Diagnostics

Research

16 pages, 1071 KiB

Open AccessArticle

Experience of Low-Pass Whole-Genome Sequencing-Based Copy Number Variant Analysis: A Survey of Chinese Tertiary Hospitals

by Yu Zheng, Baosheng Zhu, Jichun Tan, Yichun Guan, The Chinese Genomic Structural Variants Consortium, Cynthia C. Morton and Guangxiu Lu

Diagnostics 2022, 12(5), 1098; https://doi.org/10.3390/diagnostics12051098 - 27 Apr 2022

Cited by 5 | Viewed by 3306

Abstract

In China, low-pass whole-genome sequencing (low-pass WGS) is emerging as an alternative diagnostic test to detect copy number variants (CNVs). This survey aimed to study the laboratory practice, service quality, and case volumes of low-pass WGS-based CNV analysis among national accredited Chinese tertiary [...] Read more.

In China, low-pass whole-genome sequencing (low-pass WGS) is emerging as an alternative diagnostic test to detect copy number variants (CNVs). This survey aimed to study the laboratory practice, service quality, and case volumes of low-pass WGS-based CNV analysis among national accredited Chinese tertiary hospitals that have routinely applied low-pass WGS for more than a year and that have been certified in next-generation sequencing (NGS) clinical applications for more than three years. The questionnaire focused on (1) the composition of patients’ referral indications for testing and annual case volumes; (2) the capacity of conducting laboratory assays, bioinformatic analyses, and reporting; (3) the sequencing platforms and parameters utilized; and (4) CNV nomenclature in reports. Participants were required to respond based on their routine laboratory practices and data audited in a 12-month period from February 2019 to January 2020. Overall, 24 participants representing 24 tertiary referral hospitals from 21 provincial administrative regions in China returned the questionnaires. Excluding three hospitals routinely applying low-pass WGS for non-invasive prenatal testing (NIPT) only, the analysis only focused on the data submitted by the rest 21 hospitals. These hospitals applied low-pass WGS-based CNV analysis for four primary applications: high-risk pregnancies, spontaneous abortions, couples with adverse pregnancy history, and children with congenital birth defects. The overall estimated annual sample volume was over 36,000 cases. The survey results showed that the most commonly reported detection limit for CNV size (resolution) was 100 kb; however, the sequencing methods utilized by the participants were variable (single-end: 61.90%, 13/21; paired-end: 28.57%, 6/21; both: 9.52%, 2/21). The diversity was also reflected in the sequencing parameters: the mean read count was 13.75 million reads/case (95% CI, 9.91–17.60) and the read-length median was 65 bp (95% CI, 75.17–104.83). To assess further the compliance of the CNV reporting nomenclature according to the 2016 edition of International System for Human Cytogenomics Nomenclature (ISCN 2016), a scoring metric was applied and yielded responses from 19 hospitals; the mean compliance score was 7.79 out of 10 points (95% CI, 6.78–8.80). Our results indicated that the low-pass WGS-based CNV analysis service is in great demand in China. From a quality control perspective, challenges remain regarding the establishment of standard criteria for low-pass WGS-based CNV analysis and data reporting formats. In summary, the low-pass WGS-based method is becoming a common diagnostic approach, transforming the possibilities for genetic diagnoses for patients in China. Full article

(This article belongs to the Special Issue Advances in Prenatal Diagnostics)

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11 pages, 1587 KiB

Open AccessArticle

WisecondorFF: Improved Fetal Aneuploidy Detection from Shallow WGS through Fragment Length Analysis

by Tom Mokveld, Zaid Al-Ars, Erik A. Sistermans and Marcel Reinders

Diagnostics 2022, 12(1), 59; https://doi.org/10.3390/diagnostics12010059 - 28 Dec 2021

Cited by 2 | Viewed by 2420

Abstract

In prenatal diagnostics, NIPT screening utilizing read coverage-based profiles obtained from shallow WGS data is routinely used to detect fetal CNVs. From this same data, fragment size distributions of fetal and maternal DNA fragments can be derived, which are known to be different, [...] Read more.

