Whole genome non-invasive prenatal testing in prenatal screening algorithm: clinical experience from 12700 pregnancies

Background: A fast adoption of a non–invasive prenatal testing (NIPT) in clinical practice is a global tendency last years. The aim of the study - to assess efficiency of using NIPT as a second-line first trimester screening test in Moscow. Methods: Based on the results of the first trimester combined prenatal screening 12700 pregnant women were classified as a high-risk (cut-off ≥1:100) and an intermediate-risk (cut-off 1:101 – 1:2500) groups followed by whole genome NIPT. Women from high-risk group and those who had positive NIPT results were considered for invasive prenatal diagnostic. Results: 258 (2,0%) samples with positive NIPT results were detected including 126 cases of trisomy 21 (T21), 40 cases of T18, 12 cases of T13, 41 cases of sex chromosome aneuploidies (SCAs) and 39 cases of rare autosomal aneuploidies (RAAs) and significant copy number variations (CNVs). Statistically significant associations (p<0.05) were revealed for fetal fraction (FF) and both for some patient’s (body mass index and weight) and fetus’s characteristics (sex and high risk of aneuploidies). NIPT showed high sensitivity and specificity for common trisomies and SCAs with an overall false positive rate 0.3%. Conclusions: NIPT demonstrated high sensitivity and specificity. As a second-line screening test it has shown high efficiency in detecting fetus chromosomal anomalies as well as it could potentially lower the number of invasive procedures in pregnant women.