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Non-invasive prenatal aneuploidy testing: Critical diagnostic performance parameters predict sample z-score values
- Source :
- Clinical Biochemistry. 59:69-77
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Non-invasive prenatal aneuploidy testing (NIPT) by next-generation sequencing of circulating cell-free DNA in maternal plasma relies on chromosomal ratio (chrratio) measurements to detect aneuploid values that depart from euploid ratios. Diagnostic performances are known to depend on the fraction of fetal DNA (FF) present in maternal plasma, although how this translates into specific quantitative changes in specificity/positive predictive values and which other variables might also be important is not well understood.To explore this issue, theoretical relationships between FF and various measures of diagnostic performances were assessed for a range of parameter values. Empirical data from three NIPT assays were then used to validate theoretical calculations.For a given positivity threshold, dramatic changes in specificity and positive predictive values (PPV) as a function of both FF and the coefficient of variation (CV) of the chrratio measurement were observed. Theoretically predicted and observed chrratio z-scores agreed closely, confirming the determinant impact of small changes in both FF and chrratio CV.Evaluation of NIPT assay performances therefore requires knowledge of the FF distribution in the population in which the test is intended to be used and, in particular, of the precise value of the assay chrratio CV for each chromosome or genomic region of interest. Laboratories offering NIPT testing should carefully measure these parameters to ensure test reliability and clinical usefulness in interpreting individual patients' results.
- Subjects :
- Adult
0301 basic medicine
Coefficient of variation
Clinical Biochemistry
Population
Aneuploidy
Chromosome Disorders
Prenatal diagnosis
030105 genetics & heredity
Standard score
03 medical and health sciences
0302 clinical medicine
Predictive Value of Tests
Pregnancy
Prenatal Diagnosis
Statistics
medicine
Humans
Genetic Testing
education
Mathematics
Genetic testing
education.field_of_study
030219 obstetrics & reproductive medicine
medicine.diagnostic_test
High-Throughput Nucleotide Sequencing
Reproducibility of Results
General Medicine
Models, Theoretical
medicine.disease
3. Good health
Cell-free fetal DNA
Predictive value of tests
Female
Subjects
Details
- ISSN :
- 00099120
- Volume :
- 59
- Database :
- OpenAIRE
- Journal :
- Clinical Biochemistry
- Accession number :
- edsair.doi.dedup.....82ffe905f0d7ee8a374a95653f74ab7f