Clinical performance of non-invasive prenatal served as a first-tier screening test for trisomy 21, 18, 13 and sex chromosome aneuploidy in a pilot city in China

Yanhui Liu,Hailiang Liu,Yuanru Liu,Zheng He,Wei Lei,Qiulin Ma,Fubing Yu,Wanfang Xu,Jiayi Huang,Quanfei Huang,Jianan Liu,Yi He,Yuzhen He,Guoquan Chen

doi:10.1186/s40246-020-00268-2

Abstract

BackgroundCell-free fetal DNA (cffDNA) has opened up new approaches for non-invasive prenatal testing (NIPT), and it is often used as the second-tier test for high-risk pregnant women in detecting trisomy (T) 21, T18, and T13 after serum biochemistry screening. This study aims to discuss the clinical performance of NIPT as an alternative first-tier screening test for pregnant women in detecting T21, T18, T13, and sex chromosome aneuploidies (SCAs) in China.MethodsA total of 42,924 samples were recruited. The cell-free plasma DNA was directly sequenced. Each of the chromosome aneuploidies of PPV was analyzed. A total of 22 placental samples were acquired, including 14 FP and 8 TP samples. The placental verification of FP NIPT results was performed.ResultsAmong 42,924 samples, 281 (0.65%) positive cases, including 87 of T21, 31 of T18, 22 of T13, and 141 of SCAs were detected. For the detection of T21, the positive predictive value (PPV) was 78.46%, for trisomy 18, 62.96%, for trisomy 13, 10.00%, for SCAs, 47.22% in the total samples. For trisomy 21, the PPV was 86.67%, for trisomy 18, 80.00%, for trisomy 13, 20.00%, for SCAs, 56.52% in advanced maternal age (AMA) women. The PPV of T21 increased with age. For T18, the PPV showed an overall upward trend. For T13 and SCAs, PPV was raised first and then lowered. Placental verification of false positive (FP) NIPT results confirmed confined placental mosaicism(CPM) was the reason for false positives.ConclusionsThis study represents the first time that NIPT has been used as a first-tier screening test for fetal aneuploidies in a pilot city with large clinical samples in China. We propose that NIPT could replace serum biochemistry screening as a first-tier test.

Highlights

Non-invasive prenatal testing (NIPT) uses cell-free fetal DNA in maternal plasma to detect certain genetic conditions during pregnancy
A recent meta-analysis showed that the weighted pooled detection rate (DR) and false-positive rate (FPR) for T21 were 99.7% and 0.04%, respectively
NIPT screened for other chromosome aneuploidy needs more validation to determine accurately its detection rate, and false-positive rate

Summary

Introduction

Non-invasive prenatal testing (NIPT) uses cell-free fetal DNA (cffDNA) in maternal plasma to detect certain genetic conditions during pregnancy. NIPT detects fetal chromosome abnormalities and has become increasingly common in prenatal care based on the clinical implementation of the new genomics-based technique [1], and this technique is very likely to replace standard prenatal trisomy (T) 21 screening for all pregnancies in the near future [2, 3]. Cell-free fetal DNA (cffDNA) has opened up new approaches for non-invasive prenatal testing (NIPT), and it is often used as the second-tier test for high-risk pregnant women in detecting trisomy (T) 21, T18, and T13 after serum biochemistry screening. This study aims to discuss the clinical performance of NIPT as an alternative first-tier screening test for pregnant women in detecting T21, T18, T13, and sex chromosome aneuploidies (SCAs) in China

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