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

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. 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.

Accuracy of in-utero MRI to detect fetal brain abnormalities and prognosticate developmental outcome: postnatal follow-up of the MERIDIAN cohort

“…For project three, with approximately 140 cases and assuming poor outcome was less than 10%, allowing estimation of the prevalence to within a standard error of 2·5%. 13 For project one, the updated imaging was used to recalculate diagnostic accuracy. Developmental outcome in relation to ultrasonography and iuMRI was summarised by sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV; table 1).…”

“…19 (22%) of 86 participants diagnosed with IMVM had abnormal development and 12 (14%) of 86 participants were considered at risk. 13 None of the children received a poor prognosis category on antenatal imaging with either modality. Abnormal outcome was less likely in cases of resolved IMVM than persisting IMVM: IMVM resolved in 62 (72%) of 86 participants, nine (15%) of whom had abnormal outcome, and was persistent in 24 (28%) of 86 participants, ten (42%) of whom had abnormal outcome.…”

“…The recalculated diagnostic accuracies for ultrasonography and iuMRI, based on the refreshed ORD from 574 cases in total, were similar to those in the MERIDIAN study and the statistically significant difference in diagnostic accuracy was maintained (absolute difference 25%, 95% CI 21-29; p<0·0001; table 3). 13 Developmental outcome data were available for 190 participants, of whom 164 had iuMRI within 2 weeks of ultra sonography (appendix p 3). Eight participants did not have a prognosis recorded after ultrasonography or iuMRI because the clinician did not record this at the time of counselling, leaving 156 participants who had been given an antenatal prognosis by obstetricians for analysis.…”

“…Developmental outcome for cognition, language, and motor skills of iuMRI and ultrasonography by prognosis13 The box represents the first (bottom) and third (top) quartiles, the line through the centre of the box represents the median. The lower whisker extends from the smallest observation greater than or equal to the first quartile minus 1·5 × IQR and the upper whisker extends to the largest observation less than or equal to the third quartile plus 1·5 × IQR.…”

Utility of Magnetic Resonance Imaging in Diagnosis of Prenatal Non-Visualization of the Fetal Gallbladder: A Case-Series Study

“…However, complicated pathological conditions or abnormalities are extremely difficult to show clearly due to the limited visual field [ 17 ]. MRI, a highly sensitive imaging method without ionizing radiation, can show the delicate fetal anatomy, such as the brain, chest, abdomen, and vasculature, and can repeatedly display obviously suspicious lesions to improve the diagnostic ability [ 18 ]. For complex fetal malformations and rare cases, MRI can provide additional information that ultrasonography is unable to show [ 19 , 20 ].…”