The failure of non-invasive prenatal testing due to maternal dermatomyositis

We experienced a case of a pregnant woman who failed to obtain a result from NIPT, due to the high level of total cell-free DNA. A subsequent ultrasound examination discovered that the fetus had severe intrauterine growth restriction, so the woman decided to abort the baby. At the same time, the woman developed slight swelling and tenderness of the proximal interphalangeal and meta-carpophalangeal joints. At first, these symptoms were not noticed, but, when the pregnant woman was admitted to the hospital, her laboratory tests were seriously abnormal, such as serum lactate dehydrogenase (640U/L), creatine phosphor kinase (4525U/L), kinase isoenzyme MB (170U/L), and a hydroxybutyrate dehydrogenase (398U/L). The patient had no other symptoms at this time. Misoprostol and subsequent forceps curettage were used for the induced abortion, a 167-g female fetus was aborted. Fetal skin tissue was taken for chromosomal microarray analysis (CMA) and placenta (biopsied in four places and tested as two composite samples) were taken for postnatal karyotyping to exclude a confined placental mosaicism, chromosomal microarray analysis of the fetal skin tissue revealed that the karyotype was 46, XX, karyotyping of placenta (100 cells) gave results of 46, XX, no abnormalities were detected. Ten days after induction, the patient had developed progressive symmetric muscle weakness in the proximal extremities. Physical examination revealed Gottron's sign and erythema. A manual muscle test showed weakness of the muscles (4/5) of her proximal extremities. Electromyography showed myogenic impairment. After excluding the possibility of neoplasia, the patient was diagnosed with dermatomyositis.     

Factors affecting the clinical use of non-invasive prenatal testing: a mixed methods systematic review

Non-invasive prenatal testing has been in clinical use for a decade; however, there is evidence that this technology will be more widely applied within the next few years. Guidance is therefore required to ensure that the procedure is offered in a way that is evidence based and ethically and clinically acceptable. We conducted a systematic review of the current relevant literature to ascertain the factors that should be considered when offering non-invasive prenatal testing in a clinical setting. We undertook a systematic search of relevant databases, journals and reference lists, and from an initial list of 298 potential papers, identified 11 that were directly relevant to the study. Original data were extracted and presented in a table, and the content of all papers was analysed and presented in narrative form. Four main themes emerged: perceived attributes of the test, regulation and ethical issues, non-invasive prenatal testing in practice and economic considerations. However, there was a basic difference in the approach of actual or potential service users, who were very positive about the benefits of the technology, compared with other research participants, who were concerned with the potential moral and ethical outcomes of using this testing method. Recommendations for the appropriate use of non-invasive prenatal testing are made. © 2013 John Wiley & Sons, Ltd.     

Ethical issues associated with prenatal screening using non-invasive prenatal testing for sex chromosome aneuploidy

Prenatal screening for sex chromosome aneuploidies (SCAs) is increasingly available through expanded non-invasive prenatal testing (NIPT). NIPT for SCAs raises complex ethical issues for clinical providers, prospective parents and future children. This paper discusses the ethical issues that arise around NIPT for SCAs and current guidelines and protocols for management. The first section outlines current practice and the limitations of NIPT for SCAs. It then outlines key guidelines before discussing the ethical issues raised by this use of NIPT. We conclude that while screening for SCAs should be made available for people seeking to use NIPT, its implementation requires careful consideration of what, when and how information is provided to users.     

The fragmentation patterns of maternal plasma cell-free DNA and its applications in non-invasive prenatal testing

The discovery of cell-free DNA (cfDNA) in maternal plasma has opened up new promises for the development of non-invasive prenatal testing (NIPT). Application of cfDNA in NIPT of fetus diseases and abnormalities is restricted by the low amount of fetal DNA molecules in maternal plasma. Fetus-derived cfDNA in maternal plasma are shorter than maternal DNA, thus leveraging the maternal and fetus-derived cfDNA molecules size difference has become a novel and more accurate method for NIPT. However, multiple biological properties such as size distribution of plasma DNA, proportion of fetal-derived DNA and methylation levels in maternal plasma across different gestational ages still remain largely unknown. Further insights into the size distribution and fragmentation pattern of circulating plasma cfDNA will shed light on the origin and fragmentation mechanisms of cfDNA during physiological and pathological processes in prenatal diseases and enhance our ability to take the advantage of plasma cfDNA as a molecular diagnostic tool. In the review, we start by summarizing the research techniques for the determination of the fragmentation profiles of cfDNA in maternal plasma. We then summarize the main progress and findings in size profiles of maternal plasma cfDNA and cffDNA. Finally, we discuss the potential diagnostic applications of plasma cfDNA size profiling.