Cell-free fetal DNA testing and its correlation with prenatal indications

Abstract

Background The prenatal test of cell-free fetal DNA (cffDNA) is also known as noninvasive prenatal testing (NIPT) with high sensitivity and specificity. This study is to evaluate the performance of NIPT and its clinical relevance with various clinical indications. Methods A retrospective analysis was conducted on 14,316 pregnant women with prenatal indications, including advanced maternal age (≥35 years), maternal serum screening abnormalities, the thickened nuchal translucency (≥2.5 mm) and other ultrasound abnormalities, twin pregnancy/IVF-ET pregnancy, etc. The whole-genome sequencing (WGS) of maternal plasma cffDNA was employed in this study. Results A total of 189 (1.32%) positive NIPT cases were identified, and 113/189 (59.79%)cases were confirmed by invasive prenatal testing. Abnormal serological screening (53.14%) was the most common indication, followed by elderly pregnancy (23.02%). The positive prediction value for T21, T18, T13, sex chromosome abnormalities, other autosomal aneuploidy abnormalities, and CNV abnormalities were 91.84, 68.75,37.50, 66.67, 14.29, and 6.45%, respectively. The positive rate and the true positive rate of nuchal translucency (NT) thickening were the highest (4.17 and 3.33%), followed by the voluntary requirement group (3.49 and 1.90%) in the various prenatal screening indications. The cffDNA concentration was linearly correlated with gestational age (≥10 weeks) and the positive NIPT group’s Z-score values. Conclusions whole-genome sequencing of cffDNA has extremely high sensitivity and specificity for T21, high sensitivity for T18, sex chromosome abnormalities, and T13. It also provides evidence for other abnormal chromosomal karyotypes (CNV and non-21/18/13 autosomal aneuploidy abnormalities). The cffDNA concentration is closely related to the gestational age and determines the specificity of NIPT. Our results highlight NIPT’s clinical significance, which is an effective prenatal screening tool for high-quality care of pregnancy.

Non-invasive prenatal testing for the detection of trisomy 13, 18, and 21 and sex chromosome aneuploidies in 68,763 cases

“…We refined the screening indications for NIPT and analyzed its detection efficacy. The results showed that the highest positive rate and PPV of NIPT detection indications were both related to ultrasound abnormalities, especially ultrasound structural abnormalities and NT thickening; those results are similar to the previously reported data published by Wang et al (2021) . These results showed that pregnant women with abnormal ultrasound results are more likely to be carrying a foetus with chromosomal abnormalities, and they should be diagnosed.…”

The accuracy of cell‐free DNA screening for fetal segmental copy number variants: A systematic review and meta‐analysis

“…The study selection process is shown in Figure 1. Authors were contacted for seven articles with incomplete data; data were obtained for one 38 and six were excluded 84–89 …”

“…Authors were contacted for seven articles with incomplete data; data were obtained for one 38 and six were excluded. [84][85][86][87][88][89] Included studies were published between 2015 and 2022. Across all included studies, 1 591 459 women underwent cfDNA screening for CNVs, with 5481 receiving a high-risk result (screen-positive rate of 0.34%).…”

Fetal DNA Causes Sex-Specific Inflammation From Human Fetal Membranes

“…They have been shown to increase throughout the pregnancy, peaking at term and then dropping after birth ( Liu et al, 2007 ). Indeed, this source of cffDNA is also used for prenatal diagnostic detection of fetal chromosomal abnormalities ( Wang et al, 2021 ) as it is less invasive than sampling from the AF. Increased circulating levels of cffDNA have also been associated with adverse pregnancy outcomes and pathologies such as; preeclampsia ( Martin et al, 2014 ; Kwak et al, 2020 ), gestational diabetes ( Hopkins et al, 2020 ), and preterm birth ( Gomez-Lopez et al, 2020 ).…”