Perinatal Autopsy Research Articles

"We might get a lot more families who will agree": Muslim and Jewish perspectives on less invasive perinatal and paediatric autopsy.

BackgroundPerinatal and paediatric autopsy rates are at historically low levels with declining uptake due to dislike of the invasiveness of the procedure, and religious objections particularly amongst Muslim and Jewish parents. Less invasive methods of autopsy including imaging with and without tissue sampling have been shown to be feasible alternatives. We sought to investigate attitudes including religious permissibility and potential uptake amongst members of the Muslim and Jewish communities in the United Kingdom.MethodsSemi-structured interviews with religious and faith-based authorities (n = 16) and bereaved parents from the Jewish community (n = 3) as well as 10 focus groups with community members (60 Muslim participants and 16 Jewish participants) were conducted. Data were analysed using thematic analysis to identify key themes.FindingsMuslim and Jewish religious and faith-based authorities agreed that non-invasive autopsy with imaging was religiously permissible because it did not require incisions or interference with the body. A minimally invasive approach was less acceptable as it still required incisions to the body, although in those circumstances where it was required by law it was more acceptable than a full autopsy. During focus group discussions with community members, the majority of participants indicated they would potentially consent to a non-invasive autopsy if the body could be returned for burial within 24 hours, or if a family had experienced multiple fetal/pregnancy losses and the information gained might be useful in future pregnancies. Minimally invasive autopsy was less acceptable but around half of participants might consent if a non-invasive autopsy was not suitable, with the exception of the Jewish Haredi community who unanimously stated they would decline this alternative.ConclusionsOur research suggests less invasive autopsy offers a viable alternative to many Muslim and Jewish parents in the UK who currently decline a full autopsy. The findings may be of importance to other countries with significant Muslim and/or Jewish communities as well as to other religious communities where concerns around autopsy exist. Awareness-raising amongst religious leaders and community members will be important if these methods become routinely available.

Electron Microscopy Can Still Have a Role in the Diagnosis of Selected Inborn Errors of Metabolism.

Many anatomic pathology laboratories no longer have electron microscopy facilities. A retrospective review of autopsies was performed to identify cases of inborn errors of metabolism (IEM) and determine the contribution of electron microscopy in making the diagnosis in those cases. Over a period of 17 years, there were 900 perinatal and pediatric autopsies. There were 7 cases (1%) of IEM, including 4 cases of Pompe disease, 1 case of I-cell disease, 1 case of bile acid synthesis defect, and 1 case of mitochondrial disease (Leigh syndrome). Electron microscopy was important in the diagnosis of I-cell disease and Pompe disease in our series. This technique enabled a prenatal diagnosis to be made from a chorionic villus biopsy in 2 cases with a positive family history. In less developed countries where upfront genetic testing may be too expensive and may need international referral, electron microscopy can still be useful for diagnosis of IEM, providing an affordable alternative with a more rapid turnaround time compared to gene mutation analysis or enzyme assay. Results can be used both for patient management and as a screen for which cases might benefit from genetic testing.

Stillbirth at Tikur Anbessa Hospital a retrospective study

AbstractBackground: Stillbirths are believed to contribute to the overwhelming majority of perinatalmortality in some developing countries. Though the facilities and expertise for perinatal postmortem examination are lacking in Ethiopia, studies have indicated that useful informationcould be obtained from careful review of clinical records.Objective: This study is aimed at identifying probable causes, comparison of selected fetaland maternal variables between cases and controls and suggests possible preventive options.Methods: This study was a retrospective comparative study of stillbirths with sex matchedlive births. It was conducted at Tikur Anbessa Hospital. Addis Ababa, Ethiopia from Sept.11, 2000-Sept. 10 2001, based on information retrieved from individual patient records andusing a structured data entry format. The main study variables were maternal sociodemographicfeatures, antenatal care(ANC) attendance, and gestational age of indexpregnancy, birth weight, modes of delivery and probable causes of stillbirths.Results: The stillbirth rate (SBR) was 55.3/1000 births and contributed to 77.2% of thegross perinatal mortality (GPNM). ANC attendance (85.7%) and residence in Addis Ababa(82.3%) were significantly higher among controls than cases which had corresponding figuresof 69.4% and 55.1%, respectively. There was a statistically significant difference in low birthweight (40.5%) and preterm (32.1%) stillbirths than controls with the respective figures of15% and 11%, respectively. Mechanical factors were the commonest probable causes of deathaccounting for 44.2% of all stillbirths, while 21.8% were unexplained stillbirths and antepartum hemorrhage contributed to 15.7%.Conclusion: It is suggested that proper antenatal and intra partum care can reducestillbirth.Keywords: Stillbirth rate, peri-natal mortality, intra-partum care

