MRI in the diagnosis of fetal developmental brain abnormalities: the MERIDIAN diagnostic accuracy study

Ultrasonography has been the mainstay of antenatal screening programmes in the UK for many years. Technical factors and physical limitations may result in suboptimal images that can lead to incorrect diagnoses and inaccurate counselling and prognostic information being given to parents. Previous stu...

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Veröffentlicht in:Health technology assessment (Winchester, England) Jg. 23; H. 49; S. 1 - 144
Hauptverfasser: Griffiths, Paul D, Bradburn, Michael, Campbell, Michael J, Cooper, Cindy L, Embleton, Nicholas, Graham, Ruth, Hart, Anthony R, Jarvis, Deborah, Kilby, Mark D, Lie, Mabel, Mason, Gerald, Mandefield, Laura, Mooney, Cara, Pennington, Rebekah, Robson, Stephen C, Wailoo, Allan
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England NIHR Journals Library 01.09.2019
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ISSN:1366-5278, 2046-4924, 2046-4924
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Abstract Ultrasonography has been the mainstay of antenatal screening programmes in the UK for many years. Technical factors and physical limitations may result in suboptimal images that can lead to incorrect diagnoses and inaccurate counselling and prognostic information being given to parents. Previous studies suggest that the addition of in utero magnetic resonance imaging (iuMRI) may improve diagnostic accuracy for fetal brain abnormalities. These studies have limitations, including a lack of an outcome reference diagnosis (ORD), which means that improvements could not be assessed accurately. To assess the diagnostic impact, acceptability and cost consequence of iuMRI among fetuses with a suspected fetal brain abnormality. A pragmatic, prospective, multicentre, cohort study with a health economics analysis and a sociological substudy. Sixteen UK fetal medicine centres. Pregnant women aged ≥ 16 years carrying a fetus (at least 18 weeks' gestation) with a suspected brain abnormality detected on ultrasonography. Participants underwent iuMRI and the findings were reported to their referring fetal medicine clinician. Pregnancy outcome was followed up and an ORD from postnatal imaging or postmortem autopsy/imaging collected when available. Developmental data from the Bayley Scales of Infant Development and questionnaires were collected from the surviving infants aged 2-3 years. Data on the management of the pregnancy before and after the iuMRI were collected to inform the economic evaluation. Two surveys collected data on patient acceptability of iuMRI and qualitative interviews with participants and health professionals were undertaken. The primary analysis consisted of 570 fetuses. The absolute diagnostic accuracies of ultrasonography and iuMRI were 68% and 93%, respectively [a difference of 25%, 95% confidence interval (CI) 21% to 29%]. The difference between ultrasonography and iuMRI increased with gestational age. In the 18-23 weeks group, the figures were 70% for ultrasonography and 92% for iuMRI (difference of 23%, 95% CI 18% to 27%); in the ≥ 24 weeks group, the figures were 65% for ultrasonography and 94% for iuMRI (difference of 29%, 95% CI 23% to 36%). Patient acceptability was high, with at least 95% of respondents stating that they would have iuMRI again in a similar situation. Health professional interviews suggested that iuMRI was acceptable to clinicians and that iuMRI was useful as an adjunct to ultrasonography, but not as a replacement. Across a range of scenarios, iuMRI resulted in additional costs compared with ultrasonography alone. The additional cost was consistently < £600 per patient and the cost per management decision appropriately changed was always < £3000. There is potential for reporting bias from the referring clinicians on the diagnostic and prognostic outcomes. Lower than anticipated follow-up rates at 3 years of age were observed. iuMRI as an adjunct to ultrasonography significantly improves the diagnostic accuracy and confidence for the detection of fetal brain abnormalities. An evaluation of the use of iuMRI for cases of isolated microcephaly and the diagnosis of fetal spine abnormalities is recommended. Longer-term follow-up studies of children diagnosed with fetal brain abnormalities are required to fully assess the functional significance of the diagnoses. Current Controlled Trials ISRCTN27626961. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 23, No. 49. See the NIHR Journals Library website for further project information.
