Background: Biochemical prenatal screening tests are used to determine the risk of fetal aneuploidy based on the concentration of several biomarkers. The concentration of these biomarkers could be affected by preanalytical factors (PAFs) such as sample type (whole blood vs serum), storage time, and storage temperature. The impact of these factors on posttest risk is unknown.
Methods: Blood samples were collected from 25 pregnant patients. Each sample was divided into 24 aliquots, and each aliquot was subjected to 1 of 24 different treatments (2 sample types × 2 temperatures × 6 storage times). The impact of each PAF on calculated risk was estimated using mixed-effects regression and simulation analysis.
Results: PAFs were associated with statistically significant changes in concentration for some analytes. Simulation studies showed that PAFs accounted for 6% of the variation in posttest risk, and analytical imprecision accounted for 94% of the variation. We estimated that the background misclassification rate due to analytical imprecision is approximately 1.37% for trisomy 21 and 0.12% for trisomy 18. Preanalytical factors increased the probability of misclassification by 0.46% and 0.06% for trisomies 21 and 18, respectively.
Conclusions: Relaxing sample specifications for biochemical prenatal serum screening tests to permit analysis of serum samples stored for up to 72 h at room temperature or 4 °C as well as serum obtained from whole blood stored similarly has a small impact in calculated posttest aneuploidy risk.
Authors' Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form.
Employment or Leadership: D.G. Grenache, AACC; R.L. Schmidt, ARUP Laboratories.
Consultant or Advisory Role: None declared.
Stock Ownership: None declared.
Honoraria: None declared.
Research Funding: D.G. Grenache, Beckman Coulter.
Expert Testimony: None declared.
Patents: None declared.
Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.
- Received October 25, 2016.
- Accepted December 28, 2016.
- © 2017 American Association for Clinical Chemistry