Prenatal Diagnostic Testing Following High-Risk Result from Serological Screening: Which Shall We Select?

Abstract

Purpose We retrospectively analyzed the results of prenatal diagnosis in women with high-risk (HR) serological screening results, and discussed the reasonable application of diagnostic testing. Patients and Methods Diagnostic testing was done in 2239 pregnant women who had HR results from serological screening in two prenatal diagnosis centers. According to the HR results, they were divided into simple HR, HR combined with ultrasound abnormalities, and HR combined with other indication groups. After receiving counselling from clinicians, they were allowed to choose either the traditional karyotype analysis and/or chromosomal microarray analysis (CMA). Results Those who underwent CMA comprised 49.3%, 97.6%, and 100% of the HR group, HR combined with ultrasound abnormalities, and HR combined with other indication groups, respectively. Among the 100 (4.47%) clinically significant results, 55 (2.46%), 15 (0.67%), and 30 (1.34%) were chromosomal aneuploidies, chromosomal structural abnormalities, and pathogenic copy number variations (CNVs), respectively. The rate of abnormalities was 3.77%, 13.71%, and 19.05% in the simple HR, HR combined with ultrasound abnormalities, and HR combined with other indication groups, respectively. The increasing rate of clinical pathogenic CNVs was 1.34% using CMA in HR pregnant women, 9.52% in the HR combined with other indication group, and 1.24% in the simple HR group. Among the 573 women who chose both diagnostic tests, 45 had abnormal results. Only one case detected using karyotype analysis was missed on CMA. The incidence of chromosomal aneuploidy tended to increase with increase in HR values. However, chromosomal structural abnormalities and pathogenic CNVs did not increase. Conclusion CMA should be recommended as the first-line diagnostic testing for women with HR screening results, especially combined with other abnormal indications.

Chromosomal Microarray Analysis Compared With Noninvasive Prenatal Testing in Pregnancies With Abnormal Maternal Serum Screening

“…Excluding NIPT-detectable anomalies, the residual risk for abnormal chromosomal microarray analysis was calculated as 2.5% (1/40) in pregnancies with combined first-trimester screening risk greater than 1:50, 6.8% (1/15) in combined first-trimester screening risk 1:50-1:100, and 3.7% (1/27) in combined first-trimester screening risk 1:100-1:300. Wang et al 29 have also presented the rates of abnormal chromosomal microarray analysis by specific maternal serum screening risks; however, this analysis also included pregnancies with abnormal ultrasonogram results and thus was not presented in our analysis.…”

“…One author was contacted for data clarification. 26 Finally, six articles encompassing 4,890 pregnancies with abnormal maternal serum screening and normal ultrasonogram results were included in the review, 12,13,[26][27][28][29] four involving retrospective cohorts and two involving prospective cohorts (Table 4). Four studies specifically focused on pregnancies with abnormal maternal serum screening, and the remaining articles examined pregnancies undergoing chromosomal microarray analysis for various prenatal indications, including abnormal maternal serum screening.…”

“…Finally, the specific maternal serum screening risk was not uniformly recorded, and the information about the maternal serum screening method (whether first-trimester, triple test, quadruple test, or integrated screening) was unavailable. Clinically significant chromosomal microarray analysis aberrations can be found in 1 of every 50 pregnancies with high-risk maternal serum screening after omission of NIPT-detectable findings, 26 Vogel (2018) 12 Wang (2018) 13 Xiang (2020) 27 Wu (2021) 28 Wang (2021) 29 Current Study (2022) 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.…”