Study Summary

Magnetic Resonance Imaging to Enhance the Diagnosis of Fetal Developmental Brain Abnormalities in Utero (MERIDIAN) (ISRCTN27626961)


The main study is now complete. You can download a results summary to the right of this page or to find out more detailed results of MERIDIAN, please follow the link to access our publication in The Lancet: Lancet Publication

Study Investigators

Chief Investigator:
Professor Paul D Griffiths
Academic Unit of Radiology
University of Sheffield
Royal Hallamshire Hospital
Sheffield, S10 2JF UK
Tel: +44 (0)114 215 9605
Fax: +44 (0)114 271 1607
Email: p.griffiths@sheffield.ac.uk

Co-investigators:
Steve Robson (Newcastle upon Tyne Hospitals NHS Trust); Sarah Russell (Central Manchester University Hospitals NHS Trust); Gerald Mason (Leeds Teaching Hospitals NHS Trust); Nick Embleton, Ruth Graham (Newcastle University); Mike Campbell, Cindy Cooper, Katie Biggs, Allan Wailoo (Sheffield Clinical Trials Research Unit & School of Health and Related Research, University of Sheffield).

Site Principal Investigators:
Samina Dornan (Belfast), Mark Kilby (Birmingham), Janet Wright (Bradford), Jeremy Brocklesby (Cambridge) , Graham Tydeman (Fife), Anne Marie Coady (Hull and East Yorkshire), Gerald Mason (Leeds), Ian Scudamore (Leicester), Christoph Lees (London Imperial), Edward Johnstone (Manchester), Steve Robson (Newcastle), Richard Smith (Norfolk and Norwich), Pam Loughna (Nottingham), George Bugg (Nottingham QMC), Dilly Anumba (Sheffield), Geraldine Masson (Stoke).

On behalf of the MERIDIAN Study Group.

This study is supported by Sheffield CTRU www.shef.ac.uk/scharr/sections/dts/ctru

Background

Fetal imaging with ultrasound (US) has been the mainstay of screening programmes and detailed anomaly scanning for many years. No imaging methodology is perfect and various technical factors and physical limitations may conspire to produce a situation in which suboptimal images of the fetus are obtained. This may lead to an erroneous diagnosis of structural abnormalities and incorrect prognostic information being given to parents. The fetal brain is a particular area of concern because of the relatively high frequency of developmental abnormalities and also the number of clinically significant pathologies which can give rise to quite subtle imaging changes. Existing research suggests that in utero magnetic resonance (MR) imaging for fetal brain abnormalities can be a powerful adjunct to ultrasound from as early as 18 weeks gestational age. Nevertheless, clinical uncertainty remains around the range of indications, timing of examination, effect on management and the extent of any improvement in patient care.

Aims

The aim of this study is to assess MR imaging as a technology to aid the prenatal diagnosis of fetal developmental brain abnormalities. The primary objective is to establish whether the accuracy of prenatal diagnosis is improved by performing in utero MR after detailed antenatal US. Secondary objectives are to establish how often prenatal counselling and management choices are affected by the information provided by in utero MR, and also to sample the views of patients and health professionals on the contribution it makes to the antenatal care pathway.

Methods

MERIDIAN is a multicentre cohort study which will recruit 750 pregnant women, from 18 weeks gestation onwards, where the fetus is known or suspected of having some form of developmental brain abnormality based on antenatal US examination. Study participants will be recruited from specialist fetal medicine units drawn from a large and varied geographic/socio-economic referral area within the United Kingdom.

 The primary outcome measure will be the diagnostic accuracy achieved following in utero MR imaging in comparison to that achieved by the preceding detailed US examination. This will be judged by an independent expert panel comparing the prenatal diagnosis, both before and after in utero MR, with an anatomical reference diagnosis gained from either post-natal imaging in live born infants (up to 6 months of age) or post-mortem examination in the event of termination of pregnancy, stillbirth or neonatal death.

The primary outcome analysis will report diagnostic accuracy as a percentage figure within 95% confidence intervals. McNemar’s test will be used to assess significant difference between diagnostic accuracy achieved with and without MR. In addition there will be conditional logistic regression analysis to look at effect modifiers such as gestational age and the nature of the suspected brain abnormality (e.g. ventriculomegaly, posterior fossa abnormalities and abnormalities of the corpus callosum).

Secondary outcomes relevant to the clinical impact of in utero MR imaging will be measured both quantitatively, as prospectively reported changes in clinical management attributable to MR imaging results, and qualitatively by assessing the impact of the 'new technique' on the clinicians who interact with the pregnant women. In parallel, the opinions of the women included in the study will be sought, by questionnaire and sub-sample interviews, in order to assess perceptions of MR imaging on acceptability and decision making. Finally, health economic modelling will be performed for the specific changes in management attributable to the inclusion of MR imaging in the diagnostic pathway.

Funder: This project is funded by the NIHR Health Technology Assessment (HTA) programme (project number 09/06/01), with the support of the Comprehensive Clinical Research Network. A full project report will be published in Health Technology Assessment. Any views or opinions expressed are those of the authors and do not necessarily reflect those of the HTA programme, NIHR, NHS or the Department of Health.

Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust.

Date started: March, 2011.

Expected end date: May, 2015.

Expected reporting date: December, 2015.