Post‐mortem confirmation of fetal brain abnormalities: challenges highlighted by the MERIDIAN cohort study

Abstract

Objectives To assess and analyse the concordance between post‐mortem findings and in utero magnetic resonance imaging (iuMRI) in the MERIDIAN (MRI to enhance the diagnosis of fetal developmental brain abnormalities in utero) cohort. Design Prospective cohort study. Setting Fetal medicine units in the UK. Population Pregnant women with a diagnosis of fetal brain abnormality identified on ultrasound at 18 weeks of gestation or later. Methods All pregnancies from the MERIDIAN study that resulted in a abortion were included and the rate of uptake and success of post‐mortem examinations were calculated. In the cases in which diagnostic information about the fetal brain was obtained by post‐mortem, the results were compared with the diagnoses from iuMRI. Main outcome measure Outcome reference diagnosis from post‐mortem examination. Results A total of 155 from 823 pregnancies (19%) ended in a termination of pregnancy and 71 (46%) had post‐mortem brain examinations, 62 of which were diagnostically adequate. Hence, the overall rate of successful post‐mortem investigation was 40%, and for those cases there was a concordance rate of 84% between iuMRI and post‐mortem examination. Detailed information is provided when the results of the post‐mortem examination and the iuMRI study differed. Conclusions We have shown tissue‐validation of radiological diagnosis is hampered by a low rate of post‐mortem studies in fetuses aborted with brain abnormalities, a situation further compounded by a 12% rate of autopsy being technically unsuccessful. The agreement between iuMRI and post‐mortem findings is high, but our analysis of the discrepant cases provides valuable clues for improving how we provide information for parents. Tweetable abstract iuMRI should be considered a reliable indicator of fetal brain abnormalities when post‐mortem is not performed.

Are non-invasive or minimally invasive autopsy techniques for detecting cause of death in prenates, neonates and infants accurate? A systematic review of diagnostic test accuracy

“… 182 The study by Griffiths et al had a high risk of bias as it did not employ consecutive or random sampling, as assessed in domain 1. 237 This study was favourable for antenatal MRI and removal of this high risk study would alter the findings of this review.…”

“…Out of 62 articles, eight (13%) articles had a low risk of bias,182–189 45 (72%) articles had some concerns,185 190–234 and nine (15%) articles had a high risk of bias235–243 (figure 2).…”

“…The overall ratings of the applicability of the articles to the review question found one (2%) article had a high level of concern,241 20 (31%) had some concerns,195 200 205 206 212 214 215 217 220 222 225 226 231–234 237–240 and 41 (67%) had a low level of concern 182–194 196–199 201–204 207–211 213 216 218 219 221 223 224 227–229 235 236 242 243…”

The utility of pathologic examination and comprehensive phenotyping for accurate diagnosis with perinatal exome sequencing

“…13,14 In studies assessing the concordance of prenatal MRI and postnatal diagnoses made with postnatal imaging or autopsy, prenatal MRI missed relevant findings in 4%-37% of cases with variation by organ system. [15][16][17][18] Further, one study reanalyzed prenatal cases of anomalies that had normal results of ES based on the prenatal phenotype alone, and found a missed genetic diagnosis in 20% of cases when the postnatal or pediatric phenotype was incorporated into the sequencing analysis. 12 There are undoubtedly many opportunities to improve our phenotyping abilities with prenatal imaging, although some limitations may be unavoidable, such as early stage of a developing fetus.…”

“…In studies evaluating the concordance of prenatal ultrasound and autopsy, autopsy provided additional information in 22%–58% of cases and changed the initial diagnosis in 1%–33% of cases 13,14 . In studies assessing the concordance of prenatal MRI and postnatal diagnoses made with postnatal imaging or autopsy, prenatal MRI missed relevant findings in 4%–37% of cases with variation by organ system 15–18 . Further, one study reanalyzed prenatal cases of anomalies that had normal results of ES based on the prenatal phenotype alone, and found a missed genetic diagnosis in 20% of cases when the postnatal or pediatric phenotype was incorporated into the sequencing analysis 12 .…”