Performance capabilities of prenatal diagnosis of chromosomal anomalies: what changed with the introduction of non-invasive prenatal test (NIPT)?

Abstract

This review systematizes scientific data on the possibilities and limitations of combined prenatal screening for detecting common chromosomal abnormalities (CA) in the first trimester of pregnancy, as well as an innovative technology – non-invasive prenatal test (NIPT) based on free fetal DNA fraction. A review of current clinical guidelines on the place of NIPT in models of prenatal screening, the experience of various countries on the implementation of NIPT in national programs for prenatal screening of CA was carried out. Also, a synthesis of evidence and expert opinions on the controversial issues of the feasibility of using the extended options of NIPT (beyond the identification of common aneuploidies as trisomy 21, 13, 18) was carried out, a review of current data on the possibilities and limitations of various NIPT techniques was carried out. Despite the general increase in the sensitivity of prenatal screening for CA due to the combination of clinical, biochemical and ultrasound indicators, its main disadvantage is insufficient specificity (the frequency of false positive results of 5%). One of the ways to increase the effectiveness of prenatal screening for CA is the study of free fraction of fetal DNA (NIPT). According to a 2017 meta-analysis, the sensitivity of NIPT is more than 99% for trisomy 21, 98% for trisomy 18, and 99% for trisomy 13 with a specificity of 99%. This high efficacy has been confirmed in subsequent studies, making NIPT the best screening test for the most common trisomies – Down syndrome (trisomy 21), Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13). NIPT can be used as the first line of prenatal screening or as a second line after combined first trimester screening. Since 2015, NIPT has been included in the clinical guidelines of international and national professional societies. Common to the 11 reviewed documents is the recognition of NIPT as an important tool for increasing the efficiency of prenatal detection of CA, information about which should be provided to all pregnant women. In order for the pregnant woman to receive the maximum benefit from NIPT, pre- and post-test counseling with an explanation of the possibilities and limitations of the method in general and in the given clinical situation is crucial.

Keywords

• cell-free fetal dna fraction (cffdna)
• combined first trimester screening
• invasive diagnostics
• aneuploidy
• chromosomal anomalies
• trisomy 21, 13, 18
• massively parallel sequencing