Health professionals’ and coroners’ views on less invasive perinatal and paediatric autopsy: a qualitative study

ObjectiveTo assess health professionals’ and coroners’ attitudes towards non-minimally and minimally invasive autopsy in the perinatal and paediatric setting.MethodsA qualitative study using semistructured interviews. Data were analysed thematically.ResultsTwenty-five health professionals...

Postmortem microfocus computed tomography for early gestation fetuses: a validation study against conventional autopsy

Perinatal autopsy provides useful clinical information in up to 40% of cases. However, there is a substantial unmet clinical need with regards to postmortem investigation of early gestation fetal loss for parents for whom standard autopsy is either not available or not acceptable. Parents dislike the invasive nature of autopsy, but current clinical imaging techniques do not provide high-enough imaging resolution in small fetuses. We hypothesized that microfocus computed tomography, which is a rapid high-resolution imaging technique, could give accurate diagnostic imaging after early gestation fetal loss. The objective of the study was to evaluate the diagnostic accuracy of microfocus computed tomography for noninvasive human fetal autopsy for early gestation fetuses, with the use of conventional autopsy as the reference standard. We compared iodinated whole body microfocus computed tomography in 20 prospectively recruited fetuses (11-21 weeks gestation from 2 centers) with conventional autopsy in a double-blinded manner for a main diagnosis and findings in specific body organs. Fetuses were prepared with 10% formalin/potassium tri-iodide. Images were acquired with a microfocus computed tomography scanner with size-appropriate parameters. Images were evaluated independently by 2 pediatric radiologists, who were blinded to formal perinatal autopsy results, across 40 individual indices to reach consensus. The primary outcome was agreement between microfocus computed tomography and conventional autopsy for overall diagnosis. Postmortem whole body fetal microfocus computed tomography gave noninvasive autopsy in minutes, at a mean resolution of 27μm, with high diagnostic accuracy in fetuses at <22 weeks gestation. Autopsy demonstrated that 13 of 20 fetuses had structural abnormalities, 12 of which were also identified by microfocus computed tomography (92.3%). Overall, microfocus computed tomography agreed with overall autopsy findings in 35 of 38 diagnoses (15 true positive, 18 true negative; sensitivity 93.8% [95% confidence interval, 71.7-98.9%], specificity 100% [95% confidence interval, 82.4-100%]), with 100% agreement for body imaging diagnoses. Furthermore, after removal of nondiagnostic indices, there was agreement for 700 of 718 individual body organ indices that were assessed on microfocus computed tomography andautopsy (agreement, 97.5%; 95% confidence interval, 96.1-98.4%), with no overall differences between fetuses at ≤14 or>14 weeks gestation (agreement, 97.2% and 97.9%, respectively). Within first-trimester fetal loss cases (<14 weeks gestation), microfocus computed tomography analysis yielded significantly fewer nondiagnostic indices than autopsy examination (22/440 vs 48/348, respectively; P<.001). Postmortem whole-body fetal microfocus computed tomography gives noninvasive, detailed anatomic examinations that are achieved in minutes at high resolution. Microfocus computed tomography may be preferable to magnetic resonance imaging in early gestation fetuses and may offer an acceptable method of examination after fetal loss for parents who decline invasive autopsy. This will facilitate autopsy and subsequent discussions between medical professionals who are involved in patient care and counselling for future pregnancies.

Impact of preterm birth on the developing myocardium of the neonate.

