MRI features of perifibrinous deposits in the placenta due to COVID-19.

COVID-19 has been linked to pregnancy complications and loss (1). Infection during pregnancy is usually mild (2). The risk is highest in the third trimester with increased hospital admission rates and maternal and fetal compromise (3). Post-COVID placentitis is uncommon but the effect on the placenta and the fetus is extensive (4). We present a case correlating clinical, imaging, and pathological findings. Case Report: A 29-year-old para 2 gravida 1, with a normal fetal anomaly scan at 22 weeks gestational age (GA) contracted COVID at 24 weeks gestation. Fully recovered but reported reduced fetal movements at 27 weeks and 1 day. Imaging: US scan showed bright echoes within the brain, small lungs, and oligohydramnios. MRI showed abnormal brain signals, small lungs, and oligohydramnios but also a very abnormal placenta. Reduced and heterogeneous T2 signal and a marked reduction in the DWI signal intensity. The placental size was markedly reduced (volume 785.6 cm3 expected for GA is 5604.8-5952.4 cm3. The surface area of attachment was 3220 mm2, expected 22180.4-29293.2 mm2). Pathology: The placenta was small (fifth centile) with massive perivillous fibrin deposition and multifocal chronic deciduitis. Histology revealed placental chorionic villi showing diffuse sclerotic changes surrounded by perivillous fibrin deposition in the intervillous space. The basal plate revealed multifocal chronic deciduitis. When imaging the fetus, it is important to examine the placenta and correlate any abnormalities. The placenta is a forgotten organ and should be routinely included and assessed to allow the detection of important abnormalities.

Why Should Clinical Autopsies Continue to Exist?

At some point in history, medicine was integrated with pathology, more precisely, with pathological anatomy [...].

Umbilical Cord Coiling and Zygosity: Is there a Link?

INTRODUCTION: The aim of this study was to analyze abnormalities of umbilical coiling index (UCI) in twin gestation to test whether the coiling is genetically influenced by zygosity. METHODS: Data retrieved comprised gestational age (GA), chorionicity, fetal gender, and UCI. RESULTS: The mean UCI of hypercoiled cords in monochorionic placentas was 0.55 coils/cm and 0.49 coils/cm in dichorionic placentas with discordant fetal gender (P = 0.2629). DISCUSSION: In conclusion, no significant statistical difference between UCI in monochorionic and dichorionic twin placentas with discordant fetal gender was identified, suggesting that zygosity does not play a role in umbilical coiling induction.

Sudden unexpected early neonatal death due to undiagnosed Hirschsprung disease enterocolitis: a report of two cases and literature review.

Hirschsprung enterocolitis (HEC) is an uncommon, albeit well known, complication of Hirschsprung disease (HD). It is multifactorial and can appear in different age groups, but is particularly important in the neonatal period where it is characteristically seen in full-term neonates. Two cases of HEC are reported that were diagnosed at post-mortem examination, which presented as early sudden neonatal death, with a review the literature on fatal Hirschsprung enterocolitis. Case 1 was a 4-day old male neonate who was found unwell, struggling to breath, and with green vomitus. He was taken to hospital and pronounced dead a short time later. According to the parents meconium was passed on the first day. Post-mortem examination demonstrated necrotizing enterocolitis with isolated bowel perforation. Histology disclosed unsuspected HD. Case 2 was a 2-day old male neonate who was found wheezing with green vomitus. He arrived floppy, cyanosed, and in shock at the hospital and died a few hours later. Meconium was not passed, according to the parents. Post-mortem examination revealed necrotizing enterocolitis. There was also recto-sigmoidal aganglionosis and acetylcholinesterase staining confirmed HD. HEC is a multifactorial and sometimes recurrent complication of HD which characteristically develops in full-term neonates. Presentation with early sudden neonatal death is rare but should be considered in the diagnostic work-up of sudden deaths in this age group.

Comparison of the larynx-associated lymphoid tissue in the false vocal cords and subglottis in pediatric autopsies.