In prenatal diagnostics, NIPT screening utilizing read coverage-based profiles obtained from shallow WGS data is routinely used to detect fetal CNVs. From this same data, fragment size distributions of fetal and maternal DNA fragments can be derived, which are known to be different, and often used to infer fetal fractions. We argue that the fragment size has the potential to aid in the detection of CNVs. By integrating, in parallel, fragment size and read coverage in a within-sample normalization approach, it is possible to construct a reference set encompassing both data types. This reference then allows the detection of CNVs within queried samples, utilizing both data sources. We present a new methodology, WisecondorFF, which improves sensitivity, while maintaining specificity, relative to existing approaches. WisecondorFF increases robustness of detected CNVs, and can reliably detect even at lower fetal fractions (<2%). Full article

(This article belongs to the Special Issue Advances in Prenatal Diagnostics)

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22 pages, 7450 KiB

Open AccessArticle

Clinical Validation of Fetal cfDNA Analysis Using Rolling-Circle-Replication and Imaging Technology in Osaka (CRITO Study)

by Ritsuko Kimata Pooh, Chika Masuda, Risa Matsushika, Megumi Machida, Takako Nakamura, Masayoshi Takeda, Hiroyasu Ohashi, Mami Kumagai, Kohtaro Uenishi, Fredrik Roos, Fredrik Persson and Osamu Shimokawa

Diagnostics 2021, 11(10), 1837; https://doi.org/10.3390/diagnostics11101837 - 4 Oct 2021

Cited by 9 | Viewed by 9832

Abstract

Background: Noninvasive prenatal genetic testing (NIPT) has been adopted as the first choice for aneuploidy screening. The purposes of this study were to investigate the accuracy of Vanadis^® NIPT (hereafter CRITO-NIPT) in order to gain a deeper insight into the reasons for [...] Read more.

Background: Noninvasive prenatal genetic testing (NIPT) has been adopted as the first choice for aneuploidy screening. The purposes of this study were to investigate the accuracy of Vanadis^® NIPT (hereafter CRITO-NIPT) in order to gain a deeper insight into the reasons for discrepancies, as well as to discuss the role of fetal ultrasound. Methods: Between 2019 and 2020, CRITO-NIPT was performed in 1218 cases of patients who underwent CVS or amniocentesis after a detailed fetal ultrasound exam and genetic counseling. The CRITO-NIPT results were compared with the genetic results. In cases of test discrepancies, the placentae were collected for detailed genetic research, and the pre-procedure fetal ultrasound findings were referred to. Results: The positive predictive value of T21, T18, and T13 was 93.55%, 88.46%, and 100%, respectively. In 90% of the of false positive (FP) cases, the placentae were examined. In 75% of the CRITO FP-T21 cases, placental mosaicism, or a demised twin’s T21, were confirmed. There were complicated mosaic cases, including tetrasomy 21/trisomy7 and monosomy 21/trisomy21 cases. In one of three no-call cases, an intermediate deletion of chromosome 13 was detected. Conclusions: The CRITO study investigated the mechanism of false positives, and the detailed mechanisms in mosaic and no-call cases. There have hitherto been no reports that have provided insight by partitioning the placenta to compare the NIPT and invasive test results, nor that have provided detailed ultrasound findings in the cases of discordant results, revealing the demonstrated importance of, and necessity for, detailed ultrasonography. This article describes the potential of rolling-circle replication as a powerful biosensing platform, as well as the importance of examining the fetus in detail with ultrasound. However, we should remember that the potential applications raise ethical and social concerns that go beyond aneuploidy and its methodology. Full article

(This article belongs to the Special Issue Advances in Prenatal Diagnostics)

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10 pages, 738 KiB

Open AccessArticle

The Influence of Maternal Cell Contamination on Fetal Aneuploidy Detection Using Chip-Based Digital PCR Testing

by Anna Nykel, Rafał Woźniak and Agnieszka Gach

Diagnostics 2021, 11(9), 1607; https://doi.org/10.3390/diagnostics11091607 - 3 Sep 2021

Viewed by 2823

Abstract

Prenatal samples obtained by amniocentesis or chorionic villus sampling are at risk of maternal cell contamination (MCC). In traditional prenatal analysis, MCC is recommended to be assayed by special tests, such as the short tandem repeat analysis and, if detected at a high [...] Read more.

Prenatal samples obtained by amniocentesis or chorionic villus sampling are at risk of maternal cell contamination (MCC). In traditional prenatal analysis, MCC is recommended to be assayed by special tests, such as the short tandem repeat analysis and, if detected at a high level, may result in failed analysis report. The objective of this study was to test the ability of chip-based digital PCR to detect fetal aneuploidies in the presence of MCC. To determine the level of accuracy of MCC detection, an aneuploid male sample was subjected to serial dilution with an euploid female sample. DNA was extracted from prenatal samples and analyzed with QuantStudio 3D Digital PCR. Digital PCR analysis allowed the detection of trisomy 21, trisomy 18, and X monosomy accurately in samples with 90%, 85%, and 92% of MCC, respectively. Moreover, our results indicated that digital PCR was able to accurately confirm the presence of Y chromosome at up to 95% contamination. The amniotic fluid and chorionic villus sampling (CVS) received in our clinical laboratory was subjected to further analysis of MCC based on the aneuploidy assessment algorithm, resulting in the identification of 10 contaminated samples and four cases of true fetal mosaicism. We conclude that chip-based digital PCR analysis enables the detection of fetal aneuploidy with high levels of accuracy, even in cases of significant MCC. Importantly, the algorithm eliminates the need for maternal DNA and additional MCC tests, which reduces costs and simplifies the diagnostic procedure. The method is easy to set up and suitable for routine clinical practice. Full article

