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BMJ Open Jan 2016To measure test accuracy of non-invasive prenatal testing (NIPT) for Down, Edwards and Patau syndromes using cell-free fetal DNA and identify factors affecting accuracy. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To measure test accuracy of non-invasive prenatal testing (NIPT) for Down, Edwards and Patau syndromes using cell-free fetal DNA and identify factors affecting accuracy.
DESIGN
Systematic review and meta-analysis of published studies.
DATA SOURCES
PubMed, Ovid Medline, Ovid Embase and the Cochrane Library published from 1997 to 9 February 2015, followed by weekly autoalerts until 1 April 2015.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
English language journal articles describing case-control studies with ≥ 15 trisomy cases or cohort studies with ≥ 50 pregnant women who had been given NIPT and a reference standard.
RESULTS
41, 37 and 30 studies of 2012 publications retrieved were included in the review for Down, Edwards and Patau syndromes. Quality appraisal identified high risk of bias in included studies, funnel plots showed evidence of publication bias. Pooled sensitivity was 99.3% (95% CI 98.9% to 99.6%) for Down, 97.4% (95.8% to 98.4%) for Edwards, and 97.4% (86.1% to 99.6%) for Patau syndrome. The pooled specificity was 99.9% (99.9% to 100%) for all three trisomies. In 100,000 pregnancies in the general obstetric population we would expect 417, 89 and 40 cases of Downs, Edwards and Patau syndromes to be detected by NIPT, with 94, 154 and 42 false positive results. Sensitivity was lower in twin than singleton pregnancies, reduced by 9% for Down, 28% for Edwards and 22% for Patau syndrome. Pooled sensitivity was also lower in the first trimester of pregnancy, in studies in the general obstetric population, and in cohort studies with consecutive enrolment.
CONCLUSIONS
NIPT using cell-free fetal DNA has very high sensitivity and specificity for Down syndrome, with slightly lower sensitivity for Edwards and Patau syndrome. However, it is not 100% accurate and should not be used as a final diagnosis for positive cases.
TRIAL REGISTRATION NUMBER
CRD42014014947.
Topics: Biomarkers; Chromosome Disorders; Chromosomes, Human, Pair 13; Chromosomes, Human, Pair 18; DNA; Down Syndrome; Female; Humans; Pregnancy; Prenatal Diagnosis; Sensitivity and Specificity; Trisomy; Trisomy 13 Syndrome; Trisomy 18 Syndrome
PubMed: 26781507
DOI: 10.1136/bmjopen-2015-010002 -
Genetics in Medicine : Official Journal... Jul 2022Noninvasive prenatal screening (NIPS) using cell-free DNA has been assimilated into prenatal care. Prior studies examined clinical validity and technical performance in... (Review)
Review
PURPOSE
Noninvasive prenatal screening (NIPS) using cell-free DNA has been assimilated into prenatal care. Prior studies examined clinical validity and technical performance in high-risk populations. This systematic evidence review evaluates NIPS performance in a general-risk population.
METHODS
Medline (PubMed) and Embase were used to identify studies examining detection of Down syndrome (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies, rare autosomal trisomies, copy number variants, and maternal conditions, as well as studies assessing the psychological impact of NIPS and the rate of subsequent diagnostic testing. Random-effects meta-analyses were used to calculate pooled estimates of NIPS performance (P < .05). Heterogeneity was investigated through subgroup analyses. Risk of bias was assessed.
RESULTS
A total of 87 studies met inclusion criteria. Diagnostic odds ratios were significant (P < .0001) for T21, T18, and T13 for singleton and twin pregnancies. NIPS was accurate (≥99.78%) in detecting sex chromosome aneuploidies. Performance for rare autosomal trisomies and copy number variants was variable. Use of NIPS reduced diagnostic tests by 31% to 79%. Conclusions regarding psychosocial outcomes could not be drawn owing to lack of data. Identification of maternal conditions was rare.
CONCLUSION
NIPS is a highly accurate screening method for T21, T18, and T13 in both singleton and twin pregnancies.
