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

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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Evaluation of Maternal Serum sHLA-G Levels for Trisomy 18 Fetuses Screening at Second Trimester

Frontiers in Genetics ◽

10.3389/fgene.2020.497264 ◽

2021 ◽

Vol 11 ◽

Author(s):

Danping Xu ◽

Yiyang Zhu ◽

Lanfang Li ◽

Yingping Xu ◽

Weihua Yan ◽

...

Keyword(s):

Pregnant Women ◽

Prenatal Screening ◽

Maternal Serum ◽

Trisomy 18 ◽

Second Trimester ◽

Serum Samples ◽

Predictive Values ◽

Second Trimester Screening ◽

Β Hcg ◽

Screening Marker

Human leukocyte antigen-G (HLA-G) has been widely acknowledged to play critical roles in fetal-maternal maintenance. However, the significance of using maternal serum sHLA-G to detect prenatal chromosomal abnormality has not been investigated. In China, prenatal screening using maternal α-fetoprotein (AFP), unconjugated estriol (uE3), and free β subunit human chorionic gonadotropin (β-hCG) in the second trimester has been widely applied. In this study, we evaluated the use of sHLA-G as a screening marker, compared with traditional second trimester prenatal screening. Serum samples from 1,019 singleton women in their second trimester were assessed. Among them, 139 infants were confirmed with trisomy 21 (T21) by karyotyping, 83 were confirmed with trisomy 18 (T18), and the remaining 797 infants had no abnormalities. The sHLA-G levels in maternal sera were significantly lower in pregnant women with T18 fetuses (median: 47.8 U/ml, range: 9.8–234.2 U/ml) and significantly higher in those with T21 fetuses (median: 125.7 U/ml, range: 28.7–831.7 U/ml), compared with the normal controls (median: 106.3 U/ml, range: 50.5–1136.4 U/ml) (p < 0.001). The risk values of the screening of T21 or T18 fetuses were assessed using mean and standard deviation log10 analyte multiples of median (MoM) which showed that the predictive values of sHLA-G were the same as free β-hCG, and superior to AFP and uE3 for T18 screening. Logistic regression analysis revealed that sHLA-G MoM was the highest risk factor associated with pregnant women carrying T18 fetuses [Exp(B): 171.26, 95% CI: 36.30–807.97, p < 0.001]. Receiver operating characteristic (ROC) analysis revealed that the area under ROC curve for sHLA-G MoM was 0.915 (95% CI, 0.871–0.959, p < 0.001), for AFP MoM was 0.796 (95% CI, 0.730–0.861, p < 0.001), for free β-hCG MoM was 0.881 (95% CI, 0.829–0.934, p < 0.001), and for uE3 MoM was 0.876 (95% CI, 0.828–0.923, p < 0.001) in the T18 group. sHLA-G MoM demonstrated the best sensitivity and negative predictive value. For the first time, our findings reveal that sHLA-G is a better second trimester screening marker for the detection of T18 fetuses and the combined application of sHLA-G with AFP, free β-hCG, and uE3 could improve clinical screening for T18 fetuses.

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Efficiency of Non-invasive Prenatal Screening in Pregnant Women at Advanced Maternal Age

10.21203/rs.3.rs-52792/v1 ◽

2020 ◽

Author(s):

Hui Zhu ◽

Xiaoxiao Jin ◽

Yuqing Xu ◽

Weihua Zhang ◽

Xiaodan Liu ◽

...

Keyword(s):

Pregnant Women ◽

Predictive Value ◽

Trisomy 21 ◽

Maternal Age ◽

Prenatal Screening ◽

Screening Method ◽

Advanced Maternal Age ◽

Trisomy 13 ◽

Noninvasive Prenatal Screening ◽

Fetal Aneuploidies

Abstract Background: To evaluate the efficiency of noninvasive prenatal screening (NIPS) in the prenatal screening for fetal aneuploidies in pregnant women at advanced maternal age (AMA). Results: From February 1, 2015, to December 31, 2018, 29,443 pregnant women at AMA underwent NIPS and followed-up were recruited. Their detailed clinical data and follow-up outcomes were collected and analyzed. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of NIPS for detecting fetal trisomy 21 were 99.11%, 99.96%, 90.98%, and 100%, respectively. These same parameters for detecting fetal trisomy 18 were 100%, 99.94%, 67.92%, and 100%, respectively. Finally, these parameters for detecting trisomy 13 were 100%, 99.96%, 27.78%, and 100%, respectively. The prevalence of fetal trisomy 21 increased with maternal age. There were significant differences in the prevalence of fetal trisomy 21 among the groups I (35-37-year-old), II (38-40-year-old) and III (41-year-old and older) ( P <0.05). Conclusion: It is indicated that NIPS is an effective prenatal screening method in pregnant women at AMA. Keywords: Advanced maternal age, Trisomy, Noninvasive prenatal screening, Fetal aneuploidies , Prenatal screening method

