Ushering in a new dawn in obstetrics and gynecology: the industry of cell‐free DNA testing

It gives me great pleasure to welcome our readers to the January 2015 issue of Ultrasound in Obstetrics & Gynecology (UOG), which is dedicated to new and emerging technologies in obstetrics and gynecology. In anticipation of the obvious implications of new technology on current clinical practice, we took the decision to issue a ‘call for papers’ in this field late last year. I have to acknowledge that it was not a unanimous editorial decision to issue this call because of the perceived risks – those of a poor response to the call from researchers in this field who are not used to publishing in UOG and of potentially alienating the readership of UOG, with their natural bias towards articles on imaging. Thankfully, there was an overwhelming response from researchers to the call and an exceptionally high quality of work was submitted, much of which is published in this issue. As for the matter of whether such work is suitable for UOG, we have been there before, with the inclusion of articles on array comparative genomic hybridization (CGH) testing – considered rather novel some 2 years ago1. It is now apparent that array CGH is part of routine clinical practice for the majority of prenatal diagnostic testing and that we may be ushering in a new dawn with research on the role of exome sequencing in prenatal diagnosis2. I have no doubt that our readers are cognizant of the implications of measuring cell-free DNA (cfDNA) and of non-invasive prenatal testing (NIPT) for clinical practice both now and in the future – our patients are for sure3. The advent of new technologies has seen surges in improved patient care over the last few decades. To most, it is clear that the ability to exclude fetal aneuploidy with a high degree of certainty using cfDNA testing has an enormous role to play in providing parental reassurance and reducing the risk of miscarriage. It is therefore inevitable that such technology will have an impact on the practice of clinicians involved in the fields of obstetric ultrasound, prenatal diagnosis and maternal–fetal medicine. What is different on this occasion is the speed at which the technology has arrived and the manner in which it is being imposed on clinical practice. For the first time, in our specialized field, new technological advances are being pioneered by several private scientific enterprises backed by venture capital and being marketed directly to patients and non-specialists. This scenario, which is more commonly seen in other areas of medicine, whilst facilitating a much more rapid translation into the clinical interface, produces conflicts that hamper the embedding of such technology into routine clinical practice. Even though the scientific endeavor and innovation of these companies is not in question, there lies a fundamental conflict of interest between the need to make a profit to remunerate investors and the desire to provide an affordable healthcare solution; it is evident that the exponential rise in share prices or market values of these institutions seen over the last couple of years has by no means been matched by the relatively modest drop in the commercial price of cfDNA testing. Furthermore, the marketing of cfDNA testing directly to expectant mothers and general obstetricians has led to a misunderstanding regarding its value and role, as highlighted in several articles in this issue. Briefly, the importance of the fraction of fetal cfDNA was highlighted in UOG 2 years ago4 and yet the common practice in industry of not assessing the fetal cfDNA fraction remains unaddressed. It is evident that fetal cfDNA fraction below about 5% is one of the most important contributors to false-negative results, yet the majority of NIPT providers do not measure it routinely5, 6. The rationale often given to mitigate its lack of measurement is that routine testing of fetal fraction is inaccurate and would affect deleteriously the price of NIPT without improving significantly the overall screening efficiency of NIPT for fetal aneuploidy. Another concern is the failure to include the calculated a-priori aneuploidy risk when interpreting cfDNA test results. It is accepted that the increased aneuploidy risk in the presence of a fetal cardiac or other major abnormality mandates invasive prenatal diagnosis rather than cfDNA testing: not only are the results obtained more quickly and are more informative7, but also it appears that invasive procedures are much safer than was previously assumed8. Yet, there seems to be reluctance, on the part of both companies and clinicians, to use the combined test result as an a-priori risk for interpretation of cfDNA tests, despite evidence that combining nuchal screening with NIPT would only serve to improve the reliability of cfDNA testing9. Articles on NIPT and array CGH accounted for a small but significant portion of the UOG articles most downloaded and cited last year10. However, this was not at the expense of other clinically relevant topics, with some of our most cited and downloaded articles being systematic reviews11, 12, and studies on late fetal growth restriction13, 14, pre-eclampsia15, endometrial cancer16 and pelvic floor anatomy17. It is clear that UOG is on track, achieving academic