Genetics Institute, Carmel Medical Center, affiliated to the Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, and the Recanati Genetics Institute, Beilinson Hospital, Rabin Medical Center, the Pediatric Genetics Unit, Schneider Children's Medical Center of Israel, and the Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, Israel.
Obstet Gynecol. 2022 May 1;139(5):877-887. doi: 10.1097/AOG.0000000000004758. Epub 2022 Apr 5.
To examine the effect of maternal age on the rate of clinically significant chromosomal microarray analysis results in pregnancies with abnormal maternal serum screening and to establish the residual risk for abnormal microarray findings after omitting noninvasive prenatal testing (NIPT)-detectable aberrations in pregnancies with abnormal maternal serum screening.
This retrospective study included all chromosomal microarray analysis tests performed in pregnancies with abnormal maternal serum screening and normal ultrasonogram results over the years 2013-2021. The rate of clinically significant (pathogenic and likely pathogenic) chromosomal microarray analysis findings was compared with a local control cohort of 7,235 pregnancies with normal maternal serum screening and ultrasonogram results, stratified by maternal age. Calculation of residual risk for clinically significant chromosomal microarray analysis results after normal NIPT was performed by omission of common NIPT-detectable anomalies. Systematic review for studies examining the yield of chromosomal microarray analysis in pregnancies with abnormal maternal serum screening was performed from inception to October 2021, with no time or language restrictions.
Of the 559 amniocenteses performed due to abnormal maternal serum screening, 21 (3.8%; 95% CI 2.4-5.7%) clinically significant chromosomal microarray analysis results were found. The residual risk for chromosomal microarray analysis aberrations after theoretically normal NIPT was estimated to be 2.0% (95% CI 1.1-3.6%) (1/50) and was significantly higher for women younger than age 35 years with abnormal maternal serum screening, compared with women with low-risk pregnancies. Systematic review yielded six articles encompassing 4,890 chromosomal microarray analysis results in pregnancies with abnormal maternal serum screening, demonstrating 2.3% residual risk for chromosomal microarray analysis anomalies after theoretically normal NIPT.
Clinically significant chromosomal microarray analysis findings can be found in 1 of every 50 pregnancies with high-risk maternal serum screening after theoretically normal NIPT, implying that invasive testing and not NIPT should be recommended in such pregnancies. In addition, NIPT use as a first-tier screening modality instead of maternal serum screening would miss pregnancies at increased risk not only for common autosomal trisomies but for additional chromosomal microarray analysis-detectable disorders.
探讨母体年龄对母体血清筛查异常妊娠中临床显著染色体微阵列分析结果发生率的影响，并确定母体血清筛查异常妊娠中排除非侵入性产前检测（NIPT）可检测到的异常后，异常微阵列结果的残留风险。
本回顾性研究纳入了 2013 年至 2021 年间所有因母体血清筛查异常且超声结果正常而进行的染色体微阵列分析检测。将临床显著（致病性和可能致病性）的染色体微阵列分析发现率与一个当地的对照队列进行比较，该对照队列包括 7235 例母体血清筛查和超声结果正常的妊娠，按母体年龄分层。通过排除常见的 NIPT 可检测到的异常，计算母体血清筛查异常妊娠中 NIPT 正常后临床显著染色体微阵列分析结果的残留风险。从研究开始到 2021 年 10 月，对母体血清筛查异常妊娠中染色体微阵列分析的研究进行了系统综述，无时间和语言限制。
在因母体血清筛查异常而进行的 559 例羊膜穿刺术中，发现 21 例（3.8%；95%CI 2.4-5.7%）临床显著的染色体微阵列分析结果。理论上 NIPT 正常后，染色体微阵列分析异常的残留风险估计为 2.0%（95%CI 1.1-3.6%）（1/50），且对于母体血清筛查异常的年轻女性（<35 岁），风险明显高于低危妊娠的女性。系统综述得出了六篇文章，涵盖了 4890 例母体血清筛查异常妊娠的染色体微阵列分析结果，显示理论上 NIPT 正常后，染色体微阵列分析异常的残留风险为 2.3%。
在理论上 NIPT 正常的高风险母体血清筛查妊娠中，每 50 例妊娠中就有 1 例可发现临床显著的染色体微阵列分析结果，这意味着在这种情况下，应推荐进行侵入性检测而不是 NIPT。此外，将 NIPT 用作一线筛查方法而不是母体血清筛查，不仅会错过常见常染色体三体的风险增加的妊娠，还会错过其他可通过染色体微阵列分析检测到的疾病。
