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American Journal of Obstetrics and... Mar 2023The diagnostic accuracy of cell-free fetal DNA in screening for rare autosomal trisomies is uncertain. We conducted a systematic review and meta-analysis aiming to... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The diagnostic accuracy of cell-free fetal DNA in screening for rare autosomal trisomies is uncertain. We conducted a systematic review and meta-analysis aiming to determine the predictive value of cell-free DNA in screening for rare autosomal trisomies.
DATA SOURCES
PubMed, Embase, and Web of Science were searched from inception to January 2022.
STUDY ELIGIBILITY CRITERIA
All studies that reported on the diagnostic accuracy of cell-free DNA in the detection of rare autosomal trisomies were included. Case series were included if they contained at least 10 cases with diagnostic test results or postnatal genetic testing.
METHODS
Study appraisal was completed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Statistical analysis was performed using random-effects meta-analysis of double-arcsine transformed proportions of confirmed results in the fetus out of the positive tests to obtain a pooled estimate of the positive predictive value.
RESULTS
The search identified 7553 studies, of which 1852 were duplicates. After screening 5701 titles and abstracts, 380 studies proceeded to the full-text screen; 206 articles were retrieved for data extraction, of which another 175 articles were excluded. A total of 31 studies, with a total of 1703 women were included for analysis. The pooled positive predictive value of cell-free DNA for the diagnosis of rare autosomal trisomies was 11.46% (95% confidence interval, 7.80-15.65). Statistical heterogeneity was high (I=82%). Sensitivity analysis restricted to 5 studies at low risk of bias demonstrated a pooled positive predictive value of 9.13% (95% confidence interval, 2.49-18.76). There were insufficient data to provide accurate ascertainment of sensitivity and specificity because most studies only offered confirmatory tests to women with high-risk results.
CONCLUSION
The positive predictive value of cell-free DNA in diagnosing rare autosomal trisomies is approximately 11%. Clinicians should provide this information when offering cell-free DNA for screening of conditions outside of common autosomal trisomies.
Topics: Pregnancy; Female; Humans; Trisomy; Down Syndrome; Cell-Free Nucleic Acids; Trisomy 13 Syndrome; Genetic Testing; Prenatal Diagnosis
PubMed: 36027954
DOI: 10.1016/j.ajog.2022.08.034 -
The European Journal of Health... Sep 2018The aim of this paper was to conduct a systematic review of the cost-effectiveness of the analysis of cell-free DNA in maternal blood, often called the non-invasive... (Review)
Review
The aim of this paper was to conduct a systematic review of the cost-effectiveness of the analysis of cell-free DNA in maternal blood, often called the non-invasive prenatal test (NIPT), in the prenatal screening of trisomy in chromosomes 21, 18 and 13. MEDLINE, MEDLINE in process, EMBASE, and Cochrane Library were searched in April 2017. We selected: (1) economic evaluations that estimated the costs and detected cases of trisomy 21, 18 or 13; (2) comparisons of prenatal screening with NIPT (universal or contingent strategies) and the usual screening without NIPT, (3) in pregnant women with any risk of foetal anomalies. Studies were reviewed by two researchers. Data were extracted, the methodological quality was assessed and a narrative synthesis was prepared. In total, 12 studies were included, four of them performed in Europe. Three studies evaluated NIPT as a contingent test, three studies evaluated a universal NIPT, and six studies evaluated both. The results are heterogeneous, especially for the contingent NIPT where the results range from NIPT being dominant to a dominated strategy. Universal NIPT was found to be more effective but also costlier than the usual screening, with very high incremental cost-effectiveness ratios. One advantage of screening with NIPT is lower invasive procedure-related foetal losses than with usual screening. In conclusion, the cost-effectiveness of contingent NIPT is uncertain according to several studies, while the universal NIPT is not cost-effective currently.
Topics: Cell-Free Nucleic Acids; Cost-Benefit Analysis; Down Syndrome; Europe; Female; Humans; Pregnancy; Trisomy; Trisomy 13 Syndrome; Trisomy 18 Syndrome
PubMed: 29249015
DOI: 10.1007/s10198-017-0946-y -
Prenatal Diagnosis Mar 2020To evaluate the test accuracy of non-invasive prenatal testing (NIPT) for fetal trisomy 21, 18, and 13 using cell-free (cf) DNA analysis in maternal plasma with... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the test accuracy of non-invasive prenatal testing (NIPT) for fetal trisomy 21, 18, and 13 using cell-free (cf) DNA analysis in maternal plasma with microarray quantitation.