success with a stable impact factor, and is making a valuable clinical impact, as evidenced by the magnitude of downloads of articles with practice-changing messages as well as of clinical guidelines. One mechanism on which UOG has relied, in order to preclude a persistent bias towards certain topics, is to encourage submission of articles in other areas of clinical and research interests, for example on fetal surgery18-20 and morbidly adherent placentation21-23. In order to maintain the impetus, I am pleased to announce that there will be further formal calls for papers, with specific subject areas including late fetal growth restriction, maternal hemodynamics and reproductive medicine. UOG is also facing a new dawn, with 2015 bringing a number of changes. The Journal editors, like our reviewers, are a group of intelligent, hard-working and conscientious researchers, who, for no reason other than academic endeavor, dedicate hours of their time each week towards the sole purpose of selecting the best scientific and most clinically relevant research articles for our readers. The editor's toil goes largely unrewarded and unnoticed except by those in the UOG editorial team and office. After many years of loyal service, several editors are now stepping down: Nick Raine-Fenning as Deputy Editor-in-Chief, as well as Zarko Alfirevic and Julene Carvalho. They have all served, with equal enthusiasm, either one or two full terms for the Journal and have made invaluable contributions to make the Journal a success. Without their efforts, UOG would not be enjoying its position as one of the top ranked journals in obstetrics and gynecology, with an impact factor to match those of its competitors. Although these editors will be sorely missed for their personal contribution and work ethic, I know that our new editors, Helena Gardiner, Lisa Hui, Wellington Martins and Alex Sotiriadis will be effective and able replacements. I would like to take this opportunity to sincerely thank the editors who are retiring for all their hard work and to welcome our new editors to the team. The editorial office must not be allowed to go unacknowledged. Most members of the Society and readers of the Journal are blissfully unaware of the relentless workload managed by Sarah Hatcher, Heather Bhasin, Oliver Stirrup and our new editorial assistant, Alice Garrett. Thanks to their dedication to the Journal, UOG is produced in a timely manner each month and has a reputation for quality that can be matched by few other journals in the publication industry. UOG is currently reviewing its publisher contract and, irrespective of the outcome of the publisher tender process, we can be assured of improved access to the Journal. Even though many of our readers enjoy their interaction with the paper content of the Journal, there is no doubt that the younger generation of doctors and the emerging markets of Asia, the Far East and South America are predisposed to accessing UOG electronically, and increasingly, using mobile devices. Given the surfeit of medical publications worldwide, estimated at approximately 1500 medical articles daily, making UOG articles discoverable and disseminating our Journal are important priorities for the publisher with which we sign a contract. Improving access through free and open-access articles, dedicated mobile apps and multifunctional electronic rather than pdf article formats are some of the solutions to improve access. The age of social media engagement is upon us and, in order to engage the young, emerging practitioners of imaging in women's health, we will need to be active in this arena. Here, we intend to rely on our editors-for-trainees to spread news about Journal Clubs as well as clinically relevant and free-access papers. To help in this effort, we welcome to the team Shireen Meher, Maddalena Morlando and Joel Naftalin who take up the baton from Tomasso Bignardi, Ligita Jokubkiene and Leona Poon, three stalwart editors-for-trainees who are retiring and to whom we extend our sincere thanks for their hard work and valuable contributions. We have continued to receive positive feedback on the referee commentaries and it is my intention to continue this article type for the foreseeable future. Not all initiatives, however, can be successful, and it is with a little regret that I have to announce that the ‘How To’ article format on fundamental imaging techniques and procedures is to cease. Despite the potential for this sort of article type, feedback has been lacking (rather than poor). Creation of the ‘How To’ series is very labor intensive and, without any discernible response from our younger readers, the decision to suspend the production of this article type has been made. The Journal will continue to be focused on current topics of research and will remain responsive to authors and accessible to readers, whilst maintaining a fast and effective editorial service. Thankfully, this task is made much easier by the efforts of my fellow editors and the Journal office staff. I am confident that, with this support, the Journal will remain an invaluable resource for researchers, readers and trainees alike. I would like to thank you for your continued loyalty to the Journal and, as always, would welcome your opinions and thoughts about how UOG can be made even better.