BackgroundGlobally, ∼10% of infants are born before full term. Preterm birth exposes the heart to the demands of postnatal cardiovascular function before cardiac development is complete. Our aim was to examine, in hearts collected from infants at autopsy, the effects of preterm birth on myocardial structure and on cardiomyocyte development.Methods and resultsHeart tissue was collected at perinatal autopsies of 16 infants who died following preterm birth between 23 and 36 weeks of gestation, and survived for 1-42 days; the hearts of 37 appropriately grown stillborn infants, aged 20-40 weeks of gestation, were used for comparison. Using confocal microscopy and image analysis, cardiomyocyte proliferation, maturation, ploidy, and size were quantified, and interstitial collagen and myocardial capillarization were measured. Preterm birth resulted in a marked reduction in the proliferation of cardiomyocytes relative to age-matched stillborn infant controls (preterm vs. control P<0.0001). In contrast, preterm birth did not affect heart weight, capillarization, interstitial collagen or cardiomyocyte maturation, ploidy, and size.ConclusionsPreterm birth appears to lead to an abrupt reduction in cardiomyocyte cell division. This reduced cardiomyocyte proliferation in preterm infants may adversely impact upon the final number of cardiomyocytes which may reduce cardiac functional reserve, and impair the reparative capacity of the myocardium.

Perinatal Lethal Gaucher Disease due to RecNcil Recombinant Mutation in the GBA Gene Presenting with Hydrops Fetalis and Severe Congenital Anemia

A 35-year-old woman presented at 27-week gestation with hypertension and pedal edema. Antenatal scan showed hydrops fetalis and growth restriction. Cordocentesis showed severe fetal anemia. This was treated with multiple in utero blood transfusions with no clinically significant improvement and intrauterine death occurred at 28 weeks. Perinatal autopsy confirmed severe hydrops with hepatosplenomegaly and visceral effusions. Microscopic examination of the reticuloendothelial organs showed widespread infiltration by large mono- and multinucleate histiocytic cells with fibrillary appearance (“Gaucher cells”). DNA extracted from fetal tissue was submitted for analysis by next generation sequencing which revealed homozygosity for the RecNcil mutation in the GBA gene. Both parents were found to be heterozygous for the variant. The case report highlights a severe form of Gaucher disease with histopathological and molecular confirmation that presents with hydrops fetalis and severe refractory anemia. It also emphasizes the importance of perinatal autopsy coupled with exome sequencing in confirming syndromic diagnosis in the modern area.

Study of Congenital Malformations in Fetal and Early neonatal autopsies

Background: Antenatal care in India is rising due to improvement in awareness; still few congenital malformations can be missed in routine check-ups. One lost baby due to birth defects raises questions like; did the malformation led to death, what was the exact nature of malformation, will it recur in next pregnancy and are there any preventive measures? Few congenital malformations can be diagnosed prenatally with ultrasonography techniques, various maternal serum assays, confirmation relies on actual examination of the fetus or neonate. These techniques cannot identify large proportion of congenital malformations for which perinatal autopsy remains the gold standard investigation. The result of a perinatal autopsy may have broad impact, in that obstetrical, fetal, maternal, paternal, and familial conditions may be uncovered. Methods: The descriptive analytical study was carried out in Department of Pathology of a tertiary care hospital from June 2014 to May 2016 for detection of congenital malformations in fetal and early neonatal autopsies in 5 years. Conclusion: Despite advances in imaging such as antenatal ultrasonography and serology, perinatal autopsy is superior and continues to play an important role in diagnosing congenital malformations. The findings of autopsy are not only of theoretical importance but also of practical significance to clinicians in the form of estimating the risk of recurrence and in genetic counseling. DOI: 10.21276/APALM.1272

Diagnostic value of perinatal autopsies: analysis of 486 cases.