METHOD
Systematic review and meta-analysis. Searches in MEDLINE, Pre-MEDLINE, EMBASE, Web of Science, and the Cochrane Library to 09.07.2018.
RESULTS
Five studies analyzing 3074 samples, including 187 trisomy 21, 43 trisomy 18, and 19 trisomy 13 cases, were identified. Risk of bias was high in all studies, introduced particularly by exclusions from analysis and by the role of the sponsor. Sensitivity of microarray-based cfDNA testing was 99.5% (95%CI 96.3%-99.9%) for trisomy 21, 97.7% (95%CI 87.9%-99.6%) for trisomy 18, and 100% (95%CI 83.2%-100%) for trisomy 13. Specificity was 100% (95% CI 99.87%-100%) for trisomy 21, 99.97% (95%CI 99.81%-99.99%) for trisomy 18, and 99.97% (95%CI 99.81%-99.99%) for trisomy 13. Pooled test failure rate was 1.1%. A direct comparison of microarray- and sequencing-based cfDNA found equivalent test accuracy.
CONCLUSION
Included studies suggest that NIPT using microarray-based cfDNA testing has high sensitivity and specificity for detecting fetal trisomy 21, 18, and 13. However, the evidence base is small and at high risk of bias.
Topics: Cell-Free Nucleic Acids; Down Syndrome; Female; High-Throughput Nucleotide Sequencing; Humans; Microarray Analysis; Noninvasive Prenatal Testing; Pregnancy; Sensitivity and Specificity; Sequence Analysis, DNA; Trisomy 13 Syndrome; Trisomy 18 Syndrome
PubMed: 31834626
DOI: 10.1002/pd.5621 -
BMC Pregnancy and Childbirth Jan 2019Non-invasive prenatal testing (NIPT) can be used to accurately detect fetal chromosomal anomalies early in pregnancy by assessing cell-free fetal DNA present in maternal...
BACKGROUND
Non-invasive prenatal testing (NIPT) can be used to accurately detect fetal chromosomal anomalies early in pregnancy by assessing cell-free fetal DNA present in maternal blood. The rapid diffusion of NIPT, as well as the ease and simplicity of the test raises concerns around informed decision-making and the potential for routinization. Introducing NIPT in a way that facilitates informed and autonomous decisions is imperative to the ethical application of this technology. We approach this imperative by systematically reviewing and synthesizing primary qualitative research on women's experiences with and preferences for informed decision-making around NIPT.
METHODS
We searched multiple bibliographic databases including Ovid MEDLINE, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), and ISI Web of Science Social Sciences Citation Index (SSCI). Our review was guided by integrative qualitative meta-synthesis, and we used a staged coding process similar to that of grounded theory to conduct our analysis.
RESULTS
Thirty empirical primary qualitative research studies were eligible for inclusion. Women preferred to learn about NIPT from their clinicians, but they expressed dissatisfaction with the quality and quantity of information provided during counselling and often sought information from a variety of other sources. Women generally had a good understanding of test characteristics, and the factors of accuracy, physical risk, and test timing were the critical information elements that they used to make informed decisions around NIPT. Women often described NIPT as easy or just another blood test, highlighting threats to informed decision-making such as routinization or a pressure to test.
CONCLUSIONS
Women's unique circumstances modulate the information that they value and require most in the context of making an informed decision. Widened availability of trustworthy information about NIPT as well as careful attention to the facilitation of counselling may help facilitate informed decision-making.
TRIAL REGISTRATION
PROSPERO 2018 CRD42018086261 .
Topics: Cell-Free Nucleic Acids; Choice Behavior; Decision Making; Down Syndrome; Female; Humans; Informed Consent; Patient Preference; Pregnancy; Pregnant Women; Prenatal Diagnosis; Qualitative Research; Trisomy 13 Syndrome; Trisomy 18 Syndrome
PubMed: 30642270
DOI: 10.1186/s12884-018-2168-4