Topics: Cell-Free Nucleic Acids; Down Syndrome; Female; Humans; Noninvasive Prenatal Testing; Pregnancy; Prenatal Diagnosis; Sex Chromosome Aberrations; Trisomy; Trisomy 13 Syndrome; Trisomy 18 Syndrome
PubMed: 35608568
DOI: 10.1016/j.gim.2022.03.019 -
American Journal of Medical Genetics.... Sep 2016Constitutional trisomy 18 causes Edwards syndrome, which is characterized by intellectual disability and a particular set of malformations. Although this condition... (Review)
Review
Constitutional trisomy 18 causes Edwards syndrome, which is characterized by intellectual disability and a particular set of malformations. Although this condition carries high mortality during prenatal and early postnatal life, some of the rare infants who survive the first months develop benign and malignant tumors. To determine the tumor profile associated with Edwards syndrome, we performed a systematic review of the literature. This review reveals a tumor profile differing from those of Down (trisomy 21) and Patau (trisomy 13) syndromes. The literature covers 45 malignancies: 29 were liver cancers, mainly hepatoblastomas found in Japanese females; 13 were kidney tumors, predominantly nephroblastomas; 1 was neuroblastoma; 1 was a Hodgkin disease; and 1 was acute myeloid leukemia in an infant with both trisomy 18 and type 1 neurofibromatosis. No instances of the most frequent malignancies of early life-cerebral tumors, germ cell tumors, or leukemia--are reported in children with pure trisomy 18. Tumor occurrence does not appear to correlate with body weight, tissue growth, or cancer genes mapping to chromosome 18. Importantly, the most recent clinical histories report successful treatment; this raises ethical concerns about cancer treatment in infants with Edwards syndrome. In conclusion, knowledge of the Edwards' syndrome tumor profile will enable better clinical surveillance in at-risk organs (i.e., liver, kidney). This knowledge also provides clues to understanding oncogenesis, including the probably reduced frequency of some neoplasms in infants and children with this genetic condition. © 2016 Wiley Periodicals, Inc.
Topics: Carcinogenesis; Child, Preschool; Chromosomes, Human, Pair 18; Humans; Infant; Infant, Newborn; Neoplasms; Trisomy; Trisomy 18 Syndrome
PubMed: 27474103
DOI: 10.1002/ajmg.c.31511 -
International Journal of Dermatology Mar 2021Hidradenitis suppurativa (HS) is a chronic inflammatory follicular disorder that involves painful nodules, abscesses, and tunnels of intertriginous sites. Although the... (Review)
Review
Hidradenitis suppurativa (HS) is a chronic inflammatory follicular disorder that involves painful nodules, abscesses, and tunnels of intertriginous sites. Although the etiology has not been fully elucidated, recent studies have highlighted its association with chromosomal abnormalities.We present a rare case of HS in a patient with Trisomy 1q;13 and systematically summarize the association between HS and chromosomal abnormalities. A search was conducted using MEDLINE and EMBASE in OVID database. Original studies reporting HS among human subjects with chromosomal abnormalities were included. Patient demographics, disease symptomology, clinical features, and treatment histories were extracted and summarized.Thirteen studies describing 428 cases met the inclusion criteria. Of the 13 articles, nine studies reported patients with HS and Down syndrome (DS), one article investigated HS and Smith-Magenis syndrome (SMS), and three articles analyzed HS and Patau syndrome (PS). While increased prevalence of HS was found in populations with DS, with suggested mechanisms involving amyloid precursor protein cleavage product, keratinocyte proliferation, and follicular plugging, the associations between HS and both SMS and PS remain inconclusive because of limited studies with small sample size.Although evidence suggests that the genetic regulation of chromosome 21 may be implicated in the association between HS and DS, this association may be confounded by additional factors that increase the risk of HS. Further research with larger sample sizes must be conducted to strengthen our understanding of the association between HS and chromosomal abnormalities.
