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

Acta Obstet Gynecol Scand. 2017 Jan;96(1):7-18. doi: 10.1111/aogs.13047. Epub 2016 Dec 9.


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.

Keywords: NIPT; Trisomy; cell-free DNA; cfDNA; chromosome aberration; fetus; non-invasive prenatal testing; prenatal diagnosis.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Cell-Free System*
  • Chromosome Disorders / diagnosis*
  • Chromosome Disorders / genetics
  • Chromosomes, Human, Pair 13 / genetics
  • Chromosomes, Human, Pair 18 / genetics
  • DNA / blood*
  • Down Syndrome / diagnosis*
  • Down Syndrome / genetics
  • Female
  • Genetic Testing / methods
  • Humans
  • Pregnancy
  • Pregnancy, High-Risk
  • Prenatal Diagnosis*
  • Sensitivity and Specificity
  • Trisomy / diagnosis*
  • Trisomy / genetics
  • Trisomy 13 Syndrome
  • Trisomy 18 Syndrome


  • DNA