Perinatal outcomes following cell‐free DNA screening in &gt;32 000 women: Clinical follow‐up data from a single tertiary center

Liu, Dong; Lin, Ying; Qiao, Fengxiang; Li, Hang; Wang, Yan; Zhang, Jingjing; Liu, An; Ji, Xiuqing; Ma, Dong‐Lai; Jiang, Tao; Hu, Ping; Xu, Zhengfeng

doi:10.1002/pd.5328

Cited by 45 publications

(53 citation statements)

References 48 publications

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“…A limitation of our study was the poor confirmation rate of positive NIPT results by amniocentesis and karyotyping, with 23% lost to follow‐up. This is not uncommon in China; in previous studies on perinatal outcome following NIPT, around 30% of Chinese pregnant women did not follow up their positive test result with their primary clinician and thus data are commonly lost to follow‐up. Despite this limitation, our findings on the performance of NIPT are in line with previous reports worldwide.…”

Section: Discussionsupporting

confidence: 85%

Non‐invasive cell‐free fetal DNA testing for aneuploidy: multicenter study of 31 515 singleton pregnancies in southeastern China

Huang

Lin

et al. 2020

Ultrasound in Obstet & Gyne

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Objective To analyze the non‐invasive prenatal testing (NIPT) for aneuploidy results of 31 515 singleton pregnancies in Fujian province, southeastern China, and assess its performance in low‐, moderate‐ and high‐risk pregnancies. Methods Women were categorized into groups according to whether their risk for fetal abnormality was low, moderate or high. Cell‐free plasma DNA extracted from peripheral blood samples was subjected to low‐coverage whole‐genome sequencing. Standard Z‐score analysis of the mapped sequencing reads was used to identify fetal aneuploidy, including the three main trisomies (T21, T18 and T13) and sex chromosome aneuploidy (SCA). NIPT‐positive results were confirmed by amniocentesis and karyotyping. The performance of NIPT for detection of T21, T18, T13 and SCA was assessed by calculating the sensitivity and specificity. Results The rate of chromosomal abnormality detected by NIPT in the study population was 1.38%. A higher rate of chromosomal abnormality was found in the high‐risk group (1.57%) compared to the moderate‐risk (1.05%) and low‐risk (1.18%) groups (P < 0.05). Sensitivity and specificity, respectively, were 98.96% (95/96) and 99.94% (31 274/31 292) for detection of T21, 100% (25/25) and 99.96% (31 352/31 363) for T18, 100% (7/7) and 99.97% (31 373/31 381) for T13 and 100% (61/61) and 99.74% (31 245/31 327) for SCA. Positive predictive values were high for T21 (84.07%) and T18 (69.44%) and moderate for T13 (46.67%) and SCA (42.66%). Conclusion Our findings support the application of NIPT for reliable and accurate testing of the general population of reproductive‐age women for clinically significant fetal aneuploidy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

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Section: Discussionsupporting

confidence: 85%

Non‐invasive cell‐free fetal DNA testing for aneuploidy: multicenter study of 31 515 singleton pregnancies in southeastern China

Huang

Lin

et al. 2020

Ultrasound in Obstet & Gyne

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“…One of the main study limitations was that this was a selected set of pregnancy samples and thus may not be truly representative of a larger general pregnancy population. Other recent publications have looked at genome-wide NIPT in patient populations of at least 10,000 patients [5,6,34,43], with a few publications reporting results from populations of over 50,000 patients [28,44,45]. However, the observed assay failure rate and FF distribution in our study population were consistent with those observed in the referral population, suggesting the data is representative.…”

Section: Discussionsupporting

confidence: 82%

“…In recent years, test menu options have expanded to include sex chromosome aneuploidies [24,25], select microdeletions/duplications [26,27], and ACAs [5,6,28]. Although ACAs are rarer, NIPT studies have shown a screen-positive rate of 0.1% for SUAs and 0.34% for RAAs [29].…”

Section: Introductionmentioning

confidence: 99%

Strategy for Use of Genome-Wide Non-Invasive Prenatal Testing for Rare Autosomal Aneuploidies and Unbalanced Structural Chromosomal Anomalies

Kleinfinger

Lohmann

Luscan

et al. 2020

JCM

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Atypical fetal chromosomal anomalies are more frequent than previously recognized and can affect fetal development. We propose a screening strategy for a genome-wide non-invasive prenatal test (NIPT) to detect these atypical chromosomal anomalies (ACAs). Two sample cohorts were tested. Assay performances were determined using Cohort A, which consisted of 192 biobanked plasma samples—42 with ACAs, and 150 without. The rate of additional invasive diagnostic procedures was determined using Cohort B, which consisted of 3097 pregnant women referred for routine NIPT. Of the 192 samples in Cohort A, there were four initial test failures and six discordant calls; overall sensitivity was 88.1% (37/42; CI 75.00–94.81) and specificity was 99.3% (145/146; CI 96.22–99.88). In Cohort B, there were 90 first-pass failures (2.9%). The rate of positive results indicating an anomaly was 1.2% (36/3007) and 0.57% (17/3007) when limited to significant unbalanced chromosomal anomalies and trisomies 8, 9, 12, 14, 15, 16, and 22. These results show that genome-wide NIPT can screen for ACAs with an acceptable sensitivity and a small increase in invasive testing, particularly for women with increased risk following maternal serum screening and by limiting screening to structural anomalies and the most clinically meaningful trisomies.

