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

Nancy C Rose; Elizabeth S Barrie; Jennifer Malinowski; Gabrielle P Jenkins; Monica R McClain; Danielle LaGrave; Marco L Leung; ACMG Professional Practice and Guidelines Committee. Electronic address: documents@acmg.net

doi:10.1016/j.gim.2022.03.019

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.

Authors

Nancy C Rose¹, Elizabeth S Barrie², Jennifer Malinowski³, Gabrielle P Jenkins³, Monica R McClain⁴, Danielle LaGrave⁵, Marco L Leung⁶; ACMG Professional Practice and Guidelines Committee. Electronic address: documents@acmg.net³

Affiliations

¹ Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, School of Medicine, University of Utah, Salt Lake City, UT.
² Department of Pathology, VCU School of Medicine, Virginia Commonwealth University, Richmond, VA.
³ American College of Medical Genetics and Genomics, Bethesda, MD.
⁴ Genesis Research, Hoboken, NJ.
⁵ ARUP Laboratories, Salt Lake City, UT.
⁶ The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH; Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH; Departments of Pathology and Pediatrics, The Ohio State University College of Medicine, Columbus, OH.

PMID: 35608568
DOI: 10.1016/j.gim.2022.03.019

Abstract

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

Substances

Cell-Free Nucleic Acids