Clinical-pathological features in placentas of pregnancies with SARS-CoV-2 infection and adverse outcome: case series with and without congenital transmission.

OBJECTIVE: To correlate clinical outcomes to pathology in SARS-CoV-2 infected placentas in stillborn and live-born infants presenting with fetal distress. DESIGN: Retrospective, observational. SETTING: Nationwide. POPULATION: Five stillborn and nine live-born infants from 13 pregnant women infected with SARS-CoV-2 seeking care at seven different maternity units in Sweden. METHODS: Clinical outcomes and placental pathology were studied in 14 cases (one twin pregnancy) of maternal SARS-CoV-2 infection with impaired fetal outcome. Outcomes were correlated to placental pathology in order to investigate the impact of virus-related pathology on the villous capillary endothelium, trophoblast and other cells. MAIN OUTCOME MEASURES: Maternal and fetal clinical outcomes and placental pathology in stillborn and live-born infants. RESULTS: Reduced fetal movements were reported (77%) and time from onset of maternal COVID-19 symptoms to signs of fetal distress among live-born infants was 6 (3-12) days and to diagnosis of stillbirth 11 (2-25) days. Two of the live-born infants died during the postnatal period. Signs of fetal distress led to emergency caesarean section in all live-born infants with umbilical cord blood gases and low Apgar scores confirming intrauterine hypoxia. Five stillborn and one live-born neonate had confirmed congenital transmission. Massive perivillous fibrinoid deposition, intervillositis and trophoblast necrosis were associated with SARS-CoV-2 placental infection and congenital transmission. CONCLUSIONS: SARS-CoV-2 can cause rapid placental dysfunction with subsequent acute fetal hypoxia leading to intrauterine fetal compromise. Associated placental pathology included massive perivillous fibrinoid deposition, intervillositis and trophoblast degeneration.

Excessive Subchorionic Fibrinoid Deposition as a Component of Massive Perivillous Fibrin Deposition: A Case With Maternal Immune Thrombocytopenia.

Maternal floor infarction (MFI) and massive perivillous fibrin deposition (MPFD) are overlapping placental disorders of unknown etiology, associated with adverse obstetric outcome, and a significant risk of recurrence. We describe a 31-year-old mother with asymptomatic thrombocytopenia throughout pregnancy and a positive lupus anticoagulant. She delivered a normal female neonate at term, whose weight was small for gestational age, with a placenta weighing less than the 10th percentile. Placental examination showed MPFD together with excessive subchorionic fibrinoid deposition. The placenta showed diffuse C4d deposition and an immune-mediated reaction was postulated for the pathogenesis of the placental changes. We suggest that excessive subchorionic fibrinoid deposition may be part of the morphologic spectrum of MFI/MPFD.

Combined Placental Maternal Floor Infarction and Cytomegalovirus Placentitis: A Case Report.

BackgroundMaternal floor infarction (MFI) and massive perivillous fibrin deposition (MPFD) are uncommon, related placental conditions secondary to trophoblastic cell damage. The etiology is unknown but MPFD/MFI is associated with adverse obstetric outcome and a significant risk of recurrence. Case report: We report a case of MPFD/MFI associated with cytomegalovirus (CMV) placentitis. A 27-year-old mother delivered a stillborn male fetus with a postmortem diagnosis of congenital CMV. The placenta showed a lymphohistiocytic villitis with isolated CMV inclusions, in combination with MFI. The villitis had features intermediate between CMV placentitis and villitis of unknown etiology (VUE). Conclusion: VUE is considered to be a maternal anti-fetal immune reaction resembling allograft rejection. We postulate that the viral infection in our case may have triggered this immune response, given that CMV antigens are known to cross react with some human antigens, in particular HLA. The subsequent trophoblastic cell damage could then lead to MFI/MFPD.

Massive Perivillous Fibrin Deposition Associated With Placental Syphilis: A Case Report.

Massive perivillous fibrin deposition (MPFD) and the related entity of maternal floor infarction (MFI) are uncommon placental disorders of unknown etiology, associated with adverse obstetric outcome and a significant risk of recurrence. We describe a 19-year-old mother with untreated syphilis who delivered a male neonate with low birth weight, skin desquamation, and pneumonia. Placenta examination showed the expected changes for syphilis but unexpectedly, also showed MPFD. To our knowledge, this is the first report of MPFD associated with placental syphilis, thus expanding the list of etiologies that may be related to MPFD/MFI. It is postulated that the syphilis infection in our case led to a hypercoaguable state, eventually resulting in MPFD. In the right clinical setting, syphilis might be considered in the differential diagnosis when MPFD/MFI is observed on placental examination. The recurrence risk of MFPD/MFI associated with infections is believed to be lower than idiopathic cases and, by extrapolation, this lower risk should apply to syphilis as well.

CD42b Immunostaining as a Marker for Placental Fibrinoid in Normal Pregnancy and Complications.

BACKGROUND: There are two types of fibrinoids within the placenta, fibrin-type and matrix-type. The clinical importance of these fibrinoids is poorly understood. Design: Fibrinoid deposits occurring in normal and complicated pregnancies were studies with H&E stain and CD42b as a marker for platelet aggregates. Results: Fibrin-like fibrinoid was associated with platelet aggregates positive by CD42b immunostaining in the subchorionic and basal plate areas, facing the maternal circulation and intervillous spaces. Matrix-type fibrinoid did not stain with CD42b, and it was found in the intervillous spaces, trophoblastic cysts, intravillous tissue areas, and vascular walls in decidual vasculopathy. Conclusion: Fibrin-type fibrinoid within the intervillous spaces are mostly from maternal circulation and these fibrinoids are likely the result of the laminar flow change at specific anatomic locations, leading to activation of coagulatory cascades. The pathogenesis of matrix-like fibrinoid is unclear. CD42b immunostaining is helpful in differentiation of the types of fibrinoid in difficult cases.

Chronic inflammation of the placenta: definition, classification, pathogenesis, and clinical significance.

Chronic inflammatory lesions of the placenta are characterized by the infiltration of the organ by lymphocytes, plasma cells, and/or macrophages and may result from infections (viral, bacterial, parasitic) or be of immune origin (maternal anti-fetal rejection). The 3 major lesions are villitis (when the inflammatory process affects the villous tree), chronic chorioamnionitis (which affects the chorioamniotic membranes), and chronic deciduitis (which involves the decidua basalis). Maternal cellular infiltration is a common feature of the lesions. Villitis of unknown etiology (VUE) is a destructive villous inflammatory lesion that is characterized by the infiltration of maternal T cells (CD8+ cytotoxic T cells) into chorionic villi. Migration of maternal T cells into the villi is driven by the production of T-cell chemokines in the affected villi. Activation of macrophages in the villi has been implicated in the destruction of the villous architecture. VUE has been reported in association with preterm and term fetal growth restriction, preeclampsia, fetal death, and preterm labor. Infants whose placentas have VUE are at risk for death and abnormal neurodevelopmental outcome at the age of 2 years. Chronic chorioamnionitis is the most common lesion in late spontaneous preterm birth and is characterized by the infiltration of maternal CD8+ T cells into the chorioamniotic membranes. These cytotoxic T cells can induce trophoblast apoptosis and damage the fetal membranes. The lesion frequently is accompanied by VUE. Chronic deciduitis consists of the presence of lymphocytes or plasma cells in the basal plate of the placenta. This lesion is more common in pregnancies that result from egg donation and has been reported in a subset of patients with premature labor. Chronic placental inflammatory lesions can be due to maternal anti-fetal rejection, a process associated with the development of a novel form of fetal systemic inflammatory response. The syndrome is characterized by an elevation of the fetal plasma T-cell chemokine. The evidence that maternal anti-fetal rejection underlies the pathogenesis of many chronic inflammatory lesions of the placenta is reviewed. This article includes figures and histologic examples of all chronic inflammatory lesions of the placenta.

Maternal floor infarction: management of an underrecognized pathology.

Maternal floor infarction is a relatively rare condition characterized clinically by severe early onset fetal growth restriction with features of uteroplacental insufficiency. It has a very high recurrence rate and carries a significant risk or fetal demise. Pathological characteristics include massive and diffuse fibrin deposition along the decidua basalis and the perivillous space of the basal plate. We present a case of recurrent maternal floor infarction and propose diagnostic clues as well as potential therapeutic options.

Incorporating placental pathology into clinical care and research.

Despite recent standardization of placental evaluation and establishment of criteria for diagnosis of major patterns of placental injury, placental pathological examination remains undervalued and under-utilized. The placenta can harbor a significant amount of information relevant to both the pregnant person and offspring. Placental pathology can also provide a significant context for pathophysiological study of adverse pregnancy outcomes, helping to optimally subcategorize the 'great obstetric syndromes' of pre-eclampsia (PE), spontaneous preterm birth (sPTB), and fetal growth restriction (FGR), and to identify causes of stillbirth. We hereby propose that placental evaluation should be incorporated into routine delivery of obstetric and neonatal care, and further suggest that its integration into clinical, translational, and basic research could significantly advance our understanding of pregnancy complications and adverse neonatal outcomes.

Follow-up and management of recurrent pregnancy losses due to massive perivillous fibrinoid deposition.

Massive perivillous fibrinoid deposition is a rare placental pathology associated with significant adverse pregnancy outcome and can recur. We provide a detailed case review of a woman through 10 of her pregnancies, including 8 consecutive pregnancy losses and 2 live births. We also conducted a retrospective chart review of all massive perivillous fibrinoid deposition placenta specimens at our institution over an eight-year period. A total of 42 cases of massive perivillous fibrinoid deposition were identified from 2007 to 2015, yielding an incidence of 0.16%. Recurrence was seen in subsequent pregnancy in eight out of nine (88.9%) cases with more than one specimen. The clinical characteristics, perinatal outcomes and α-feto protein level of the 42 cases are presented. Also, presented is a review of the literature discussing placental pathology, pathogenetic mechanisms and management of this condition.

Maternal Floor Infarction/Massive Perivillous Fibrin Deposition Associated with Hypercoiling of a Single-Artery Umbilical Cord: A Case Report.

Maternal floor infarction is a rare and idiopathic placental disorder associated with adverse obstetric outcomes and a high rate of recurrence in subsequent pregnancies. The pathogenesis of maternal floor infarction is unclear but has been linked to diverse underlying maternal conditions, including gestational hypertension/preeclampsia, immune-mediated diseases, and thrombophilia. Few reports link maternal floor infarction to fetoplacental conditions. We report a 34-week, macerated, growth-restricted male fetus for which the placenta showed maternal floor infarction. The umbilical cord showed excessive coiling and a single umbilical artery. These cord changes are postulated to have resulted in increased placental villous resistance and decreased fetal blood flow, creating a hydrostatic pressure gradient between the villous stroma and the intervillous space. The pressure changes could then lead to trophoblast damage and fibrinoid deposition, contributing to the maternal floor infarction in this case.

Pravastatin to prevent recurrent fetal death in massive perivillous fibrin deposition of the placenta (MPFD).

Massive perivillous fibrin deposition of the placenta (MPFD) or maternal floor infarction (MFI) is a serious condition associated with recurrent complications including fetal death and severe fetal growth restriction. There is no method to evaluate the risk of adverse outcome in subsequent pregnancies, or effective prevention. Recent observations suggest that MFI is characterized by an imbalance in angiogenic/anti-angiogenic factors in early pregnancy; therefore, determination of these biomarkers may identify the patient at risk for recurrence. We report the case of a pregnant woman with a history of four consecutive pregnancy losses, the last of which was affected by MFI. Abnormalities of the anti-angiogenic factor, sVEGFR-1, and soluble endoglin (sEng) were detected early in the index pregnancy, and treatment with pravastatin corrected the abnormalities. Treatment resulted in a live birth infant at 34 weeks of gestation who had normal biometric parameters and developmental milestones at the age of 2. This is the first reported successful use of pravastatin to reverse an angiogenic/anti-angiogenic imbalance and prevent fetal death.