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“…Based on 10 genome-wide studies [10][11][12][13][14][15][16][17][18][19] , the weighted average rate of positive results for RATs (Table 1) was 0.32% (634/196 662; 95% CI, 0.30-0.36%). The frequency of RATs varied by more than 8-fold between the studies, ranging from 0.12% (95% CI, 0.08-0.17%) 17 to 1.03% (95% CI, 0.69-1.53%) 15 .…”

Section: Cfdna Detection Of Ratsmentioning

confidence: 99%

“…This includes mosaic and non-mosaic rare autosomal trisomies (RATs), which are defined as any autosomal trisomy other than trisomy 21, 18 or 13. Despite scant evidence of clinical utility 9 , some laboratories have introduced genome-wide screening, and clinical decisions are being taken based on the results it provides [10][11][12][13][14][15][16][17][18][19] .…”

Section: Introductionmentioning

confidence: 99%

Rare autosomal trisomies: comparison of detection through cell‐free DNA analysis and direct chromosome preparation of chorionic villus samples

Benn

Malvestiti²,

Grimi³

et al. 2019

Ultrasound in Obstet & Gyne

109

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Objective Direct chromosome preparations of chorionic villus samples (CVS) and cell‐free DNA (cfDNA) testing both involve analysis of the trophoblastic cell lineage. The aim of this study was to compare the spectrum of rare autosomal trisomies (RATs) detected by these two approaches and assess the available information on their clinical significance. Methods Data from 10 reports on genome‐wide cfDNA testing were pooled to determine which chromosomes were most frequently involved in RAT‐positive cases, and pregnancy outcome information was reviewed. CVS information was obtained from an updated database of 76 102 consecutive CVS analyses performed over a period of 18 years at TOMA laboratory, in which trophoblastic and mesenchymal layers were analyzed and amniotic fluid cell analysis was recommended for RAT‐positive cases. Chromosomes involved and presence of confined placental mosaicism, true fetal mosaicism and uniparental disomy (UPD) for imprinted chromosomes were assessed. Also evaluated were the frequency and types of RATs in products of conception. Results RATs were present in 634 of 196 662 (0.32%) cfDNA samples and 237 of 57 539 (0.41%) CVS trophoblast samples (P < 0.01). The frequency of RATs varied over 8‐fold between the cfDNA reports. Confirmation of abnormality through amniocentesis was more likely when RATs were ascertained through cfDNA (14 of 151; 9.3%) than through CVS trophoblasts (seven of 237; 3.0%) (P < 0.01). In cfDNA‐ascertained cases, trisomies 15, 16 and 22, which are associated with fetal loss, were identified proportionately more often. Of 151 cases with RAT identified by cfDNA and outcome information available, 41.1% resulted in normal live birth; 27.2% in fetal loss; 7.3% had phenotypic abnormality detected through ultrasound or other follow‐up evaluation; 2.0% had a clinically significant UPD; and 14.6% had fetal growth restriction or low birth weight. All autosomes were involved in trisomies in products of conception; the most common RATs detected were trisomies 16, 22 and 15 with a frequency of > 9% each. Conclusions Although there are strong parallels between RATs ascertained through cfDNA analysis and direct chromosome preparation of CVS, caution is needed in applying conclusions from CVS analysis to cfDNA testing, and vice versa. RATs identified through genome‐wide cfDNA tests have uncertain risks for fetal loss, growth restriction or fetal abnormality. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

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Perinatal outcomes following cell‐free DNA screening in >32 000 women: Clinical follow‐up data from a single tertiary center

Cited by 45 publications

References 48 publications

Non‐invasive cell‐free fetal DNA testing for aneuploidy: multicenter study of 31 515 singleton pregnancies in southeastern China

Non‐invasive cell‐free fetal DNA testing for aneuploidy: multicenter study of 31 515 singleton pregnancies in southeastern China

Strategy for Use of Genome-Wide Non-Invasive Prenatal Testing for Rare Autosomal Aneuploidies and Unbalanced Structural Chromosomal Anomalies

Rare autosomal trisomies: comparison of detection through cell‐free DNA analysis and direct chromosome preparation of chorionic villus samples

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