Noninvasive prenatal screening (NIPS), which detect cell-free fetal DNA (cffDNA) by massively parallel sequencing (MPS), is widely used in the prenatal screening of fetal chromosome abnormalities Undoubtedly, it has brought great innovation to prenatal screening and diagnosis, and greatly improved the prevention of severe fetal birth defects. At first, it was mainly used in the prenatal screening of trisomy 21 (T21), trisomy 18 (T18) and trisomy 13 (T13) with considerable accuracy. A lot of studies have proved its effectiveness, and the targeted diseases might far exceed T21/T18/T13 [2], such as sex chromosome aneuploidy (SCAs) [3], fetal genome copy number variations (CNVs) [4] and single gene genetic diseases [5], although their detection abilities were lower than T21/T18/T13. At the same time, NIPS is also being applied more and more to the population. It was originally applied to the women with an intermediate risk of prenatal screening. But it was widely used in the women at advanced maternal age (AMA) [6], twins [7] and even the low-risk population [8]. However, with the accumulation of clinical data, we should have a clearer understanding of its technical limitations to help better clinical application.

With the popularization and development of prenatal ultrasound examinations, fetal ultrasound abnormalities have become a prominent problem in prenatal screening and diagnosis. When fetus abnormalities occur and are detected by ultrasound, his/her risk of genetic disease will be greatly increased (up to 20-fold) [9]. So, a consensus has been basically reached that the mother should receive prenatal diagnosis to find serious fetal genetic diseases when the baby has an abnormal ultrasound. Common genetic testing techniques included karyotype testing, chromosomal microarray analysis (CMA), copy number variation sequencing (CNV-seq), whole exome sequencing (WES) and so on. Among them, CMA is recommended as the preferred method for prenatal diagnosis[ 10,11]. CMA could detect 8.2% of pathogenic CNVs in the fetuses with normal karyotype results [12]. On this basis, the application of WES technology could additionally increase the abnormal detection rate by 10%∼24%[ 12,13]. In China, ultrasound abnormalities are considered as an unsuitable population of NIPS. This reasoning is worth discussing, especially after the development of NIPS technology. Recently, we have carried out some studies on the effectiveness of NIPS[ 16,17]. We found that the detection effect of NIPS varies greatly in different populations. At the same time, the types of fetal ultrasound abnormalities are very complex. There were also great differences in chromosome abnormalities among different types. Some types are mainly chromosome aneuploidy and large fragment CNVs, while others were mainly single gene mutations.

Therefore, we carried out an interesting discussion in the present study. What are the consequences if the mothers with fetal ultrasound abnormalities receive NIPS? Which ultrasound abnormalities also have good effect of accepting NIPS? In fact, we focused on the parameters that accurately predict the ability of NIPS prenatal screening, instead of carrying out the NIPS test in the present study. We hope to further improve its clinical application.