Noninvasive Prenatal Screening Based on Second-Trimester Ultrasonographic Soft Markers in Low-Risk Pregnant Women

Abstract

Background: We aimed to assess the clinical application of noninvasive prenatal screening (NIPS) based on second-trimester ultrasonographic soft markers (USMs) in low-risk pregnant women.Methods: Data of pregnant women between April 2015 and December 2019 were retrospectively analyzed. Pregnant women [age at expected date of confinement (EDC) of <35 years; low risks for trisomy 21 (T21) and trisomy 18 (T18) based on maternal serum screening; presenting second-trimester USMs (7 types)] who successfully underwent NIPS and had available follow-up information were included in our study. Cases with positive NIPS results were prenatally diagnosed. All patients were followed up for 6 months to 2 years after NIPS, and their clinical outcomes were obtained. Subgroup analyses were performed according to the different USMs.Results: NIPS suggested that among a total of 10,023 cases, 37 (0.37%) were at high risk of aneuploidy, including 4 T21, 6 trisomy 13 (T13), and 27 sex chromosome abnormalities (SCA). Ten cases with aneuploidy (0.10%) were confirmed by prenatal diagnosis, consisting of two T21 and eight SCA. The eight fetuses with SCA consisted of one monosomy X, two XXY, one XXXY, one XXX, one XYY, and two mosaicisms. T21 was detected in one fetus with absent or hypoplastic nasal bone and one fetus with echogenic intracardiac focus (EICF). SCA was detected in five fetuses with EICF, two fetuses with multiple soft markers, and one fetus with echogenic bowel. The positive rate of chromosomal aneuploidy was significantly higher in fetuses with absent or hypoplastic nasal bone (6.25 vs. 0.10%, p = 0.017), echogenic bowel (3.7 vs. 0.10%, p = 0.029), and multiple soft markers (0.678 vs. 0.10%, p = 0.045) than in the total fetuses. The positive predictive values (PPVs) of NIPS in these three groups were 100%, 50%, and 100%, respectively. EICF accounted for 93.25% (9,346/10,023) of the study population, whereas the PPV of NIPS was only 20%.Conclusion: NIPS is an advanced screening test for low-risk pregnant women. In the 10,023 pregnant women sampled, SCA were more common than autosomal trisomy, and EICF was the most frequent USM but the least predictive aneuploidy. Further aneuploidy evaluation is suggested for low-risk pregnant women whose ultrasound indicates absent or hypoplastic nasal bone, echogenic bowel, or multiple soft markers. NIPS can serve as a second-line complementary screening for these women.

Identification of copy number variations among fetuses with isolated ultrasound soft markers in pregnant women not of advanced maternal age

“…In addition, the proportion of various types of USM in the study population was also different; EIF accounted for 23.72% in a previous study [12], whereas in our study, EIF was the most frequent USM (81.71%). We have previously reported [20] that the incidence and PPV of NIPS for aneuploidy in fetuses with EIF were signi cantly low, which was con rmed here.…”

“…This may be because the population included in our study was predominantly young (below the age of 35 years at the expected date of con nement), while there were 9.37% pregnant women of an advanced maternal age in previous studies [12]. According to the relevant regulations (Article 20 of the Measures for the Implementation of Law of the Peoples Republic of China on Maternal and Infant Health Care (promulgated on June 20, 2001) ), prenatal diagnosis is often recommended for pregnant women in China who are at high risk based on maternal serum screening [20,21], advanced maternal age and fetuses with structural abnormalities, therefore, the risk of potential chromosomal aberrations was higher in those studies [12,19]. In addition, the proportion of various types of USM in the study population was also different; EIF accounted for 23.72% in a previous study [12], whereas in our study, EIF was the most frequent USM (81.71%).…”

Comparison of Chromosomal Microarray Analysis and Noninvasive Prenatal Testing in Pregnant Women with Fetal Ultrasonic Soft Markers

“…Despite the elevated incidence of EICF, its predictive value for chromosome abnormalities remains notably low, aligning with findings from previous studies. 18 Initially, EICF was found to be associated with a heightened risk of Down Syndrome. 19 However, contemporary research has indicated that isolated EICF does not increase the risk of aneuploidy.…”

Echogenic intracardiac foci detection and location in the second-trimester ultrasound and association with fetal outcomes: A systematic literature review

“…Ten studies [18,19,22,27,31,32,[34][35][36][37] reported chromosomal abnormalities and the rate of abnormalities was 1.98% (range 0-5.7%) among those with EIF. The chromosomal abnormalities identified with EIF were Trisomy 18, 46, 21 XXY, XYY and Turner's syndrome.…”