AbstractList Ultrasonography has been the mainstay of antenatal screening programmes in the UK for many years. Technical factors and physical limitations may result in suboptimal images that can lead to incorrect diagnoses and inaccurate counselling and prognostic information being given to parents. Previous studies suggest that the addition of in utero magnetic resonance imaging (iuMRI) may improve diagnostic accuracy for fetal brain abnormalities. These studies have limitations, including a lack of an outcome reference diagnosis (ORD), which means that improvements could not be assessed accurately. To assess the diagnostic impact, acceptability and cost consequence of iuMRI among fetuses with a suspected fetal brain abnormality. A pragmatic, prospective, multicentre, cohort study with a health economics analysis and a sociological substudy. Sixteen UK fetal medicine centres. Pregnant women aged ≥ 16 years carrying a fetus (at least 18 weeks' gestation) with a suspected brain abnormality detected on ultrasonography. Participants underwent iuMRI and the findings were reported to their referring fetal medicine clinician. Pregnancy outcome was followed up and an ORD from postnatal imaging or postmortem autopsy/imaging collected when available. Developmental data from the Bayley Scales of Infant Development and questionnaires were collected from the surviving infants aged 2-3 years. Data on the management of the pregnancy before and after the iuMRI were collected to inform the economic evaluation. Two surveys collected data on patient acceptability of iuMRI and qualitative interviews with participants and health professionals were undertaken. The primary analysis consisted of 570 fetuses. The absolute diagnostic accuracies of ultrasonography and iuMRI were 68% and 93%, respectively [a difference of 25%, 95% confidence interval (CI) 21% to 29%]. The difference between ultrasonography and iuMRI increased with gestational age. In the 18-23 weeks group, the figures were 70% for ultrasonography and 92% for iuMRI (difference of 23%, 95% CI 18% to 27%); in the ≥ 24 weeks group, the figures were 65% for ultrasonography and 94% for iuMRI (difference of 29%, 95% CI 23% to 36%). Patient acceptability was high, with at least 95% of respondents stating that they would have iuMRI again in a similar situation. Health professional interviews suggested that iuMRI was acceptable to clinicians and that iuMRI was useful as an adjunct to ultrasonography, but not as a replacement. Across a range of scenarios, iuMRI resulted in additional costs compared with ultrasonography alone. The additional cost was consistently < £600 per patient and the cost per management decision appropriately changed was always < £3000. There is potential for reporting bias from the referring clinicians on the diagnostic and prognostic outcomes. Lower than anticipated follow-up rates at 3 years of age were observed. iuMRI as an adjunct to ultrasonography significantly improves the diagnostic accuracy and confidence for the detection of fetal brain abnormalities. An evaluation of the use of iuMRI for cases of isolated microcephaly and the diagnosis of fetal spine abnormalities is recommended. Longer-term follow-up studies of children diagnosed with fetal brain abnormalities are required to fully assess the functional significance of the diagnoses. Current Controlled Trials ISRCTN27626961. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 23, No. 49. See the NIHR Journals Library website for further project information.
