Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Center for Fetal Diagnostics, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Acta Obstet Gynecol Scand. 2023 Nov;102(11):1505-1510. doi: 10.1111/aogs.14631. Epub 2023 Jul 21.
In 2011, it was decided to implement chromosomal microarray in prenatal testing in the Central Denmark Region, mainly due to the expected higher diagnostic yield. Chromosomal microarray was introduced gradually for an increasing number of pregnancies and without a transition period where both karyotyping and chromosomal microarray were performed: first malformations (2011), then large nuchal translucency (2013), then high risk at combined first trimester risk screening (2016) and finally for all indications (2018). This retrospective study summarizes 11 years of using chromosomal microarray in invasive prenatal testing and presents the effect on diagnostic yield and turnaround time. Furthermore, the concerns when introducing chromosomal microarray are presented and discussed.
Registry data from the Danish Fetal Medicine Database, the regional fetal medicine database, the Danish Cytogenetic Central Register and the local laboratory database at Department of Clinical Genetics were all combined, and a cohort of 147 158 singleton pregnancies with at least one ultrasound examination was established RESULTS: Of the 147 158 pregnancies, invasive sampling was performed (chorionic villi or amniocytes) in 8456, corresponding to an overall invasive rate of 5.8%. Between 2016 and 2018, 3.4% (95% confidence interval [CI] 2.8-4.2%; n = 86) of the invasive samples (n = 2533) had a disease causing copy number variant and 5.3% (95% CI 4.4-6.2%; n = 133) had trisomies and other aneuploidies. The turnaround time more than halved from 14 days to an average of 5.5 days for chorionic villus sampling.
Chromosomal microarray identified 5.3% trisomies and 3.4% copy number variants, thereby increased the diagnostic yield by more than 64% compared with karyotype only and it also more than halved the turnaround time. Some preliminary concerns proved real, eg prenatal counseling complexity, but these have been resolved over time in a clinical path with expert consultations.
2011 年，丹麦中部大区决定在产前检测中引入染色体微阵列技术，主要是因为预期其具有更高的诊断率。染色体微阵列技术逐渐应用于越来越多的妊娠病例，没有过渡期同时进行核型分析和染色体微阵列技术：首先是先天畸形（2011 年），然后是大的颈项透明层（2013 年），接着是联合早孕期风险筛查高风险（2016 年），最后是所有适应症（2018 年）。本回顾性研究总结了 11 年来在侵袭性产前检测中使用染色体微阵列的经验，介绍了其对诊断率和周转时间的影响。此外，还提出并讨论了引入染色体微阵列技术时的一些关注点。
将丹麦胎儿医学数据库、区域胎儿医学数据库、丹麦细胞遗传学中央登记处和临床遗传学系的本地实验室数据库中的登记数据合并，建立了一个包含 147158 例单胎妊娠的队列，这些妊娠均至少有一次超声检查。结果：在 147158 例妊娠中，有 8456 例（总体侵袭率为 5.8%）进行了侵袭性取样（绒毛或羊水细胞）。在 2016 年至 2018 年期间，3.4%（95%置信区间[CI]2.8-4.2%；n=86）的侵袭性样本（n=2533）发现了致病拷贝数变异，5.3%（95%CI 4.4-6.2%；n=133）发现了三体和其他非整倍体。绒毛取样的周转时间从 14 天缩短至平均 5.5 天，减少了一半以上。
染色体微阵列技术发现了 5.3%的三体和 3.4%的拷贝数变异，与仅核型分析相比，诊断率提高了 64%以上，同时也将周转时间缩短了一半以上。一些初步的关注点被证明是真实存在的，例如产前咨询的复杂性，但随着时间的推移，通过专家咨询，这些问题已经在临床路径中得到解决。