(This article belongs to the Special Issue Advances in Prenatal Diagnostics)

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10 pages, 2726 KiB

Open AccessArticle

Placental Types and Effective Perinatal Management of Vasa Previa: Lessons from 55 Cases in a Single Institution

by Daisuke Tachibana, Takuya Misugi, Ritsuko K. Pooh, Kohei Kitada, Yasushi Kurihara, Mie Tahara, Akihiro Hamuro, Akemi Nakano and Masayasu Koyama

Diagnostics 2021, 11(8), 1369; https://doi.org/10.3390/diagnostics11081369 - 29 Jul 2021

Cited by 11 | Viewed by 5565

Abstract

Background: We aimed to identify clinical characteristics and outcomes for each placental type of vasa previa (VP). Methods: Placental types of vasa previa were defined as follows: Type 1, vasa previa with velamentous cord insertion and non-type 1, vasa previa with a multilobed [...] Read more.

Background: We aimed to identify clinical characteristics and outcomes for each placental type of vasa previa (VP). Methods: Placental types of vasa previa were defined as follows: Type 1, vasa previa with velamentous cord insertion and non-type 1, vasa previa with a multilobed or succenturiate placenta and vasa previa with vessels branching out from the placental surface and returning to the placental cotyledons. Results: A total of 55 cases of vasa previa were included in this study, with 35 cases of type 1 and 20 cases of non-type 1. Vasa previa with type 1 showed a significantly higher association with assisted reproductive technology, compared with non-type 1 (p = 0.024, 60.0% and 25.0%, respectively). The diagnosis was significantly earlier in the type 1 group than in the non-Type 1 group (p = 0.027, 21.4 weeks and 28.6 weeks, respectively). Moreover, the Ward technique for anterior placentation to avoid injury of the placenta and/or fetal vessels was more frequently required in non-type 1 cases (p < 0.001, 60.0%, compared with 14.3% for type 1). Conclusion: The concept of defining placental types of vasa previa will provide useful information for the screening of this serious complication, improve its clinical management and operative strategy, and achieve more preferable perinatal outcomes. Full article

(This article belongs to the Special Issue Advances in Prenatal Diagnostics)

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9 pages, 4402 KiB

Open AccessArticle

Can Fetal Echocardiographic Measurements of the Left Ventricular Outflow Tract Angle Detect Fetuses with Conotruncal Cardiac Anomalies?

by Alona Raucher Sternfeld, Tal Betzer, Akiva Tamir, Yossi Mizrachi, Sagie Assa, Jacob Bar and Liat Gindes

Diagnostics 2021, 11(7), 1185; https://doi.org/10.3390/diagnostics11071185 - 29 Jun 2021

Cited by 2 | Viewed by 6137

Abstract

Objectives: The angle between the inter-ventricular septum and the ascending aorta can be measured during a sonographic fetal survey while viewing the left ventricular outflow tract (LVOT angle). Our aim was to compare the LVOT angle between fetuses with and without conotruncal cardiac [...] Read more.

Objectives: The angle between the inter-ventricular septum and the ascending aorta can be measured during a sonographic fetal survey while viewing the left ventricular outflow tract (LVOT angle). Our aim was to compare the LVOT angle between fetuses with and without conotruncal cardiac anomaliesrmations. Methods: In this prospective observational study, we compared the LVOT angle between normal fetuses, at different gestational age, and fetuses with cardiac malformations. Results: The study included 302 fetuses screened at gestational age of 12–39 weeks. The LVOT angle ranged from 127 to 163 degrees (mean 148.2), in 293 fetuses with normal hearts, and was not correlated with gestational age. The LVOT angle was significantly wider in fetuses with D-transposition of the great arteries (D-TGA, eight fetuses) and valvar aortic stenosis (AS, three fetuses), than in fetuses with normal hearts (164.8 ± 5.0 vs. 148.2 ± 5.4, respectively, p < 0.001). Conversely, the LVOT angle was significantly narrower in fetuses with complete atrioventricular canal defect (AVC, eight fetuses), than in fetuses with normal hearts (124.8 ± 2.4 vs. 148.2 ± 5.4, respectively, p < 0.001). On ROC analysis, an angle of 159.6 degrees or higher had a sensitivity of 100% and a specificity of 97.3% for the detection of TGA or AS, whereas an angle of 128.8 degrees or lower had a sensitivity of 100% and a specificity of 99.7% for the detection of AVC defect. Conclusions: The LVOT angle is constant during pregnancy, and differs significantly in fetuses with TGA/AS, and AVC, compared to fetuses with normal hearts (wider and narrower, respectively). Full article