Ultrasonography has been the mainstay of antenatal screening programmes in the UK for many years. Technical factors and physical limitations may result in suboptimal images that can lead to incorrect diagnoses and inaccurate counselling and prognostic information being given to parents. Previous studies suggest that the addition of in utero magnetic resonance imaging (iuMRI) may improve diagnostic accuracy for fetal brain abnormalities. These studies have limitations, including a lack of an outcome reference diagnosis (ORD), which means that improvements could not be assessed accurately.BACKGROUNDUltrasonography has been the mainstay of antenatal screening programmes in the UK for many years. Technical factors and physical limitations may result in suboptimal images that can lead to incorrect diagnoses and inaccurate counselling and prognostic information being given to parents. Previous studies suggest that the addition of in utero magnetic resonance imaging (iuMRI) may improve diagnostic accuracy for fetal brain abnormalities. These studies have limitations, including a lack of an outcome reference diagnosis (ORD), which means that improvements could not be assessed accurately.To assess the diagnostic impact, acceptability and cost consequence of iuMRI among fetuses with a suspected fetal brain abnormality.OBJECTIVESTo assess the diagnostic impact, acceptability and cost consequence of iuMRI among fetuses with a suspected fetal brain abnormality.A pragmatic, prospective, multicentre, cohort study with a health economics analysis and a sociological substudy.DESIGNA pragmatic, prospective, multicentre, cohort study with a health economics analysis and a sociological substudy.Sixteen UK fetal medicine centres.SETTINGSixteen UK fetal medicine centres.Pregnant women aged ≥ 16 years carrying a fetus (at least 18 weeks' gestation) with a suspected brain abnormality detected on ultrasonography.PARTICIPANTSPregnant women aged ≥ 16 years carrying a fetus (at least 18 weeks' gestation) with a suspected brain abnormality detected on ultrasonography.Participants underwent iuMRI and the findings were reported to their referring fetal medicine clinician.INTERVENTIONSParticipants underwent iuMRI and the findings were reported to their referring fetal medicine clinician.Pregnancy outcome was followed up and an ORD from postnatal imaging or postmortem autopsy/imaging collected when available. Developmental data from the Bayley Scales of Infant Development and questionnaires were collected from the surviving infants aged 2-3 years. Data on the management of the pregnancy before and after the iuMRI were collected to inform the economic evaluation. Two surveys collected data on patient acceptability of iuMRI and qualitative interviews with participants and health professionals were undertaken.MAIN OUTCOME MEASURESPregnancy outcome was followed up and an ORD from postnatal imaging or postmortem autopsy/imaging collected when available. Developmental data from the Bayley Scales of Infant Development and questionnaires were collected from the surviving infants aged 2-3 years. Data on the management of the pregnancy before and after the iuMRI were collected to inform the economic evaluation. Two surveys collected data on patient acceptability of iuMRI and qualitative interviews with participants and health professionals were undertaken.The primary analysis consisted of 570 fetuses. The absolute diagnostic accuracies of ultrasonography and iuMRI were 68% and 93%, respectively [a difference of 25%, 95% confidence interval (CI) 21% to 29%]. The difference between ultrasonography and iuMRI increased with gestational age. In the 18-23 weeks group, the figures were 70% for ultrasonography and 92% for iuMRI (difference of 23%, 95% CI 18% to 27%); in the ≥ 24 weeks group, the figures were 65% for ultrasonography and 94% for iuMRI (difference of 29%, 95% CI 23% to 36%). Patient acceptability was high, with at least 95% of respondents stating that they would have iuMRI again in a similar situation. Health professional interviews suggested that iuMRI was acceptable to clinicians and that iuMRI was useful as an adjunct to ultrasonography, but not as a replacement. Across a range of scenarios, iuMRI resulted in additional costs compared with ultrasonography alone. The additional cost was consistently < £600 per patient and the cost per management decision appropriately changed was always < £3000. There is potential for reporting bias from the referring clinicians on the diagnostic and prognostic outcomes. Lower than anticipated follow-up rates at 3 years of age were observed.RESULTSThe primary analysis consisted of 570 fetuses. The absolute diagnostic accuracies of ultrasonography and iuMRI were 68% and 93%, respectively [a difference of 25%, 95% confidence interval (CI) 21% to 29%]. The difference between ultrasonography and iuMRI increased with gestational age. In the 18-23 weeks group, the figures were 70% for ultrasonography and 92% for iuMRI (difference of 23%, 95% CI 18% to 27%); in the ≥ 24 weeks group, the figures were 65% for ultrasonography and 94% for iuMRI (difference of 29%, 95% CI 23% to 36%). Patient acceptability was high, with at least 95% of respondents stating that they would have iuMRI again in a similar situation. Health professional interviews suggested that iuMRI was acceptable to clinicians and that iuMRI