title: 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.
abstract: BACKGROUND
  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.
  
  
  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.
authors: Department of Molecular Medicine and Surgery, Clinical Genetics Unit, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
authors: Erik
authors: E
authors: Iwarsson
authors: Department of Obstetrics and Gynecology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.|Department of Genetics and Bioinformatics, Area of Health Data and Digitalisation, Institute of Public Health, Oslo, Norway.
authors: Bo
authors: B
authors: Jacobsson
authors: Swedish Agency for Health Technology Assessment and Assessment of Social Services (SBU), Stockholm, Sweden.
authors: Jessica
authors: J
authors: Dagerhamn
authors: Swedish Agency for Health Technology Assessment and Assessment of Social Services (SBU), Stockholm, Sweden.|Division of Health Care Analysis, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors: Thomas
authors: T
authors: Davidson
authors: Division of Population and Patient Health, King's College London Dental Institute at Guy's, King's College and St Thomas Hospitals, London, UK.
authors: Eduardo
authors: E
authors: Bernabé
authors: Swedish Agency for Health Technology Assessment and Assessment of Social Services (SBU), Stockholm, Sweden.|Medical Management Center/LIME, Karolinska Institute, Stockholm, Sweden.
authors: Marianne
authors: M
authors: Heibert Arnlind
mesh_terms: D002474:Cell-Free System; D025063:Chromosome Disorders / Q000175:diagnosis* / Q000235:genetics; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D004247:DNA / Q000097:blood*; D004314:Down Syndrome / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D011247:Pregnancy; D018566:Pregnancy, High-Risk; D011296:Prenatal Diagnosis; D012680:Sensitivity and Specificity; D014314:Trisomy / Q000175:diagnosis* / Q000235:genetics; D000073839:Trisomy 13 Syndrome; D000073842:Trisomy 18 Syndrome
chemical_list: D004247:DNA
keywords: 
  NIPT
  ; Trisomy; cell-free DNA; cfDNA; chromosome aberration; fetus; non-invasive prenatal testing; prenatal diagnosis