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. 2016 Dec 5;6:38359.
doi: 10.1038/srep38359.

NIPTRIC: An Online Tool for Clinical Interpretation of Non-Invasive Prenatal Testing (NIPT) Results

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Free PMC article

NIPTRIC: An Online Tool for Clinical Interpretation of Non-Invasive Prenatal Testing (NIPT) Results

Birgit Sikkema-Raddatz et al. Sci Rep. .
Free PMC article

Abstract

To properly interpret the result of a pregnant woman's non-invasive prenatal test (NIPT), her a priori risk must be taken into account in order to obtain her personalised a posteriori risk (PPR), which more accurately expresses her true likelihood of carrying a foetus with trisomy. Our aim was to develop a tool for laboratories and clinicians to calculate easily the PPR for genome-wide NIPT results, using diploid samples as a control group. The tool takes the a priori risk and Z-score into account. Foetal DNA percentage and coefficient of variation can be given default settings, but actual values should be used if known. We tested the tool on 209 samples from pregnant women undergoing NIPT. For Z-scores < 5, the PPR is considerably higher at a high a priori risk than at a low a priori risk, for NIPT results with the same Z-score, foetal DNA percentage and coefficient of variation. However, the PPR is effectively independent under all conditions for Z-scores above 6. A high PPR for low a priori risks can only be reached at Z-scores > 5. Our online tool can assist clinicians in understanding NIPT results and conveying their true clinical implication to pregnant women, because the PPR is crucial for individual counselling and decision-making.

Figures

Figure 1
Figure 1. Estimation of the PPR for a specific a priori risk for a given observed Z-score and in the absence of information on the percentage of foetal DNA for a woman at low risk (1:1000) [square boxes], at high risk (1:100) [circles], and at very high risk (1:10) [triangles].
The PPR for the woman at low risk (1:1000 (0.001)) is <1% at a Z-score of 3, increasing to 11% for a Z-score of 4. This means that with a positive NIPT result, with a Z-score of 3 or 4, the actual chance of the woman carrying a foetus with Down syndrome is <1% or 11%, respectively. The woman at high risk (1:100 (0.01)) has a chance of 4% with a Z-score of 3, but a chance of 38% with a Z-score of 4. For the woman at very high risk (1:10 (0.1)), the PPR is 21% for a Z-score of 3 and 76% for a Z-score of 4.
Figure 2
Figure 2. Estimation of the PPR given an observed Z-score and percentage of foetal DNA at a coefficient of variation of 0.5%.
(a) a priori risk of 0.1 (1:10); (b) a priori risk of 0.01(1:100); and (c) a priori risk of 0.01(1:1000). x-axis: Z-score range 1–7. y-axis: Personalised a posteriori risk (%). After a positive NIPT result at a Z-score of 3 and at 4% foetal DNA, the low-risk woman has a 5% chance of carrying a foetus with Down syndrome and thus a 95% chance of the result being false-positive. In contrast, the higher-risk women have a 36% (1:100) and an 86% (1:10) chance of carrying a foetus with Down syndrome. Thus, the chance of a false-positive result at a risk of 1:100 and 1:10 is 64% and 14%, respectively.

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