Application of non-invasive prenatal testing for fetal chromosomal disorders in low-risk pregnancies: a follow-up study in central China

Abstract

Objective: To evaluate the performance and screening value of noninvasive prenatal testing (NIPT) in low-risk pregnancies.

Methods: A retrospective analysis was conducted on 60193 low-risk pregnancies over the last 5 years. Whole-genome sequencing of maternal plasma cell-free DNA was performed using next-generation sequencing. NIPT-positive results were confirmed using amniocentesis with karyotyping and/or copy number variation sequencing and chromosomal microarray analysis. Fetal outcomes were assessed using electronic medical records or telephone calls.

Results: Overall, 598 (0.99%) NIPT-positive cases were identified. The distribution of chromosomal abnormalities included sex chromosome aneuploidies (SCAs; 55.85%), rare autosomal aneuploidies (RAAs; 20.40%), copy number variations (CNVs; 11.20%), trisomy 21 (T21; 6.86%), trisomy 13 (T13; 4.01%), and trisomy 18 (T18; 1.67%). A total of 572 (95.65%) patients with NIPT-positive results underwent amniocentesis, and 55.77% (319/572) cases were confirmed. The positive predictive values (PPV) for T21, T18, T13, SCAs, RAAs, and CNVs were 87.50%, 60.00%, 34.78%, 58.97%, 32.50%, and 69.70%, respectively, and the PPV for the trisomy was higher than that for the X-monomer in SCAs. NIPT-positive results for RAAs were common in T8, T10, T16 and T20, but T16 was the most common true positive result, accounting for 33.33% (13/39) of the cases. The termination rates of true-positive pregnancies were 100% (T21, T18 and T13), 79.49% (RAAs), 67.39% (CNVs) and 78.07% (SCAs).

Conclusion: This study highlights the importance of genome-wide screening based on NIPT in low-risk pregnancies. Prenatal screening by NIPT has a high sensitivity and PPV. Moreover, it can greatly reduce invasive procedures and birth defects.

Keywords: aneuploidy; copy number variations (CNVs); follow-up; low-risk; non-invasive prenatal testing (NIPT).

FIGURE 1

Sample size inclusion flow chart. T21, trisomy 21; T18, trisomy 18; T13, trisomy 13; SCAs, sex chromosome aneuploidies; RAAs, rare autosomal aneuploidies; CNVs, copy number variations; TP, true positive; FP, false positive.

FIGURE 2

Maternal age and gestational age of NIPT in low-risk pregnant women. The black dots represent the total population of pregnant women (y-axis) plotted against the corresponding maternal age ((a–c), the age interval between each black dot is 1 year), gestational weeks ((d–f), the week interval between each black dot is 1 week) and fetal fraction (g–i), the interval between each black dot is 1%) (x-axis).

FIGURE 3

Distribution of NIPT positive and true positive of RAAs. T, trisomy; M, monosomy; CB; Complex abnormality. There were no rare autosomal aneuploidies observed on chromosomes 1 and 19.