Follow-up in Patients With Non-invasive Prenatal Screening Failures: A Reflection on the Choice of Further Prenatal Diagnosis

Li, Sha; Liu, Hongqian; Liu, Jianlong; Bai, Ting; Jing, Xiangyi; Xia, Tianyu; Deng, Cechuan; Liu, Yunyun; Cheng, Jing; Wei, Xiangjin; Xing, Lingling; Luo, Youfu; Zhou, Quanfang; Zhu, Qian

doi:10.3389/fgene.2021.666648

Cited by 7 publications

(8 citation statements)

References 38 publications

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“…Next, 20 µl of cfDNA libraries was constructed by end filling and adapter ligation, and qPCR analysis was performed to verify whether the concentration and quality of cfDNA libraries were satisfactory. The cfDNA libraries were subjected to massive parallel sequencing using the NextSeq CN500 high-throughput sequencing kit (Illumina) on a NextSeq CN500 platform (Illumina), generating approximately 5 million raw data with 36-bp reads ( Liu et al, 2021 ).…”

Section: Maternal Serum Screeningmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Maternal Serum Screeningmentioning

confidence: 99%

“…Sequencing reads were uniquely mapped to the hg19 human reference genome. The Z -score values of the 24 chromosomes were further calculated using normalized chromosome representation and GC correction ( Liu et al, 2021 ). The fetal autosomal trisomy status was determined based on Z -scores (normal range, −3 < Z < 3).…”

Section: Maternal Serum Screeningmentioning

confidence: 99%

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

et al. 2021

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“…Our analysis revealed that the fetal fraction decreases with an increase in BMI, which was in line with previous results ( 10 ). In addition, our previous study analyzed test failure cases of NIPS, and the primary reason (79.44%) for test failure in 394/123,291 cases was fetal fraction <4%, other reasons included sequencing failure and DNA concentration higher than the quality control standard ( 12 ). The gestational age of the low fetal fraction group was 17.40 ± 2.27 weeks and the BMI was 25.66 ± 3.67 kg/m 2 , which were significantly different from those of the sequencing failure group and the DNA concentration outside of laboratory quality control group (all P < 0.05).…”

Section: Discussionmentioning

confidence: 99%

“…NIPS was performed by collecting 8–10 ml of peripheral blood from the expectant mother. Extraction of cfDNA, library construction, and massive parallel sequencing were carried out as described in a previous study ( 12 ). Fetal fraction of male and female fetuses were estimated based on the Y chromosome-based method ( 13 ) and distribution of plasma cfDNA fragment length, respectively ( 14 ).…”

Section: Methodsmentioning

confidence: 99%

Maternal and fetal factors influencing fetal fraction: A retrospective analysis of 153,306 pregnant women undergoing noninvasive prenatal screening

Deng

Liu

et al. 2023

Front. Pediatr.

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BackgroundGenetic factors are important causes of birth defects. Noninvasive prenatal screening (NIPS) is widely used for prenatal screening of trisomy 21, trisomy 18, and trisomy 13, which are the three most common fetal aneuploidies. Fetal fraction refers to the proportion of cell-free fetal DNA in maternal plasma, which can influence the accuracy of NIPS. Elucidating the factors that influence fetal fraction can provide guidance for the interpretation of NIPS results and genetic counseling. However, there is currently no broad consensus on the known factors that influence fetal fraction.ObjectiveThe study aimed to explore the maternal and fetal factors influencing fetal fraction.MethodsA total of 153,306 singleton pregnant women who underwent NIPS were included. Data on gestational age; maternal age; body mass index (BMI); z-scores for chromosomes 21, 18, and 13; and fetal fraction in NIPS were collected from the study population, and the relationships between fetal fraction and these factors were examined. The relationship between fetal fraction and different fetal trisomy types was also analyzed.ResultsThe results showed that the median gestational age, maternal age, and BMI of the pregnant women were 18 (16, 20) weeks, 29 (25, 32) years, and 22.19 (20.40, 24.24) kg/m2, respectively. The median fetal fraction was 11.62 (8.96, 14.7)%. Fetal fraction increased with gestational age and decreased with maternal age and BMI (P < 0.001). Fetal fraction of fetuses with trisomies 21, 18, and 13 was similar to that of the NIPS-negative group. The z-scores of pregnant women with trisomy 21 and 18 fetuses were positively correlated with fetal fraction, but not with that of the trisomy 13 cases.ConclusionsThe factors that influence fetal fraction need to be taken into consideration before NIPS for quality control and after NIPS for result interpretation.

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“…Maternal peripheral blood (10 ml) was collected in a cell-free BCT tube (Streck, Omaha, NE, United States). The procedural details of the experimental operation and analysis methods have been published previously (Liu et al, 2021). The test results for all 24 chromosomes were presented using Z-scores (normal range, −3 < Z < 3).…”

Section: Noninvasive Prenatal Screeningmentioning

confidence: 99%

Clinical Selection of Prenatal Diagnostic Techniques Following Positive Noninvasive Prenatal Screening Results in Southwest China

et al. 2022

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Background: This study aims to evaluate prenatal diagnosis methods following positive noninvasive prenatal screening (NIPS) results.Methods: According to the positive noninvasive prenatal screening results, 926 pregnant women were divided into three groups: main target disease group (high risk for trisomy 21, trisomy 18, or trisomy 13), sex chromosome aneuploidy (SCA) group, and other chromosomal abnormalities group [abnormal Z-scores for chromosomes other than trisomy (T)21/T18/T13 or SCAs]. The verification methods and results were then retrospectively analysed.Results: In the main target disease group, the positive rate of chromosomal abnormalities confirmed by quantitative fluorescence polymerase chain reaction (QF-PCR) was 75.18% (212/282), which was not significantly different from that by karyotyping (79.36%, 173/218) and copy number variation (CNV) detection methods (71.43%, 65/91). The positive rate of additional findings confirmed by karyotyping and copy number variation detection methods in main target disease group was 0.46% (1/218) and 8.79% (8/91), respectively. The positive rate of chromosomal abnormalities confirmed by karyotyping and CNV detection methods were 27.11% (45/166) and 38.46% (95/247) in the SCA group and 4.17% (1/24) and 20% (36/180) in the other chromosomal abnormalities group, respectively. Fetal sex chromosome mosaicism was detected in 16.13% (20/124) of the confirmed SCA cases. There were no significant differences in the detection rates of chromosomal microarray analysis (CMA) and CNV sequencing (CNVseq) among the three groups (p > 0.05).Conclusion: QF-PCR can quickly and accurately identify aneuploidies following NIPS-positive results for common aneuploidy, and in combination with karyotyping and CNV detection techniques can provide more comprehensive results. With the NIPS-positive results for SCA or other abnormalities, CMA and CNVseq may have the same effect on increasing the detection rate. The addition of fluorescence in situ hybridization assay may help to identify true fetal mosaicism.

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Follow-up in Patients With Non-invasive Prenatal Screening Failures: A Reflection on the Choice of Further Prenatal Diagnosis

Cited by 7 publications

References 38 publications

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

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

Maternal and fetal factors influencing fetal fraction: A retrospective analysis of 153,306 pregnant women undergoing noninvasive prenatal screening

Clinical Selection of Prenatal Diagnostic Techniques Following Positive Noninvasive Prenatal Screening Results in Southwest China

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