Performances of a Snp-Based Noninvasive Prenatal Test

Abstract

Noninvasive prenatal tests based on cell free DNA have spread broadly, with many studies regarding their performance and improvement being published in the last few years. Their use in the clinical practice, in most countries, is not included in the common screening and must be paid by the patient. In this study we analyzed the performance of a noninvasive test based on single nucleotide polymorphisms (Panorama® by Natera) on patients handled in the prenatal diagnostic unit of the University Hospital of Giessen and Marburg in Giessen (Germany) from July 2016 to July 2018. We analyzed the results of the tests in 440 patients, in a mixed population of high-risk and low-risk women. For "high risk" and "no call" results in the cell free DNA analysis, we were able to collect follow-up information. For the validation of our high-risk results we considered informations obtained from a prenatal karyotype or from the clinical evaluation at birth and postpartal episode. 426/440 patients received a result, with 16 High Risk results and 410 Low Risk results. The combined high risk rate for all indications was 3.75% (16/426), with 11 cases of trisomy 21, 2 of trisomy 18, 1 of trisomy 13 and 2 of sex chromosome aneuploidies (XXY and XXX). The total no call rate was 23/460 submitted tests (5.00%). The main reason for the no call results was a low fetal fraction (< 3.5%). The total rate of aneuploidies in the population with a call is 2.91% (12/412, patients with follow up informations). The aneuploidy rate in no call results is 31,6% and is thus much higher. This difference is statistically significative (p-value <0.0001). The calculated test performance shown as positive predictive value for trisomy 21 was 90.9% and for all four aneuploidies combined was 92.9%.

In Conclusion, the performance of Panorama® (calculated with positive predictive value) proved much better than that of standard screening (First trimester scan) and is comparable to the NIPT test performance described in the literature. In addition, a no call result might be linked with a higher risk of aneuploidies.