Autopsy is a beneficial procedure to determine the cause of death and the frequency of anomalies in perinatal losses. Even in the event of an autopsy not providing any additional information, completion of the procedure confirming the clinical diagnoses gives reassurance to both clinicians and parents. Here we present a 15-year archival study based on findings of perinatal autopsies. Four hundred and eighty-six cases from our archive were reviewed and according to the findings they were divided into three subcategories; (1) miscarriages (MCF); (2) fetuses terminated (FTA) for vital anomalies detected by prenatal ultrasonography; (3) premature or term newborns died within first month of life (neonates: NN). Autopsies were documented and classified according to week/age of cases, anomalies and causes of abortion or death. Two hundred and twenty-six of 486 cases (46.5%) were in MCF group while 227 (46.7%) and 33 (6.8%) were of them in FTA and NN groups, respectively. In FTA group, the most frequent anomaly detected was neural tube defects. In NN group, prematurity related complications were the most common cause of death. The autopsy process was found valuable in 39.7% of all cases. We suggest that autopsy procedure is diagnostically valuable even in situations when there is USG findings that are confirming FTAs or there is no important major fetal or placental anomaly detected in MCFs.

Lethal Congenital Malformations in Fetuses—Antenatal Ultrasound or Perinatal Autopsy

ABSTRACTBackground: Congenital malformations (CMF) are major causes of fetal demise which can be detected antenatally by Ultrasonography (USG). Methods: We studied 100 perinatal autopsies for CMF. Sensitivity of USG was determined and accuracy of USG with that of autopsy was compared. Results: At Autopsy 134 individual CMF were seen in 40 cases. The sensitivity of USG in detecting major CMF was 54.47%. A complete agreement between autopsy and USG findings was seen in 13/40 (32.5%) and partial agreement in 17/40 (42.5%) fetuses while autopsy completely changed antenatal diagnosis in 10/40 (25%) fetuses. Major findings were added in all 17 fetuses with partial agreement. In 2 cases, CMF suspected on USG were not detected on autopsy due to fetal maceration. Conclusion: Autopsy significantly adds to the prenatal USG diagnosis and may help in predicting the probability of recurrence, and thus counseling the affected couple to prevent any such future event.

Perinatal autopsy rates in the ACT between 2011 and 2015

Perinatal autopsy rates in the ACT between 2011 and 2015

Historical Aspects of Osteochondral Junction Studies in Perinatal Autopsies

Microscopic examination of the fetal ribs rsquo osteochondral junction OCJ during perinatal autopsies is a reliable method to determine intrauterine fetal growth abnormalities The ribs are ideal bones for studying fetal growth and development as they have the highest growth from a linear point of view during intrauterine life and are easy to access during autopsy examination Understanding the normal histology of rib bones at different gestational ages is fundamental to recognize the postmortem pathological alterations Moreover examination of the OCJ can help to estimate the timing of the intrauterine insult that ultimately leads to the perinatal death

ПЕРСПЕКТИВЫ РАЗВИТИЯ МЕТОДОВ ВЕРИФИКАЦИИ ДИАГНОЗА В ДЕТСКОЙ ПАТОЛОГОАНАТОМИЧЕСКОЙ ПРАКТИКЕ

The aim of the study is to highlight the modern methods for solving the problem of failure relatives of perinatal autopsies in a policonfessional population of the Russian Federation. Material and methods. The analysis of publications on the topic in 35 years on databases Scopus and RSCI. Of the more than 10 thousand sources selected for the review of more than 30 foreign and domestic publications. Results. Modern technical basis of modern medicine allows postmortem studies for medical purposes without violating the integrity of the patient's body. Conclusion. The use of diagnostic methods (RG, ultrasound, CT, MRI) in the post-mortem diagnosis allows to observe and enhance the interests of medicine in the analysis of post-mortem changes. Also observe the tradition of religious denominations.

Legal, Social &amp; Ethical Issues During Performing Peri-natal Autopsy in India-A Practical Experience

Legal, Social &amp; Ethical Issues During Performing Peri-natal Autopsy in India-A Practical Experience

Stillbirth: a lot done… a lot more to do.

Stillbirth: a lot done… a lot more to do.

Pathologist Effort in the Performance of Fetal, Perinatal, and Pediatric Autopsies: A Survey of Practice.