The aim this work was to compare the distribution of cellular phenotypes of the LF in the FVC to the ones in the subglottic region in pediatric autopsy, relating this distribution to age and different causes of death. We analyzed 60 larynges of newborns and children autopsied in the period from 1993 to 2003. The fragments were prepared in order to perform histochemical and immunohistochemical techniques. The morphological analysis showed cases that presented LF only in FVC (35%), LF only in the subglottic region (20%), lack of LF in FVC (30%) and lymphoid aggregates, which did not characterize an LF (15%). The cases of LF in the subglottic region were significantly younger compared to the ones that presented LF in the FVC (p=0.017). The LF in the subglottic region was bigger than the LF in the FVC (p=0.020). There was no significant difference between the cause of death and cellular phenotype for both FVC and the subglottic region. In conclusion, the cells that make up the LF in the FVC in newborns and children younger than one year have functional characteristics similar to LF cells in the subglottic region, suggesting that there are similarities with LALT.

Necrotic epithelial cells in proximal renal tubules of 2nd trimester fetuses: is this "acute tubular necrosis"?

PURPOSE: The aim of this study is to describe the occurrence of necrotic tubular cells in kidneys of non-macerated fetuses. METHODS: Description of histology and immunostaining results using C9 immunostain of proximal tubular epithelium of kidneys from 30 consecutive non-macerated fetuses' autopsies. RESULTS: the gestational age ranged from 13 to 22 weeks. The mean gestational age was 18.6 weeks; the cause of death was acute chorioamnionitis in 13 cases (43.3%), termination of pregnancy for fetal anomalies in 13 (43.3%) and other causes in 4 (13.3%). Histology of the kidneys revealed vacuolation of proximal tubule epithelial cells (100%), dilatation of tubules (93.4%) and tubular cell necrosis (53.4%). C9 immunostaining was positive in 24 cases (80%) and was seen in all gestational ages. CONCLUSIONS: These results indicate that tubular cell necrosis is not an uncommon finding in the kidneys of 2(nd) trimester fetuses and may represent acute tubular necrosis (ATN). C9 is a helpful marker in confirming this diagnosis. Future studies may further explore this preliminary observation.

Overestimation of umbilical cord coiling index with segmental versus total length assessment.

The umbilical cord is the only communication between the fetus and the placenta and, not surprisingly, lesions or conditions affecting it may have detrimental effects in both. One important feature of the umbilical cord is its coiling index (UCI), with hypo- and hypercoiling being associated with fetal thrombotic vasculopathy, intolerance of labor, intrauterine growth restriction, cord stricture, thrombosis of cord and chorionic blood vessels, and fetal demise. It is essential that every placenta report include the UCI. The UCI could also be assessed prenatally, but there is currently no way of accurately assessing the entire length of the umbilical cord. The aim of this study was to compare UCI measured in a segment of cord 10 cm long (UCI-10) and over its total length (UCI-T). One hundred fifty consecutive placenta reports in which both measurements were recorded were retrieved from the files and analyzed. Gestational age ranged from 16 to 42 weeks, with a mean of 33.67 ± 5.96 weeks and a median of 36 weeks. Mean UCI-10 was 0.4360 ± 0.2625 coils/cm and mean UCI-T was 0.3530 ± 0.2022 coils/cm; the difference between these measurements was highly statistically significant (P < 0.0001). Counting the number of umbilical cord coils in 10 cm led to an overestimation of the UCI-T by 23.5%; it can be concluded, therefore, that the latter should be used.

Splitting of the umbilical cord in a 13-week-old fetus.

There is an increasing interest in the physiology and pathology of the umbilical cord because it is recognized as an important source of placental and, consequently, fetal problems. During the postmortem examination of a severely macerated 13-week-old fetus, a split umbilical cord was noted. This rare finding was seen in the middle segment of the cord, the fetal and placental ends both being normal. The pathogenesis of this lesion is not fully understood, and it is possible that it results through focal degeneration of previously formed Wharton's jelly or secondary loss of Wharton's jelly due to incomplete fusion or hypoplasia of the amniotic covering. Whatever the pathogenesis, it is assumed that an umbilical vessel devoid of its protective Wharton's jelly is more prone to compression and thrombosis with all its deleterious effects. Death in this case was probably associated with the congenital heart defect also presented by the fetus. The rarity of this lesion is probably explained by the fact that it represents the end of the spectrum of longitudinal deficiency of Wharton's jelly, a relatively common finding.

