Non-invasive molecular genetic prenatal tests (NIPT) for detection of trisomy 13, 18 and 21

Background: Non-invasive molecular genetic prenatal tests (NIPTs) for trisomy have long been part of non-invasive prenatal diagnostics. In Germany it is currently being examined whether and for whom these tests should be paid for by statutory health insurance in the future. Objective: (I) Diagnostic properties of NIPTs for the detection of trisomy 13, 18 and 21, and (II) hypothetical calculation of the possible use of NIPTs in different groups. Methods: (I) Systematic search for primary literature and systematic reviews in MEDLINE and four other databases. Inclusion criteria: Studies in pregnant women; index test: NIPT using molecular genetic analysis of cell-free fetal DNA in maternal blood to determine the trisomy risk; reference test: cytogenetic diagnostics or postnatal clinical examination. (II) Exploratory search. Hypothetical calculations for (1) all pregnant women following the current procedure without NIPTs using the example of first-trimester screening (FTS), (2) application in pregnant women with an increased risk (e.g., after preceding FTS), and (3) application of NIPT in a population with and without an increased trisomy risk. Results: In the 22 studies included, sensitivity and specificity for trisomy 21 detection were 99.13% (95% CI: [97.39%; 99.72%]) and 99.95% (95% CI: [99.88%; 99.98%]). The possible influence of test failures was not considered in the calculations, and thus the sensitivity or specificity of NIPTs may have been overestimated. For the detection of trisomy 13 and 18, the sensitivity could not be robustly estimated. Discussion: In pregnant women with an increased risk, NIPT can probably reduce the number of invasive tests and thus the number of test-related miscarriages.