Histopathological lesions and exposure to Plasmodium falciparum infections in the placenta increases the risk of preeclampsia among pregnant women

Obiri, Dorotheah; Erskine, Isaac Joe; Oduro, Daniel; Kusi, Kwadwo Asamoah; Amponsah, Jones A.; Gyan, Ben; Adu‐Bonsaffoh, Kwame; Ofori, Michael F.

doi:10.1038/s41598-020-64736-4

Cited by 22 publications

(17 citation statements)

References 46 publications

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“…The extent to which PM and PM/HIV coinfection may contribute to preeclampsia via MPO production or modification of other neutrophil functions remains to be determined. This may be an exciting avenue to pursue given increasing evidence that malaria predisposes women to this hypertensive disorder ( 91 , 92 ).…”

Section: Discussionmentioning

confidence: 99%

Myeloperoxidase and Other Markers of Neutrophil Activation Associate With Malaria and Malaria/HIV Coinfection in the Human Placenta

et al. 2021

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IntroductionPlacental malaria (PM) is characterized by accumulation of inflammatory leukocytes in the placenta, leading to poor pregnancy outcomes. Understanding of the underlying mechanisms remains incomplete. Neutrophils respond to malaria parasites by phagocytosis, generation of oxidants, and externalization of Neutrophil Extracellular Traps (NETs). NETs drive inflammation in malaria but evidence of NETosis in PM has not been reported. Neutrophil activity in the placenta has not been directly investigated in the context of PM and PM/HIV-co-infection.MethodsUsing peripheral and placental plasma samples and placental tissue collected from Kenyan women at risk for malaria and HIV infections, we assessed granulocyte levels across all gravidities and markers of neutrophil activation, including NET formation, in primi- and secundigravid women, by ELISA, western blot, immunohistochemistry and immunofluorescence.ResultsReduced peripheral blood granulocyte numbers are observed with PM and PM/HIV co-infection in association with increasing parasite density and placental leukocyte hemozoin accumulation. In contrast, placental granulocyte levels are unchanged across infection groups, resulting in enhanced placental: peripheral count ratios with PM. Within individuals, PM- women have reduced granulocyte counts in placental relative to peripheral blood; in contrast, PM stabilizes these relative counts, with HIV coinfection tending to elevate placental counts relative to the periphery. In placental blood, indicators of neutrophil activation, myeloperoxidase (MPO) and proteinase 3 (PRTN3), are significantly elevated with PM and, more profoundly, with PM/HIV co-infection, in association with placental parasite density and hemozoin-bearing leukocyte accumulation. Another neutrophil marker, matrix metalloproteinase (MMP9), together with MPO and PRTN3, is elevated with self-reported fever. None of these factors, including the neutrophil chemoattractant, CXCL8, differs in relation to infant birth weight or gestational age. CXCL8 and MPO levels in the peripheral blood do not differ with infection status nor associate with birth outcomes. Indicators of NETosis in the placental plasma do not vary with infection, and while structures consistent with NETs are observed in placental tissue, the results do not support an association with PM.ConclusionsGranulocyte levels are differentially regulated in the peripheral and placental blood in the presence and absence of PM. PM, both with and without pre-existing HIV infection, enhances neutrophil activation in the placenta. The impact of local neutrophil activation on placental function and maternal and fetal health remains unclear. Additional investigations exploring how neutrophil activation and NETosis participate in the pathogenesis of malaria in pregnant women are needed.

