Clinical application of expanded noninvasive prenatal testing for fetal chromosome abnormalities in a cohort of 39,580 pregnancies

Chen, Yisheng; Lu, Loukaiyi; Zhang, Ying; Wang, Feifei; Ni, Yuan; Wang, Qiang; Ying, Chunmei

doi:10.1002/ajmg.a.62657

Cited by 15 publications

(16 citation statements)

References 30 publications

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“…In present study, a cohort of 23,116 singleton pregnancies from a single center were enrolled to investigate the performance of NIPT-Plus. Our study showed that NIPT-Plus had a comparable PPV for T21 (86.21%) and T18 (55.88%) but a relatively low PPV for T13 (23.08%) compared to previous studies (Chen et al, 2022). The low PPV for T13 may be related to the small number of T13 positive cases in this study, which would increase the fluctuation of PPV.…”

Section: Discussioncontrasting

confidence: 49%

Performance of expanded non-invasive prenatal testing for fetal aneuploidies and copy number variations: A prospective study from a single center in Jiangxi province, China

et al. 2023

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To evaluate the performance of expanded non-invasive prenatal testing (expanded noninvasive prenatal testing, NIPT-Plus) in screening for fetal chromosomal abnormalities includes aneuploidies and copy number variations, a total of 23,116 pregnant women with a singleton pregnancy were recruited for NIPT-Plus. Screening positive results were verified by karyotype analysis and chromosomal microarray analysis after amniocentesis. A total of 264 pregnancies (1.14%) were positive results as predicted by NIPT-Plus, including 233 aneuploidies and 31 copy number variations. Following genetic counseling, 233 (88.26%) pregnant women underwent invasive prenatal diagnosis and 136 were verified as true positives, comprising 72 common trisomies (T21, T18, T13), 47 sex chromosomal abnormalities two rare autosomal aneuploidies (RATs) and 15 copy number variations The positive predictive value for common trisomies, SCAs, RATs and CNVs were 68.57%, 68.12%, 6.67% and 51.72%, respectively. Pregnant women with screen-positive results for common trisomies have higher rates of invasive prenatal diagnosis and pregnancy termination than those with positive results for SCAs, RATs, and CNVs. NIPT-Plus showed a good performance in detecting common trisomies, SCAs and also contributed to detecting pathogenic CNVs, but higher accuracy was required in the detection of RATs. In summary, this study provides a reference for the clinical application of NIPT-Plus for screening fetal chromosomal abnormalities in this region. Therefore, we suggest that NIPT-Plus could be widely used in clinical screening for fetal chromosomal abnormalities in combination with prenatal diagnosis and genetic counseling.

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Section: Discussioncontrasting

confidence: 49%

Performance of expanded non-invasive prenatal testing for fetal aneuploidies and copy number variations: A prospective study from a single center in Jiangxi province, China

et al. 2023

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“…In total, 7845 search results were identified, of which 1862 were duplicates. After screening the remaining 5983 results, 63 articles satisfied the inclusion criteria 12,14–16,18,26–83 . The study selection process is shown in Figure 1.…”

Section: Resultsmentioning

confidence: 99%

“…Authors were contacted for seven articles with incomplete data; data were obtained for one 38 and six were excluded. [84][85][86][87][88][89] Included studies were published between 2015 and 2022. Across all included studies, 1 591 459 women underwent cfDNA screening for CNVs, with 5481 receiving a high-risk result (screen-positive rate of 0.34%).…”

Section: Study Characteristicsmentioning

confidence: 99%

The accuracy of cell‐free DNA screening for fetal segmental copy number variants: A systematic review and meta‐analysis

