Missed abortion in the 11-21-week period: Fetal autopsy and placental histopathological analysis of 794 cases.

INTRODUCTION: Missed abortion (MA) is a type of miscarriage with multiple etiological factors that refers to fetal death with a failure of the retained intrauterine product of conception to be discharged spontaneously. Currently fetal death in missed abortion is categorized according to three main causes: Fetal, placental, and maternal factors. The aim of the current study was to contribute and increase knowledge in clinical practice of late first and second trimester MA (Gestational age: week 11 + 0 - week 20 + 6). MATERIAL AND METHODS: This retrospective case series study includes 794 cases of fetuses and matching placentas sent to the Section of Perinatal Pathology, Department of Pathology, Karolinska Hospital between 2003 and 2019 from five different gynecology departments in the Stockholm region, Sweden. RESULTS: The cases were divided into two groups according to gestational length; gestational week 11 + 0-14 + 6 (group A) and 15 + 0-20 + 6 (group B) respectively, and comparisons were made between groups. Fetal growth restriction and placental pathology were more common in late MA, but number of cases with malformation were higher in early MA. Cord pathology was seen in approximately 40 % of the cases and equally distributed in the gestational weeks included. DISCUSSION: Fetal growth restriction and placental pathology were more common in late second trimester MA. This might demonstrate an early placental dysfunction affecting fetal growth and may be associated to maternal comorbidity such as autoimmune disease and cardiovascular disease. It is advisable to investigate maternal factors more closely after late second trimester MA before a future pregnancy. The risk for recurrent MA is believed to be low in cases of significant cord pathology. CONCLUSION: Cord complications were over-represented in missed abortion suggesting a probable etiopathogenetic link to fetal demise in this condition.

Time Required for Gross Examination of Routine Second and Third Trimester Singleton Placentas by Pathologists' Assistants.

INTRODUCTION: In both Canada and the United States, workload measurement for anatomic pathology is mainly based on complexity and clinical significance of specimens, with gross examination being a considerable contributor. While Pathologists' Assistants (PAs) play an increasing role in gross examination, there is little known regarding the time required for PAs to complete grossing tasks. This information is essential for effective staffing and workload management in pathology laboratories. The objective of our study was to determine the time required for PAs to gross second and third trimester singleton placentas in a large tertiary hospital with a significant perinatal pathology service. MATERIALS AND METHODS: For our study, 7 certified PAs each grossed a minimum of 10 second and third trimester singleton placentas using a standard placental grossing protocol, an electronic laboratory information system, and voice recognition dictation software. Placental specimens requiring photography, sampling for ancillary studies, or immediate pathologist's consultation were excluded. We calculated average and standard deviation of grossing times for each PA, overall average grossing time, and 95% confidence interval using a mixed linear regression model. We analyzed the impact of PA job experience, degree obtained, and number of blocks prepared on overall average in a multivariate analysis. RESULTS: The mean grossing times for each PA ranged from 11.0 (standard deviation [sd] = 2.0) to 17.8 (sd = 4.5) minutes. The overall average grossing time was 14.5 minutes, with a 95% confidence interval of 11.7 to 17.3 minutes. In multivariate analysis, an increase in the number of blocks prepared was significantly associated with longer overall average grossing time. If 4 blocks were prepared consistently, the model predicted a slightly lower overall average of 13.3 minutes, with a 95% confidence interval of 10.9 to 15.7 minutes. DISCUSSION: To our knowledge, our study is the first to objectively report time required for PAs to perform gross examinations of routine second and third trimester singleton placentas. The methodology of our study is replicable and can be applied to other specimen types and laboratory settings. Previously, estimated grossing times for specimens were primarily based on retrospective surveys, which were susceptible to recall errors and subjectivity. However, our study demonstrates objective data collection is achievable. Furthermore, the data collected from this study offer valuable insights into the accuracy of previous and current pathology workload models for second and third trimester singleton placentas.

Assessing Intrauterine Retention according to Microscopic Stillbirth Features: A Cluster Analysis Approach.