was useful as an adjunct to ultrasonography, but not as a replacement. Across a range of scenarios, iuMRI resulted in additional costs compared with ultrasonography alone. The additional cost was consistently < £600 per patient and the cost per management decision appropriately changed was always < £3000. There is potential for reporting bias from the referring clinicians on the diagnostic and prognostic outcomes. Lower than anticipated follow-up rates at 3 years of age were observed.iuMRI as an adjunct to ultrasonography significantly improves the diagnostic accuracy and confidence for the detection of fetal brain abnormalities. An evaluation of the use of iuMRI for cases of isolated microcephaly and the diagnosis of fetal spine abnormalities is recommended. Longer-term follow-up studies of children diagnosed with fetal brain abnormalities are required to fully assess the functional significance of the diagnoses.CONCLUSIONSiuMRI as an adjunct to ultrasonography significantly improves the diagnostic accuracy and confidence for the detection of fetal brain abnormalities. An evaluation of the use of iuMRI for cases of isolated microcephaly and the diagnosis of fetal spine abnormalities is recommended. Longer-term follow-up studies of children diagnosed with fetal brain abnormalities are required to fully assess the functional significance of the diagnoses.Current Controlled Trials ISRCTN27626961.TRIAL REGISTRATIONCurrent Controlled Trials ISRCTN27626961.This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 49. See the NIHR Journals Library website for further project information.FUNDINGThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 49. See the NIHR Journals Library website for further project information.
Background: Ultrasonography has been the mainstay of antenatal screening programmes in the UK for many years. Technical factors and physical limitations may result in suboptimal images that can lead to incorrect diagnoses and inaccurate counselling and prognostic information being given to parents. Previous studies suggest that the addition of in utero magnetic resonance imaging (iuMRI) may improve diagnostic accuracy for fetal brain abnormalities. These studies have limitations, including a lack of an outcome reference diagnosis (ORD), which means that improvements could not be assessed accurately. Objectives: To assess the diagnostic impact, acceptability and cost consequence of iuMRI among fetuses with a suspected fetal brain abnormality. Design: A pragmatic, prospective, multicentre, cohort study with a health economics analysis and a sociological substudy. Setting: Sixteen UK fetal medicine centres. Participants: Pregnant women aged ≥ 16 years carrying a fetus (at least 18 weeks’ gestation) with a suspected brain abnormality detected on ultrasonography. Interventions: Participants underwent iuMRI and the findings were reported to their referring fetal medicine clinician. Main outcome measures: Pregnancy outcome was followed up and an ORD from postnatal imaging or postmortem autopsy/imaging collected when available. Developmental data from the Bayley Scales of Infant Development and questionnaires were collected from the surviving infants aged 2–3 years. Data on the management of the pregnancy before and after the iuMRI were collected to inform the economic evaluation. Two surveys collected data on patient acceptability of iuMRI and qualitative interviews with participants and health professionals were undertaken. Results: The primary analysis consisted of 570 fetuses. The absolute diagnostic accuracies of ultrasonography and iuMRI were 68% and 93%, respectively [a difference of 25%, 95% confidence interval (CI) 21% to 29%]. The difference between ultrasonography and iuMRI increased with gestational age. In the 18–23 weeks group, the figures were 70% for ultrasonography and 92% for iuMRI (difference of 23%, 95% CI 18% to 27%); in the ≥ 24 weeks group, the figures were 65% for ultrasonography and 94% for iuMRI (difference of 29%, 95% CI 23% to 36%). Patient acceptability was high, with at least 95% of respondents stating that they would have iuMRI again in a similar situation. Health professional interviews suggested that iuMRI was acceptable to clinicians and that iuMRI was useful as an adjunct to ultrasonography, but not as a replacement. Across a range of scenarios, iuMRI resulted in additional costs compared with ultrasonography alone. The additional cost was consistently < £600 per patient and the cost per management decision appropriately changed was always < £3000. There is potential for reporting bias from the referring clinicians on the diagnostic and prognostic outcomes. Lower than anticipated follow-up rates at 3 years of age were observed. Conclusions: iuMRI as an adjunct to ultrasonography significantly improves the diagnostic accuracy and confidence for the detection of fetal brain abnormalities. An evaluation of the use of iuMRI for cases of isolated microcephaly and the diagnosis of fetal spine abnormalities is recommended. Longer-term follow-up studies of children diagnosed with fetal brain abnormalities are required to fully assess the functional significance of the diagnoses. Trial registration: Current Controlled Trials ISRCTN27626961. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 49. See the NIHR Journals Library website for further project information.
