-The group agreed on sets of uniform sampling criteria, placental gross descriptors, pathologic terminologies, and diagnostic criteria. The terminology and microscopic descriptions for maternal vascular malperfusion, fetal vascular malperfusion, delayed villous maturation, patterns of ascending intrauterine infection, and villitis of unknown etiology were agreed upon. Topics requiring further discussion were highlighted. Ongoing developments in our understanding of the pathology of the placenta, scientific bases of the maternofetoplacental triad, and evolution of the clinical significance of defined lesions may necessitate further refinements of these consensus guidelines. The proposed structure will assist in international comparability of clinicopathologic and scientific studies and assist in refining the significance of lesions associated with adverse pregnancy and later health outcomes.

Consensus-based definitions for early and late FGR, as well as cut-off values for parameters involved, were agreed upon by a panel of experts. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Angiotensin‐converting enzyme 2 (ACE2) has been established as the functional host receptor for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the virus responsible for the current devastating worldwide pandemic of coronavirus disease 2019 (COVID‐19). ACE2 is abundantly expressed in a variety of cells residing in many different human organs. In human physiology, ACE2 is a pivotal counter‐regulatory enzyme to ACE by the breakdown of angiotensin II, the central player in the renin–angiotensin–aldosterone system (RAAS) and the main substrate of ACE2. Many factors have been associated with both altered ACE2 expression and COVID‐19 severity and progression, including age, sex, ethnicity, medication, and several co‐morbidities, such as cardiovascular disease and metabolic syndrome. Although ACE2 is widely distributed in various human tissues and many of its determinants have been well recognised, ACE2‐expressing organs do not equally participate in COVID‐19 pathophysiology, implying that other mechanisms are involved in orchestrating cellular infection resulting in tissue damage. Reports of pathologic findings in tissue specimens of COVID‐19 patients are rapidly emerging and confirm the established role of ACE2 expression and activity in disease pathogenesis. Identifying pathologic changes caused by SARS‐CoV‐2 infection is crucially important as it has major implications for understanding COVID‐19 pathophysiology and the development of evidence‐based treatment strategies. Currently, many interventional strategies are being explored in ongoing clinical trials, encompassing many drug classes and strategies, including antiviral drugs, biological response modifiers, and RAAS inhibitors. Ultimately, prevention is key to combat COVID‐19 and appropriate measures are being taken accordingly, including development of effective vaccines. In this review, we describe the role of ACE2 in COVID‐19 pathophysiology, including factors influencing ACE2 expression and activity in relation to COVID‐19 severity. In addition, we discuss the relevant pathological changes resulting from SARS‐CoV‐2 infection. Finally, we highlight a selection of potential treatment modalities for COVID‐19. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

The most important function of the placenta is the exchange of nutrients and oxygen between a mother and her fetus. To establish a healthy functioning placenta, placentation needs to occur with adequate remodelling of spiral arteries by extravillous trophoblasts. When this process is impaired, the resulting suboptimal and inadequate placenta function results in the manifestation of pregnancy complications. Impaired placenta function can cause preeclampsia and leads to fetal growth restriction due to hypoxia. Presence of hypoxia leads to oxidative stress due to an imbalance between reactive oxygen species and antioxidants, thereby causing damage to proteins, lipids and DNA. In the placenta, signs of morphological adaptation in response to hypoxia can be found. Different placental lesions like maternal or fetal vascular malperfusion or chronic villitis lead to a decreased exchange of oxygen between the mother and the fetus. Clinically, several biomarkers indicative for oxidative stress, e.g. malondialdehyde and reduced levels of free thiols are found. This review aims to give an overview of the causes and (potential) role of placental oxidative stress in the development of placental parenchymal pathology and its clinical consequences. Also, therapeutic options aiming at prevention or treatment of hypoxia of the placenta and fetus are described.

No abstract

Consensus-based diagnostic features of sFGR in both MC and DC twin pregnancies, as well as cut-off values for the parameters involved, were agreed upon by a panel of experts. Future studies are needed to validate these diagnostic features before they can be used in clinical trials of interventions.

