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

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%).

Methods of detection and isolation of trophoblast cells from trans-cervical specimens – a historical overview

Trophoblast cells can be detected and isolated from the cervical epithelial cells obtained via various techniques of trans-cervical samples collection such as a mucus aspiration, endocervical lavage, or standard cervical brushing in the early first trimester, even from the 5 weeks’ gestation. Isolated fetal cells can be used in the early prediction of fetal sex, prenatal diagnostics of the most common aneuploidies, and any other genetic abnormalities. Nevertheless, the collection of trophoblastic cells has limited efficacy compared to currently used methods of detection of free fetal DNA in maternal circulation or other protocols of invasive prenatal diagnostics available at later stages of pregnancy. In the past years, trans-cervical cell samples were collected mainly in women before planned pregnancy termination. The early trophoblastic cells isolation from women in ongoing pregnancies opens new perspectives for further studies focused on the elucidation of pathophysiology of numerous pregnancy-related complications.

Noninvasive prenatal testing in megacity

Introduction. The article presents an analysis of the use of non-invasive prenatal testing for chromosomal abnormalities in the fetal extracellular DNA in the blood of pregnant women in Moscow. Materials and methods. When processing materials and research results, authors considered all available clinical data: findings of an ultrasound examination, medical history and results of additional laboratory tests. Results. The article presents results of invasive prenatal diagnostics and pregnancy outcomes in patients with high NIPT risks. Discussion. Authors analyzed diagnostic capabilities of NIPT, its limitations, false-positive and false- negative results, and described 3 cases of prenatal diagnosis of fetal aneuploidy identified in patients who are in the «gray zone» of risk based on the results of combined screening of the first trimester of pregnancy. Conclusion. Prenatal diagnosis of the described aneuploidy is difficult due to individual risk of developing chromosomal abnormalities of the fetus based on the results of combined first-trimester screening in the range of 1:101-1: 2500 and lack of indications for invasive prenatal diagnostics.

Utilisation of Prenatal Diagnostics During Pregnancy in Germany: Cross-sectional Study Using Data From the KUNO Kids Health Study

Background: Appropriate health system utilisation during pregnancy is fundamental for maintaining maternal and child’s health. This study provides comprehensive data on supplementary prenatal diagnostics use and its influencing factors in Germany. Methods: We obtained data from a recently established prospective German birth cohort study, the KUNO Kids Health Study, with a study sample of 1886 participating mothers. Analyses are based on Andersen’s Behavioural Model of health system use, which distinguishes between predisposing, enabling and need factors. We examined bi- and multivariate association with the use of supplementary prenatal diagnostics using logistic regression. Results: One fifth of the mothers investigated did not use any supplementary prenatal diagnostics. Notably, the chance of using supplementary prenatal diagnostics more than doubled if the pregnant woman had a private health insurance. Higher maternal age and environmental tobacco smoke exposure increased the use of supplementary prenatal diagnostics. However, regarding need factors only having a risk-pregnancy showed an independent association.Conclusion: Although a shift in the importance of need factors towards enabling factors for preventive health services has been described before, the important role of the type of health insurance and the relatively small influence of need factors was surprising and worrisome. Especially with respect to equity in accessing health care, this needs further attention.

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

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.

Non-invasive prenatal diagnostics (NIPD) in the system of medical care. Ethical and legal issues

The procedures of prenatal and preimplantation diagnostics are discussed critically again and again in our community. In addition to the permanently controversial issues of embryo protection and abortion, considerations that discrimination on the basis of disability could occur with problematic consequences also for already born people with disabilities and their relatives now play a central role.

The isolation and analysis of fetal nucleated red blood cells using multifunctional microbeads with a nanostructured coating toward early noninvasive prenatal diagnostics

An innovative platform is demonstrated based on multifunctional microbeads with a nanostructured coating for fNRBC isolation and release.