(This article belongs to the Special Issue Advances in Prenatal Diagnostics)

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10 pages, 919 KiB

Open AccessArticle

sFlt-1, Not PlGF, Is Related to Twin Gestation Choronicity in the First and Third Trimesters of Pregnancy

by Szymon Kozłowski, Anna Stelmaszczyk-Emmel, Iwona Szymusik, Aleksandra Saletra-Bielińska, Robert Brawura-Biskupski-Samaha, Paweł Pietruski, Agnieszka Osińska and Katarzyna Kosińska-Kaczyńska

Diagnostics 2021, 11(7), 1181; https://doi.org/10.3390/diagnostics11071181 - 29 Jun 2021

Cited by 8 | Viewed by 2113

Abstract

Background: Preeclampsia occurs more often in dichorionic than in monochorionic twin pregnancy. We hypothesize that serum concentrations of biomarkers: placental growth factor (PlGF), serum soluble fms-like tyrosine kinase-1 (sFlt-1), and endoglin (Eng) differ between monochorionic and dichorionic twin pregnancies. Methods: A prospective observational [...] Read more.

Background: Preeclampsia occurs more often in dichorionic than in monochorionic twin pregnancy. We hypothesize that serum concentrations of biomarkers: placental growth factor (PlGF), serum soluble fms-like tyrosine kinase-1 (sFlt-1), and endoglin (Eng) differ between monochorionic and dichorionic twin pregnancies. Methods: A prospective observational study including 43 monochorionic and 36 dichorionic twin gestation was conducted. Blood samples were collected twice from all participants: between 11 + 0 and 13 + 6 and between 32 + 0 and 34 + 0 weeks of gestation. PlGF, sFlt-1 and Eng were measured using immnunoenzymatic assays. Results: We found a significantly higher concentration of sFlt-1 in dichorionic in comparison to monochorionic pregnancies in both the first and third trimesters. PlGF and sEng levels did not differ between mono- and dichorionic gestation in both study periods. sFlt-1 level was related to twin gestation chorionicity, while PlGF expression was not. PlGF, sFlt-1 and sEng concentrations increased significantly during gestation and were much higher in the third trimester compared to the values measured in the first trimester. Conclusions: Angiogenic biomarkers expression differ between dichorionic and monochorionic twin pregnancy. The sFlt-1 level is related to chorionicity of a twin gestation. Full article

(This article belongs to the Special Issue Advances in Prenatal Diagnostics)

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Graphical abstract

11 pages, 1153 KiB

Open AccessArticle

Clinical Validation of Novel Chip-Based Digital PCR Platform for Fetal Aneuploidies Screening

by Anna Nykel, Rafał Woźniak and Agnieszka Gach

Diagnostics 2021, 11(7), 1131; https://doi.org/10.3390/diagnostics11071131 - 22 Jun 2021

Cited by 6 | Viewed by 2725

Abstract

Fetal aneuploidy is routinely diagnosed by karyotyping. The development of techniques for rapid aneuploidy detection based on the amplification reaction allows cheaper and rapid diagnosis. However, the currently available solutions have limitations. We tested a novel approach as a diagnostic tool in clinical [...] Read more.

Fetal aneuploidy is routinely diagnosed by karyotyping. The development of techniques for rapid aneuploidy detection based on the amplification reaction allows cheaper and rapid diagnosis. However, the currently available solutions have limitations. We tested a novel approach as a diagnostic tool in clinical practice. The objective of this study was to provide a clinical performance of the sensitivity and specificity of a novel chip-based digital PCR approach for fetal aneuploidy screening. The study was conducted in 505 pregnant women with increased risk for fetal aneuploidy undergoing invasive prenatal diagnostics. DNA extracted from amniotic fluid or CVS was analyzed for the copy number of chromosomes 13, 18, 21, X, and Y using a new chip-based solution. Performance was assessed by comparing results with findings from karyotyping. Aneuploidy was confirmed in 65/505 cases positive for trisomy 21, 30/505 cases positive for trisomy 18, 14/505 cases positive for trisomy 13 and 21/505 with SCAs. Moreover, 2 cases with triploidy and 2 cases with confirmed mosaicisms of 21 and X chromosomes were detected. Clinical sensitivity and specificity within this study was determined at 100% for T21 (95% CI, 99.26–100%), T18 (95% CI, 99.26–100%), and T13 (95% CI, 99.26–100%). Chip-based digital PCR provides equally high sensitivity and specificity in rapid aneuploidy screening and can be implemented into routine prenatal diagnostics. Full article