-Autopsy is an important tool for quality assurance and improving patient care. Fetal, perinatal, and pediatric autopsies have the additional benefit of identifying conditions that may have increased risk of recurrence. In contrast to adult autopsies, special collections and testing are frequently used. Pathologist effort in fetal, perinatal, and pediatric autopsy has not been well documented. -To prospectively quantify pathologist time required to complete fetal, perinatal, and pediatric autopsies, and to gather information on special studies and whether or not a cause of death was identified. -The Society for Pediatric Pathology Practice Committee disseminated a survey to pathologists to complete for each autopsy performed. Surveys recorded age/gestation, time spent on chart review, prosection, and microscopy, special testing performed, time spent on a discussion or presentation of findings, and whether a cause of death was found. -We report results of 351 surveys. Pathologist effort in fetal cases was, on average, 5.9 hours; in perinatal cases, 9.8 hours; and in pediatric cases, 15.4 hours. Reflecting complexity, a total of 603 collections for ancillary studies were performed, most commonly karyotype, frozen tissue, and microbiology cultures. A cause of death was identified in 295 of 351 cases (84%). Most cases were presented at conferences. -Fetal, perinatal, and pediatric autopsies are time intensive and frequently complex. They have high clinical value, guiding risk assessment and reproductive decision-making by families. Understanding the time contribution by pathologists allows departments and hospitals to predict staffing.

Morphometric profile of large intestinal neuronal plexuses in normal perinatal autopsies and Hirschsprung disease.

To derive objective values for the diagnosis of Hirschsprung disease (HSCR) from a comparison of the morphometric profile of large intestinal neuronal plexuses in normal perinatal autopsies and surgical specimens of HSCR. A cross-sectional comparative study with 40 subjects each in (i) non-HSCR perinatal group encompassing neonates and stillborn babies beyond 30weeks of gestation on whom autopsies were conducted and (ii) HSCR group comprising all patients clinicoradiologically diagnosed as HSCR. The morphometric assessment was done on hematoxylin-and-eosin-stained sections. The morphometric profile in terms of average number of ganglia/linear mm of colon, interganglion distance, number of ganglion cells/ganglion, average ganglion cell length, ganglion cell nuclear area, ganglion cell nuclear diameter, nerve trunk thickness, and density has been outlined. On comparison with the neuroanatomically normal zone of HSCR, the cut-offs to identify hypertrophic nerve trunks (nerve trunk thickness of >37.85μm) and reduced number of ganglia (number of ganglia/linear mm of colon <2.05 and interganglion distance of >229μm) were derived. The determined objective values, after testing on diagnostic rectal biopsies, may serve to formulate a diagnostic algorithm along with immunostaining for diagnosis of HSCR in colorectal specimens.

Quantification of maceration changes using post mortem MRI in fetuses.

BackgroundPost mortem imaging is playing an increasingly important role in perinatal autopsy, and correct interpretation of imaging changes is paramount. This is particularly important following intra-uterine fetal death, where there may be fetal maceration. The aim of this study was to investigate whether any changes seen on a whole body fetal post mortem magnetic resonance imaging (PMMR) correspond to maceration at conventional autopsy.MethodsWe performed pre-autopsy PMMR in 75 fetuses using a 1.5 Tesla Siemens Avanto MR scanner (Erlangen, Germany). PMMR images were reported blinded to the clinical history and autopsy data using a numerical severity scale (0 = no maceration changes to 2 = severe maceration changes) for 6 different visceral organs (total 12). The degree of maceration at autopsy was categorized according to severity on a numerical scale (1 = no maceration to 4 = severe maceration). We also generated quantitative maps to measure the liver and lung T2.ResultsThe mean PMMR maceration score correlated well with the autopsy maceration score (R2 = 0.93). A PMMR score of ≥4.5 had a sensitivity of 91 %, specificity of 64 %, for detecting moderate or severe maceration at autopsy. Liver and lung T2 were increased in fetuses with maceration scores of 3–4 in comparison to those with 1–2 (liver p = 0.03, lung p = 0.02).ConclusionsThere was a good correlation between PMMR maceration score and the extent of maceration seen at conventional autopsy. This score may be useful in interpretation of fetal PMMR.

