Title: What is the value of undertaking a study to determine the clinical and cost effectiveness of late pregnancy ultrasound to prevent adverse perinatal outcome in nulliparous women?
Funder: Department of Health and Social Care

Abstract: The aims of the project relate to universal screening of nulliparous women in late pregnancy using ultrasound and are as follows: 1. To develop an evidence-based protocol which aims to identify women at high risk of adverse perinatal outcome on the basis of a late pregnancy ultrasound scan. 2. To develop an evidence-based, protocolised management plan for the care of such women. 3. To conduct an economic analysis of such a programme of screening and intervention. 4. To conduct a value of information analysis to determine if research to reduce uncertainty in this area would be efficient. 5. Conditional on the results of (1-4), to design an RCT. The diagnostic effectiveness of ultrasound will be assessed by a systematic review of the evidence, using the approach of the Cochrane Collaboration Handbook for Diagnostic Test Accuracy Reviews. The internal validity of studies will be assessed using the QUADAS-2 tool. The external validity of studies will be assessed with reference to the specification outlined in the commissioning brief including when the studies were conducted, whether the participants were broadly representative of those who might be recruited to a future trial, the gestational age at which the ultrasound examination(s) were performed, and the outcomes studied. Features of the ultrasound scans which offer clinically useful prediction of the risk of adverse perinatal outcome will be determined by the process above. The development of a management plan for pregnancies which screen positive in the study will be based around current UK clinical guidelines, where available. Where national guidelines are not available for a given ultrasound finding which has been identified as potentially informative (or where any guideline is out of date), new systematic reviews of the international literature will be conducted. The research will be informed by the views of healthcare professionals (HCPs), and women and the public. In relation to HCPs, the primary method of interaction will be a web-based tool which allows the elicitation, editing, refinement, and prioritisation of ideas (Codigital). This will be used to gather the views of a range of professional stakeholders on the elements of the screening test, the intervention, maternal and infant outcomes, the design of a screening trial, and the feasibility of population screening. In relation to women and the public, we plan to use a deliberative workshop methodology. These methods will be used to determine the acceptability of a screening test, the importance attached to different maternal and fetal outcomes, and the design and conduct of research to address these questions. An economic analysis of the proposed programme of screening and intervention, any specific variants thereof, as well as the status quo, will be performed to determine whether, on current evidence, one or more of the options is likely to be cost-effective. Uncertainty in cost-effectiveness will be used to assess whether further research would be efficient, and if so, the expected return on investment from specific study designs via value of information analysis. Finally, on the basis of the above, we will develop the parameters for a future study. including the eligible population, the screening test, the timing of randomisation, the intervention, the control group, the primary and secondary outcomes, the sample size, cost, and whether the definitive study should be preceded by a feasibility study.

Lay abstract: The aims of the project relate to pregnant women expecting their first baby. Currently, women are offered a scan in early pregnancy and one at 20 weeks, but are not offered any scans after that unless a problem is identified. It is currently known that some babies with problems are not picked up by the usual method of the midwife or doctor examining the mother’s abdomen during antenatal check-ups. Examples include babies that have not grown normally during pregnancy, or are not head first for birth. As babies that are small, large or not head first prior to birth are more likely to be sick at birth or not survive, it is thought an extra scan in late pregnancy may be helpful and improve outcomes for babies. There are a number of other findings from a late pregnancy scan that might also be helpful, so we want to see if a study could be developed to look at whether there is benefit to offering women another scan late in pregnancy. It might seem so obvious that such a scan would be helpful that we should just go ahead and do it anyway. However, this was done in France. Researchers looking at the effect of this found that it was difficult to see any benefit from scanning everyone, but they did see more premature births among women where the scan suggested a problem but got it wrong. So any study has to take into account that scanning everyone has potential to cause harm as well as good. We plan detailed and careful review of the evidence to see if a research study could be designed which answered this question for good. First, we will look at previous studies around scanning to see what sort of problems scans can detect. We also want to know how many times scans identify real problems, how often they suggest that there is a problem that doesn’t really exist, and how often they miss a potential problem. We will then draw up a list of findings which should be evaluated at the time of the late pregnancy scan. Second, we will plan what care the woman should be offered if a scan in late pregnancy does find a problem. We will look for existing national guidelines for the given finding, bring them up to date if they are old, and perform new reviews of the evidence where there isn’t a guideline. Third, we will check the financial impact of screening all women in late pregnancy. We will look at how much it would cost to offer all women a scan in late pregnancy, how much it would cost to look after the women who are found to have a problem, and then look at the expected benefit in terms of preventing babies from dying and preventing illness in surviving babies. Fourth, all of this work will be in preparation for a future study. The future study may require very large numbers of pregnant women to be recruited and may need the mothers and babies to be followed up for several years. This means that the trial itself could be very expensive, so we will look at whether the cost of the trial is justified by the potential benefit it could yield to future mothers and babies. Finally, having taken into account all of the factors above, we will design a study of scanning in late pregnancy. We will think about how women should be invited to join a study of scanning in late pregnancy, what would happen to them, and how many women would need to join a study to see if scanning in late pregnancy is helpful. After all of this, the HTA will have the information required to consider whether or not a trial of scanning in late pregnancy for all women should go ahead.

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