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NIHR Signal Antenatal MRI can aid ultrasound when fetal brain abnormality is suspected

Published on 29 January 2020

doi: 10.3310/signal-000867

In utero magnetic resonance imaging (iuMRI) can provide a more accurate diagnosis when used after ultrasound in pregnancy. Adding iuMRI when a brain abnormality is suspected but unclear from ultrasound could help clinicians provide better prognostic advice and support to parents during pregnancy.

This NIHR-funded cohort study compared ultrasound and iuMRI in 570 women at more than 18 weeks' pregnancy carrying a fetus with a suspected brain abnormality. It found that iuMRI was more accurate than ultrasound at correctly identifying a brain abnormality, with an overall difference in accuracy of 25%. Both methods were similarly effective at providing prognostic information on abnormal development. However, iuMRI was better at correctly predicting that the child would have ‘normal’ or ‘at risk’ development than ultrasound.

This suggests that iuMRI would be valuable to further investigate abnormal ultrasound findings.

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Why was this study needed?

Ultrasound is the main method used for antenatal screening to identify structural abnormalities during a baby’s development. However, there are limits to its accuracy and sensitivity and this can sometimes lead to incorrect diagnoses. As a result, parents may be given inaccurate advice and prognostic information about their unborn baby. This is a particular concern with brain abnormalities, which affect 3 in 1,000 pregnancies and can lead to serious long-term complications for babies who survive.

Some studies suggest that iuMRI could be a useful addition to ultrasound for detecting brain abnormalities from 18 weeks of pregnancy but the limitations of these studies make it difficult to draw firm conclusions. This clinical study aimed to assess whether iuMRI could aid the prenatal diagnosis of brain abnormalities in babies where ultrasound suggests there may be a problem.

What did this study do?

MERIDIAN was a pragmatic, prospective study involving 570 pregnant women aged over 16 years, carrying a fetus of longer than 18 weeks’ gestation with a suspected brain abnormality detected on ultrasound.

The women were referred for iuMRI at one of six UK hospitals. Radiologists used the iuMRI images to assess each abnormality detected by ultrasound and indicated their confidence in the diagnosis. They either added a diagnosis if appropriate or used ‘diagnosis excluded’ if they disagreed with the ultrasound diagnosis.

Follow-up brain imaging was carried out after birth, pregnancy termination, stillbirth or neonatal death and compared with the original diagnoses to show if the brain abnormalities had been diagnosed correctly (the reference standard against which scans were compared). Data on the subsequent development of surviving infants at age two to three years was collected using the Bayley Scales of Infant Development questionnaire.

What did it find?

  • In 386 out of 570 cases (67.7%) both ultrasound and iuMRI were correct at identifying brain abnormalities. In 144 out of 570 cases (25.3%), the ultrasound was incorrect but the iuMRI report was correct. Two fetuses (0.4%) had a correct ultrasound and incorrect iuMRI, and both techniques were incorrect for 38 fetuses (6.8%).
  • The overall diagnostic accuracy of ultrasound was 68% and iuMRI 93%. This equates to a difference in accuracy of 25% (95% confidence interval [CI] 21% to 29%). This difference in accuracy was more pronounced as gestational age increased: in the 18-23-week age group, the difference was 23% (95% CI 18% to 27%); in the ≥ 24 weeks group, the difference was 29% (95% CI 23% to 36%).
  • Analysis of children’s development after two to three years follow-up showed that the overall difference in diagnostic accuracy was still 24.8% in favour of iuMRI (95% CI 21% to 28.5%). There was little difference in the accuracy of ultrasound and iuMRI for the prognosis of abnormal development. However, iuMRI had a higher number of correct prognoses in surviving infants who were assessed as developmentally ‘normal’ or ‘at risk’.
  • Patient acceptability of iuMRI was high, with 95% to 97% of patients stating that they would agree to have iuMRI as part of their care in future. IuMRI was also broadly acceptable to clinicians, although as an adjunct rather than a replacement for ultrasound.

