体的建模检出率分别为87%、90%和95%。在两阶段方法中，估计检出率为91%，假阳性率为2.6%。