(This article belongs to the Special Issue Advances in Prenatal Diagnostics)

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9 pages, 1814 KiB

Open AccessArticle

A New Method for Improving Extraction Efficiency and Purity of Urine and Plasma Cell-Free DNA

by Selena Y. Lin, Yue Luo, Matthew M. Marshall, Barbara J. Johnson, Sung R. Park, Zhili Wang and Ying-Hsiu Su

Diagnostics 2021, 11(4), 650; https://doi.org/10.3390/diagnostics11040650 - 3 Apr 2021

Cited by 10 | Viewed by 4095

Abstract

This study assessed three commercially available cell-free DNA (cfDNA) extraction kits and the impact of a PEG-based DNA cleanup procedure (DNApure) on cfDNA quality and yield. Six normal donor urine and plasma samples and specimens from four pregnant (PG) women carrying male fetuses [...] Read more.

This study assessed three commercially available cell-free DNA (cfDNA) extraction kits and the impact of a PEG-based DNA cleanup procedure (DNApure) on cfDNA quality and yield. Six normal donor urine and plasma samples and specimens from four pregnant (PG) women carrying male fetuses underwent extractions with the JBS cfDNA extraction kit (kit J), MagMAX Cell-Free DNA Extraction kit (kit M), and QIAamp Circulating Nucleic Acid Kit (kit Q). Recovery of a PCR product spike-in, endogenous TP53, and Y-chromosome DNA was used to assess kit performance. Nucleosomal-sized DNA profiles varied among the kits, with prominent multi-nucleosomal-sized peaks present in urine and plasma DNA isolated by kits J and M only. Kit J recovered significantly more spike-in DNA than did kits M or Q (p < 0.001) from urine, and similar amounts from plasma (p = 0.12). Applying DNApure to kit M- and Q-isolated DNA significantly improved the amplification efficiency of spike-in DNA from urine (p < 0.001) and plasma (p ≤ 0.013). Furthermore, kit J isolated significantly more Y-chromosome DNA from PG urine compared to kit Q (p = 0.05). We demonstrate that DNApure can provide an efficient means of improving the yield and purity of cfDNA and minimize the effects of pre-analytical biospecimen variability on liquid biopsy assay performance. Full article

(This article belongs to the Special Issue Advances in Prenatal Diagnostics)

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21 pages, 1764 KiB

Open AccessArticle

D-karyo—A New Prenatal Rapid Screening Test Detecting Submicroscopic CNVs and Mosaicism

by Osamu Shimokawa, Masayoshi Takeda, Hiroyasu Ohashi, Akemi Shono-Ota, Mami Kumagai, Risa Matsushika, Chika Masuda, Kohtaro Uenishi and Ritsuko Kimata Pooh

Diagnostics 2021, 11(2), 337; https://doi.org/10.3390/diagnostics11020337 - 18 Feb 2021

Cited by 1 | Viewed by 3730

Abstract

Chromosomal microarray analysis (CMA), recently introduced following conventional cytogenetic technology, can detect submicroscopic copy-number variations (CNVs) in cases previously diagnosed as “cytogenetically benign”. At present, rapid and accurate chromosomal analysis is required in prenatal diagnostics, but prenatal CMA is not widely used due [...] Read more.

Chromosomal microarray analysis (CMA), recently introduced following conventional cytogenetic technology, can detect submicroscopic copy-number variations (CNVs) in cases previously diagnosed as “cytogenetically benign”. At present, rapid and accurate chromosomal analysis is required in prenatal diagnostics, but prenatal CMA is not widely used due to its high price and long turnaround time. We introduced a new prenatal screening method named digital karyotyping (D-karyo), which utilizes a preimplantation genetic test for the aneuploidy (PGT-A) platform. First, we conducted a preliminary experiment to compare the original PGT-A method to our modified method. Based on the preliminary results, we decided to implement the modified strategy without whole-genome amplification (WGA) and combined it with three analytical software packages. Next, we conducted a prospective study with 824 samples. According to the indication for invasive tests, the D-karyo positive rates were 2.5% and 5.0%, respectively, in the screening positive group with NT ≥ 3.5 mm and the group with fetal abnormalities by ultrasound. D-karyo is a breakthrough modality that can detect submicroscopic CNVs ≥ 1.0 Mb accurately in only 10.5 h for 24 samples at a low cost. Implementing D-karyo as a prenatal rapid screening test will reduce unnecessary CMA and achieve more accurate prenatal genetic testing than G-banding. Full article