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False Low-Risk Single Nucleotide Polymorphism–Based Noninvasive Prenatal Screening in Pentasomy 49,XXXXY

American Journal of Perinatology Reports ◽

10.1055/s-0037-1621722 ◽

2018 ◽

Vol 08 (01) ◽

pp. e4-e6 ◽

Cited By ~ 1

Author(s):

Manesha Putra ◽

Melissa Hicks ◽

Jacques Abramowicz

Keyword(s):

Single Nucleotide Polymorphism ◽

Prenatal Screening ◽

Sex Chromosome ◽

Low Risk ◽

Chromosome Anomaly ◽

Fetal Anomalies ◽

Nucleotide Polymorphism ◽

Third Trimester ◽

Single Nucleotide ◽

Noninvasive Prenatal Screening

Abstract Introduction Pentasomy 49,XXXXY is a sex chromosome anomaly difficult to be diagnosed prenatally. We describe a patient of pentasomy 49,XXXXY with false low-risk results using a noninvasive prenatal screening (NIPS). A 30-year-old G1P0 woman presented at 336/7 weeks, secondary to sonographic fetal anomalies. She had low-risk NIPS at 136/7 weeks. Anatomy survey showed bilateral clubfeet, clinodactyly of the left fifth digit, micropenis, and echogenic bowel. Cytogenetics analysis revealed pentasomy 49,XXXXY syndrome. We report third-trimester sonographic features of a fetus with pentasomy 49,XXXXY and the importance of thorough pre- and posttest counseling for NIPS.

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Is Noninvasive Prenatal Screening Appropriate for Pregnant Women Age 35 or Older In Cases if Isolated Fetal Nasal Bone Abnormalities in The Chinese Han Population?

Medical Science Monitor ◽

10.12659/msm.924387 ◽

2020 ◽

Vol 26 ◽

Author(s):

Yuan Chen ◽

Min Lv ◽

Tian Dong ◽

Qinqing Chen ◽

Yeqing Qian ◽

...

Keyword(s):

Pregnant Women ◽

Prenatal Screening ◽

Nasal Bone ◽

Chinese Han Population ◽

Chinese Han ◽

Han Population ◽

Noninvasive Prenatal Screening ◽

Fetal Nasal Bone ◽

Bone Abnormalities

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The relation between second-trimester placental elasticity and poor obstetric outcomes in low-risk pregnancies

Journal of Perinatal Medicine ◽

10.1515/jpm-2020-0464 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Murat Akbas ◽

Faik Mumtaz Koyuncu ◽

Burcu Artunç-Ülkümen ◽

Gökce Akbas

Keyword(s):

Birth Weight ◽

Pregnant Women ◽

Value Added ◽

Shear Wave Elastography ◽

Multiple Regression Model ◽

Low Risk ◽

Obstetric Outcomes ◽

Second Trimester ◽

The Mean ◽

Random Measurements

AbstractObjectivesIncreased placental stiffness is associated with various pathological conditions. Our objective was to evaluate the relation between the second-trimester placental elasticity value in low-risk pregnant women and poor obstetric outcomes.MethodsA total of 143 pregnant women were enrolled. Placental elasticity values were measured using the transabdominal point shear wave elastography method. 10 random measurements were obtained from different areas of the placenta. The mean was accepted as the mean placental elasticity value. Logistic regression analyses were performed to identify independent variables associated with obstetric outcomes.ResultsSecond-trimester placental elasticity value was significantly and positively associated with the poor obstetric outcomes (p=0.038). We could predict a poor outcome with 69.2% sensitivity and 60.7% specificity if we defined the placental elasticity cut-off as 3.19 kPa. Furthermore, in the multiple regression model, the placental elasticity value added significantly to the prediction of birth weight (p=0.043).ConclusionsOur results showed that the pregnancies with a stiffer placenta in the second trimester were associated with an increased likelihood of exhibiting poor obstetric outcomes. Also, placental elasticity was independently associated with birth weight.

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Expanded noninvasive prenatal testing for fetal aneuploidy and copy number variations and parental willingness for invasive diagnosis in a cohort of 18,516 cases

BMC Medical Genomics ◽

10.1186/s12920-021-00955-6 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Yunsheng Ge ◽

Jia Li ◽

Jianlong Zhuang ◽

Jian Zhang ◽

Yanru Huang ◽

...