Background: Previous studies identified microscopic changes associated with intrauterine retention of stillbirths based on clinical time of death. The objective of this study was to utilize unsupervised machine learning (not reliant on subjective measures) to identify features associated with time from death to delivery. Methods: Data were derived from the Stillbirth Collaborative Research Network. Features were chosen a priori for entry into hierarchical cluster analysis, including fetal and placental changes. Results: A four-cluster solution (coefficient = 0.983) correlated with relative time periods of "no retention," "mild retention," "moderate retention," and "severe retention." Loss of nuclear basophilia within fetal organs were found at varying rates among these clusters. Conclusions: Hierarchical cluster analysis is able to classify stillbirths based on histopathological changes, roughly correlating to length of intrauterine retention. Such clusters, which rely solely on objective fetal and placental findings, can help clinicians more accurately assess the interval from death to delivery.

Perinatal Stressors as a Factor in Impairments to Nervous System Development and Functions: Review of In Vivo Models.

The human body is faced with stress throughout ontogeny. At the stage of intrauterine development, the mother's body serves as a source of resources and most of the humoral factors supporting the development of the fetus. In normal conditions, maternal stress-related humoral signals (e.g., cortisol) regulate fetal development; however, distress (excessive pathological stress) in the perinatal period leads to serious and sometimes irreversible changes in the developing brain. The mother being in an unfavorable psychoemotional state, toxins and teratogens, environmental conditions, and severe infectious diseases are the most common risk factors for the development of perinatal nervous system pathology in the modern world. In this regard, the challenge of modeling situations in which prenatal or early postnatal stresses lead to serious impairments to brain development and functioning is extremely relevant. This review addresses the various models of perinatal pathology used in our studies (hypoxia, exposure to valproate, hyperserotoninemia, alcoholization), and assesses the commonality of the mechanisms of the resulting disorders and behavioral phenotypes forming in these models, as well as their relationship with models of perinatal pathology based on the impact of psychoemotional stressors.

Isolated fetal pericardial effusion follow-up: Should we worry?

INTRODUCTION AND OBJECTIVES: Fetal pericardial effusion appears in different pathologies such as hydrops fetalis, heart structural or rhythm alterations, however, it can be observed in isolation but an increase in its incidence has been observed in relation to the presence of severe pathologies. METHODS: Analysis of all cases of IFPE detected in Aragon and assessed in a cardiological consultation for prenatal diagnosis of a tertiary hospital collected over ten years, as well as the evolution of the patients to the present. RESULTS: A sample of 38 fetuses was obtained from 37 pregnant women diagnosed with DPFA with spontaneous resolution in 86.8%. Two abortions (voluntary interruptions after prenatal diagnosis of 22q13 deletion and primary infection by cytomegalovirus) and one spontaneous fetal death were recorded. Pathological alterations were observed in 10/38 newborns: two patients with metabolic disease, two patients with chromosomopathies, one patient with pulmonary hypoplasia and unilateral hydronephrosis, one patient with hypertrophic cardiomyopathy, and four patients studied for alterations in psychomotor development and/or congenital ophthalmological or hearing disorders. The overall morbidity rate was 34.2% and death rate 15.7%. The detection of other ultrasound alterations and the alteration in the first trimester screening were significantly associated with the presence of pathology. CONCLUSIONS: IFPE has been classically associated with a good prognosis, although it is sometimes related to clinical entities with high morbidity and mortality: more than a third of the patients in our sample are affected. An exhaustive pre and postnatal follow-up of these cases is recommended in order to perform an early intervention.

Seguimiento del derrame pericárdico fetal aislado: ¿debemos preocuparnos? / Isolated fetal pericardial effusion follow-up: Should we worry?

Introducción y objetivos: El derrame pericárdico fetal aparece en diferentes enfermedades como hidropesía fetal, alteraciones estructurales o del ritmo cardiaco, aunque puede observarse de manera aislada. Se ha observado un incremento de su incidencia con relación a la presencia de enfermedades graves. Métodos: Análisis de la totalidad de casos de derrame pericárdico fetal aislado (DPFA) detectados en Aragón y valorados en consulta cardiológica de diagnóstico prenatal de un hospital terciario recogidos durante 10años, así como la evolución de los pacientes hasta la actualidad. Resultados: Se obtuvo una muestra de 38 fetos en 37 gestantes diagnosticados de DPFA con resolución espontánea en el 86,8%. Se registraron 2abortos (interrupciones voluntarias tras diagnóstico prenatal de deleción 22q13 y de primoinfección por citomegalovirus) y una muerte fetal espontánea. Se objetivaron alteraciones patológicas en 10/38 recién nacidos: 2pacientes con metabolopatía, 2pacientes con cromosomopatía, un paciente con hipoplasia pulmonar e hidronefrosis unilateral, un paciente con miocardiopatía hipertrófica y 4pacientes estudiados por alteraciones del desarrollo psicomotor o alteraciones congénitas oftalmológicas o auditivas. La tasa de morbilidad fue del 34,2% y de fallecimiento del 15,7%. La detección de otras alteraciones ecográficas y la alteración en el cribado del primer trimestre se asociaron de forma significativa con la presencia de patología. Conclusiones: El DPFA se ha asociado clásicamente a buen pronóstico, aunque en ocasiones se relaciona con entidades clínicas con elevada morbimortalidad: más de un tercio de los pacientes en nuestra muestra. Se recomienda un seguimiento estrecho pre y posnatal de estos casos para poder realizar una intervención precoz. (AU)

