染色体微阵列分析技术在高龄孕妇产前诊断中的应用价值

Application of chromosome microarray analysis in prenatal diagnosis of pregnant women with advanced age

目的探讨染色体微阵列分析(chromosomal microarray analysis,CMA)对于高龄孕妇异常妊娠的检测价值。方法回顾分析562例高龄孕妇的CMA检测结果、妊娠结局及新生儿的随访结果。结果在562份羊水样本中,共检出胎儿染色体异常73例(12.99%),包括21例(3.73%)染色体非整倍体和52例(9.25%)染色体拷贝数变异(copy number variations,CNVs),其中包括病理性变异27例(4.80%)、可能致病变异4例(0.71%)、临床意义未知变异42例(7.47%)。与非高龄孕妇相比,在自愿检测、超声结构异常、超声软指标异常、无创产前检测异常指征下,高龄孕妇胎儿染色体非整倍体的检出率均高于非高龄孕妇。在染色体CNVs的检出率方面,高龄与非高龄孕妇、以及单纯高龄与非单纯高龄孕妇的差异均无统计学意义(P>0.05)。成功随访552例(98.22%)孕妇。在CMA检测提示病理性和可能致病变异的31例孕妇中,25例终止妊娠,6例(19.35%)正常分娩且新生儿未见明显异常。CMA检测提示为临床意义未知变异的41例孕妇中,3例选择终止妊娠,1例胎儿出生后发现畸形。在CMA检测未见明显异常、且成功随访的480例孕妇中,5例(1.04%)出现妊娠异常或胎儿出生后发现畸形。结论通过CMA检测预测的妊娠结局与实际存在一定的差异。CMA检测提示为临床意义未知变异的孕妇不良妊娠结局的比例较高,应重点关注。高龄孕妇无论是否合并其他症状,均建议其接受CMA检测。CMA联合其他检测手段是为这类孕妇进行产前诊断的趋势。

Objective To assess the value of chromosomal microarray analysis(CMA)for the detection of fetal anomalies among pregnant women with advanced age.Methods CMA results of 562 cases,in addition with the outcome of pregnancy and neonatal follow-up were reviewed.Results Among the 562 amniotic fluid samples,73 cases(12.99%)of fetal chromosomal abnormalities were detected,which included 21 cases(3.73%)of chromosomal aneuploidies and 52 cases(9.25%)of copy number variations(CNVs).The latters included 27 cases of pathological CNVs(4.80%),4 cases of possible pathogenic CNVs(0.71%)and 42 cases of variants with unknown clinical significance(7.47%).Compared with those under 35,the detection rate of fetal chromosomal aneuploidies for women with advanced age was higher under the indications of voluntary test,abnormal ultrasonic structures,abnormal ultrasonic soft index and risks indicated by non-invasive prenatal testing(NIPT).No significant difference was found in the detection rate of CNVs between those≥35 and<35 and between those with age factor only and with additional indications(P>0.05).552 cases(98.22%)of pregnant women have completed the followed up.Among 31 women with pathological and possible pathogenic fetal CNVs detected by CMA,25 had terminated the pregnancy,6(19.35%)have delivered without obvious abnormality.41 pregnant women with fetal CNVs of unknown clinical significance have completed the follow up,among whom 3 had terminated the pregnancy,1 newborn was found with malformation after birth,which yielded an abnormal pregnancy rate of 9.76%.480 pregnant women with negative CMA results have completed the follow up,among whom 5(1.04%)had abnormal pregnancy or delivered a child with birth defect.Conclusion There is a certain difference between the outcome of pregnancy predicted by CMA testing and the actual outcome.The pregnancies with fetal CNVs with unknown clinical significance detected by CMA have a high adverse rate,which should attract clinical attention.CMA testing should be recommended for pregnant women with advanced age regardless of whether they have other symptoms.CMA combined with other detection methods is the trend for prenatal diagnosis.