Ultrasonography is routine in pregnancy to check that the baby’s brain is developing as expected. However, no medical test is perfect and ultrasonography may miss some brain abnormalities, may get some brain abnormalities wrong or may diagnose an abnormality that is not really present. Magnetic resonance imaging (MRI) may help clarify difficult cases during pregnancy. We wanted to find out if MRI was better than ultrasonography alone in making an accurate diagnosis. We recruited pregnant women whose ultrasound scan, performed by an expert, suggested that their baby had a brain abnormality, and referred them for a MRI scan. The results of the two tests were compared with each other and to the final outcome of the pregnancy. Our results showed that using MRI in addition to ultrasonography improved the accuracy of the diagnosis in about one in four pregnancies. It changed the prediction of how the baby would develop in at least one in five cases. In many cases, the pregnancy was managed differently because of the MRI result. The MRI was acceptable to women, with 95% saying that they would have MRI again in a similar situation. Neither MRI nor ultrasonography accurately identified children who went on to have delayed development at the age of 2–3 years, but MRI was better than ultrasonography at ruling out developmental problems at this age. The MRI cost more than ultrasonography alone; therefore, whether or not it is worthwhile depends on the value placed on the decisions that changed as a result of its use.
Author Pennington, Rebekah
Mason, Gerald
Hart, Anthony R
Jarvis, Deborah
Mooney, Cara
Bradburn, Michael
Embleton, Nicholas
Wailoo, Allan
Lie, Mabel
Griffiths, Paul D
Campbell, Michael J
Kilby, Mark D
Robson, Stephen C
Cooper, Cindy L
Mandefield, Laura
Graham, Ruth
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  givenname: Paul D
  orcidid: 0000-0002-2706-5897
  surname: Griffiths
  fullname: Griffiths, Paul D
  organization: Academic Unit of Radiology, University of Sheffield, Sheffield, UK
– sequence: 2
  givenname: Michael
  orcidid: 0000-0002-3783-9761
  surname: Bradburn
  fullname: Bradburn, Michael
  organization: Clinical Trials Research Unit, School of Health and Related Research, University of Sheffield, Sheffield, UK
– sequence: 3
  givenname: Michael J
  orcidid: 0000-0003-3529-2739
  surname: Campbell
  fullname: Campbell, Michael J
  organization: Clinical Trials Research Unit, School of Health and Related Research, University of Sheffield, Sheffield, UK
– sequence: 4
  givenname: Cindy L
  orcidid: 0000-0002-2995-5447
  surname: Cooper
  fullname: Cooper, Cindy L
  organization: Clinical Trials Research Unit, School of Health and Related Research, University of Sheffield, Sheffield, UK
– sequence: 5
  givenname: Nicholas
  orcidid: 0000-0003-3750-5566
  surname: Embleton
  fullname: Embleton, Nicholas
  organization: Newcastle Neonatal Service, Royal Victoria Infirmary, Newcastle upon Tyne, UK
– sequence: 6
  givenname: Ruth
  orcidid: 0000-0001-9432-760X
  surname: Graham
  fullname: Graham, Ruth
  organization: School of Geography, Politics and Sociology, Newcastle University, Newcastle upon Tyne, UK
– sequence: 7
  givenname: Anthony R
  orcidid: 0000-0003-4018-3238
  surname: Hart
  fullname: Hart, Anthony R
  organization: Department of Perinatal and Paediatric Neurology, Sheffield Children’s Hospital NHS Foundation Trust, Sheffield, UK
– sequence: 8
  givenname: Deborah
  orcidid: 0000-0002-0133-1771