Introduction and objectives: Fetal pericardial effusion appears in different pathologies such as hydrops fetalis, heart structural or rhythm alterations, however, it can be observed in isolation but an increase in its incidence has been observed in relation to the presence of severe pathologies. Methods: Analysis of all cases of IFPE detected in Aragon and assessed in a cardiological consultation for prenatal diagnosis of a tertiary hospital collected over 10years, as well as the evolution of the patients to the present. Results: A sample of 38 fetuses was obtained from 37 pregnant women diagnosed with DPFA with spontaneous resolution in 86.8%. Two abortions (voluntary interruptions after prenatal diagnosis of 22q13 deletion and primary infection by cytomegalovirus) and one spontaneous fetal death were recorded. Pathological alterations were observed in 10/38 newborns: 2patients with metabolic disease, 2patients with chromosomopathies, one patient with pulmonary hypoplasia and unilateral hydronephrosis, one patient with hypertrophic cardiomyopathy, and 4patients studied for alterations in psychomotor development and/or congenital ophthalmological or hearing disorders. The overall morbidity rate was 34.2% and death rate 15.7%. The detection of other ultrasound alterations and the alteration in the first trimester screening were significantly associated with the presence of pathology. Conclusions: IFPE has been classically associated with a good prognosis, although it is sometimes related to clinical entities with high morbidity and mortality: more than a third of the patients in our sample are affected. An exhaustive pre- and posnatal follow-up of these cases is recommended in order to perform an early intervention. (AU)

[Isolated fetal pericardial effusion follow-up: Should we worry?] / Seguimiento del derrame pericárdico fetal aislado: ¿debemos preocuparnos?

INTRODUCTION AND OBJECTIVES: Fetal pericardial effusion appears in different pathologies such as hydrops fetalis, heart structural or rhythm alterations, however, it can be observed in isolation but an increase in its incidence has been observed in relation to the presence of severe pathologies. METHODS: Analysis of all cases of IFPE detected in Aragon and assessed in a cardiological consultation for prenatal diagnosis of a tertiary hospital collected over 10years, as well as the evolution of the patients to the present. RESULTS: A sample of 38 fetuses was obtained from 37 pregnant women diagnosed with DPFA with spontaneous resolution in 86.8%. Two abortions (voluntary interruptions after prenatal diagnosis of 22q13 deletion and primary infection by cytomegalovirus) and one spontaneous fetal death were recorded. Pathological alterations were observed in 10/38 newborns: 2patients with metabolic disease, 2patients with chromosomopathies, one patient with pulmonary hypoplasia and unilateral hydronephrosis, one patient with hypertrophic cardiomyopathy, and 4patients studied for alterations in psychomotor development and/or congenital ophthalmological or hearing disorders. The overall morbidity rate was 34.2% and death rate 15.7%. The detection of other ultrasound alterations and the alteration in the first trimester screening were significantly associated with the presence of pathology. CONCLUSIONS: IFPE has been classically associated with a good prognosis, although it is sometimes related to clinical entities with high morbidity and mortality: more than a third of the patients in our sample are affected. An exhaustive pre- and posnatal follow-up of these cases is recommended in order to perform an early intervention.

Placental Pathology in COVID-19: Case Series in a Community Hospital Setting.