Mosaic trisomy 11 in a fetus with bilateral renal agenesis: co-incidence or new association?

We report a fetus with mosaic trisomy 11 who also had bilateral renal agenesis. We describe the post-mortem examination findings in the fetus and cytogenetic analysis. There are no earlier reports of full trisomy 11, presumably because it is lethal and results in early spontaneous miscarriages. There is only one report published earlier in a fetus with mosaic trisomy 11. There have been a few case reports of trisomy 11 identified in pre-natal samples, where it was associated with normal outcome. Bilateral renal agenesis has not been reported earlier in association with mosaic nor non-mosaic trisomy 11. We describe this rare cytogenetic finding in a fetus with bilateral renal agenesis. We also discuss the issues around genetic counselling when this is encountered in clinical practice.

Proliferation and cell death in an experimental model of brain tissue heterotopia in the lung.

PURPOSE: To investigate the proliferation and neuronal death in brain tissue heterotopia in the lung in an experimental model during both fetal and neonatal periods. METHODS: Twenty four pregnant female Swiss mice were used to induce brain tissue heterotopia on the 15th gestational day. Briefly, the brain of one fetus of each dam was extracted, disaggregated and injected into the right hemithorax of siblings. Six of these fetuses with pulmonary brain tissue implantation (PBI) were collected on the 18th gestational day (group E18) and six other on the 8th postnatal day (group P8). Immunohistochemical staining for PCNA and Bcl2 were used to assess proliferation and cell death. RESULTS: PCNA Labelling Index (LI) in heterotopic brain tissue was greater in fetal than postnatal period (E18 > P8) (p<0.05) and the immunostaining with Bcl2 antibody did not show difference. CONCLUSION: Cell proliferation is maintained in brain tissue heterotopia, although apoptosis is also observed.

Proliferation and cell death in an experimental model of brain tissue heterotopia in the lung / Proliferação e morte celular na heterotopia encefálica experimental

PURPOSE: To investigate the proliferation and neuronal death in brain tissue heterotopia in the lung in an experimental model during both fetal and neonatal periods. METHODS: Twenty four pregnant female Swiss mice were used to induce brain tissue heterotopia on the 15th gestational day. Briefly, the brain of one fetus of each dam was extracted, disaggregated and injected into the right hemithorax of siblings. Six of these fetuses with pulmonary brain tissue implantation (PBI) were collected on the 18th gestational day (group E18) and six other on the 8th postnatal day (group P8). Immunohistochemical staining for PCNA and Bcl2 were used to assess proliferation and cell death. RESULTS: PCNA Labelling Index (LI) in heterotopic brain tissue was greater in fetal than postnatal period (E18 > P8) (p<0.05) and the immunostaining with Bcl2 antibody did not show difference. CONCLUSION: Cell proliferation is maintained in brain tissue heterotopia, although apoptosis is also observed.

OBJETIVO: Investigar a proliferação e morte neuronal na heterotopia encefálica pulmonar em modelo experimental durante o período fetal e neonatal. MÉTODOS: Foram utilizados 24 camundongos Swiss fêmeas prenhes para induzir a heterotopia encefálica no pulmão. O tecido encefálico de um feto de cada fêmea prenha foi removido, picotado e injetado no pulmão dos irmãos. Seis fetos com Implantação Encefálica Pulmonar (IEP) foram coletados no 18º dia gestacional (grupo E18) e seis outros fetos no 8º dia pós-natal (grupo P8). Foi realizada a reação Imuno-histoquímica para PCNA e Bcl2 para analisar a proliferação e morte celular. RESULTADOS: O índice de marcação (IM) para PCNA era maior no período fetal quando comparado com o período pós-natal (E8 > P18) (p<0,05) e a imunomarcação para o anticorpo Bcl2 não apresentou diferença. CONCLUSÃO: A proliferação celular foi mantida no tecido heterotópico encefálico, embora a apoptose também foi observada.