(This article belongs to the Special Issue Advances in Prenatal Diagnostics)

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Review

Jump to: Research, Other

16 pages, 862 KiB

Open AccessReview

Human Breast Milk: The Key Role in the Maturation of Immune, Gastrointestinal and Central Nervous Systems: A Narrative Review

by Margarita Dimitroglou, Zoi Iliodromiti, Evangelos Christou, Paraskevi Volaki, Chrysa Petropoulou, Rozeta Sokou, Theodora Boutsikou and Nicoletta Iacovidou

Diagnostics 2022, 12(9), 2208; https://doi.org/10.3390/diagnostics12092208 - 12 Sep 2022

Cited by 13 | Viewed by 3983

Abstract

Premature birth is a major cause of mortality and morbidity in the pediatric population. Because their immune, gastrointestinal and nervous systems are not fully developed, preterm infants (<37 weeks of gestation) and especially very preterm infants (VPIs, <32 weeks of gestation) are more [...] Read more.

Premature birth is a major cause of mortality and morbidity in the pediatric population. Because their immune, gastrointestinal and nervous systems are not fully developed, preterm infants (<37 weeks of gestation) and especially very preterm infants (VPIs, <32 weeks of gestation) are more prone to infectious diseases, tissue damage and future neurodevelopmental impairment. The aim of this narrative review is to report the immaturity of VPI systems and examine the role of Human Breast Milk (HBM) in their development and protection against infectious diseases, inflammation and tissue damage. For this purpose, we searched and synthesized the data from the existing literature published in the English language. Studies revealed the significance of HBM and indicate HBM as the best dietary choice for VPIs. Full article

(This article belongs to the Special Issue Advances in Prenatal Diagnostics)

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13 pages, 336 KiB

Open AccessReview

The Management of Pregnancy Complicated with the Previable Preterm and Preterm Premature Rupture of the Membranes: What about a Limit of Neonatal Viability?—A Review

by Stepan Feduniw, Zuzanna Gaca, Olga Malinowska, Weronika Brunets, Magdalena Zgliczyńska, Marta Włodarczyk, Anna Wójcikiewicz and Michał Ciebiera

Diagnostics 2022, 12(8), 2025; https://doi.org/10.3390/diagnostics12082025 - 22 Aug 2022

Cited by 7 | Viewed by 3949

Abstract

Preterm premature rupture of the membranes (PPROM) at the limit of viability is associated with low neonatal survival rates and a high rate of neonatal complications in survivors. It carries a major risk of maternal morbidity and mortality. The limit of viability can [...] Read more.

Preterm premature rupture of the membranes (PPROM) at the limit of viability is associated with low neonatal survival rates and a high rate of neonatal complications in survivors. It carries a major risk of maternal morbidity and mortality. The limit of viability can be defined as the earliest stage of fetal maturity when a fetus has a reasonable chance, although not a high likelihood, for extra-uterine survival. The study reviews available data on preventing preterm delivery caused by the previable PPROM, pregnancy latency, therapeutic options including the use of antibiotics and steroids, neonatal outcomes, and future directions and opportunities. Full article

(This article belongs to the Special Issue Advances in Prenatal Diagnostics)

18 pages, 4551 KiB

Open AccessReview

Applications of Advanced Ultrasound Technology in Obstetrics

by Kwok-Yin Leung

Diagnostics 2021, 11(7), 1217; https://doi.org/10.3390/diagnostics11071217 - 6 Jul 2021

Cited by 18 | Viewed by 10441

Abstract

Over the years, there have been several improvements in ultrasound technologies including high-resolution ultrasonography, linear transducer, radiant flow, three-/four-dimensional (3D/4D) ultrasound, speckle tracking of the fetal heart, and artificial intelligence. The aims of this review are to evaluate the use of these advanced [...] Read more.

Over the years, there have been several improvements in ultrasound technologies including high-resolution ultrasonography, linear transducer, radiant flow, three-/four-dimensional (3D/4D) ultrasound, speckle tracking of the fetal heart, and artificial intelligence. The aims of this review are to evaluate the use of these advanced technologies in obstetrics in the midst of new guidelines on and new techniques of obstetric ultrasonography. In particular, whether these technologies can improve the diagnostic capability, functional analysis, workflow, and ergonomics of obstetric ultrasound examinations will be discussed. Full article

(This article belongs to the Special Issue Advances in Prenatal Diagnostics)

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10 pages, 801 KiB

Open AccessReview

Understanding False Negative in Prenatal Testing

by Mark I. Evans, Ming Chen and David W. Britt

Diagnostics 2021, 11(5), 888; https://doi.org/10.3390/diagnostics11050888 - 17 May 2021

Cited by 6 | Viewed by 4283

Abstract

A false negative can happen in many kinds of medical tests, regardless of whether they are screening or diagnostic in nature. However, it inevitably poses serious concerns especially in a prenatal setting because its sequelae can mark the birth of an affected child [...] Read more.

