Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, 610041, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, 610041, China.
Sci Rep. 2020 Jun 1;10(1):8864. doi: 10.1038/s41598-020-65904-2.
The widespread application of high-resolution chromosome detection technology in clinical practice has identified many variants of unknown significance (VOUS) in prenatal diagnosis. The purpose of this study was to prospectively analyze the chromosomal results of parents and the follow-up information of pregnancy outcomes of prenatal samples with VOUS, so as to determine the influence of the detection of parent-of-origin on the pregnancy outcomes of fetuses with VOUS. The present study analyzed amniotic fluid samples obtained from women with different risk indications between February 2017 and December 2018. The samples were subjected to copy number variation sequencing, and detection of parent-of-origin was suggested in cases of samples with VOUS. The pregnancy outcome was followed up. In a total of 14073 amniotic fluid samples, 729 cases of VOUS were detected (5.2%, 729/14073) and 721 cases were followed up successfully. Among the 721 cases, 525 patients agreed to detect the parent-of-origin (72.8%, 525/721). It was revealed that the VOUS in 460 of the fetuses were hereditary (87.6%, 460/525). The percentages of abnormal pregnancy outcomes (included pregnancy loss, fetal pathological abnormality, preterm delivery, neonatal death, birth defects) in the inherited, de novo, and refusal to detect the parent-of-origin (i.e. unknown origin) groups were 4.3% (20/460), 6.2% (4/65), and 6.6% (13/196), respectively. There was no significant difference among the three groups (P > 0.05). The rate of voluntary termination of pregnancy (TOP) in the unknown origin group was significantly higher than that in the group that had determined the parent-of-origin (14.3% vs 7.4%, P = 0.005). There is currently no evidence that suggests that the proportion of abnormal pregnancy outcomes is higher in fetuses with VOUS than in other fetuses. However, the present study revealed that determining the parent-of-origin affects the decision to undergo voluntary TOP, as the rate of voluntary TOP in the group that refused detection was higher than that in the group that consented.
高分辨率染色体检测技术在临床实践中的广泛应用，在产前诊断中发现了许多意义不明的变异（VOUS）。本研究旨在前瞻性分析产前样本 VOUS 中父母的染色体结果和妊娠结局的随访信息，以确定检测亲本来源对 VOUS 胎儿妊娠结局的影响。本研究分析了 2017 年 2 月至 2018 年 12 月间不同风险指征的女性羊水样本。对样本进行拷贝数变异测序，对 VOUS 样本建议检测亲本来源。随访妊娠结局。在总共 14073 例羊水样本中，检测到 729 例 VOUS（5.2%，729/14073），并成功随访 721 例。在 721 例中，525 例患者同意检测亲本来源（72.8%，525/721）。结果显示，460 例胎儿 VOUS 为遗传性（87.6%，460/525）。在遗传性、新发和拒绝检测亲本来源（即未知来源）组中，异常妊娠结局（包括妊娠丢失、胎儿病理性异常、早产、新生儿死亡、出生缺陷）的百分比分别为 4.3%（20/460）、6.2%（4/65）和 6.6%（13/196）。三组间无显著性差异（P>0.05）。未知来源组自愿终止妊娠（TOP）率明显高于已确定亲本来源组（14.3%比 7.4%，P=0.005）。目前尚无证据表明 VOUS 胎儿的异常妊娠结局比例高于其他胎儿。然而，本研究显示，确定亲本来源会影响自愿 TOP 的决定，因为拒绝检测组的自愿 TOP 率高于同意组。