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Section: Discussionmentioning

confidence: 99%

Myeloperoxidase and Other Markers of Neutrophil Activation Associate With Malaria and Malaria/HIV Coinfection in the Human Placenta

et al. 2021

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“…Increased levels of pro-inflammatory cytokines, oxidative stress [ 27 ], and apoptosis lead to pathological changes in the placenta and poor pregnancy outcomes [ 28 ]. It has been shown that histopathological changes and placental malaria enhance the risk of preeclampsia in pregnant women, especially in primigravidas [ 29 ]. Histopathological changes during placental malaria include presence of hemozoin, perivillous fibrin deposition [ 30 , 31 ], syncytial knot formation [ 32 ], and decrease in villous surface area (Fig.…”

Section: Introductionmentioning

confidence: 99%

Placental Malaria

2020

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Purpose of Review Placental malaria is the primary mechanism through which malaria in pregnancy causes adverse perinatal outcomes. This review summarizes recent work on the significance, pathogenesis, diagnosis, and prevention of placental malaria. Recent Findings Placental malaria, characterized by the accumulation of Plasmodium-infected red blood cells in the placental intervillous space, leads to adverse perinatal outcomes such as stillbirth, low birth weight, preterm birth, and small-forgestational-age neonates. Placental inflammatory responses may be primary drivers of these complications. Associated factors contributing to adverse outcomes include maternal gravidity, timing of perinatal infection, and parasite burden. Summary Placental malaria is an important cause of adverse birth outcomes in endemic regions. The main strategy to combat this is intermittent preventative treatment in pregnancy; however, increasing drug resistance threatens the efficacy of this approach. There are studies dissecting the inflammatory response to placental malaria, alternative preventative treatments, and in developing a vaccine for placental malaria.

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“…In their study, the placenta showed a signi cant number of syncytial knots, brinoid necrosis, calci cation and hyalinization. Meanwhile, Obiri et al (26) in Ghana revealed syncytial knots as the main contributor to placental pathology in women diagnosed with preeclampsia; this was about ten-fold more frequent in preeclampsia than non-preeclampsia placentas. For our case however, endarteritis 93(57.4%) was the most common pathological lesion noted.…”

Section: Discussionmentioning

confidence: 99%

Predicting Risk of Chronic Hypertension in Women with Preeclampsia Based on Placenta Histology. A Prospective Cohort Study in Cuba.

Byonanuwe

Fajardo

Nápoles³

et al. 2020

Preprint

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Background: Chronic hypertension is one of the major sequelae of preeclampsia with associated long term morbidity and mortality among previously normotensive women diagnosed with preeclampsia. We identified the predictors of developing this complication in women with preeclampsia admitted at the Carlos Manuel de Cèspedes Teaching Hospital in Cuba based on histological assessment of their placenta so as to guide the health care providers in early identification of the patients at risk for timely intervention against this vicious condition. Methods: A three-year prospective cohort study was conducted between March 2017 and March 2020. A cohort of 178 women diagnosed with preeclampsia was recruited and followed up at 12 weeks postpartum for chronic hypertension. Histological studies were done on their placenta following delivery and the respective result forms used to collect the data. Cox’s hazards regression model was applied to estimate the risk using STATA version 14.2.Results: Chorioamnionitis (HR=1.697, 95%CI: 1.443-3.416, p=0.038), villositary infarcts (HR=1.657, 95%CI: 1.264-2.848, p=0.048), intervillositary thrombus (HR=1.529, 95%CI: 1.231-3.197, p=0.020), and endarteritis (HR=1.242, 95%CI: 1.115-1.804, p=0.025) placental lesions were predictive of chronic hypertension at 12 weeks postpartum.Conclusion: Placental histology in women with preeclampsia is key towards improving the ability to diagnose and monitor those likely to develop chronic hypertension before its onset for timely intervention.

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Histopathological lesions and exposure to Plasmodium falciparum infections in the placenta increases the risk of preeclampsia among pregnant women

Cited by 22 publications

References 46 publications

Myeloperoxidase and Other Markers of Neutrophil Activation Associate With Malaria and Malaria/HIV Coinfection in the Human Placenta

Myeloperoxidase and Other Markers of Neutrophil Activation Associate With Malaria and Malaria/HIV Coinfection in the Human Placenta

Placental Malaria

Predicting Risk of Chronic Hypertension in Women with Preeclampsia Based on Placenta Histology. A Prospective Cohort Study in Cuba.

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