A false negative can happen in many kinds of medical tests, regardless of whether they are screening or diagnostic in nature. However, it inevitably poses serious concerns especially in a prenatal setting because its sequelae can mark the birth of an affected child beyond expectation. False negatives are not a new thing because of emerging new tests in the field of reproductive, especially prenatal, genetics but has occurred throughout the evolution of prenatal screening and diagnosis programs. In this paper we aim to discuss the basic differences between screening and diagnosis, the trade-offs and the choices, and also shed light on the crucial points clinicians need to know and be aware of so that a quality service can be provided in a coherent and sensible way to patients so that vital issues related to a false negative result can be appropriately comprehended by all parties. Full article

(This article belongs to the Special Issue Advances in Prenatal Diagnostics)

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Other

Jump to: Research, Review

11 pages, 6199 KiB

Open AccessCase Report

A Maternally Inherited Rare Case with Chromoanagenesis-Related Complex Chromosomal Rearrangements and De Novo Microdeletions

by Jui-Hung Yen, Shao-Yin Chu, Yann-Jang Chen, Yi-Chieh Su, Chun-Ching Chien, Chun-Ying Weng and Pei-Yi Chen

Diagnostics 2022, 12(8), 1900; https://doi.org/10.3390/diagnostics12081900 - 5 Aug 2022

Viewed by 1513

Abstract

Chromoanagenesis is a phenomenon of highly complex rearrangements involving the massive genomic shattering and reconstitution of chromosomes that has had a great impact on cancer biology and congenital anomalies. Complex chromosomal rearrangements (CCRs) are structural alterations involving three or more chromosomal breakpoints between [...] Read more.

Chromoanagenesis is a phenomenon of highly complex rearrangements involving the massive genomic shattering and reconstitution of chromosomes that has had a great impact on cancer biology and congenital anomalies. Complex chromosomal rearrangements (CCRs) are structural alterations involving three or more chromosomal breakpoints between at least two chromosomes. Here, we present a 3-year-old boy exhibiting multiple congenital malformations and developmental delay. The cytogenetic analysis found a highly complex CCR inherited from the mother involving four chromosomes and five breakpoints due to forming four derivative chromosomes (2, 3, 6 and 11). FISH analysis identified an ultrarare derivative chromosome 11 containing three parts that connected the 11q telomere to partial 6q and 3q fragments. We postulate that this derivative chromosome 11 is associated with chromoanagenesis-like phenomena by which DNA repair can result in a cooccurrence of inter-chromosomal translocations. Additionally, chromosome microarray studies revealed that the child has one subtle maternal-inherited deletion at 6p12.1 and two de novo deletions at 6q14.1 and 6q16.1~6q16.3. Here, we present a familial CCR case with rare rearranged chromosomal structures and the use of multiple molecular techniques to delineate these genomic alterations. We suggest that chromoanagenesis may be a possible mechanism involved in the repair and reconstitution of these rearrangements with evidence for increasing genomic imbalances such as additional deletions in this case. Full article

(This article belongs to the Special Issue Advances in Prenatal Diagnostics)

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13 pages, 1626 KiB

Open AccessCase Report

Diagnosis, Management, and Therapy of Fetal Ovarian Cysts Detected by Prenatal Ultrasonography: A Report of 36 Cases and Literature Review

by Takeya Hara, Kazuya Mimura, Masayuki Endo, Makoto Fujii, Tatsuya Matsuyama, Kazunobu Yagi, Yoko Kawanishi, Takuji Tomimatsu and Tadashi Kimura

Diagnostics 2021, 11(12), 2224; https://doi.org/10.3390/diagnostics11122224 - 28 Nov 2021

Cited by 10 | Viewed by 13030

Abstract

Background: Fetal ovarian cysts are the most frequently diagnosed intra-abdominal cysts; however, the evidence for perinatal management remains controversial. Methods: We retrospectively reviewed cases of fetal ovarian cysts diagnosed by prenatal ultrasonography at our institution between January 2010 and January 2020. The following [...] Read more.