Objective To report the histopathologic findings in the placentas of pregnant women with coronavirus disease-19 (COVID-19). Methods Pregnant women with COVID-19 delivering between April 2020 to June 2020 were identified. A retrospective study of placentas from COVID positive women received in the Department of Pathology, Monmouth Medical Center affiliate of Robert Wood Johnson Barnabas Health were examined and compared to control cohort of placentas from COVID negative women. The mothers were tested for coronavirus through nasopharyngeal swab upon admission to labor and delivery. The placentas from mothers who tested negative for the virus were sent to Pathology for examination based on the obstetrician's clinical judgment. Results Fifty surgical specimens (49 placentas and one product of conception) from patients positive for COVID-19 were examined and compared with fifty placentas from women with negative COVID-19 test results, who delivered during the same period. Most of the neonates had Appearance, Pulse, Grimace, Activity and Respiration (APGAR) scores of 9 and 9 at 1 and 5 minutes, respectively. Increased incidence of the COVID-19 positivity was noted in individuals with Rh-positive blood group A and Jewish heritage. Compared to the control group, the COVID-19 positive placentas showed increased features of malperfusion (microcalcifications, fibrin thrombi, syncytial knotting, and villous agglutination). However, there was no significant dysregulation in other variables, such as inflammation or coagulation. There was no case of maternal or fetal death (greater than eight weeks) or evidence of worse fetal outcomes noted due to a mother's positive COVID-19 status.  Conclusions The COVID-19 positive placentas showed an increased prevalence of microcalcifications and fibrin thrombi, which may reflect an underlying hypercoagulable state induced by COVID-19 infection or could be due to excessive syncytiotrophoblast injury.

Parameters for estimating the time of death at perinatal autopsy of stillborn fetuses: a systematic review.

BACKGROUND: Stillbirth is defined by the WHO as birth of a fetus with no vital signs, at or over 28 weeks of pregnancy age. The estimation of time of death in stillbirth appears crucial in forensic pathology. However, there are no validated methods for this purpose. OBJECTIVE: To perform a systematic review of the available literature regarding the estimation of the time of death in stillborn fetuses, in terms of hours or days. METHODS: Electronic databases were searched from their inception to August 2018 for relevant articles. Macroscopic, histologic, and radiologic parameters were evaluated. RESULTS: Nine studies with 664 stillborns were included. The evaluation of extent and location of fetal maceration signs showed good accuracy in estimating the time of death; by contrast, a dichotomous assessment of maceration (present vs absent) was found to be unreliable in a subsequent study. Histologic assessment of the loss of nuclear basophilia in fetal and placental tissues showed excellent accuracy; an "autolysis equation" was proposed to achieve an even higher accuracy in fetuses who had been dead for < 24 h. Magnetic resonance imaging of the lung parenchyma, pleural fluids, and brain parenchyma could estimate the death-to-autopsy time, but the results appeared weak and conflicting. CONCLUSION: Pathologic examination, based on the assessment of maceration, and even more of the loss of nuclear basophilia, may be a reliable method to estimate the time of death in stillborn fetuses. Further studies should be encouraged to validate these results. Imaging techniques have not yet found application in this field.

Incidence and serotype characterisation of Streptococcus agalactiae in a Portuguese hospital.

AIMS: Streptococcus agalactiae, commonly known as group B Streptococcus (GBS), has been recognised as a worldwide causative pathogenic agent of neonatal sepsis, meningitis and pneumonia. To better understand the behaviour of S. agalactiae in pregnant women from a hospital from the North of Portugal, retrospective analyses were performed to describe epidemiological, clinical and microbiological characteristics of the isolates obtained. METHODS: Based on laboratorial records and the hospital's patient files, a 6-year retrospective study was performed to analyse S. agalactiae isolates from screened pregnant women between 35 and 37 weeks of gestation and hospitalised neonates from pregnant women between 24 and 41 weeks of gestation admitted in Hospital Pedro Hispano. Serotype characterisation was also performed in 67 GBS strains. RESULTS: In 6692 pregnant women between 35 and 37 weeks of gestation screened between 2011 and 2016, a total of 1377 S. agalactiae isolates (21%) were found. A high percentage (40%) of unknown colonisation status among hospitalised neonates from pregnant women between 24 and 41 weeks of gestations was also found. The incidence of neonatal sepsis was 8.7 (95% CI 7.0 to 10.8) cases per 1000 live births. Regarding serotype characterisation, serotype III (22.4%) was the most frequent, followed by serotype Ia (19.4%) and serotypes Ib and V (both with 17.9%). CONCLUSION: High epidemiological values of GBS colonisation and incidence were found in this study. In Portugal studies on the epidemiology and behaviour of S. agalactiae remain limited, reinforcing the importance and need for S. agalactiae screening across the country.