What does current guidance say on this issue?

Guidance from the Royal College of Obstetricians and Gynaecologists acknowledges that the use of ultrasound to screen for fetal abnormalities at 18-20 weeks results in variable detection rates, depending on the type of abnormality.

It recommends that iuMRI can be effective as an adjunct to ultrasound in diagnosing and evaluating structural abnormalities, particularly those involving the fetal central nervous system.

What are the implications?

This study shows that iuMRI is more accurate where a brain abnormality is suspected and that it could be beneficial as an adjunct to ultrasound for providing prognostic information to parents during pregnancy.

It is the first study to include outcome reference diagnosis data, allowing comparison between the initial diagnosis and the outcome of the pregnancy.

IuMRI is a new technique only available at some hospitals, and collaboration between radiologists (for example, the establishment of expert panels) may be required if it is to be offered as part of the diagnostic pathway for fetal abnormalities.

Citation and Funding

Griffiths P, Bradburn M, Campbell M et al. MRI in the diagnosis of fetal developmental brain abnormalities: the MERIDIAN diagnostic accuracy study. Health Technol Assess. 2019;23(49).

This project was funded by the NIHR Health Technology Assessment Programme (project number 09/06/01).

Bibliography

RCOG. Termination of pregnancy for fetal abnormality in England, Scotland and Wales. London: Royal College of Obstetricians and Gynaecologists; 2010.

Why was this study needed?

Ultrasound is the main method used for antenatal screening to identify structural abnormalities during a baby’s development. However, there are limits to its accuracy and sensitivity and this can sometimes lead to incorrect diagnoses. As a result, parents may be given inaccurate advice and prognostic information about their unborn baby. This is a particular concern with brain abnormalities, which affect 3 in 1,000 pregnancies and can lead to serious long-term complications for babies who survive.

Some studies suggest that iuMRI could be a useful addition to ultrasound for detecting brain abnormalities from 18 weeks of pregnancy but the limitations of these studies make it difficult to draw firm conclusions. This clinical study aimed to assess whether iuMRI could aid the prenatal diagnosis of brain abnormalities in babies where ultrasound suggests there may be a problem.

What did this study do?

MERIDIAN was a pragmatic, prospective study involving 570 pregnant women aged over 16 years, carrying a fetus of longer than 18 weeks’ gestation with a suspected brain abnormality detected on ultrasound.

The women were referred for iuMRI at one of six UK hospitals. Radiologists used the iuMRI images to assess each abnormality detected by ultrasound and indicated their confidence in the diagnosis. They either added a diagnosis if appropriate or used ‘diagnosis excluded’ if they disagreed with the ultrasound diagnosis.

Follow-up brain imaging was carried out after birth, pregnancy termination, stillbirth or neonatal death and compared with the original diagnoses to show if the brain abnormalities had been diagnosed correctly (the reference standard against which scans were compared). Data on the subsequent development of surviving infants at age two to three years was collected using the Bayley Scales of Infant Development questionnaire.

What did it find?

  • In 386 out of 570 cases (67.7%) both ultrasound and iuMRI were correct at identifying brain abnormalities. In 144 out of 570 cases (25.3%), the ultrasound was incorrect but the iuMRI report was correct. Two fetuses (0.4%) had a correct ultrasound and incorrect iuMRI, and both techniques were incorrect for 38 fetuses (6.8%).
  • The overall diagnostic accuracy of ultrasound was 68% and iuMRI 93%. This equates to a difference in accuracy of 25% (95% confidence interval [CI] 21% to 29%). This difference in accuracy was more pronounced as gestational age increased: in the 18-23-week age group, the difference was 23% (95% CI 18% to 27%); in the ≥ 24 weeks group, the difference was 29% (95% CI 23% to 36%).
  • Analysis of children’s development after two to three years follow-up showed that the overall difference in diagnostic accuracy was still 24.8% in favour of iuMRI (95% CI 21% to 28.5%). There was little difference in the accuracy of ultrasound and iuMRI for the prognosis of abnormal development. However, iuMRI had a higher number of correct prognoses in surviving infants who were assessed as developmentally ‘normal’ or ‘at risk’.
  • Patient acceptability of iuMRI was high, with 95% to 97% of patients stating that they would agree to have iuMRI as part of their care in future. IuMRI was also broadly acceptable to clinicians, although as an adjunct rather than a replacement for ultrasound.