Topics: Chromosome Aberrations; Down Syndrome; Hidradenitis Suppurativa; Humans; Prevalence
PubMed: 33599294
DOI: 10.1111/ijd.15111 -
Acta Obstetricia Et Gynecologica... Jan 2017The aim of this study was to review the performance of non-invasive prenatal testing (NIPT) for detection of trisomy 21, 18 and 13 (T21, T18 and T13) in a general... (Meta-Analysis)
Meta-Analysis Review
Analysis of cell-free fetal DNA in maternal blood for detection of trisomy 21, 18 and 13 in a general pregnant population and in a high risk population - a systematic review and meta-analysis.
INTRODUCTION
The aim of this study was to review the performance of non-invasive prenatal testing (NIPT) for detection of trisomy 21, 18 and 13 (T21, T18 and T13) in a general pregnant population as well as to update the data on high-risk pregnancies.
MATERIAL AND METHODS
Systematic review and meta-analysis. PubMed, Embase and the Cochrane Library were searched. Methodological quality was rated using QUADAS and scientific evidence using GRADE. Summary measures of diagnostic accuracy were calculated using a bivariate random-effects model.
RESULTS
In a general pregnant population, there is moderate evidence that the pooled sensitivity is 0.993 (95% CI 0.955-0.999) and specificity was 0.999 (95% CI 0.998-0.999) for the analysis of T21. Pooled sensitivity and specificity for T13 and T18 was not calculated in this population due to the low number of studies. In a high-risk pregnant population, there is moderate evidence that the pooled sensitivities for T21 and T18 are 0.998 (95% CI 0.981-0.999) and 0.977 (95% CI 0.958-0.987) respectively, and low evidence that the pooled sensitivity for T13 is 0.975 (95% CI 0.819-0.997). The pooled specificity for all three trisomies is 0.999 (95% CI 0.998-0.999).
CONCLUSIONS
This is the first meta-analysis using GRADE that shows that NIPT performs well as a screen for trisomy 21 in a general pregnant population. Although the false positive rate is low compared with first trimester combined screening, women should still be advised to confirm a positive result by invasive testing if termination of pregnancy is under consideration.
Topics: Cell-Free System; Chromosome Disorders; Chromosomes, Human, Pair 13; Chromosomes, Human, Pair 18; DNA; Down Syndrome; Female; Genetic Testing; Humans; Pregnancy; Pregnancy, High-Risk; Prenatal Diagnosis; Sensitivity and Specificity; Trisomy; Trisomy 13 Syndrome; Trisomy 18 Syndrome
PubMed: 27779757
DOI: 10.1111/aogs.13047 -
Prenatal Diagnosis Jun 2023To perform a systematic review and meta-analysis of the available literature on low fetal fraction (LFF) in cell-free DNA (cfDNA) screening and the risk of fetal... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To perform a systematic review and meta-analysis of the available literature on low fetal fraction (LFF) in cell-free DNA (cfDNA) screening and the risk of fetal chromosomal aberrations.
METHOD
We searched articles published between January 2010 and May 2021 in PubMed and EMBASE databases. Risk of bias was assessed using QUADAS-2.
RESULTS
Twenty-seven studies met the inclusion criteria, comprising data of 243,700 singleton pregnancies. Compared to normal fetal fraction, LFF was associated with a higher risk of trisomy 13 (OR 5.99 [3.61-9.95], I of heterogeneity = 0%, n = 22 studies), trisomy 18 (OR 4.46 [3.07-6.47], I = 0%, n = 22 studies), monosomy X (OR 5.88 [2.34-14.78], I = 18%, n = 10 studies), and triploidy (OR 36.39 [9.83-134.68], I = 61%, n = 6 studies), but not trisomy 21 (OR 1.25 [0.76-2.03], I = 36%, n = 23 studies). LFF was also associated with a higher risk of various other types of fetal chromosomal aberrations (OR 4.00 [1.78-9.00], I = 2%, n = 11 studies). Meta-analysis of proportions showed that absolute rates of fetal chromosomal aberrations ranged between 1% and 2% in women with LFF. A limitation of this review is the potential risk of ascertainment bias because of differences in outcome assessment between pregnancies with LFF and those with normal fetal fraction. Heterogeneity in population characteristics or applied technologies across included studies may not have been fully addressed.
