F. A. Jessop

Minimally‐invasive fetal autopsy using magnetic resonance imaging and percutaneous organ biopsies: clinical value and comparison to conventional autopsy

Autopsy is an important investigation following fetal death or termination for fetal abnormality. Postmortem magnetic resonance imaging (MRI) can provide macroscopic information of comparable quality to that of conventional autopsy in the event of perinatal death. It does not provide tissue for histological examination, which may limit the quality of counseling for recurrence risks and elucidation of the cause of death. We sought to examine the comparability and clinical value of a combination of postmortem MRI and percutaneous fetal organ biopsies (minimally invasive autopsy (MIA)) with conventional fetal autopsy.

Feasibility of percutaneous organ biopsy as part of a minimally invasive perinatal autopsy.

To determine the feasibility of percutaneous fetal organ biopsies in the context of a ‘minimally invasive’ perinatal autopsy after stillbirth and termination for abnormality is the aim of this study. We assessed successful biopsy rate and the proportion adequate for histological examination in 30 fetuses undergoing organ sampling before autopsy. The relationship between gestational age, body weight, death–biopsy interval, operator experience and successful biopsy rate was investigated. Significant findings from conventional block histology were compared with corresponding percutaneous biopsies. Of 210 organ biopsies attempted from seven target organs, 107 were obtained, of which 94 were adequate for pathological comment. The median delivery–autopsy interval was 4 (range 2–11) days. Adequate samples were obtained from the lung in 86% cases (95% CI 68, 96%), liver 76% (95% CI 56, 90%) and less frequently for the myocardium, kidney, adrenal, thymus and spleen. There was no relationship between biopsy success and time to biopsy, gestational age, body weight and user experience. No histological abnormalities found at autopsy were diagnosed from needle biopsies. Although targeted percutaneous biopsies appear feasible for some organs, fewer than 50% of all biopsies are adequate for histological examination. This technique cannot be considered to provide useful clinical information as part of a ‘minimally invasive’ perinatal autopsy.

Use of a confidence scale in reporting postmortem fetal magnetic resonance imaging

Postmortem magnetic resonance imaging (MRI) may be an alternative to conventional autopsy. However, it is unclear how confident radiologists are in reporting such studies. We sought to determine the confidence with which radiologists report on various fetal organs by developing a scale to express their confidence of normality and abnormality, and to place this in the context of a pathological diagnosis of whether the organ was in fact normal or abnormal.

Perinatal Postmortems: What Is Important to Parents and How Do They Decide?

BACKGROUND Falling consent rates for postmortems, regardless of age of death, have been widely reported in recent years. The aim of this study was to explore parental attitudes to, and decision-making about, a perinatal postmortem after termination for fetal abnormality, late miscarriage, or stillbirth. METHODS A prospective self-completion questionnaire was given to 35 women and their partners. The participants had experienced second or third trimester pregnancy loss in a single fetal medicine and delivery unit in the United Kingdom and were making decisions about having a postmortem. They were asked to complete a questionnaire about their attitudes to, and expectations of, a perinatal postmortem. RESULTS Thirty-one questionnaires were received from parents of 17 babies (49% of those asked; 16 from mothers, 15 from fathers). Parents of nine babies (53%) said they would agree to a full postmortem, of three babies to a limited postmortem, and of four babies to an external examination only; one couple were undecided. The most important issues for the parents in this study that related to their decisions about a postmortem centered on the need for information, both for future planning and about what had happened. Moderately important issues related to altruism, which is, improving medical knowledge and helping other parents experiencing similar bereavement. Among the lowest scoring issues were potential barriers, such as concerns about cultural or religious acceptability of a postmortem, funeral delays, and what would happen to the babys body. CONCLUSIONS Bereaved parents who participated in this study, where postmortem consent rates were relatively high, thought that their need for knowledge eclipsed assumed barriers when deciding whether or not to have a postmortem for their baby.

Placental weight, digitally derived placental dimensions at term and their relationship to birth weight.

Objective. A few recent studies have investigated the relationship between birth weight and digitally derived placental dimensions, and no standardised methodology has been used. The aims of this study are to compare manually derived placental measurements with those derived digitally and to establish the relationship of birth weight to the placental weight and circumference. Methods. Three hundred fifty-one consecutive unselected women with singleton pregnancy delivering in a tertiary maternity unit at 37–42 weeks were recruited. Manual and digital placental axis measurements (using calibrated digital imaging and ‘Image J’ software) were obtained and the circumference derived. The relationship between the two methods was assessed using a Bland–Altman plot analysed. The relationship between z-scores of birth weight, placental weight and placental circumference was investigated. Results. Manually and digitally obtained placental long axis, short axis and circumference measurements show close correlation (r = 0.70, 0.70 and 0.83, respectively). The z score of birth weight is significantly correlated with the z score of placental weight (r = 0.59, p < 0.001) and z score placental digital circumference (r = 0.40, p < 0.001). Birth weight:placental weight ratio is 7.20 and birth weight:placental circumference = 64.57 g/cm. Conclusion. There is close though not perfect agreement between the manual and digital placental measurements. Birth weight is strongly correlated with placental weight and circumference at term.

