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.

Cell-Free Fetal DNA Screening Analysis in Korean Pregnant Women: Six Years of Experience and a Retrospective Study of 9327 Patients Analyzed from 2017 to 2022

“…In our study, the differences in the FF according to the pregnancy method were consistent with the findings of other studies demonstrating a reduced FF for single pregnancies after ART compared to that for natural conception [24]. Elena et al reported that in a cohort of 12,000 mothers, the FF in male fetuses was 9.9% and the FF in female fetuses was 6.8%, indicating that the FF in male fetuses was higher [25]. In our study, the male FF was 2.76% higher than was the female FF.…”

Approach and Management of Pregnancies with Risk Identified by Non-Invasive Prenatal Testing

“…Knowing from previous studies [14] that a low FF can lead to inconclusive results in older women (>35 years), significantly higher weight and increased BMI, we recommended delaying the test from week 10 to week 12 and we obtained conclusive results in almost all cases. Only 0.14% (2/1400) cases remained without NIPT results after a new collection.…”

“…Despite differences in the risk cut-offs for considering pregnancy as high risk (e.g., in France, the cut-off risk is ≥1:51, while in England, it is ≥1:150), the primary discussion concentrates around the criteria for reimbursing the test. In Russia, a pilot study in 2022 in Moscow considered a cut-off risk of ≥1:100, with the intention of deciding whether to use NIPT as second-line screening in the first trimester [14]. In Romania, despite patients covering the entire cost of the genetic testing, we observe an increase in the number of tests (Figure 2) and an increased interest from pregnant women.…”

Applications of non-invasive prenatal testing in 91280 spontaneous pregnancies and 3477 pregnant women undergoing in vitro Fertilization

“…In recent years, NIPT has been proven superior in screening for SP fetal chromosomal aneuploidy disorders by a large number of studies at home and abroad and it was recognized as an almost perfect screening method [12][13][14]. Galeva Slavyana [23]et al reported that the screening effect of twins and singleton was similar, especially the effectiveness of T21 was better.…”

“…NIPT is now performed globally and many countries have adopted NIPT as part of their clinical screening. Despite a large number of studies demonstrating the advantages of NIPT [12][13][14][15], NIPT also has its limitations. In the Technical Speci cation for Prenatal Screening and Diagnosis of Fetal Free DNA in Peripheral Blood of Pregnant Women issued by the General O ce of the Health and Family Planning Commission in China, pregnant women with IVF-ET pregnancy belong to a cautious population [16].…”