Beta1 integrin and VEGF expression in an experimental model of brain tissue heterotopia in the lung.

INTRODUCTION: Integrins and vascular endothelial growth factor (VEGF) are crucially involved in interaction, proliferation, migration, and survival of the cells. However, there is no report in the literature about beta1 integrin and VEGF expression in heterotopic brain tissue. PURPOSE: The aim of this study was to assess beta1 integrin and VEGF expression in experimental brain tissue heterotopia in the lung during both fetal and neonatal periods. MATERIALS AND METHODS: Twenty-four pregnant female Swiss mice were used to induce brain tissue heterotopia on the 15th gestational day. Briefly, the brain of one fetus of each dam was extracted, disaggregated, and injected into the right hemithorax of siblings. Six of these fetuses with pulmonary brain tissue implantation were collected on the 18th gestational day (group E18) and six other on the eighth postnatal day (group P8). RESULTS: Immunohistochemistry of the fetal trunks showed implantation of glial fibrillary acidic protein- and neuronal nuclei-positive heterotopic brain tissue, which were also positive for beta1 integrin and VEGF in both groups E18 and P8. CONCLUSION: These results indicate that brain tissue heterotopia during fetal and postnatal period is able to complete integration with the lung tissue as well as to induce vascular proliferation which are the necessary steps for a successful implantation.

Effect of alloxan-induced diabetes mellitus and ethanol on pregnancy outcome in mice / Efeito do diabetes mellitus induzido por aloxana e etanol na gestação de camundongos

INTRODUCTION AND OBJECTIVES: To investigate the effects of ethanol, diabetes mellitus and the combination of both on mouse fetuses. METHODS: We used 24 female Swiss mice, dividing them into four groups of 6 each: control (C), ethanol (E), diabetes (D) (blood glucose > 200 mg/dL) and diabetes + ethanol (DE). Diabetes was induced by alloxan (40 mg/kg) on day 7 of pregnancy. Groups E and DE received 4 g/kg of 25 percent v/v ethanol intraperitoneally, whereas groups C and D received saline. On day 18, all fetuses were harvested. RESULTS: In group DE the following anomalies were found: exencephaly, situs inversus totalis, situs inversus partialis, eyelid skin tag and one animal from group E had pulmonary artery hypoplasia. Ethanol administration partially reverted diabetes-fetal resorption caused by diabetes, yet it induced late fetal death. Both diabetes and ethanol reduced placental diameter and increased its weight. Ethanol had more effect on fetal length in males than in females, however, such bias was not found for diabetes. Ethanol prevented diabetes-induced tail shortening in both genders. CONCLUSIONS: These results show that, although ethanol might improve energy metabolism in early gestation, it causes cell damage that leads to cardiovascular, limb and neural tube defects, late fetal death and reduced placental size.

INTRODUÇÃO E OBJETIVOS: Investigar o efeito do etanol, do diabetes mellitus (DM) e da associação de ambos sobre os fetos de camundongo. MÉTODOS: Foram utilizadas 24 fêmeas de camundongos Swiss divididas em quatro grupos de seis animais cada: controle (C); etanol (E); diabetes (D) (glicemia > 200 mg/dl), e diabetes + etanol (DE). O diabetes foi induzido pela aloxana (40 mg/kg) no dia 7 da gestação. Os animais dos grupos E e DE receberam 4 g/kg de solução a 25 por cento v/v de etanol intraperitoneal (IP), enquanto os animais dos grupos C e D receberam salina. No dia 18, todos os fetos foram coletados. RESULTADOS: Foram encontradas as seguintes anomalias no grupo DE: exencefalia, situs inversus totalis, situs inversus partialis e apêndice cutâneo palpebral. Um animal do grupo E apresentou hipoplasia da artéria pulmonar. A administração de etanol reverteu parcialmente a reabsorção fetal induzida pelo diabetes, porém aumentou a morte fetal tardia. Ambos, diabetes e etanol, reduziram o diâmetro placentário e aumentaram o seu peso. O etanol teve mais efeito no comprimento de fetos machos, contudo isso não ocorreu com o diabetes. O etanol preveniu a redução da cauda induzida pelo diabetes em ambos os sexos. CONCLUSÃO: Esses resultados indicam que, embora o etanol possa melhorar o metabolismo energético no início da gestação, ele causa lesão celular que leva a defeitos cardiovasculares, dos membros e do tubo neural, além de morte fetal tardia e redução do tamanho da placenta.