CONCLUSION
An LFF test result in cfDNA screening is associated with an increased risk of fetal trisomy 13, trisomy 18, monosomy X, and triploidy, but not trisomy 21. Further research is needed to assess the association between LFF and other specific types of fetal chromosomal aberrations.
Topics: Pregnancy; Female; Humans; Trisomy 18 Syndrome; Trisomy 13 Syndrome; Turner Syndrome; Triploidy; Cell-Free Nucleic Acids; Prenatal Diagnosis; Down Syndrome
PubMed: 37143173
DOI: 10.1002/pd.6366 -
Prenatal Diagnosis Jun 2023The screening performance of non-invasive prenatal testing (NIPT) in vanishing twin (VT) pregnancies is relatively unknown. To close this knowledge gap, we conducted a... (Review)
Review
The screening performance of non-invasive prenatal testing (NIPT) in vanishing twin (VT) pregnancies is relatively unknown. To close this knowledge gap, we conducted a systematic review of the available literature. Studies describing the test performance of NIPT for trisomy 21, 18, 13, sex chromosomes and additional findings in pregnancies with a VT were retrieved from a literature search with a publication date until October 4, 2022. The methodological quality of the studies was assessed with the quality assessment tool for diagnostic accuracy studies-2 (QUADAS-2). The screen positive rate of the pooled data and the pooled positive predictive value (PPV) were calculated using a random effects model. Seven studies, with cohort sizes ranging from 5 to 767, were included. The screen positive rate of the pooled data for trisomy 21 was 35/1592 (2.2%), with a PPV of 20% (confirmation in 7/35 cases [95% CI 9.8%-36%]). For trisomy 18, the screen positive rate was 13/1592 (0.91%) and the pooled PPV 25% [95% CI 1.3%-90%]. The screen positive rate for trisomy 13 was 7/1592 (0.44%) and confirmed in 0/7 cases (pooled PPV 0% [95% CI 0%-100%]). The screen positive rate for additional findings was 23/767 (2.9%), of which none could be confirmed. No discordant negative results were reported. There is insufficient data to fully evaluate NIPT performance in pregnancies with a VT. However, existing studies suggest that NIPT can successfully detect common autosomal aneuploidies in pregnancies affected by a VT but with a higher false positive rate. Further studies are needed to determine the optimal timing of NIPT in VT pregnancies.
Topics: Pregnancy; Female; Humans; Pregnancy, Twin; Down Syndrome; Chromosome Disorders; Abortion, Spontaneous; Trisomy 13 Syndrome; Trisomy 18 Syndrome; Fetal Death; Prenatal Diagnosis; Aneuploidy; Trisomy
PubMed: 37226326
DOI: 10.1002/pd.6388 -
BJOG : An International Journal of... Jan 2017Cell-free fetal DNA (cffDNA) non-invasive prenatal testing (NIPT) is rapidly expanding, and is being introduced at varying rates depending on country and condition. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cell-free fetal DNA (cffDNA) non-invasive prenatal testing (NIPT) is rapidly expanding, and is being introduced at varying rates depending on country and condition.
OBJECTIVES
Determine accuracy of cffDNA-based NIPT for all conditions. Evaluate influence of other factors on test performance.
SEARCH STRATEGY
Medline, Embase, CINAHL, Cochrane Library, from 1997 to April 2015.
SELECTION CRITERIA
Cohort studies reporting cffDNA-based NIPT performance in singleton pregnancies.
DATA COLLECTION AND ANALYSIS
Bivariate or univariate meta-analysis and subgroup analysis performed to explore influence of test type and population risk.