[The role of a nutritional factor in the development of obstetric and perinatal pathology in obese women].

The review presents the literature data on the effect of the nutrition of women on the course of pregnancy and the condition of a fetus. The mother's body during pregnancy is the only source of nutrients for a developing fetus. The woman's nutrition before and during pregnancy affects not only her own health and the development of a fetus, but can also results in the risk of non-infectious diseases and obesity among their children throughout their lives. The data on the effect of poor nutrition of a woman in a pregravidal period on pregnancy and the health of a future child have been presented. This is especially important for pregnant women with obesity because metabolic disorders they have are aggravated by poor nutrition. It has been shown that the lack or excess of nutrients in the presence of maternal obesity contributes to the development of gestational complications and programs the development of metabolic disorders in children.

Stillbirth evaluation: a stepwise assessment of placental pathology and autopsy.

BACKGROUND: The American Congress of Obstetricians and Gynecologists places special emphasis on autopsy as one of the most important tests for evaluation of stillbirth. Despite a recommendation of an autopsy, many families will decline the autopsy based on religious/cultural beliefs, fear of additional suffering for the child, or belief that no additional information will be obtained or of value. Further, many obstetric providers express a myriad of barriers limiting their recommendation for a perinatal autopsy despite their understanding of its value. Consequently, perinatal autopsy rates have been declining. Without the information provided by an autopsy, many women are left with unanswered questions regarding cause of death for their fetus and without clear management strategies to reduce the risk of stillbirth in future pregnancies. To avoid this scenario, it is imperative that clinicians are knowledgeable about the benefit of autopsy so they can provide clear information on its diagnostic utility and decrease potential barriers; in so doing the obstetrician can ensure that each family has the necessary information to make an informed decision. OBJECTIVE: We sought to quantify the contribution of placental pathologic examination and autopsy in identifying a cause of stillbirth and to identify how often clinical management is modified due to each result. STUDY DESIGN: This is a cohort study of all cases of stillbirth from 2009 through 2013 at a single tertiary care center. Records were reviewed in a stepwise manner: first the clinical history and laboratory results, then the placental pathologic evaluation, and finally the autopsy. At each step, a cause of death and the certainty of that etiology were coded. Clinical changes that would be recommended by information available at each step were also recorded. RESULTS: Among the 144 cases of stillbirth examined, 104 (72%) underwent autopsy and these cases constitute the cohort of study. The clinical and laboratory information alone identified a cause of death in 35 (24%). After placental pathologic examination, 88 (61%) cases had a probable cause of death identified. The addition of autopsy resulted in 78 (74%) cases having an identifiable probable cause of death. Placental examination alone changed clinical management in 52 (36%) cases. Autopsy led to additional clinical management changes in 6 (6%) cases. CONCLUSION: This stepwise assessment of the benefit of both placental pathological examination and autopsy in changing probable cause of death beyond traditional clinical history and laboratory results emphasizes the need to implement more comprehensive evaluation of all stillbirths. With the aim of providing a cause of stillbirth to the parents, and to prevent future stillbirths, it behooves health care professionals to understand the value of this more comprehensive approach and convey that information to the bereaved parents.

Bilateral congenital adrenal agenesis: a rare disease entity and not a result of poor autopsy technique.

Congenital adrenal agenesis is an extremely rare condition wherein the adrenal glands fail to develop. The absence of adrenal tissue results in the complete absence of hormones produced in the adrenal cortex (cortisol, aldosterone) and medulla (catecholamines), and is not compatible with postnatal life without artificial hormone replacement therapy. To date, 9 cases of adrenal agenesis have been reported, many of which are associated with additional congenital anomalies. Most cases were not detected on antenatal imaging and were detected incidentally at postmortem examination. We present a case of adrenal agenesis, detected incidentally at postmortem examination after termination of pregnancy for suspected fetal hydrops, and review the heterogeneous phenotype of this condition with associated abnormalities and molecular genetics. This case reinforces the role of the perinatal autopsy to investigate cause of perinatal mortality, allowing correlation of pathology with antenatal imaging findings and clinical details.