Whole genome non-invasive prenatal testing in prenatal screening algorithm: clinical experience from 12,700 pregnancies

Abstract

Background: A fast adoption of a non-invasive prenatal testing (NIPT) in clinical practice is a global tendency last years. Firstly, in Russia according a new regulation it was possible to perform a widescale testing of pregnant women in chromosomal abnormality risk. 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 first trimester combined prenatal screening results 12,700 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 from intermediate-risk group 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 (sex and high risk of aneuploidies) characteristics. NIPT showed as a high sensitivity as 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 a high efficiency in detecting fetus chromosomal anomalies as well as it could potentially lower the number of invasive procedures in pregnant women.

Keywords: Amniocentesis; Fetal aneuploidy; NIPT; Non-invasive prenatal testing; Prenatal screening; Rare autosomal trisomies; Trisomy 13; Trisomy 18; Trisomy 21; cfDNA.

Fig. 1

Recruitment criteria for samples that were able to undergo NIPT. *Low-risk group samples were not included into the study. **IPD is obligatory for a high-risk group of pregnant women and is optional for an intermediate-risk group. Abbreviations: NIPT, non–invasive prenatal testing; IPD, invasive prenatal diagnostic

Fig. 2

Flowchart of non-invasive prenatal test (NIPT) results and invasive prenatal diagnostics outcomes of pregnant women undergoing screening for aneuploidies between 1 April 2020 and 5 April 2021. Abbreviations: T, trisomy; SCA, sex chromosomal aneuploidy; RAA, rare autosomal aneuploidy; CNV, copy number variation; aCGH, array comparative genomic hybridization

Fig. 3

A density distribution of fetal fraction and its relationship with gestational weeks of pregnant women. The average fetal fraction in each week is shown by a black line

Fig. 4

The average level of fetal fraction for patients depending on the BMI (a), fetus sex (b) and NIPT results: risk of T21 (c) and T18 (d). Abbreviations: NIPT, non-invasive prenatal testing; T, trisomy; BMI, body mass index.