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

Area of Science:

• Genetics
• Prenatal Diagnostics
• Molecular Biology

Background:

• Cell-free fetal DNA (cffDNA) analysis, known as noninvasive prenatal testing (NIPT), offers high sensitivity and specificity.
• This study evaluates the performance and clinical relevance of NIPT across diverse indications.

Purpose of the Study:

• To assess the clinical utility and performance of NIPT in a large cohort of pregnant women.
• To analyze NIPT's effectiveness for various prenatal indications, including advanced maternal age and ultrasound abnormalities.

Main Methods:

• Retrospective analysis of 14,316 pregnant women undergoing NIPT.
• Whole-genome sequencing (WGS) of maternal plasma cffDNA was utilized.
• Inclusion criteria covered advanced maternal age, abnormal screening, ultrasound findings, and multiple gestations.

Main Results:

• 189 positive NIPT cases (1.32%) were identified, with 59.79% confirmed by invasive testing.
• Abnormal serological screening and advanced maternal age were the most frequent indications.
• Positive prediction values varied by condition, with T21 showing 91.84% and T18 68.75%. Nuchal translucency thickening had the highest positive and true positive rates.

Conclusions:

• Whole-genome sequencing NIPT demonstrates high sensitivity and specificity for Trisomy 21 (T21), T18, T13, and sex chromosome abnormalities.
• NIPT provides valuable information on other chromosomal abnormalities like CNVs and non-21/18/13 autosomal aneuploidies.
• CffDNA concentration correlates with gestational age, influencing NIPT specificity, underscoring its role as an effective prenatal screening tool.