Analysis of placenta vascularization in patients with uterine altered artery Doppler flow velocity exams.

BACKGROUND: One of the frequent questions in obstetric practice is to determine placental vascular changes that may account for abnormal Doppler flow velocity alterations in maternal uterine vessels from women and fetuses without pregnancy pathology. METHODS: A retrospective morphometric study was realized using 27 placentas from patients submitted for Doppler flow velocity exam during pregnancy. The placentas were morphologically examined using hematoxylin-eosin staining. Measurements of villi were made with the use of a video camera coupled to a common light microscope and a computer with automatic image analyzing software. RESULTS: Of the 27 placentas, 13 (48%) were of patients showing unaltered Doppler and 14 (52%) showing altered Doppler. The number of stem villi vessels was significantly larger in the placentas of patients with Doppler exam alterations (P = 0.003). This group also presented greater stem villi vessel thickness, although without significant difference. The number of intermediary and terminal villi vessels was greater in the placentas of patients with altered Doppler exams (P < 0.001), and a greater terminal villi area was observed in these cases (P < 0.001). CONCLUSION: The morphological proof that uterine artery Doppler flow velocity exam alterations are associated with placental vascular alterations demonstrates the importance of this exam during prenatal care, even in the absence of maternal-fetal alterations.

Influence of amplicon size on the polymerase chain reaction of Parvovirus B19 genome in formalin-fixed specimens / Influência do tamanho do amplicon na reação em cadeia da polimerase na detecção do genoma do PB19 em amostras fixadas em formalina

The polymerase chain reaction (PCR) has provided diagnosis of archival material, but some fixation methods such as formalin damage DNA and, subsequently, affect PCR analysis, particularly paraffin-embedded tissues. PCR is known due to its high specificity and sensitivity, although some difficulties arise when formalinfixed and paraffin-embedded tissue is used. Not only does this occur due to protein cross-linking, which increases with longer fixation time, but it also happens due to the direct damage that formalin causes in the DNA itself. PCR was used to analyze placenta and fetal organs from 34 samples with suspected Parvovirus B19 infection. It was not possible to amplify Parvovirus B19 DNA using nested-PCR, probably due to the size of the amplicon generated with the first set of primers. We approached this problem by using only the second set of primers. Two out of 34 tissue samples (5,9 percent) were positive by PCR. However, PCR performed on corresponding fetal organs was negative in one of the two. We also observed a negative relation between the thickness of the tissue fragment and the positivity of the samples. In conclusion, although PCR is highly specific and sensitive in fresh or ideally fixed material, a careful standardization of PCR assays is necessary when using formalin fixed paraffin-embedded tissues by applying primers that require smaller DNA fragments for amplification.