What does current guidance say on this issue?

Guidance from the Royal College of Obstetricians and Gynaecologists acknowledges that the use of ultrasound to screen for fetal abnormalities at 18-20 weeks results in variable detection rates, depending on the type of abnormality.

It recommends that iuMRI can be effective as an adjunct to ultrasound in diagnosing and evaluating structural abnormalities, particularly those involving the fetal central nervous system.

What are the implications?

This study shows that iuMRI is more accurate where a brain abnormality is suspected and that it could be beneficial as an adjunct to ultrasound for providing prognostic information to parents during pregnancy.

It is the first study to include outcome reference diagnosis data, allowing comparison between the initial diagnosis and the outcome of the pregnancy.

IuMRI is a new technique only available at some hospitals, and collaboration between radiologists (for example, the establishment of expert panels) may be required if it is to be offered as part of the diagnostic pathway for fetal abnormalities.

Citation and Funding

Griffiths P, Bradburn M, Campbell M et al. MRI in the diagnosis of fetal developmental brain abnormalities: the MERIDIAN diagnostic accuracy study. Health Technol Assess. 2019;23(49).

This project was funded by the NIHR Health Technology Assessment Programme (project number 09/06/01).

Bibliography

RCOG. Termination of pregnancy for fetal abnormality in England, Scotland and Wales. London: Royal College of Obstetricians and Gynaecologists; 2010.

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

Published on 20 September 2019

Griffiths P, Bradburn M, Campbell M, Cooper C, Embleton N, Graham R et al.

Health Technology Assessment Volume 23 Issue 49 , 2019

Abstract 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.

Expert commentary

All pregnant women in the UK are offered ultrasound screening for fetal anomalies. The finding of a suspected brain abnormality causes particular concern because of the implications for the future development of their child.

This large pragmatic study demonstrates that intrauterine MRI is a useful adjunct to ultrasound in the assessment of suspected fetal brain abnormalities. It improves diagnostic confidence, improves diagnostic accuracy and helps improve management when there is concern about the development of the fetal brain.

The strength of the study was the outcome reference data enabling confirmation of the diagnoses suspected on either ultrasound or MRI, strengthened by the follow up at age two to three. The study shows particular benefits in the use of iuMRI in the assessment of mild ventriculomegaly, posterior fossa abnormalities and failed commisuration (agenesis and hypogenesis of the corpus callosum) suggesting this should now become a routine part of the assessment of these abnormalities.

Mr David Howe, Consultant in Feto-Maternal Medicine, Princess Anne Hospital, Southampton

The commentator declares that he was on the Data Monitoring Committee for MERIDIAN but was not involved in the design, performance or analysis of the study

Expert commentary

Accurate prenatal diagnosis of fetal brain abnormalities and defining their prognosis can be challenging.

This important study confirms that when fetal brain abnormality is suspected on ultrasound, MRI should be arranged, as it significantly increases the diagnostic accuracy. This improvement carries significant implications for parents’ counselling and decision-making.  

This study relates to UK practice. Clinicians in some other countries have argued that, because neurosonography is better there, the added benefit of MRI might not apply. Training of fetal medicine specialists in neurosonography and fetal brain MRI, as well as increasing its availability, are needed in order to improve current practice. 

Asma Khalil, Professor of Obstetrics and Maternal-Fetal Medicine, St George’s University Hospital, University of London

The commentator declares no conflicting interests.