Background: Fetal ovarian cysts are the most frequently diagnosed intra-abdominal cysts; however, the evidence for perinatal management remains controversial. Methods: We retrospectively reviewed cases of fetal ovarian cysts diagnosed by prenatal ultrasonography at our institution between January 2010 and January 2020. The following were investigated: gestational age at diagnosis, cyst size, appearance, prenatal ultrasound findings, and postnatal outcomes. Prior to 2018, expectant management was applied in all cases; after 2018, in utero aspiration (IUA) of simple cysts ≥40 mm was performed. Results: We diagnosed 29 and seven simple and complex cysts, respectively. Fourteen patients had simple cysts with a maximum diameter <40 mm, and two of them progressed to complex cysts during follow-up; however, when the diameter was limited to <35 mm, no cases showed progression to complex cyst. Fifteen of the simple cysts were ≥40 mm; three progressed to complex cysts, and two of them were confirmed to be ovarian necrosis. In four patients who underwent IUA, the ovaries could be preserved. Conclusions: IUA is a promising therapy for preserving ovaries with simple cysts ≥40 mm in diameter; however, the indications for fetal surgery and the appropriate timing of intervention require further study. Full article

(This article belongs to the Special Issue Advances in Prenatal Diagnostics)

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6 pages, 1030 KiB

Open AccessCase Report

Prenatal Sonographic and Molecular Genetic Diagnosis of Popliteal Pterygium Syndrome

by Kuntharee Traisrisilp, Suchaya Luewan, Sirinart Sirilert, Phudit Jatavan and Theera Tongsong

Diagnostics 2021, 11(10), 1819; https://doi.org/10.3390/diagnostics11101819 - 1 Oct 2021

Cited by 2 | Viewed by 3617

Abstract

Popliteal pterygium syndrome (PPS) is an extremely rare autosomal dominant disorder, characterized by the cleft palate with or without cleft lip, limbs abnormalities with highly characteristic features of popliteal webbing, syndactyly, and genital abnormalities and nail anomalies. Prenatal diagnosis of PPS has been [...] Read more.

Popliteal pterygium syndrome (PPS) is an extremely rare autosomal dominant disorder, characterized by the cleft palate with or without cleft lip, limbs abnormalities with highly characteristic features of popliteal webbing, syndactyly, and genital abnormalities and nail anomalies. Prenatal diagnosis of PPS has been extremely rare. We describe a unique case of fetal PPS at 20 weeks of gestation. The diagnosis of PPS was based on the ultrasound findings of bilateral popliteal webbings, extending from posterior aspects of the upper thighs through the lower legs, resulting in restriction in knee extension, bilateral equinovarus feet with syndactyly, ambiguous genitalia and the grooved lip. Anatomical structures were otherwise normal. Trio whole-exome sequencing revealed a de novo heterozygous IRF6 gene mutation in the fetus, confirming the diagnosis with PPS. In conclusion, popliteal webbing or combination of facial cleft or cleft variants and bilateral abnormal postures of the lower limbs is suggestive of PPS and genetic diagnosis should be warranted. Full article

(This article belongs to the Special Issue Advances in Prenatal Diagnostics)

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8 pages, 1697 KiB

Open AccessCase Report

A Fetus with Congenital Microcephaly, Microphthalmia and Cataract Was Detected with Biallelic Variants in the OCLN Gene: A Case Report

by Vivian Kwun Sin Ng, Tze Kin Lau, Anita Sik Yau Kan, Brian Hon Yin Chung, Ho Ming Luk, Wai Fu Ng, Mengmeng Shi, Kwong Wai Choy, Ye Cao and Wing Cheong Leung

Diagnostics 2021, 11(9), 1576; https://doi.org/10.3390/diagnostics11091576 - 30 Aug 2021

Viewed by 2747

Abstract

Microcephaly and microphthalmia are both rare congenital abnormalities, while concurrently, these two are even rarer. The underlying etiology would be complex interplaying between heterogeneous genetic background and the environmental pathogens, particularly during critical periods of early tissue development. Here, we reported a prenatal [...] Read more.

Microcephaly and microphthalmia are both rare congenital abnormalities, while concurrently, these two are even rarer. The underlying etiology would be complex interplaying between heterogeneous genetic background and the environmental pathogens, particularly during critical periods of early tissue development. Here, we reported a prenatal case with microcephaly, microphthalmia, and bilateral cataracts detected by ultrasonography and confirmed by autopsy. Various routine infection-related tests and invasive genetic testing were negative. Whole genome sequencing of fetus and parents revealed OCLN gene defects may be associated with these multiple congenital abnormalities. Full article

(This article belongs to the Special Issue Advances in Prenatal Diagnostics)

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