无创产前检测对常规染色体数目异常之外的拷贝数变异的检出意义:205例临床分析

Detection of copy number variations for chromosome non-numerical abnormality with non-invasive prenatal testing: clinical analysis of 205 cases

目的探讨无创产前检测(non-invasive prenatal testing,NIPT)检出胎儿拷贝数变异(copy number variations,CNVs)的临床价值。方法2015年1月1日至2018年9月1日在广东省妇幼保健院行NIPT的孕妇37845例,除常规染色体数目异常外检出205例CNVs,纳入回顾性分析。205例检出CNVs的孕妇中137例接受了介入性产前诊断。随访妊娠结局。分析NIPT对于CNVs的检测效能。采用描述性统计分析。结果NIPT对CNVs的检出率为0.54%(205/37845),110例经产前诊断未发现染色体核型异常,2例产前诊断结果与NIPT检出CNVs不符,25例产前诊断结果与NIPT一致。NIPT筛查CNVs的阳性预测值为18.2%(25/137),灵敏度为100.0%(25/25),特异度为99.7%(37625/37737)。27例产前诊断结果异常孕妇中5例失访,8例引产终止妊娠,14例活产且新生儿表型正常。110例产前诊断未发现异常孕妇中87例足月分娩,其中2例存在卵圆孔未闭,余85例新生儿表型正常;3例早产;1例孕28周+2因子痫前期终止妊娠;另有2例难免流产;2例孕妇要求引产;15例失访。结论常规NIPT对于胎儿CNVs具有一定的检测效能,但阳性结果须结合介入性产前诊断结果、超声随访结果等进行详细的遗传咨询。

Objective To evaluate the clinical value of non-invasive prenatal testing(NIPT)in detecting copy number variations(CNVs).Methods There were 37845 pregnant women undergoing NIPT in Guangdong Women and Children Hospital from January 1,2015 to September 1,2018,of which 205 with CNVs were detected in addition to chromosome numerical abnormality and retrospectively analyzed.Among the 205 cases,137 received invasive prenatal diagnosis.Pregnant outcomes were followed up and the efficiency of NIPT in detecting CNVs was analyzed by descriptive statistical analysis.Results The detection rate of NIPT for CNVs was 0.54%(205/37845).Among the 137 cases undergoing invasive prenatal diagnosis,110 showed normal karyotype,27 with abnormal including two having CNVs that were inconsistent with NIPT findings and 25 with consistent results.The positive predictive value,sensitivity and specificity of NIPT for CNVs were 18.2%(25/137),100.0%(25/25)and 99.7%(37625/37737),respectively.Among the 27 pregnant women with positive findings in prenatal diagnosis,five were lost to follow-up;eight terminated their pregnancies;14 gave birth to alive baby with normal phenotype.While among the 110 pregnant women with negative results in prenatal diagnosis,87 delivered full-term neonates including two having patent foramen ovale and 85 with normal phenotype;three gave birth prematurely;one terminated pregnancy at 28+2 gestational weeks due to preeclampsia;two had inevitable abortion;two requested termination and 15 were lost to follow-up.Conclusions Routine NIPT has high performance in screening CNVs but those pregnant women with positive NIPT results should be counseled after referring to their invasive prenatal diagnosis results,ultrasound scan and clinical information.