Hubungan Umur Ibu, Paritas dan Penolong Persalinan dengan Kematian Neonatal di Wilayah Kerja Puskesmas Kabupaten Banjarnegara tahun 2013

Background: The neonatal mortality rate is Banjarnegara district is high compared with a target of IMR in Central Java province. In 2012 the neonatal mortality rate in Banjarnegara reached 316 cases, whereas in 2013 there were 115 cases in all health centers working area. The high neonatal mortality rate in Banjarnegara influenced by the persistence of early marriage in woman, birth attendant by non skilled health worker (dukun bayi) and women’s parity more than 4.Objective: The purpose of this study is to analyze the correlation between maternal age, parity and birth attendants with the incidence of neonatal mortality and examine the most dominant factors influencing the incidence neonatal mortality in the Health Center working area in Banjarnegara.Method: This study is a case control study design with retrospective approach. The data consists of perinatal verbal autopsy and medical records as many as 136 respondents consisting of 68 mothers who gave birth to her child and neonatal death and 68 maternal and child alive. Subjects were mothers who gave birth a baby who died aged 0-28 days.Result and Discussion: Statistical analysis using Chi Square, Mann Whitney, and multiple logistic regression. The results showed maternal age and parity variables were not significantly corerelated with neonatal mortality (p&gt; 0.05), the variables significantly corerelated with neonatal mortality was birth attendants with p = 0.001. The results of logistic regression showed the strength of the corerelation from the most dominant variable to the smallest variable were birth attendants with OR: 5.64 (95% CI: 1.81 to 17.4), maternal age OR 3.97 (CI 95%, from 1.54 to 10.22), and parity OR: 0.32 (CI 95% 0.12 to 0.87).Conclusion: In conclusion, there was no relationship between maternal age and parity with neonatal mortality but there was a relationship between birth attendants with neonatal mortality. Based on the results of the multivariable analysis, birth attendants’ effect on the incidence of neonatal deaths was 5 times greater than mother’s age and parity.Keywords: Neonatal mortality, maternal age, parity, birth attendants

Clinical utility of post-mortem micro-CT of the fetal heart: an exploratory study of diagnostic imaging versus macroscopic dissection

BackgroundCongenital cardiac malformations are commonly seen at perinatal autopsy. Accurate diagnosis can be challenging in small, macerated fetuses. The diagnostic accuracy of post-mortem MRI is diminished below 18 gestational weeks; however, micro-CT can provide micrometre resolution images but has not been evaluated for human diagnostic accuracy. We hypothesised that micro-CT could provide useful diagnostic information in fetal congenital heart disease and compared it with the gold standard of autopsy. MethodsReferrals to Great Ormond Street Hospital were prospectively included. Ex-vivo fetal hearts underwent micro-CT examination. 21 indices normally assessed at autopsy were evaluated for each heart at both micro-CT and autopsy in a single-masked fashion. All parents provided written consent for both autopsy, including post-mortem imaging, and research. The study was part of a larger study given ethics approval (IRAS ID 13942, R&D 09MH01). FindingsWe examined six fetal hearts including five with complex congenital cardiac malformations (17–23 weeks' gestation). Heart weights ranged between 1·1 g and 5·3 g (median 4·6 g). All specimens demonstrated excellent internal contrast at micro-CT examination, and the correct overall diagnosis was made from micro-CT data in all cases. There was agreement for 114 of 126 indices assessed on micro-CT and autopsy dissection (overall concordance 95·8% (95% CI 90·5–98·2). Micro-CT was particularly useful in the assessment of ventricular morphology in macerated fetuses. Micro-CT examination for diagnosis of complex congenital heart disease had a sensitivity of 85·2% (95% CI 67·5–94·1) and specificity of 98·9% (94·1–99·8). InterpretationOur preliminary study shows that micro-CT can provide diagnostically accurate three-dimensional volumes of complex congenital fetal heart disease. This approach potentially represents a substantial advance in post-mortem imaging and confirms the potential of this technology for non-invasive examination of small fetuses and organs. Centres that do not have specialist paediatric cardiac pathology expertise might especially benefit. Limitations include the small study size. Future studies should also include in-vivo post-mortem evaluation. FundingNone.