Title: Clinical and/or cost-effectiveness of first trimester ultrasound screening for fetal anomalies: Is a prospective study an efficient investment?
Funder: Department of Health and Social Care

Abstract: Fetal anomaly screening is routinely performed in the second trimester. Our group has recently published a systematic review and meta-analysis of first trimester anomaly screening and this shows that the sensitivity for the detection of major anomalies in a low risk unselected population (19 studies, 115731 fetuses) was 46 % (95% CI, 36.88–55.46%), representing just over half of all abnormalities detected prenatally. We also showed a significant association between the sensitivity of first-trimester ultrasound and the use of an anatomical protocol for screening. These findings suggest that first trimester anomaly screening has the potential to be a valuable addition to prenatal care for all women. However, a trial assessing this in practice would be very large and expensive. This study will establish whether such a study would be feasible and cost effective. In order to define, justify and protocolise the 12 week detailed anomaly scan we will undertake an update of the existing systematic review and in particular measure uncertainties regarding the existing data (effect of gestational age at the scan; preferred route (transabdominal vs transvaginal); what specific anomalies detectable and at what false positive rates; how such anomalies should be reported; etc). We have identified four pathways of first trimester ultrasound used in the UK today and will undertake a nationwide survey of all maternity units to establish current practice; the choice that women are offered; and what impact a suspected abnormality has in changing a woman's care from the standard NICE antenatal care pathway. No UK clinical management plan for screen positive pregnancies for an abnormality in the first trimester exists, and we will perform a systematic review of possible pathways. Based on all this information a consensus procedure to develop a protocol for the first trimester scan will be undertaken, taking into account acceptability of this amongst women and caregivers. To derive an economic model and conduct a value of information (VOI) analysis, we will develop a decision analytic model to determine the expected cost and outcomes associated with current practice and with each of the discrete protocols defined above. This will be populated with evidence from the systematic reviews; additional reviews of the literature; and an existing large dataset of detected anomalies. Evidence gaps will be noted and “plugged” by systematic review findings and evidence from expert panels. A decision model to determine the most cost-effective protocol based on current evidence will be undertaken. VOI analysis will determine the model parameters for which it is worth investing research effort; this will include cost modelling for the resource of sonographers required. Based on this information a consensus meeting will be held outlining the design of plausible prospective studies, and these will include population, outcome and sample size. The VOI analysis will be rerun to predict the expected net gain of sampling of the alternatives. If a study is deemed efficient, we will develop the relevant parameters, including prospective cohort screening study with ascertainment of outcomes; randomised trial with individual women randomised, or randomising at the level of hospitals (cluster or stepped wedge). Candidate study designs will again be discussed in workshops of health care professionals and focus groups including patients and the public.

Lay abstract: During pregnancy, women in the UK are offered two routine scans. The first is at around 12 weeks and checks that the baby is alive, measures it to assess growth and how advanced the pregnancy is; and looks for twins or triplets. At this scan women are also given the option to have screening for Down syndrome and other chromosomal changes. The second scan is at 20 weeks and aims to check that everything is developing normally. Unfortunately, in about 2% of pregnancies, an important abnormality is found at this stage. As ultrasound equipment is improving, abnormalities can be picked up at an earlier stage. We have recently published a study that showed that almost half of all abnormalities can be detected already at the 12 week stage. We also showed that more abnormalities were detected when studies followed a set guideline for scanning. So, a careful 12 week scan may be a valuable addition to pregnancy care for all women. However, there are possible disadvantages too: early scanning may show a suspected abnormality that turns out to be normal; this causes a lot of anxiety and further unnecessary scans or other tests. Such tests may add a lot of cost to an already stretched healthcare service. We aim to do three things in this study: Firstly, as there is no nationally agreed protocol for the 12 week detailed anatomy scan, this needs to be created. Using available studies we will develop this protocol, and also assess gaps of knowledge – for example, when exactly in pregnancy such a scan should be done; whether this should be done through a normal, abdominal scan, or with a vaginal (internal) scan; what specific abnormalities should be picked up and how often a scan may result in a “false alarm”. We will also undertake a nationwide survey of all maternity units to establish current practice and what choices women are offered. This is because women in the UK have different levels of scan depending on where they live and “book in" for pregnancy care. The impact on pregnant women if a scan finds a problem will also be assessed. Based on all this information, we will ask women and professionals about their views on what a protocol for the first trimester scan should contain, and determine the acceptability of this. Secondly, we will check whether it all makes sense financially. We will look at how much it would cost to do detailed scanning for all women, how much it would cost to look after the women who have a problem, and then look at the expected benefit in terms of ill-health prevented. Third, this work is in preparation for a trial. The trial may require very large numbers of women to take part, and they (and their babies) may need quite long follow up. This means that the trial itself could be very expensive to fund. We will check whether the problem is big enough, and is associated with sufficiently major costs, that it justifies all the money to answer the question. Taking into account all of the factors above, we will make a plan for how the trial would actually be conducted, and how many women would need to take part. Throughout this time we will put pregnant couples at the heart of the proposal by engaging with them and support charities. They will be asked to decide key aspects - How should a study be conducted? How and when should women be approached? What information do they need? And other details. After all of this, the HTA will have the information required to know whether to proceed with funding the study.

Research activity codes: 4.4 POPULATION SCREENING
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH