Immunomodulatory Therapy Reduces the Severity of Placental Lesions in Chronic Histiocytic Intervillositis

Chronic histiocytic intervillositis (CHI) is a rare, but highly recurrent inflammatory placental lesion wherein maternal macrophages infiltrate the intervillous space. Pregnancies with CHI are at high risk of fetal growth restriction, miscarriage or stillbirth. Presently, the diagnosis can only be made after histopathological examination of the placenta. Given its proposed immunological etiology, current treatments include aspirin, heparin, and immunomodulatory agents. However, the rationale for these medications is largely based upon small case series and reports as there is a lack of larger studies investigating treatment efficacy. Therefore, this study sought to determine whether inclusion of immunomodulatory medications was effective at reducing the severity of lesions and improving pregnancy outcomes in subsequent pregnancies. Thirty-three women with a history of CHI in at least one pregnancy (index case) were identified retrospectively through medical records. Twenty-eight participants presented with a first subsequent pregnancy and a further 11 with a second subsequent pregnancy at a specialist clinic for pregnancy after loss. Data on maternal demographics, medical history, medication, pregnancy outcome, and placental pathology was collected and compared between pregnancies. Twenty-seven (69%) subsequent pregnancies were treated with at least one or both of prednisolone and hydroxychloroquine. Inclusion of at least one immunomodulatory agent in treatment regimen resulted in an almost 25% increase in overall livebirth rate (61.5 vs. 86.2%). In women treated with immunomodulatory medication a greater proportion of placentas had reduced severity of lesions compared to those treated without (86.7 vs. 33.3%, respectively). A reduction in CHI severity was associated with a 62.3% improvement in livebirth rate compared to those where severity remained unchanged in relation to the index case. These data provide preliminary evidence that the use of immunomodulatory medication in the management of CHI improves histopathological lesions and the chance of livebirth in subsequent pregnancies. Due to CHI's rarity and ethical and feasibility issues, randomized controlled trials in affected women are challenging to conduct. As a result, collaboration between centers is required in future to increase study sample sizes and elucidate the mechanisms of hydroxychloroquine and prednisolone in reducing pathology.

Changes in Maternal Platelet Physiology during Gestation and Their Interaction with Trophoblasts

Upon activation, maternal platelets provide a source of proinflammatory mediators in the intervillous space of the placenta. Therefore, platelet-derived factors may interfere with different trophoblast subtypes of the developing human placenta and might cause altered hormone secretion and placental dysfunction later on in pregnancy. Increased platelet activation, and the subsequent occurrence of placental fibrinoid deposition, are linked to placenta pathologies such as preeclampsia. The composition and release of platelet-derived factors change over gestation and provide a potential source of predicting biomarkers for the developing fetus and the mother. This review indicates possible mechanisms of platelet-trophoblast interactions and discusses the effect of increased platelet activation on placenta development.

Unique Aspects of Human Placentation

Human placentation differs from that of other mammals. A suite of characteristics is shared with haplorrhine primates, including early development of the embryonic membranes and placental hormones such as chorionic gonadotrophin and placental lactogen. A comparable architecture of the intervillous space is found only in Old World monkeys and apes. The routes of trophoblast invasion and the precise role of extravillous trophoblast in uterine artery transformation is similar in chimpanzee and gorilla. Extended parental care is shared with the great apes, and though human babies are rather helpless at birth, they are well developed (precocial) in other respects. Primates and rodents last shared a common ancestor in the Cretaceous period, and their placentation has evolved independently for some 80 million years. This is reflected in many aspects of their placentation. Some apparent resemblances such as interstitial implantation and placental lactogens are the result of convergent evolution. For rodent models such as the mouse, the differences are compounded by short gestations leading to the delivery of poorly developed (altricial) young.

Placental Pathology of COVID-19 with and without Fetal and Neonatal Infection: Trophoblast Necrosis and Chronic Histiocytic Intervillositis as Risk Factors for Transplacental Transmission of SARS-CoV-2

