背景:全基因组非侵入性产前检测在一般产科人群中发现了几种罕见的常染色体三体,但它的使用受到低阳性预测值的质疑。此外,罕见的常染色体三体的起源和报告它们的临床效果尚未得到充分研究.此外,专业协会表示,他们需要评估多年来对罕见的常染色体三体进行全基因组无创性产前检查的临床使用情况的数据.
目的:本研究旨在探讨罕见的常染色体三体的起源以及在临床环境中发现罕见的常染色体三体的临床效果。
方法:前瞻性纳入2021年3月至2022年3月接受非侵入性产前检测的女性。进行了临床随访以及细胞遗传学和分子研究。进行后分析以研究胎盘镶嵌与临床结局之间的关联。
结果:总体而言,通过非侵入性产前检测,在89,242例妊娠(0.17%)中发现了154例罕见的常染色体三体。在进行细胞遗传学和分子学研究的120例病例中,发现罕见的常染色体三体起源于真正的胎儿镶嵌(n=5),单亲性(n=5),母体镶嵌三体(n=3),孕产妇恶性肿瘤(n=1),和局限性胎盘镶嵌(n=106)。临床随访显示,所有罕见的常染色体三体性病例中有40%具有不良的围产期结局。在非侵入性产前检测结果假阳性的女性中,由于胎盘嵌合体的局限性,不良围产期结局的发生率为26%.更重要的是,在发生不良围产期结局的女性中,无创性产前检测显示的胎盘镶嵌率显著高于未发生不良围产期结局的女性(0.688vs0.332;P<.001).
结论:无创性产前检测结果提示罕见常染色体三体的女性有不良围产期结局的风险,并且可以使用染色体和非侵入性产前检测显示的镶嵌率对风险进行分层。我们的数据对于产科护理人员建议患者无创性产前检查结果提示罕见的常染色体三体性和假阳性诊断以及管理怀孕期间的风险是有价值的。
Genome-wide noninvasive prenatal testing identifies several rare autosomal trisomies in the general obstetrical population, but its use is questioned by its low positive predictive value. Furthermore, the origin of rare autosomal trisomies and the clinical effect of reporting them has not been sufficiently investigated. In addition, professional societies express their need for data assessing the clinical use of genome-wide noninvasive prenatal testing for rare autosomal trisomies for years.
This study aimed to investigate the origin of rare autosomal trisomies and the clinical effect of disclosing rare autosomal trisomies in clinical settings.
Women who received noninvasive prenatal testing between March 2021 and March 2022 were prospectively enrolled. Clinical follow-up and cytogenetic and molecular investigations were performed. Posthoc analysis was performed to investigate the association between placental mosaicism and clinical outcomes.
Overall, 154 rare autosomal trisomies were identified in 89,242 pregnancies (0.17%) through noninvasive prenatal testing. In the 120 cases in which cytogenetic and molecular investigations were carried out, the rare autosomal trisomies were found to originate from true fetal mosaicism (n=5), uniparental disomy (n=5), maternal mosaic trisomy (n=3), maternal malignancy (n=1), and confined placental mosaicism (n=106). Clinical follow-up showed that 40% of all rare autosomal trisomy cases had adverse perinatal outcomes. In women with false-positive noninvasive prenatal testing results originating from confined placental mosaicism, the frequency of adverse perinatal outcomes was 26%. More importantly, the placental mosaicism ratio revealed by noninvasive prenatal testing was significantly higher in women who experienced adverse perinatal outcomes than those who did not (0.688 vs 0.332; P<.001).
Women with noninvasive prenatal testing results indicative of rare autosomal trisomies are at risk of adverse perinatal outcomes, and that risk can be stratified using chromosomes and the mosaicism ratio revealed by noninvasive prenatal testing. Our data are valuable for obstetrical caregivers advising a patient with a noninvasive prenatal testing result indicative of a rare autosomal trisomy and a false-positive diagnosis and for managing risks during pregnancy.