title: Accuracy of non-invasive prenatal testing using cell-free DNA for detection of Down, Edwards and Patau syndromes: a systematic review and meta-analysis.
abstract: 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.
  
  
  METHODS
  Systematic review and meta-analysis of published studies.
  
  
  METHODS
  PubMed, Ovid Medline, Ovid Embase and the Cochrane Library published from 1997 to 9 February 2015, followed by weekly autoalerts until 1 April 2015.
  
  
  METHODS
  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.
  
  
  BACKGROUND
  CRD42014014947.
authors.affiliation: Warwick Medical School, The University of Warwick, Coventry, West Midlands, UK.
authors.forename: Sian
authors.initials: S
authors.lastname: Taylor-Phillips
authors.affiliation: Warwick Medical School, The University of Warwick, Coventry, West Midlands, UK.
authors.forename: Karoline
authors.initials: K
authors.lastname: Freeman
authors.affiliation: Warwick Medical School, The University of Warwick, Coventry, West Midlands, UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Geppert
authors.affiliation: Warwick Medical School, The University of Warwick, Coventry, West Midlands, UK.
authors.forename: Adeola
authors.initials: A
authors.lastname: Agbebiyi
authors.affiliation: Warwick Medical School, The University of Warwick, Coventry, West Midlands, UK.
authors.forename: Olalekan A
authors.initials: OA
authors.lastname: Uthman
authors.affiliation: Warwick Medical School, The University of Warwick, Coventry, West Midlands, UK.
authors.forename: Jason
authors.initials: J
authors.lastname: Madan
authors.affiliation: Institute of Cancer & Genetics, Cardiff University School of Medicine, Cardiff, UK.
authors.forename: Angus
authors.initials: A
authors.lastname: Clarke
authors.affiliation: Warwick Medical School, The University of Warwick, Coventry, West Midlands, UK.
authors.forename: Siobhan
authors.initials: S
authors.lastname: Quenby
authors.affiliation: Warwick Medical School, The University of Warwick, Coventry, West Midlands, UK.
authors.forename: Aileen
authors.initials: A
authors.lastname: Clarke
mesh_terms: D015415:Biomarkers / Q000097:blood; D025063:Chromosome Disorders / Q000175:diagnosis*; D002882:Chromosomes, Human, Pair 13; D002887:Chromosomes, Human, Pair 18; D004247:DNA / Q000097:blood*; D004314:Down Syndrome / Q000175:diagnosis*; D005260:Female; D006801:Humans; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D012680:Sensitivity and Specificity; D014314:Trisomy / Q000175:diagnosis*; D000073839:Trisomy 13 Syndrome; D000073842:Trisomy 18 Syndrome
chemical_list: D015415:Biomarkers; D004247:DNA
keywords: REPRODUCTIVE MEDICINE