The mechanism(s) by which neonates testing positive for coronavirus disease 2019 (COVID-19) acquire their infection has been largely unknown. Transmission of the etiological agent, SARS-CoV-2, from mother to infant has been suspected but has been difficult to confirm. This communication summarizes the spectrum of pathology findings from pregnant women with COVID-19 based upon the infection status of their infants and addresses the potential interpretation of these results in terms of the effects of SARS-CoV-2 on the placenta and the pathophysiology of maternal-fetal infection. Placentas from pregnant women with COVID-19 and uninfected neonates show significant variability in the spectrum of pathology findings. In contrast, placentas from infected maternal-neonatal dyads are characterized by the finding of mononuclear cell inflammation of the intervillous space, termed chronic histiocytic intervillositis, together with syncytiotrophoblast necrosis. These placentas show prominent positivity of syncytiotrophoblast by SARS-CoV-2, fulfilling the published criteria for transplacental viral transmission as confirmed in fetal cells through identification of viral antigens by immunohistochemistry or viral nucleic acid using RNA in situ hybridization. The co-occurrence of chronic histiocytic intervillositis and trophoblast necrosis appears to be a risk factor for placental infection with SARS-CoV-2 as well as for maternal-fetal viral transmission, and suggests a potential mechanism by which the coronavirus can breach the maternal-fetal interface.

Diagnosis of amyopathic dermatomyositis after two intrauterine fetal deaths

Chronic histiocytic intervillositis (CHIV) is an uncommon condition, characterized by an infiltrate of mononuclear cells of maternal origin in the intervillous space that has been related to placenta insufficiency and poor perinatal outcomes. The aetiology is unclear, although maternal immunological aggression toward fetal tissues has been proposed. Dermatomyositis (DM) is a multisystem autoimmune inflammatory myopathy. Different autoantibodies have been associated with particular clinical phenotypes; presence of anti-melanoma differentiation-associated gen 5 (MDA5) antibody has been associated with rapidly progressive interstitial lung disease and severe skin lesions, none of which the woman had. Described here is a case of a woman diagnosed with amyopathic DM with positive anti-MDA5 antibodies after two intrauterine fetal deaths. Pathological examination of the placenta in both pregnancies showed CHIV. The presence of a potential relationship between both processes is discussed.

Histopathological Changes of Placenta Associated with Maternal Anaemia in Northeast Ethiopia: A Comparative Study

BACKGROUND: Anaemia during pregnancy affects about half of all pregnant mothers in developing countries; it is the major causes of indirect maternal mortality. Anaemia can directly cause poor growth of fetus in utero due to inadequate oxygen flow to the placental tissue or it is indirect indicator of maternal nutritional deficiency. Mal-development of placenta is the leading cause of maternal and perinatal mortality and an important factor of fetal growth retardation. The aim of this study was to compare histopathological changes of placenta associated with maternal anaemia.METHODS: A comparative cross-sectional study was conducted from May-June, 2018 in Dessie Referral Hospital. A total of 66 placentas (33 anaemic and 33 non-anaemic) were collected after delivery. EPI data version 4.2.0 was used to enter the data while the data were analyzed by using SPSS version 22. Chi-square and oneway ANOVA were used to analyze the data.RESULTS; In pregnancies with maternal anaemia, 75.7% of anaemic placentas terminal villi vessels were increased in number, compared to 15.1% in non-anaemic (p=0.001). Placental calcification was 72.7% in anaemic groups compared to 54% in non-anaemic groups. However, it was insignificant (p=0.12). Intervillous space was wider in anaemic compared to non-anaemic groups (p<0.001).CONCLUSIONS; Chorionic villi capillaries were increased in number, and it was dilated in anaemic placenta, compared to non-anaemic. Intervillous space was significantly wider in anaemic placenta.

DOPPLER STUDY IN PREDICTING IUGR AND PRENATAL OUTCOME IN PIH

Normal fetal growth and development depends on adequate perfusion of the intervillous space through the maternal spiral arterioles. Reduced perfusion is associated with asymmetrical retardation of the fetal growth and fetal hypoxia that is the major cause of perinatal mortality. Pregnancy induced hypertension (PIH) remains the major cause of maternal and perinatal morbidity and mortality. With the help of colour Doppler, the identification of vessels that are evaluated for Doppler study can become simple1. Hence role of Doppler examination has become indispensable in screening, diagnosis and management of PIH and IUGR cases2. With the aid of colour Doppler, IUGR can be diagnosed before it is clinically evident. In the present study, we examined flow velocity waveforms in uteroplacental (uterine artery and umbilical artery) and fetoplacental (middle cerebral artery) circulations in both normal pregnancy3 and in situations of suspected placental insufficiently such as PIH and IUGR pregnancies4. Subsequently result in birth of growth retarded infant, to derive pathophysiological information about placental flow resistance and assess the diagnostic potential of this measurement.