Keyword(s):

Prenatal Diagnosis ◽

High Risk ◽

Pregnant Women ◽

Copy Number ◽

Prenatal Testing ◽

Copy Number Variations ◽

Trisomy 13 ◽

Noninvasive Prenatal Testing ◽

Predictive Values ◽

Parental Willingness

Abstract Background Noninvasive prenatal testing (NIPT) has been wildly used to screen for common aneuplodies. In recent years, the test has been expanded to detect rare autosomal aneuploidies (RATs) and copy number variations (CNVs). This study was performed to investigate the performance of expanded noninvasive prenatal testing (expanded NIPT) in screening for common trisomies, sex chromosomal aneuploidies (SCAs), rare autosomal aneuploidies (RATs), and copy number variations (CNVs) and parental willingness for invasive prenatal diagnosis in a Chinese prenatal diagnosis center. Methods A total of 24,702 pregnant women were retrospectively analyzed at the Women and Children’s Hospital from January 2013 to April 2019, among which expanded NIPT had been successfully conducted in 24,702 pregnant women. The high-risk expanded NIPT results were validated by karyotype analysis and chromosomal microarray analysis. All the tested pregnant women were followed up for pregnancy outcomes. Results Of the 24,702 cases, successful follow-up was conducted in 98.77% (401/446) of cases with common trisomies and SCAs, 91.95% (80/87) of RAT and CNV cases, and 76.25% (18,429/24,169) of cases with low-risk screening results. The sensitivity of expanded NIPT was 100% (95% confidence interval[CI], 97.38–100%), 96.67%(95%CI, 82.78–99.92%), and 100%(95%CI, 66.37–100.00%), and the specificity was 99.92%(95%CI, 99.87–99.96%), 99.96%(95%CI, 99.91–99.98%), and 99.88% (95%CI, 99.82–99.93%) for the detection of trisomies 21, 18, and 13, respectively. Expanded NIPT detected 45,X, 47,XXX, 47,XXY, XYY syndrome, RATs, and CNVs with positive predictive values of 25.49%, 75%, 94.12%, 76.19%, 6.45%, and 50%, respectively. The women carrying fetuses with Trisomy 21/Trisomy 18/Trisomy 13 underwent invasive prenatal diagnosis and terminated their pregnancies at higher rates than those at high risk for SCAs, RATs, and CNVs. Conclusions Our study demonstrates that the expanded NIPT detects fetal trisomies 21, 18, and 13 with high sensitivity and specificity. The accuracy of detecting SCAs, RATs, and CNVs is still relatively poor and needs to be improved. With a high-risk expanded NIPT result, the women at high risk for common trisomies are more likely to undergo invasive prenatal diagnosis procedures and terminate their pregnancies than those with unusual chromosome abnormalities.

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Performance of Cell-Free DNA Screening for Fetal Common Aneuploidies and Sex Chromosomal Abnormalities: A Prospective Study from a Less Developed Autonomous Region in Mainland China

Genes ◽

10.3390/genes12040478 ◽

2021 ◽

Vol 12 (4) ◽

pp. 478

Author(s):

Yunli Lai ◽

Xiaofan Zhu ◽

Sheng He ◽

Zirui Dong ◽

Yanqing Tang ◽

...

Keyword(s):

Sex Chromosome ◽

Chromosomal Abnormalities ◽

False Negative ◽

Prenatal Testing ◽

Read Depth ◽

Trisomy 13 ◽

Prognostic Information ◽

Aneuploidy Screening ◽

Predictive Values ◽

Risk Result

To evaluate the performance of noninvasive prenatal screening (NIPS) in the detection of common aneuploidies in a population-based study, a total of 86,262 single pregnancies referred for NIPS were prospectively recruited. Among 86,193 pregnancies with reportable results, follow-up was successfully conducted in 1160 fetuses reported with a high-risk result by NIPS and 82,511 cases (95.7%) with a low-risk result. The screen-positive rate (SPR) of common aneuploidies and sex chromosome abnormalities (SCAs) provided by NIPS were 0.7% (586/83,671) and 0.6% (505/83,671), respectively. The positive predictive values (PPVs) for Trisomy 21, Trisomy 18, Trisomy 13 and SCAs were calculated as 89.7%, 84.0%, 52.6% and 38.0%, respectively. In addition, less rare chromosomal abnormalities, including copy number variants (CNVs), were detected, compared with those reported by NIPS with higher read-depth. Among these rare abnormalities, only 23.2% (13/56) were confirmed by prenatal diagnosis. In total, four common trisomy cases were found to be false negative, resulting in a rate of 0.48/10,000 (4/83,671). In summary, this study conducted in an underdeveloped region with limited support for the new technology development and lack of cost-effective prenatal testing demonstrates the importance of implementing routine aneuploidy screening in the public sector for providing early detection and precise prognostic information.

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