Opening Pandora's box?: ethical issues in prenatal whole genome and exome sequencing.

OBJECTIVE: The development of genomic approaches to prenatal testing such as whole genome and exome sequencing offers the potential for a better understanding of prenatal structural anomalies in the fetus and ultimately for improved patient care and more informed reproductive decision making. In addition to the scientific and clinical challenges of achieving this, the introduction of new reproductive technologies also presents a number of ethical problems. The successful and appropriate development and introduction of prenatal genomics into clinical practice require these problems to be identified, understood and carefully analysed in the development of models of good ethical practice. METHOD: We conducted a critical review of the existing literature on ethical issues in prenatal genomics. RESULTS: We identified and discussed five areas of particular concern: valid consent, management and feed-back of information, responsibilities of health professionals, priority setting and resources and duties towards the future child. CONCLUSION: There is a need for further discussion of the issues we have outlined here, and we hope that this brief summary of ethical arguments in the literature encourages researchers, clinicians, patients and scientists to engage in further discussion of these and other important issues raised by prenatal genomics. © 2017 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.

Current status of non-invasive prenatal testing in Japan.

AIM: The purpose of this study was to report the 3-year experience of a nationwide demonstration project to introduce non-invasive prenatal testing (NIPT) of maternal plasma for aneuploidy, and review the current status of NIPT in Japan. METHODS: Tests were conducted to detect aneuploidy in high-risk pregnant women, and adequate genetic counseling was provided. The clinical data, test results, and pregnancy outcomes were recorded. We discuss the problems of NIPT on the basis of published reports and meta-analyses. RESULTS: From April 2013 to March 2016, 30 613 tests were conducted at 55 medical sites participating in a multicenter clinical study. Among the 30 613 women tested, 554 were positive (1.81%) and 30 021 were negative (98.1%) for aneuploidy. Of the 289, 128, and 44 women who tested positive for trisomies 21, 18, and 13, respectively, and underwent definitive testing, 279 (96.5%), 106 (82.8%), and 28 (63.6%) were determined to have a true-positive result. For the 13 481 women with negative result and whose progress could be traced, two had a false-negative result (0.02%). The tests were performed on the condition that a standard level of genetic counseling be provided at hospitals. CONCLUSION: Here, we report on the 3-year nationwide experience with NIPT in Japan. It is important to establish a genetic counseling system to enable women to make informed decisions regarding prenatal testing. Moreover, a welfare system is warranted to support women who decide to give birth to and raise children with chromosomal diseases.

Non-invasive prenatal testing: ethics and policy considerations.

New technologies analyzing fetal DNA in maternal blood have led to the wide commercial availability of non-invasive prenatal testing (NIPT). We present here for clinicians the ethical and policy issues related to an emerging practice option. Although NIPT presents opportunities for pregnant women, particularly women who are at increased risk of having a baby with an abnormality or who are otherwise likely to access invasive prenatal testing, NIPT brings significant ethics and policy challenges. The ethical issues include multiple aspects of informed decision-making, such as access to counselling about the possible results of the test in advance of making a decision about participation in NIPT. Policy considerations include issues related to offering and promoting a privately available medical strategy in publicly funded institutions. Ethics and policy considerations merge in NIPT with regard to sex selection and support for persons living with disabilities.

Les nouvelles techniques qui font appel à l'analyse de l'ADN fœtal dans le sang maternel ont mené à l'élargissement de la disponibilité commerciale du dépistage prénatal non effractif (DPNE). Nous présentons ici, à l'intention des cliniciens, les questions d'éthique et de politique qui sont associées à une option de pratique émergente. Bien que le DPNE offre des possibilités aux femmes enceintes (et particulièrement aux femmes qui sont exposées à des risques accrus de donner naissance à un enfant présentant une anomalie ou qui sont autrement susceptibles d'avoir recours au dépistage prénatal effractif), il donne lieu à des défis considérables en matière d'éthique et de politique. Les multiples aspects de la prise d'une décision éclairée (comme l'accès à des services de counseling au sujet des résultats possibles du test avant la prise d'une décision quant à la participation au DPNE) font partie des enjeux éthiques. Parmi les considérations en matière de politique, on trouve les questions liées à l'offre et à la promotion, au sein d'établissements subventionnés par l'État, d'une stratégie médicale offerte au privé. Les considérations en matière d'éthique et de politique s'entremêlent dans le cas du DPNE, pour ce qui est des questions relevant de la sélection du sexe et de l'offre d'un soutien aux personnes qui vivent avec des incapacités.

Non-invasive prenatal testing using massively parallel sequencing of maternal plasma DNA: from molecular karyotyping to fetal whole-genome sequencing.

The discovery of cell-free fetal DNA in maternal plasma in 1997 has stimulated a rapid development of non-invasive prenatal testing. The recent advent of massively parallel sequencing has allowed the analysis of circulating cell-free fetal DNA to be performed with unprecedented sensitivity and precision. Fetal trisomies 21, 18 and 13 are now robustly detectable in maternal plasma and such analyses have been available clinically since 2011. Fetal genome-wide molecular karyotyping and whole-genome sequencing have now been demonstrated in a number of proof-of-concept studies. Genome-wide and targeted sequencing of maternal plasma has been shown to allow the non-invasive prenatal testing of ß-thalassaemia and can potentially be generalized to other monogenic diseases. It is thus expected that plasma DNA-based non-invasive prenatal testing will play an increasingly important role in future obstetric care. It is thus timely and important that the ethical, social and legal issues of non-invasive prenatal testing be discussed actively by all parties involved in prenatal care.