Clinical experience of laboratory follow-up with noninvasive prenatal testing using cell-free DNA and positive microdeletion results in 349 cases

Prenat Diagn. 2018 Feb;38(3):210-218. doi: 10.1002/pd.5217. Epub 2018 Feb 26.

Abstract

Objective: Screening via noninvasive prenatal testing (NIPT) involving the analysis of cell-free DNA (cfDNA) from plasma has become readily available to screen for chromosomal and DNA aberrations through maternal blood. This report reviews a laboratory's experience with follow-up of positive NIPT screens for microdeletions.

Methods: Patients that were screened positive by NIPT for a microdeletion involving 1p, 4p, 5p, 15q, or 22q who underwent diagnostic studies by either chorionic villus sampling or amniocentesis were evaluated.

Results: The overall positive predictive value for 349 patients was 9.2%. When a microdeletion was confirmed, 39.3% of the cases had additional abnormal microarray findings. Unrelated abnormal microarray findings were detected in 11.8% of the patients in whom the screen positive microdeletion was not confirmed. Stretches of homozygosity in the microdeletion were frequently associated with a false positive cfDNA microdeletion result.

Conclusions: Overall, this report reveals that while cfDNA analysis will screen for microdeletions, the positive predictive value is low; in our series it is 9.2%. Therefore, the patient should be counseled accordingly. Confirmatory diagnostic microarray studies are imperative because of the high percentage of false positives and the frequent additional abnormalities not delineated by cfDNA analysis.

MeSH terms

  • Cell-Free Nucleic Acids / analysis*
  • Chromosome Aberrations
  • Female
  • Humans
  • Maternal Serum Screening Tests*
  • Predictive Value of Tests
  • Pregnancy
  • Retrospective Studies
  • Sequence Deletion*

Substances

  • Cell-Free Nucleic Acids