Nonreportable rates and cell-free DNA profiles in noninvasive prenatal testing among women with heparin treatment

Prenat Diagn. 2020 Jun;40(7):838-845. doi: 10.1002/pd.5695. Epub 2020 Apr 16.

Abstract

Objective: To evaluate the "nonreportable" rate in patients treated with heparin and to determine the effect of heparin on the results of noninvasive prenatal testing (NIPT).

Method: This was a single-center retrospective study of NIPT. The "nonreportable" rate of NIPT was evaluated according to presence or absence of heparin treatment. After excluding true-positive cases, a matched cohort study evaluating Z-scores, GC bias, and cell-free DNA (cfDNA) profiles was performed to investigate the effect of heparin on NIPT results.

Results: Overall, 2651 singleton pregnancies with available clinical information were evaluated; 23 mothers were treated with heparin. The nonreportable rate was much higher among patients treated with heparin than among those who were not (8.70% vs 0.15%). In the matched cohort study, the Z-scores for chromosomes 13, 18, and 21, and GC bias were significantly higher in the heparin group than in the matched control group. Based on cfDNA library electrophoresis data, the proportion of short-sized cfDNA was higher in the heparin group.

Conclusion: Heparin use increased the nonreportable rate of NIPT results by borderline Z-scores, possibly caused by the increased proportions of shorter and GC-rich cfDNA fragments. This information will be helpful for prenatal genetic counseling for patients requiring heparin treatment.

MeSH terms

  • Adult
  • Aneuploidy
  • Blood Coagulation Disorders* / blood
  • Blood Coagulation Disorders* / drug therapy
  • Case-Control Studies
  • Cell-Free Nucleic Acids / analysis
  • Cell-Free Nucleic Acids / blood*
  • Cohort Studies
  • Diagnostic Errors / statistics & numerical data*
  • Female
  • Fetus / metabolism
  • Genetic Testing / methods
  • Genetic Testing / standards
  • Genetic Testing / statistics & numerical data
  • Heparin / therapeutic use*
  • Humans
  • Noninvasive Prenatal Testing* / standards
  • Noninvasive Prenatal Testing* / statistics & numerical data
  • Predictive Value of Tests
  • Pregnancy
  • Pregnancy Complications, Hematologic / blood
  • Pregnancy Complications, Hematologic / drug therapy
  • Reproducibility of Results
  • Retrospective Studies
  • Trisomy / diagnosis
  • Trisomy / genetics
  • Young Adult

Substances

  • Cell-Free Nucleic Acids
  • Heparin