Attitudes to perinatal postmortem: parental views about research participation

Objective To study parental attitudes to participating in questionnaire research about perinatal postmortem immediately after late miscarriage, stillbirth and termination for fetal abnormality. Design Prospective self-completion questionnaire. Setting UK fetal medicine and delivery unit. Patients 35 women and their partners after second or third trimester pregnancy loss, making decisions about having a postmortem. Methods Participants were asked to complete a questionnaire about postmortem decision-making which included questions about their attitudes to taking part in research. Prior to giving full approval for the study, the Research Ethics Committee (REC) requested feedback after 10 questionnaires had been returned. Results Responses from the first 10 participants were positive about the research and the REC allowed the study to continue. 31 questionnaires were received from parents of 17 babies (49% of those asked; 16 from mothers, 15 from fathers). Of the 22 participants who answered a question about the impact of participating in this research, 73% stated that completing the questionnaire had helped them feel better about the decision whether or not to consent to postmortem and none reported any adverse effect of completing the questionnaire. Additional comments made by 19 participants supported this finding. Conclusion Research into this sensitive area of perinatal medicine where there is a poor outcome is possible and is indeed well received by many parents. RECs should not automatically take a negative stance towards studies of this type.

HISTOLOGICAL CHORIOAMNIONITIS: CURRENT CONCEPTS OF DIAGNOSIS, CLASSIFICATION AND CLINICAL SIGNIFICANCE

Interest in the clinical associations between maternal intrapartum fever and adverse neonatal outcome has been longstanding, with publications of a relationship between maternal fever and cerebral palsy dating from the 1950s. Further recognition of the associations between either clinically or histologically characterised chorioamnionitis, ascending infection and neonatal wellbeing followed, with numerous reports in the 1960s and 70s, particularly as the neonatal significance of group B streptococcal infections became apparent. Similarly, with the systematic introduction of diagnostic light microscopy into clinical medicine, chorioamnionitis (inflammation of the placental membranes) and funisitis (inflammation of the umbilical cord) were recognised as distinct histological entities, with increasing recognition that the aetiology was likely to be infective. There are numerous texts discussing in detail the pathogenesis and histological features of chorioamnionitis and funisitis. The aim of this review is to provide an overview of the salient associated issues for clinical practitioners and to highlight areas of ongoing uncertainty and recent developments in understanding.

OP06.04: Postmortem fetal lung volumetry using MRI and comparison to lung weights at autopsy

Introduction: Prediction of pulmonary hypoplasia remains difficult. At autopsy, pathologists use the lung weight/body weight ratio to diagnose pulmonary hypoplasia. Estimating lung volumes in utero could aid management when pulmonary hypoplasia is suspected. We measured fetal lung volumes on post mortem MRI. By comparing these volumes to organ weights at autopsy, we estimated fetal lung densities. This may allow prenatal calculation of lung weights in future. Methods: 21 fetuses underwent postmortem MRI at 1.5T prior to conventional autopsy with parental consent. Fetal weights ranged from 113–3270 g, with gestational ages of 17–40 weeks. T2-weighted sequences were used. Conventional autopsies were performed to RCPath guidelines. Lung volumes were independently estimated by two researchers using the ANALYZE (BIR, Mayo Foundation) software package’s stereology tool. Organ volumes for each observer were compared to autopsy organ weights, and the reciprocal of the gradients and R2 values were calculated. Inter-observer agreement was assessed using BlandAltman analysis. Results: There was high linear correlation between estimated lung volume and actual lung weights (R2 > 0.98 for both observers). The reciprocal of the gradient gave an average lung density of 1.15 g/cm3 which corresponds closely to the density of non-aerated adult lung (1.04–1.09). Bland-Altman analysis demonstrated good interobserver agreement, which appeared to improve with increasing organ size. Conclusions: Ex utero fetal lung volume measurements are highly correlated to lung weight at autopsy, with a calculated density that corresponds well to published figures. The technique has low interobserver variability and provides non-invasive information about fetal lung development when conventional autopsy is declined. It may also prove of value in the prenatal assessment of lung development.

OP03.03: Diagnostic sensitivity and clinical value of prenatal ultrasound, post-mortem magnetic resonance imaging and conventional autopsy for late miscarriage and stillbirth

Down syndrome risk. Of the 56 cases of trisomy 21 (1,2%), 25 were males and 31 females (P = 0,74). Detection rate for trisomy 21 was 84% in males and 87% in females (P=0,8). Free beta HCGMoM, NTMoM and PAPPAMoM were not significantly different between male and female trisomy 21 fetuses. Conclusions: There is a trend towards female fetuses having a higher chance of increased risk at the combined test. There are no gender differences in the detection rate of trisomy 21. Whether risk assessment protocols need to become gender specific needs further investigation.

OP03.02: Diagnostic sensitivity and clinical value of prenatal ultrasound, post‐mortem magnetic resonance imaging and conventional autopsy in structural fetal abnormality

Down syndrome risk. Of the 56 cases of trisomy 21 (1,2%), 25 were males and 31 females (P = 0,74). Detection rate for trisomy 21 was 84% in males and 87% in females (P=0,8). Free beta HCGMoM, NTMoM and PAPPAMoM were not significantly different between male and female trisomy 21 fetuses. Conclusions: There is a trend towards female fetuses having a higher chance of increased risk at the combined test. There are no gender differences in the detection rate of trisomy 21. Whether risk assessment protocols need to become gender specific needs further investigation.