Accuracy of non-invasive prenatal testing using cell-free DNA for detection of Down, Edwards and Patau syndromes: a systematic review and meta-analysis

BMJ Open - Tập 6 Số 1 - Trang e010002 - 2016
Siân Taylor-Phillips1, Karoline Freeman1, Julia Geppert1, Adeola Agbebiyi1, Olalekan A Uthman1, Jason Madan1, Angus Clarke2, Siobhan Quenby1, Aileen Clarke1
1Warwick Medical School, The University of Warwick, Coventry, West Midlands, UK
2Institute of Cancer & Genetics, Cardiff University School of Medicine, Cardiff, UK

Tóm tắt

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.

Từ khóa


Tài liệu tham khảo

10.1126/scitranslmed.3008704

10.1002/pd.4125

10.1159/000327159

10.1002/uog.14791

Zhang, 2015, Non-invasive prenatal testing for trisomies 21, 18 and 13: clinical experience from 146,958 pregnancies, Ultrasound Obstet Gynecol, 45, 530, 10.1002/uog.14792

10.1056/NEJMoa1407349

10.1016/j.jclinepi.2005.02.022

Hand, 2010, Evaluating diagnostic tests: the area under the ROC curve and the balance of errors, Stat Med, 29, 1502, 10.1002/sim.3859

10.1002/sim.4172

10.1059/0003-4819-155-8-201110180-00009

10.7326/0003-4819-149-12-200812160-00008

Dwamena BA . MIDAS: Stata module for meta-analytical integration of diagnostic test accuracy studies. Boston, MA: Boston College Department of Economics, 2008.

10.1136/bmj.e6717

10.1136/bmj.f2778

10.1016/S0895-4356(03)00177-X

10.1002/sim.1185

10.1016/j.jclinepi.2005.01.016

Harbord, 2008, Meta-regression in Stata, Stata J, 8, 493, 10.1177/1536867X0800800403

Harbord, 2009, metandi: Meta-analysis of diagnostic accuracy using hierarchical logistic regression, Stata J, 9, 211, 10.1177/1536867X0900900203

White, 2011, Multivariate random-effects meta-regression: updates to mvmeta, Stata J, 11, 255, 10.1177/1536867X1101100206

10.1056/NEJMoa1311037

10.1002/pd.4002

del Mar, 2014, Cell-free DNA analysis for trisomy risk assessment in first-trimester twin pregnancies, Fetal Diagn Ther, 35, 204, 10.1159/000356495

Huang, 2014, Noninvasive prenatal testing of trisomies 21 and 18 by massively parallel sequencing of maternal plasma DNA in twin pregnancies, Prenat Diagn, 34, 335, 10.1002/pd.4303

Jiang, 2012, Noninvasive Fetal Trisomy (NIFTY) test: an advanced noninvasive prenatal diagnosis methodology for fetal autosomal and sex chromosomal aneuploidies, BMC Medical Genomics, 5, 57, 10.1186/1755-8794-5-57

10.3109/14767058.2011.635730

Lau, 2014, Non-invasive prenatal testing for fetal chromosomal abnormalities by low-coverage whole-genome sequencing of maternal plasma DNA: review of 1982 consecutive cases in a single center, Ultrasound Obstet Gynecol, 43, 254, 10.1002/uog.13277

10.1002/pd.4033

Nicolaides, 2012, Noninvasive prenatal testing for fetal trisomies in a routinely screened first-trimester population, Am J Obstet Gynecol, 207, 374.e1, 10.1016/j.ajog.2012.08.033

10.1002/pd.4103

10.1016/j.ajog.2012.05.021

10.1097/AOG.0000000000000363

10.1016/j.ajog.2014.03.042

Shaw, 2014, Noninvasive prenatal testing for whole fetal chromosomal aneuploidies: a multicenter prospective cohort trial in Taiwan, Fetal Diagn Ther, 35, 13, 10.1159/000355407

10.1002/pd.4160

Stumm, 2014, Diagnostic accuracy of random massively parallel sequencing for non-invasive prenatal detection of common autosomal aneuploidies: a collaborative study in Europe, Prenat Diagn, 34, 185, 10.1002/pd.4278

Verweij, 2013, European non-invasive trisomy evaluation (EU-NITE) study: a multicenter prospective cohort study for non-invasive fetal trisomy 21 testing, Prenat Diagn, 33, 996, 10.1002/pd.4182

Beamon, 2014, A single center's experience with noninvasive prenatal testing, Genet Med, 16, 681, 10.1038/gim.2014.20

Bevilacqua, 2015, Performance of screening for aneuploidies by cell-free DNA analysis of maternal blood in twin pregnancies, Ultrasound Obstet Gynecol, 45, 61, 10.1002/uog.14690

Comas, 2015, Initial experience with non-invasive prenatal testing of cell-free DNA for major chromosomal anomalies in a clinical setting, J Matern Fetal Neonatal Med, 28, 1196, 10.3109/14767058.2014.947579

Jeon, 2014, The feasibility study of non-invasive fetal trisomy 18 and 21 detection with semiconductor sequencing platform, PLoS ONE, 9, e110240, 10.1371/journal.pone.0110240

Korostelev, 2014, Association of non-invasive prenatal testing and chromosomal microarray analysis for prenatal diagnostics, Gynecol Endocrinol, 30, 13, 10.3109/09513590.2014.945770

Quezada, 2015, Screening for trisomies 21, 18 and 13 by cell-free DNA analysis of maternal blood at 10–11 weeks’ gestation and the combined test at 11–13 weeks, Ultrasound Obstet Gynecol, 45, 36, 10.1002/uog.14664

Sago, 2015, Nationwide demonstration project of next-generation sequencing of cell-free DNA in maternal plasma in Japan: one-year experience, Prenat Diagn, 35, 331, 10.1002/pd.4539

Wax, 2015, Noninvasive prenatal testing: impact on genetic counseling, invasive prenatal diagnosis, and trisomy 21 detection, J Clin Ultrasound, 43, 1, 10.1002/jcu.22243

Zhou, 2014, Clinical application of noninvasive prenatal testing for the detection of trisomies 21, 18, and 13: a hospital experience, Prenat Diagn, 34, 1061, 10.1002/pd.4428

Song, 2015, Non-invasive prenatal testing for fetal aneuploidies in the first trimester of pregnancy, Ultrasound Obstet Gynecol, 45, 55, 10.1002/uog.13460

10.1016/j.ajog.2012.01.029

10.1097/AOG.0b013e31824fb482

10.1371/journal.pone.0021791

10.1136/bmj.c7401

10.1016/j.ajog.2010.12.060

Hall, 2014, Non-invasive prenatal detection of trisomy 13 using a single nucleotide polymorphism- and informatics-based approach, PLoS ONE, 9, e96677, 10.1371/journal.pone.0096677

10.1038/gim.2011.73

10.1373/clinchem.2011.165910

10.1016/j.ajog.2012.01.030

10.1002/pd.3993

Alberti, 2015, Non-invasive prenatal testing for trisomy 21 based on analysis of cell-free fetal DNA circulating in the maternal plasma, Prenat Diagn, 35, 471, 10.1002/pd.4561

10.1016/S0140-6736(07)60115-9

10.1002/pd.4123

10.1093/humupd/dmt001

10.1159/000333060

10.1002/(SICI)1097-0258(19981130)17:22<2537::AID-SIM953>3.0.CO;2-C

McCullough, 2014, Non-invasive prenatal chromosomal aneuploidy testing—clinical experience: 100,000 clinical samples, PLoS ONE, 9, e109173, 10.1371/journal.pone.0109173