  surname: Jarvis
  fullname: Jarvis, Deborah
  organization: Academic Unit of Radiology, University of Sheffield, Sheffield, UK
– sequence: 9
  givenname: Mark D
  orcidid: 0000-0001-9987-4223
  surname: Kilby
  fullname: Kilby, Mark D
  organization: Centre for Women’s and Newborn Health, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK, Fetal Medicine Centre, Birmingham Women’s and Children’s NHS Foundation Trust (Birmingham Health Partners), Birmingham, UK
– sequence: 10
  givenname: Mabel
  orcidid: 0000-0002-1703-283X
  surname: Lie
  fullname: Lie, Mabel
  organization: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
– sequence: 11
  givenname: Gerald
  orcidid: 0000-0003-0389-3986
  surname: Mason
  fullname: Mason, Gerald
  organization: Leeds Teaching Hospitals NHS Trust, Leeds, UK
– sequence: 12
  givenname: Laura
  orcidid: 0000-0002-4219-5673
  surname: Mandefield
  fullname: Mandefield, Laura
  organization: Clinical Trials Research Unit, School of Health and Related Research, University of Sheffield, Sheffield, UK
– sequence: 13
  givenname: Cara
  orcidid: 0000-0002-3086-7348
  surname: Mooney
  fullname: Mooney, Cara
  organization: Clinical Trials Research Unit, School of Health and Related Research, University of Sheffield, Sheffield, UK
– sequence: 14
  givenname: Rebekah
  orcidid: 0000-0002-1002-022X
  surname: Pennington
  fullname: Pennington, Rebekah
  organization: Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK
– sequence: 15
  givenname: Stephen C
  orcidid: 0000-0001-7897-7987
  surname: Robson
  fullname: Robson, Stephen C
  organization: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
– sequence: 16
  givenname: Allan
  orcidid: 0000-0002-9324-1617
  surname: Wailoo
  fullname: Wailoo, Allan
  organization: Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK
BackLink https://www.ncbi.nlm.nih.gov/pubmed/31538569$$D View this record in MEDLINE/PubMed
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2046-4924
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Issue 49
Keywords MAGNETIC RESONANCE IMAGING
PRENATAL DIAGNOSIS
ULTRASOUND
FETUS
SCAN
ULTRASONOGRAPHY
VENTRICULOMEGALY
BRAIN
MICROCEPHALY
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Snippet Ultrasonography has been the mainstay of antenatal screening programmes in the UK for many years. Technical factors and physical limitations may result in...
Ultrasonography is routine in pregnancy to check that the baby’s brain is developing as expected. However, no medical test is perfect and ultrasonography may...
Background: Ultrasonography has been the mainstay of antenatal screening programmes in the UK for many years. Technical factors and physical limitations may...
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StartPage 1
SubjectTerms BRAIN
Brain - abnormalities
Brain - diagnostic imaging
Cost-Benefit Analysis
Female
FETUS
Fetus - abnormalities
Fetus - diagnostic imaging
Gestational Age
Health Care Costs
Humans
MAGNETIC RESONANCE IMAGING
Magnetic Resonance Imaging - economics
Magnetic Resonance Imaging - methods
Male
MICROCEPHALY
Multicenter Studies as Topic
Pregnancy
PRENATAL DIAGNOSIS
Prenatal Diagnosis - economics
Prenatal Diagnosis - methods
Reproducibility of Results
SCAN
ULTRASONOGRAPHY
Ultrasonography, Prenatal
ULTRASOUND
VENTRICULOMEGALY
Title MRI in the diagnosis of fetal developmental brain abnormalities: the MERIDIAN diagnostic accuracy study
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