Background Stillbirth is a global health problem. The World Health Organization (WHO) application of the International Classification of Diseases for perinatal mortality (ICD‐PM) aims to improve data on stillbirth to enable prevention. Objectives To identify globally reported causes of stillbirth, classification systems, and alignment with the ICD‐PM. Search strategy We searched CINAHL, EMBASE, Medline, Global Health, and Pubmed from 2009 to 2016. Selection criteria Reports of stillbirth causes in unselective cohorts. Data collection and analysis Pooled estimates of causes were derived for country representative reports. Systems and causes were assessed for alignment with the ICD‐PM. Data are presented by income setting (low, middle, and high income countries; LIC, MIC, HIC). Main results Eighty‐five reports from 50 countries (489 089 stillbirths) were included. The most frequent categories were Unexplained, Antepartum haemorrhage, and Other (all settings); Infection and Hypoxic peripartum (LIC), and Placental (MIC, HIC). Overall report quality was low. Only one classification system fully aligned with ICD‐PM. All stillbirth causes mapped to ICD‐PM. In a subset from HIC, mapping obscured major causes. Conclusions There is a paucity of quality information on causes of stillbirth globally. Improving investigation of stillbirths and standardisation of audit and classification is urgently needed and should be achievable in all well‐resourced settings. Implementation of the WHO Perinatal Mortality Audit and Review guide is needed, particularly across high burden settings. Funding HR, SH, SHL, and AW were supported by an NHMRC‐CRE grant (APP1116640). VF was funded by an NHMRC‐CDF (APP1123611). Tweetable abstract Urgent need to improve data on causes of stillbirths across all settings to meet global targets. Plain Language Summary Background and methodsNearly three million babies are stillborn every year. These deaths have deep and long‐lasting effects on parents, healthcare providers, and the society. One of the major challenges to preventing stillbirths is the lack of information about why they happen. In this study, we collected reports on the causes of stillbirth from high‐, middle‐, and low‐income countries to: (1) Understand the causes of stillbirth, and (2) Understand how to improve reporting of stillbirths. FindingsWe found 85 reports from 50 different countries. The information available from the reports was inconsistent and often of poor quality, so it was hard to get a clear picture about what are the causes of stillbirth across the world. Many different definitions of stillbirth were used. There was also wide variation in what investigations of the mother and baby were undertaken to identify the cause of stillbirth. Stillbirths in all income settings (low‐, middle‐, and high‐income countries) were most frequently reported as Unexplained, Other, and Haemorrhage (bleeding). Unexplained and Other are not helpful in understanding why a baby was stillborn. In low‐income countries, stillbirths were often attribute...

Objective To introduce the pathophysiological Tulip classification system for underlying cause and mechanism of perinatal mortality based on clinical and pathological findings for the purpose of counselling and prevention.Design Descriptive.Setting Tertiary referral teaching hospital.Population Perinatally related deaths.Methods A classification consisting of groups of cause and mechanism of death was drawn up by a panel through the causal analysis of the events related to death. Individual classification of cause and mechanism was performed by assessors. Panel discussions were held for cases without consensus.Main outcome measures Inter-rater agreement for cause and mechanism of death.Results The classification consists of six main causes with subclassifications: (1) congenital anomaly (chromosomal, syndrome and single-or multiple-organ system), (2) placenta (placental bed, placental pathology, umbilical cord complication and not otherwise specified [NOS]), (3) prematurity (preterm prelabour rupture of membranes, preterm labour, cervical dysfunction, iatrogenous and NOS), (4) infection (transplacental, ascending, neonatal and NOS), (5) other (fetal hydrops of unknown origin, maternal disease, trauma and out of the ordinary) and (6) unknown. Overall kappa coefficient for agreement for cause was 0.81 (95% CI 0.80-0.83). Six mechanisms were drawn up: cardio/circulatory insufficiency, multi-organ failure, respiratory insufficiency, cerebral insufficiency, placental insufficiency and unknown. Overall kappa for mechanism was 0.72 (95% CI 0.70-0.74).Conclusions Classifying perinatal mortality to compare performance over time and between centres is useful and necessary. Interpretation of classifications demands consistency. The Tulip classification allows unambiguous classification of underlying cause and mechanism of perinatal mortality, gives a good inter-rater agreement, with a low percentage of unknown causes, and is easily applicable in a team of clinicians when guidelines are followed.