Raymond

Acreman

Bussolaro

et al. 2023

BJOG

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Background The performance of cell‐free DNA (cfDNA) screening for microscopic copy number variants (CNVs) is unclear. Objectives This was a systematic review and meta‐analysis to investigate the sensitivity, specificity and positive predictive value (PPV) of cfDNA screening for CNVs. Search Strategy Articles published in EMBASE, PubMed or Web of Science before November 2022 were screened for inclusion. This protocol was registered with PROSPERO (23 March 2021, CRD42021250849) prior to initiation. Selection Criteria Articles published in English, detailing diagnostic outcomes for at least 10 high‐risk CNV results with cfDNA were considered for inclusion. Data Collection and Analysis The PPV was calculated and pooled with random‐effects models for double‐arcsine transformed proportions, using cases with diagnostic confirmation. Overall sensitivity, specificity and a summary receiver‐operating characteristics (ROC) curve were calculated using bivariate models. The risk of bias was assessed using QUADAS‐2. Main Results In all, 63 articles were included in the final analysis, detailing 1 591 459 cfDNA results. The pooled PPV was 37.5% (95% confidence interval [CI] 30.6–44.8), with substantial statistical heterogeneity (I2 = 93.9%). Bivariate meta‐analysis estimated sensitivity and specificity to be 77.4% (95% CI 65.7–86.0) and 99.4% (95% CI 98.0–99.8), respectively, with an area under the summary ROC curve of 0.947 (95% CI 0.776–0.984). Conclusions Approximately one‐third of women who screen high‐risk for CNVs with cfDNA will have an affected fetus. This value is of importance for screening counselling.

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“…13,14 In a more recent series of Chen et al including almost 40,000 samples, the PPV in screening microdeletions and duplications was 42%. 15 As most of the studies were done in screening populations, it is unclear why the PPVs are so heterogenous. However, in screening for trisomies, the fetal fraction (FF) is considered as a quality parameter with a strong impact on the test performance and as such also on the PPV.…”

Section: Bevilacqua Et Al Examined the Test Performance In A Prospect...mentioning

confidence: 99%

“…In a more recent series of Chen et al. including almost 40,000 samples, the PPV in screening microdeletions and duplications was 42% 15 . As most of the studies were done in screening populations, it is unclear why the PPVs are so heterogenous.…”

Section: Introductionmentioning

confidence: 99%

Screen‐positive rate in cell‐free DNA screening for microdeletion 22q11.2

Lüthgens¹,

Sinzel²,

Kolar³

et al. 2023

Prenatal Diagnosis

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Objective: To examine the impact of the fetal fraction (FF) on the screen-positive rate in screening for microdeletion 22q11.2.Methods: This study is based on samples that were analyzed using the Harmony® Prenatal Test (Roche Inc). The study cohort comprised samples from women with singleton pregnancies who were at least 16 years old and at least at 11 weeks' gestation. Logistic regression analysis was used to determine significant covariates that carry an impact on the screen-positive rate. Results:The study population consisted of 52,019 pregnancies, including 309 pregnancies with a high-risk result for microdeletion 22q11.2. Thus, the overall screen-positive rate was 0.59%. In the low-risk group, the FF was 10.1%, and in the high-risk group, it was 7.3%. Regression analysis indicated a strong correlation between the FF and the screen-positive rate. In the cases with an FF of <11.0%, the screen-positive rate was 0.92%, while it was 0.13% in the group with a higher FF. Conclusion:The screen-positive rate depends on the FF. In order to keep the rate low, we recommend restricting the analysis to samples with a FF of 11% and more. Key pointsWhat is already known? � The gold standard in screening for common trisomies is based on cell-free DNA analysis (cfDNA) screening. What is new?� The screen-positive rate of prenatal cfDNA screening for microdeletion 22q11.2 is higher in patients with a low fetal fraction. | INTRODUCTIONCurrent antenatal screening for common trisomies is based on ultrasound and cell-free DNA analysis (cfDNA). [1][2][3] Several studies have summarized the test performance of cfDNA screening and reported on a detection rate for common trisomies of about 92%-99% for a false-positive rate of 0.1%. 4,5 There is an ongoing discussion on whether the scope of the cfDNA analysis should be extended to other chromosomal abnormalities, such a sex-chromosomal anomalies, rare autosomal trisomies, and structural chromosomal defects. 6 Many study groups have focused on microdeletion 22q11.2 syndrome as it belongs to the most common structural chromosomal defects. 7 The prevalence of this disorder has been estimated to rangeThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Clinical application of expanded noninvasive prenatal testing for fetal chromosome abnormalities in a cohort of 39,580 pregnancies

Cited by 15 publications

References 30 publications

Performance of expanded non-invasive prenatal testing for fetal aneuploidies and copy number variations: A prospective study from a single center in Jiangxi province, China

Performance of expanded non-invasive prenatal testing for fetal aneuploidies and copy number variations: A prospective study from a single center in Jiangxi province, China

The accuracy of cell‐free DNA screening for fetal segmental copy number variants: A systematic review and meta‐analysis

Screen‐positive rate in cell‐free DNA screening for microdeletion 22q11.2

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