血清学筛查联合胎儿非整倍体产前无创基因检测临床应用价值的研究

Clinical value of screening fetal aneuploidy using a combination of maternal serum examination and massively parallel sequencing based non-invasive prenatal diagnosis

目的探讨孕期血清学筛查联合无创性产前胎儿染色体非整倍体基因检测的临床应用,提高染色体疾病的检出率,降低出生缺陷。方法孕期适时机会血清学筛查23039例。采用时间分辨免疫荧光法检测,血清学联合二联筛查早孕9-13＋6周,妊娠相关蛋白PAPP-A和游离β-HCG,中孕15-20＋6周三联筛查甲胎蛋白AFP、游离β-HCG、游离E3检测激素水平,应用Multicalc软件评估风险值,21-三体风险分割值1：270,≥1：270为高风险,1：270~1：500临界风险。18三体风险分割值1：350,≥1：350为高风险,1：350-1：800为临界风险值。结果筛查出高风险1546例,占6.71%,临界风险值3257例,占14.17%,无创产前诊断2842例占59.17%,介入性产前诊断550例占11.54%。产前诊断确诊胎儿染色体异常共27例,其中非整倍体19例,占0.39%,其他染色体异常8例,占0.16%,知情告知签字不落实产前诊断发生出生缺陷7例,调查表明临界风险选择无创样本例数占59.17%,羊水样本例数占11.54%,无创检测高风险数经羊水再次核型分析一致性达100%。结论血清学产前筛查联合无创产前胎儿非整倍体DNA检测可提高产前诊断效率,特别对临界风险值瓶颈线的突破起关键性作用,降低胎儿染色体非整倍体病率快捷、安全,较介入性产前诊断易于接受、推广,是今后发展的必然趋势。

【Objective】To study the clinical value of screening fetal aneuploidy,using a combination of maternal serum examination and massively parallel sequencing（MPS） based non-invasive prenatal diagnosis（NIPD）.It improves the ability to identify chromosomal abnormalities for decreasing the birth defect.【Methods】The study included 23039 pregnancies between the 9th and 20＋6th gestational week,who underwent screening by Time-resolved fluoroimmunoassay technology with maternal serum alpha-fetoprotein（AFP）and free beta-subunit of human chorionic gonadotropin（free beta-hCG） in the first trimester,Free Estriol（E3）is added in the second-trimester.The risk of trisomy 21 and trisomy 18 was estimated by software Multicalc,based on a model which generated the final risk for fetal aneuploidies from the pregnant woman’s a priori age risk and the likelihood ratio of the distribution of the biochemical markers,according to the gestational weeks.The cut-off value of the final risk ＆gt; or = 1：270 for trisomy 21 and 1：350 for trisomy 18.【Resluts】Screening tests identified 6.71%（n=1546）high-risk pregnancies and 14.17%（n=3257） critical risk pregnancies in this group.59.17%（n=2842）and 11.54%（n=550） of the patients consented to non-invasive and invasive diagnosis respectively.27 fetal chromosomal abnormalities were detected,of whom,0.39%（n=19） were identified to chromosomal aneuploidies and 0.16%（n=8） were other abnormalities.According to the feedback of fetal delivery,7 cases of refused prenatal diagnosis were diagnosed as birth defect.【Conclusion】A combination of maternal serum examination and massively parallel sequencing based non-invasive prenatal diagnosis improve the effect of prenatal diagnosis.It improves the ability to decrease the birth defect.Compared to the invasive diagnosis,massively parallel sequencing based non-invasive prenatal diagnosis is safe and convenient for detecting fetal aneuploidy.