Pietersma et al. BMC Pregnancy and Childbirth (2020) 20:515 https://doi.org/10.1186/s12884-020-03180-8 STUDY PROTOCOL Open Access First trimester anomaly scan using virtual reality (VR FETUS study): study protocol for a randomized clinical trial C. S. Pietersma1, A. G. M. G. J. Mulders1, L. M. Moolenaar1, M. G. M. Hunink2,3,4, A. H. J. Koning5, S. P. Willemsen6, A. T. J. I. Go1, E. A. P. Steegers1 and M. Rousian1* Abstract Background: In recent years it has become clear that fetal anomalies can already be detected at the end of the first trimester of pregnancy by two-dimensional (2D) ultrasound. This is why increasingly in developed countries the first trimester anomaly scan is being offered as part of standard care. We have developed a Virtual Reality (VR) approach to improve the diagnostic abilities of 2D ultrasound. Three-dimensional (3D) ultrasound datasets are used in VR assessment, enabling real depth perception and unique interaction. The aim of this study is to investigate whether first trimester 3D VR ultrasound is of additional value in terms of diagnostic accuracy for the detection of fetal anomalies. Health-related quality of life, cost-effectiveness and also the perspective of both patient and ultrasonographer on the 3D VR modality will be studied. Methods: Women in the first trimester of a high risk pregnancy for a fetus with a congenital anomaly are eligible for inclusion. This is a randomized controlled trial with two intervention arms. The control group receives ‘care as usual’: a second trimester 2D advanced ultrasound examination. The intervention group will undergo an additional first trimester 2D and 3D VR ultrasound examination. Following each examination participants will fill in validated questionnaires evaluating their quality of life and healthcare related expenses. Participants’ and ultrasonographers’ perspectives on the 3D VR ultrasound will be surveyed. The primary outcome will be the detection of fetal anomalies. The additional first trimester 3D VR ultrasound examination will be compared to ‘care as usual’. Neonatal or histopathological examinations are considered the gold standard for the detection of congenital anomalies. To reach statistical significance and 80% power with a detection rate of 65% for second trimester ultrasound examination and 70% for the combined detection of first trimester 3D VR and second trimester ultrasound examination, a sample size of 2800 participants is needed. Discussion: First trimester 3D VR detection of fetal anomalies may improve patients’ quality of life through reassurance or earlier identification of malformations. Results of this study will provide policymakers and healthcare professionals with the highest level of evidence for cost-effectiveness of first trimester ultrasound using a 3D VR approach. (Continued on next page) * Correspondence: [email protected] 1Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, the Netherlands Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Pietersma et al. BMC Pregnancy and Childbirth (2020) 20:515 Page 2 of 10 (Continued from previous page) Trial registration: Dutch Trial Registration number NTR6309, date of registration 26 January 2017. Keywords: First trimester, Two-dimensional ultrasound, three-dimensional ultrasound, Virtual reality, Detection rate, Fetal anomalies Background and completeness [13]. Incomplete ultrasound examin- Congenital anomalies account for 15–20% of all fetal ation may lead to suboptimal care for these women. The deaths and nearly 25% of all neonatal deaths in Europe efforts and costs greater when compared to women with [1]. Around 2% of all pregnancies are affected by a major a BMI < 30 kg/m2. In the first trimester, transvaginal anomaly that requires extensive postnatal support [2]. A ultrasound may be used to overcome limited visibility in correct prenatal diagnosis can direct future parents to the women with an increased BMI. the best possible care. From the above mentioned, we can conclude that According to international and Dutch national postponing detection of anomalies to the second guidelines, all pregnant women are offered a second tri- trimester of pregnancy can be regarded as a missed mester two-dimensional (2D) ultrasound scan to screen opportunity. This is the most compelling argument for fetal anomalies [3–5]. Subsequently, future parents mentioned in international guidelines proposing a first are counseled about the possible diagnosis, prognosis trimester anomaly scan to be offered to all women, and treatment. However, by the end of the first trimes- accompanied by adequate counseling of the potential ter (< 14 weeks gestational age (GA)), a considerable benefits and limitations [14]. However, there is a lack amount of fetal anomalies can already be detected of implementation of the guidelines’ advice in nation- using 2D ultrasound [6, 7]. A systematic review, per- wide screening programs. The available literature con- formed in a high risk population, showed that 61% of cerning detection rates and feasibility of the first the (detectable) anomalies can already be identified by trimester anomaly scan include a low risk population a first trimester anomaly scan [6]. A more recent pro- and are retrospective in design [6]. Prospective or spective cohort study performed in The Netherlands randomized trials for a high risk population are lim- even found a detection rate of 63% within a low risk ited in number. In spite of this, some countries are population, which demonstrates the importance of per- offering a first trimester anomaly scan to their popu- forming a first trimester anomaly scan [8]. The ob- lation [15]. served high detection rate of major anomalies and Over the years several factors have contributed to the ultrasonographic markers coincides with other advan- quality of first trimester 2D ultrasound imaging. The tages. Firstly, detection of an anomaly at an early stage most important ones are the introduction of high fre- in pregnancy provides additional time for counseling, quency ultrasound probes and using the transvaginal ap- advanced genetic testing, parental thought and reflec- proach. The addition of an application providing three- tion [9]. Secondly, a first trimester scan showing no ab- dimensional (3D) renderings have further enhanced first normalities might provide parental reassurance, trimester ultrasound imaging by enabling improved especially in a population at higher risk of fetal anomal- visualization of fetal structures [16]. However, there are ies. Thirdly, if applicable, an early termination of preg- also limitations concerning 3D ultrasound examinations. nancy is considered a low risk procedure, in contrast to The 3D datasets are presented as 3D reconstructions on termination during advanced gestation, which shows a 2D screens. Therefore, the third dimension, depth, can- greater risk of maternal morbidity and mortality [10, not be used to its fullest since the images are being pre- 11]. When pregnant women opt for an early termin- sented on 2D media. Improved visualization can be ation of pregnancy, methods available are considered reached using Virtual Reality (VR) displays. VR enables less invasive when compared to termination at an ad- true depth perception and provides 3D interaction. ‘Ho- vanced stage. Moreover, it has been shown that termin- lograms’ of the 3D ultrasound scans can be created using ation of pregnancy at a more advanced gestational age the V-Scope software (Erasmus MC, Rotterdam, The is associated with an increased risk of an adverse psy- Netherlands), allowing presentation of volumetric data chological outcome [12]. in the best possible way [17, 18]. Following the acquisi- Finally, women with an increased BMI (i.e. > 30 kg/m2) tion of 3D data, using any 3D probe, application of V- could profit from a first trimester anomaly scan. It is scope imaging software enables 3D data to be displayed known that the performance of the second trimester as ‘holograms’ on a 3D display, generating depth percep- transabdominal ultrasound examination in women with tion using 3D glasses. The difference between 2D, 3D an increased BMI is limited with regards to detection and 3D VR is depicted in Fig. 1. These generated Pietersma et al. BMC Pregnancy and Childbirth (2020) 20:515 Page 3 of 10 Fig. 1 Different imaging techniques of the same pregnancy in the first trimester. Images, representing