A reação em cadeia da polimerase (PCR) tem fornecido diagnóstico de material de arquivo, mas alguns métodos de fixação, tais como formalina, provocam danos ao DNA e subsequentemente afetam sua análise, particularmente tecidos embebidos em parafina. A PCR é conhecida pela sua alta especificidade e sensibilidade, embora algumas dificuldades ocorram quando o material utilizado foi fixado em formalina e embebido em parafina. Isso não se deve somente pela formação de cross-linkings com proteínas, a qual aumenta com o maior tempo de fixação, mas também pelo dano direto que a formalina causa no DNA. PCR foi usada para analisar placenta e órgão fetais de 34 amostras com suspeita de infecção pelo Parvovírus B19 (PB19). Não foi possível amplificar o DNA do PB19 usando nested-PCR, provavelmente devido ao tamanho do amplicon gerado com o primeiro passo dos primers. Adequamos o problema utilizando somente o segundo par de primers e pudemos observar que das 34 amostras, duas eram positivas para PCR (5,9 por cento). Entretanto, a PCR dos órgãos fetais foi negativa em um de dois casos. Observamos também uma relação negativa entre a espessura do corte dos materiais com a positividade das amostras. Em conclusão, embora a PCR seja altamente específica e sensível em amostras a fresco ou idealmente fixadas, uma padronização cuidadosa para análise com a PCR é necessária quando se utiliza tecidos fixados em formalina e embebidos em parafina utilizando primers que requerem menor fragmento de DNA para a amplificação.

Sacarose como veículo de suplementação dietética de ácido fólico em camundongos prenhes / Saccharose as a vehicle for the supplementation of folic acid in pregnant mice

INTRODUÇÃO: A ingestão adequada de folato é essencial durante a embriogênese, e sua deficiência está associada à ocorrência de defeitos no fechamento do tubo neural. OBJETIVO: Determinar se a sacarose é um bom veículo para a suplementação de folato em camundongos. MATERIAL E MÉTODOS: Quarenta camundongos Swiss fêmeas foram divididos nos grupos: C: ração comercial + água ad libitum; DS: ração balanceada isenta de folato + folato adicionado à sacarose diluída na água por 14 dias; D/DS: ração balanceada isenta de folato + água com sacarose sem folato por 14 dias seguida de ração balanceada isenta de folato + folato adicionado à sacarose diluída na água por mais 14 dias; D: ração balanceada isenta de folato + água com sacarose sem folato por 14 dias. Os animais de todos os grupos experimentais receberam ração balanceada isenta de folato + folato adicionado à sacarose diluída na água durante os três dias do acasalamento e nos 15 dias restantes até o sacrifício. RESULTADOS: Os animais dos grupos D e D/DS apresentaram alopecia, palidez ocular e adinamia enquanto consumiam água com sacarose sem folato, sinais que foram revertidos quando receberam folato adicionado à sacarose diluída na água. Não houve diferença entre os grupos em relação a prenhez, implantes, fetos vivos, reabsorção, morte fetal tardia, nível sérico de folato e contagem de hemácias ao final do experimento, não tendo sido observadas anomalias congênitas em nenhum dos grupos. CONCLUSÃO: A sacarose é um meio adequado para a suplementação de folato na dieta.

Adequate folate intake is essential during embryogenesis and its deficiency is associated with neural tube defects. OBJECTIVE: To investigate if saccharose is a good vehicle for the supplementation of folate in mice. MATERIAL AND METHODS: 40 Swiss female mice were allocated into the following groups: C (commercial mouse food + ad libitum water); DS (folate-free balanced diet + saccharose with folate diluted in water for 14 days); D/DS (folate-free balanced diet + folate-free saccharose diluted in water for 14 days, followed by folate-free balanced diet + saccharose with folate diluted in water for 14 days); D (folate-free balanced diet + folate-free saccharose diluted in water for 14 days). Mice from all experimental groups received folate-free balanced diet + saccharose with folate diluted in water during their three-day mating period and thereafter 15 days until animals were put down. RESULTS: Mice from groups D and D/DS showed alopecia, pale eyes and adynamia while on folate-free saccharose water regimen. These symptoms disappeared after the introduction of saccharose with folate diluted in water. No statistical difference was noted among groups as to pregnancy, number of implants, live fetuses, reabsorption, late fetal death, serum folate levels and red blood cells count and no congenital abnormalities were identified in any groups by the end of the experiment. CONCLUSION: Saccharose is a suitable vehicle for the dietary supplementation of folate.