In this study, we analysised efficiency of NIPT to detect Chromosome aneuploidies based on SSP,and compared the performance of NIPT and NIPT-plus for detecting all fetal chromosome aneuploidies. The results revealed that there was no difference of detection performance between NIPT and NIPT-plus for aneuploidies. NIPT-plus had a better performance in detecting chromosome aneuploidies in terms of the total positive rate (1.72 vs 1.38), and NIPT-plus had a better performance in detecting T21/T18/T13. It is worth mentioning that PPVs of NIPT for other autosomal aneuploidies and sex chromosome aneuploidy was better than NIPT-plus. This would be related to the subjective will of the result reviewer.
We used PPV to evaluate the detecting performance in this study. The PPV of NIPT for T21/T18/T13 was 81.99%, 69.23%, 25.00% respectively. Results were basically consistent with the Liu’ paper (Liu et al., 2020). The PPV of NIPT-plus for T21/T18/T13 was 86.96%, 80..%, 35.00% respectively, which was better than NIPT. Sequencing depth had been increased, PPVs would be increased obviously, and further improved the detection efficiency. The PPV for other chromosome aneuploidy was 4.55%of NIPT and 8.77% of NIPT-plus. The difference was not statistically significant (Chen et al., 2019). The PPV for Sex chromosome aneuploidy was 50% of NIPT as same as NIPT-plus, This is an unexpected discovery. Similarity, zheng’s paper also showed this results (Zheng et al., 2020). Sex chromosomes became target disease. The awareness of preventing missed diagnosis directly affected the subjective judgment of result reviewers.
We have also analyzed the different PPV in different pregnancies characteristics group, and also compared the difference of PPV between NIPT and NIPT-plus. The difference in high-risk or intermediate-risk serological screening of PPV was statistically significant between NIPT and NIPT-plus (P = 0.03). The reason maybe that the proportion of T18 and T13 in NIPT-plus group was higher and PPV for T18 and T13 was relatively lower, which decreased the PPV. PPV of NIPT-plus for aneuploidy in ultrasound soft marker abnormalities was higher than NIPT, which was similar to other literature reports (T. Hu et al., 2021; Wang et al., 2018). Regardless of whether in China or international ("Screening for Fetal Chromosomal Abnormalities: ACOG Practice Bulletin, Number 226," 2020), the applicable population of NIPT had Clearly defined. However, PPV had slightly different in different clinical characteristics group. This study provided a certain reference value for clinicians about NIPT detection efficiency. In addition, characteristic of the two groups mainly due to the large difference in sample size between the two groups. Fetal fraction for NIPT-plus was higher than NIPT, because we used a method to increase the fetal fragment fraction from 2018 (P. Hu et al., 2019). While enrichment was not used earlier than 2018. NIPT-plus was started from 2019, which was all used this enrichment.
During recent years, other rare autosomal aneuploidies (RAAs) were often reported in clinical practice as the unexpected findings of NIPT. However, genetic counseling was difficult, because the limited clinical information on the incidence and pregnancy outcomes of suspected RAAs. The PPVs for other chromosome aneuploidies were lower at 8.39% and similar to those reported also in Lu’s paper (ref. (Chen et al., 2019). But compared with Liang’s paper (Liang et al., 2019), the PPV was slightly lower. The possible reason was that RAAs were less prevalent, and the incidence is relatively low, most of the RAAs fetuses had spontaneous abortions in the early stages (Li et al., 2020). And another important reason was that these aneuploidies had high rates for confined placental mosaicism (CPM). Due to cell-free fetal DNA was mainly derived from placental trophoblast cell apoptosis. Confined placental mosaicism would cause the false positive results of NIPT (Eggenhuizen, Go, Koster, Baart, & Galjaard, 2021; Hartwig, Ambye, Sørensen, & Jørgensen, 2017). Among all the rare autosomal aneuploidies, Trisomy 7 was the most common, but PPV was still low like other rare autosomal aneuploidies. The main reason was due to CPM (Qi et al., 2019). Simultaneously, the prognosis of perinatal infants was very good (Gou et al., 2020). It is worth noting that the 2 true positive cases were confirmed to be loss of heterozygosity. it was suspected to be a uniparental diploid of chromosome 16 (mixed type) and a uniparental diploid of chromosome 14 respectively. Two fetus occurred intrauterine growth retardation, but the case of uniparental diploid of chromosome 16 had intrauterine death, and the case of uniparental diploid of chromosome 14 had a normal delivery and live birth.
Follow-up was very important part of NIPT. Except refused to be followed up, all other cases were followed up for pregnancy outcome. According to the guideline of National Health Commission of the People’s Republic of China, follow-up began at week 12 after delivery. Follow-up content included complications during pregnancy and the pregnancy outcomes and the health of the newborn. The shortcoming of this study was that false-positive cases have not been verified for the placenta after delivery. On the one hand, the reason was that pregnant women were not cooperative, and on the other hand, it was relatively lack of funds.