-
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 -
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 -
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 -
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 -
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... 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 -
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