Systematic evidence-based review: The application of noninvasive prenatal screening using cell-free DNA in general-risk pregnancies

Genet Med. 2022 Jul;24(7):1379-1391. doi: 10.1016/j.gim.2022.03.019. Epub 2022 May 24.


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.

Keywords: Cell-free DNA; Down syndrome; Noninvasive prenatal screening; Trisomy.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Cell-Free Nucleic Acids* / genetics
  • Down Syndrome* / diagnosis
  • Down Syndrome* / genetics
  • Female
  • Humans
  • Noninvasive Prenatal Testing* / methods
  • Pregnancy
  • Prenatal Diagnosis / methods
  • Sex Chromosome Aberrations
  • Trisomy / diagnosis
  • Trisomy / genetics
  • Trisomy 13 Syndrome* / diagnosis
  • Trisomy 13 Syndrome* / genetics
  • Trisomy 18 Syndrome* / diagnosis
  • Trisomy 18 Syndrome* / genetics


  • Cell-Free Nucleic Acids