MERIDIAN Research Study

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).

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, the 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 the 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

Downloads

MERIDIAN Participant Summary

MERIDIAN Protocal v7.1

Add-on study and follow-up study

MERIDIAN Add-On Study

The MERIDIAN Add-On study is now closed for recruitment.

The study is recruiting at 14 of the existing MERIDIAN sites, along with PIC (Participant Identification Centre) sites at St George's Hospital, London and Liverpool Women's Hospital.

Participants will be informed about the study when attending a fetal medicine clinic appointment for an antenatal ultrasound scan with a relevant health professional (e.g. fetal medicine specialist or sonographer) at the MERIDIAN sites listed above.

Background

The aim of the project is to find out how and when MRI should be used to improve the information available to parents before birth about the health of their baby. In this part of the project we are looking at babies whose brains are developing normally. We are going to see if ultrasound and MRI give the same information about brain development. The research is set up to look at brain development only and any investigations used by us focus on this area alone.

There are two elements to the study, which is looking at those babies whose brains are developing normally.

The first (A1) is looking at babies whose brains are developing normally based on ultrasound scan by a feto-maternal expert.

The second (A2) is looking at babies whose brains are developing normally but have some other form of non-brain abnormality based on ultrasound scan by a feto-maternal expert.

Both studies A1 and A2 plan to recruit 200 women who have had a detailed ultrasound scan by a feto-maternal expert, showing no problem with the development of their baby's brain.

Design

Participants will be identified during a fetal medicine clinic visit at a participating MERIDIAN site. Participants will then have a screening telephone call to assess their eligibility for the study and to arrange a date for the MRI at the Academic Unit of Radiology in Sheffield. There will be time for further discussion and questions about the study on arrival at the Unit in Sheffield and written consent will be taken. The scan(s) will then be undertaken, looking at the brain development of the baby only.

The study has also been promoted through local media and word of mouth; this means that pregnant women can self-refer to the study by contacting the study team on the details below. They will receive a screening call to assess eligibility and will need to confirm that they have been informed that their baby’s brain is developing normally based on their detailed anomaly ultrasound scan.

Contact Us

If you would like further information or are interested in taking part in the study then please phone 0114 2159595 or email MERIDIAN@sheffield.ac.uk.

Downloads

Add-On Study Patient Information Sheet Option 1

Add-On Study Supplementary Patient Information Sheet

MERIDIAN 2-3 year follow-up study

The MERIDIAN 2-3 year follow-up study is now closed.

The study recruited children born from the original MERIDIAN study, across all 15 of the sites.

Background

There are 3 separate projects within the follow-up study, all of which are designed to find out more about the development of the brains of those babies included in the original MERIDIAN study when they are 2-3 years old.

Project 1 will look to refine our estimates of how accurate the MR imaging technology is in identifying brain abnormalities in babies during pregnancy, based on clinical information gathered about these babies up to 42 months of age.

Project 2 will look to improve the information available to doctors and patients during pregnancy by using developmental assessment methods to see how the babies are functioning and developing.

Project 3 will look to assess how much of an impact isolated, mild ventriculomegaly (a condition where ventricles in the brain are enlarged) has on the functioning and development of the babies with the condition, using developmental assessment methods. Project 3 does not require any input from hospital staff or participants.

Design

Mothers who participated in MERIDIAN, who had an MRI scan during pregnancy and whose child is two or more years old, will be contacted to see if they wish to take part in the follow up study. This contact will be from the hospital that they attended when they agreed to take part in the original study. Participants can choose to take part in Project 1 and Project 2, just Project 1, or to not participate at all. Children who are over 38 months of age will not be eligible to take part in Project 2.

If the participant wants to take part then the hospital will review their child’s clinical notes and collect information from any medical images taken from birth up to 42 months of age (Project 1). If they have also agreed to take part in project 2 then a suitable time and place will be arranged for the development assessment of their child to take place (Project 2). If a suitable time and place for the assessment cannot be arranged then participants have the option to complete a questionnaire and post it back to the study team or they can arrange to answer the questions over the telephone. After both projects, parents will be sent a letter to let them know that they have completed in the study and will include details of the findings if applicable.

Finally, the central MERIDIAN study team will look closely at cases of babies diagnosed with isolated, mild ventriculomegaly during the original study and assess their development (Project 3), using data obtained from Project 2. This element of the study requires no input from hospital staff or participants.

Additional Information

The purpose of this follow-up study is to improve and refine our estimates of diagnostic accuracy and prognosis using data available when the children of the MERIDIAN cohort are aged 2-3 years. To avoid causing emotional upset or distress by contacting the family of a deceased child we will be using data from NHS digital (previously known as the Health and Social Care Information Centre). Where the parents have agreed to be contacted for future follow up about their child’s development the research team at the University of Sheffield will provide NHS digital with the date of birth, NHS number and unique participant ID number of the children in our study. They will then return to us the unique participant ID number along with the fact of death, where applicable. We will not make contact with the family of a deceased child.

If you are a member of the MERIDIAN cohort, and would like to opt out of your data being collected, please contact the Study Manager, Cara Mooney on the details provided below.

As a university we use personally-identifiable information to conduct research to improve health, care and services. As a publicly-funded organisation, we have to ensure that it is in the public interest when we use personally-identifiable information from people who have agreed to take part in research. This means that when you agree to take part in a research study, we will use your data in the ways needed to conduct and analyse the research study. Your rights to access, change or move your information are limited, as we need to manage your information in specific ways in order for the research to be reliable and accurate. If you withdraw from the study, we will keep the information about you that we have already obtained. To safeguard your rights, we will use the minimum personally-identifiable information possible. We will keep your data from this study for 5 years after the study has finished.

Our legal basis for processing research data involving living humans is:
Article 6 (1) e: processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller
Article 9 (j): processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject

Health and care research should serve the public interest, which means that we have to demonstrate that our research serves the interests of society as a whole. We do this by following the UK Policy Framework for Health and Social Care Research.

If you wish to raise a complaint on how we have handled your personal data, you can contact our Data Protection Officer who will investigate the matter. If you are not satisfied with our response or believe we are processing your personal data in a way that is not lawful you can complain to the Information Commissioner’s Office (ICO).
Our Data Protection Officer is Anne Cutler and you can contact them at dataprotection@sheffield.ac.uk.

Contact Us

If you would like further information then you can phone the Study Manager, Cara Mooney, on 0114 222 4308 or email c.d.mooney@sheffield.ac.uk.

Downloads

MERIDIAN 2-3 year follow up study Protocol v5.0

MERIDIAN 2-3 year follow up study Parent Information Sheet (24-42 months)

MERIDIAN 2-3 year follow up study Parent Information Sheet (42 months+)

Publications