MAIN RESULTS
A total of 117 studies were included that analysed 18 conditions. Bivariate meta-analysis demonstrated sensitivities and specificities, respectively, for: fetal sex, 0.989 (95% CI 0.980-0.994) and 0.996 (95% CI 0.989-0.998), 11 179 tests; rhesus D, 0.993 (95% CI 0.982-0.997) and 0.984 (95% CI 0.964-0.993), 10 290 tests; trisomy 21, 0.994 (95% CI 0.983-0.998) and 0.999 (95% CI 0.999-1.000), 148 344 tests; trisomy 18, 0.977 (95% CI 0.952-0.989) and 0.999 (95% CI 0.998-1.000), 146 940 tests; monosomy X, 0.929 (95% CI 0.741-0.984) and 0.999 (95% CI 0.995-0.999), 6712 tests. Trisomy 13 was analysed by univariate meta-analysis, with a summary sensitivity of 0.906 (95% CI 0.823-0.958) and specificity of 1.00 (95% CI 0.999-0.100), from 134 691 tests. False and inconclusive results were poorly reported across all conditions. Although the test type affected both sensitivity and specificity, there was no evidence that population risk had any effect.
CONCLUSION
Performance of cffDNA-based NIPT is affected by condition under investigation. For fetal sex and rhesus D status, NIPT can be considered diagnostic. For trisomy 21, 18, and 13, the lower sensitivity, specificity, and disease prevalence, combined with the biological influence of confined placental mosaicism, designates it a screening test. These factors must be considered when counselling patients and assessing the cost of introduction into routine care. TWEETABLE ABSTRACT: cffDNA NIPT accuracy high, can be diagnostic for fetal sex and rhesus D, but only screening test in aneuploidy.
Topics: Biomarkers; Chromosome Disorders; DNA; Down Syndrome; Female; Humans; Predictive Value of Tests; Pregnancy; Pregnancy, High-Risk; Prenatal Diagnosis; Sensitivity and Specificity; Trisomy 13 Syndrome; Trisomy 18 Syndrome
PubMed: 27245374
DOI: 10.1111/1471-0528.14050 -
Acta Obstetricia Et Gynecologica... Jun 2020The objective of this study was to report on the clinical performance of non-invasive prenatal testing (NIPT) for trisomies 21, 18 and 13 in twin pregnancies and to... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The objective of this study was to report on the clinical performance of non-invasive prenatal testing (NIPT) for trisomies 21, 18 and 13 in twin pregnancies and to define the performance of NIPT by combining our cohort study results with published studies in a systematic meta-analysis.
MATERIAL AND METHODS
A cohort study was carried out in the First Affiliated Hospital of Sun Yat-sen University and Kanghua Hospital. Meanwhile, searches of PubMed, EMBASE, The Cochrane Library and Web of Science for all relevant peer-reviewed articles were performed with a restriction to English language publication before 15 June 2019. Quality assessments were conducted with the Quality Assessment Tool for Diagnostic Accuracy Studies-2 checklist. Data analysis, heterogeneity, subgroup analysis and publication bias were carried out using META-DISC 1.4 and STATA 12.0.
RESULTS
In all, 141 twin pregnancies included in our cohort study; confirmation revealed one true-positive case for trisomy 21 and 140 true-negative cases. The sensitivity and specificity for trisomy 21 by NIPT were both 100%. Twenty-two eligible studies were enrolled in this meta-analysis together with our study. There were 199 cases of trisomy 21, 58 cases of trisomy 18, 14 cases of trisomy 13 and 6347 cases of euploids in total. For trisomy 21, NIPT showed the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 0.99, 1.00, 145.81, 0.06 and 1714.09, respectively. For trisomy 18, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 0.88, 1.00, 200.98, 0.19 and 483.68, respectively.
CONCLUSIONS
The performance of NIPT for trisomy 21 in twin pregnancy was excellent and it was similar to that reported in singleton pregnancy. However, due to publication bias (trisomy 18) and small number of cases (trisomy 13), accurate assessment of the predictive performance of NIPT for trisomies 18 and 13 could not be achieved.
Topics: Adolescent; Adult; Cohort Studies; Down Syndrome; Female; Humans; Likelihood Functions; Noninvasive Prenatal Testing; Pregnancy; Pregnancy, Twin; Sensitivity and Specificity; Trisomy 13 Syndrome; Trisomy 18 Syndrome; Young Adult
PubMed: 32166736
DOI: 10.1111/aogs.13842 -
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