Cytokine see‐saw across pregnancy, its related complexities and consequences

Meyyazhagan, Arun; Bhotla, Haripriya Kuchi; Pappuswamy, Manikantan; Цибизова, В. И.; Qasem, Malek Atif Mohd Al; Renzo, Gian Carlo Di

doi:10.1002/ijgo.14333

Cited by 12 publications

(11 citation statements)

References 97 publications

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“…IL-10, etc.) are also increased to prevent excessive inflammatory responses ( 20 ). It has been shown that inflammatory cytokines/chemokines are significantly dysregulated in mothers infected with SARS-CoV-2 prior to delivery, but uninfected pregnant controls may also exhibit a large degree of variability in their cytokine/chemokine levels ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

Case report: Complex evaluation of coagulation, fibrinolysis and inflammatory cytokines in a SARS-CoV-2 infected pregnant woman with fetal loss

Tóth,

Orbán-Kálmándi,

Bagoly

et al. 2024

Front. Immunol.

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BackgroundSARS-CoV-2 infection during pregnancy increases the risk of severe obstetrical complications. Detailed evaluation of COVID-19-associated coagulopathy in a pregnancy with stillbirth hasn’t been described so far. Besides knowledge gaps in the pathomechanism leading to stillbirth in COVID-19 pregnancies, currently, no prognostic biomarker is available to identify pregnant patients who are at imminent risk of COVID-19-associated maternal and fetal complications, requiring immediate medical attention.CaseHere we report the case of a 28-year-old SARS-CoV-2 infected pregnant patient, admitted to our hospital at 28 weeks of gestation with intrauterine fetal loss. The presence of SARS-CoV-2 placentitis was confirmed by immunohistological evaluation of the placenta. She had only mild upper respiratory symptoms and her vital signs were within reference throughout labor and postpartum. The stillborn infant was delivered per vias naturales. Fibrinogen concentrate was administered before and after labor due to markedly decreased fibrinogen levels (1.49 g/l) at admission and excessive bleeding during and after delivery. Although coagulation screening tests were not alarming at admission, the balance of hemostasis was strikingly distorted in the patient. As compared to healthy age- and gestational age-matched pregnant controls, increased D-dimer, low FVIII activity, low FXIII level, marked hypocoagulability as demonstrated by the thrombin generation assay, together with shortened clot lysis and decreased levels of fibrinolytic proteins were observed. These alterations most likely have contributed to the increased bleeding observed during labor and in the early postpartum period. Interestingly, at the same time, only moderately altered inflammatory cytokine levels were found at admission. Serum ACE2 activity did not differ in the patient from that of age- and gestational age-matched healthy controls, suggesting that despite previous speculations in the literature, ACE2 may not be used as a potential biomarker for the prediction of COVID-19 placentitis and threatening fetal loss in SARS-CoV-2-infected pregnancies.ConclusionsAlthough based on this case report no prognostic biomarker could be identified for use in pregnant patients with imminent risk of fetal loss associated with COVID-19 placentitis, the above-described hemostasis alterations warrant awareness of postpartum hemorrhagic complications and could be helpful to identify patients requiring intensified medical attention.

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Section: Discussionmentioning

confidence: 99%

Case report: Complex evaluation of coagulation, fibrinolysis and inflammatory cytokines in a SARS-CoV-2 infected pregnant woman with fetal loss

Tóth,

Orbán-Kálmándi,

Bagoly

et al. 2024

Front. Immunol.

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“…In addition to the increase of pro-inflammatory cytokines, we also found increase of anti-inflammatory cytokines; perhaps as an attempt to contain the local inflammatory process without threatening the pregnancy. Anti-inflammatory cytokines such as IL-10 and transforming growth factor (TGF-β) are typically increased primarily in the second trimester, and decrease during the first and third trimesters ( Bränn et al, 2019 ; Meyyazhagan et al, 2022 ). For the two cytokines we noted statistical difference between controls and cases.…”

Section: Discussionmentioning

confidence: 99%

Histopathological and immunological characteristics of placentas infected with chikungunya virus

et al. 2022

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Although vertical transmission of CHIKV has been reported, little is known about the role of placenta in the transmission of this virus and the effects of infection on the maternal-fetal interface. In this work we investigated five placentas from pregnant women who became infected during the gestational period. Four formalin-fixed paraffin-embedded samples of placenta (cases 1–4) were positive for CHIKV by RT-PCR. One (case 5) had no positive test of placenta, but had positive RT-PCR for CHIKV in the serum of the mother and the baby, confirming vertical transmission. The placentas were analyzed regarding histopathological and immunological aspects. The main histopathological changes were: deciduitis, villous edema, deposits, villous necrosis, dystrophic calcification, thrombosis and stem vessel obliteration. In infected placentas we noted increase of cells (CD8+ and CD163+) and pro- (IFN-γ and TNF-α) and anti-inflammatory (TGF-β and IL-10) cytokines compared to control placentas. Moreover, CHIKV antigen was detected in decidual cell, trophoblastic cells, stroma villi, Hofbauer cells, and endothelial cells. In conclusion, CHIKV infection seems to disrupt placental homeostasis leading to histopathological alterations in addition to increase in cellularity and cytokines overproduction, evidencing an altered and harmful environment to the pregnant woman and fetus.

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“…Although the role of cytokines as critical mediators in the inflammatory process that triggering labor has been demonstrated [ 21 ], very few predictive models consider their measurement in the PB screening process [ 22 , 23 , 24 ]. However, none have been implemented in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

A Novel Predictive Machine Learning Model Integrating Cytokines in Cervical-Vaginal Mucus Increases the Prediction Rate for Preterm Birth

Borboa-Olivares,

Rodríguez-Sibaja,

Espejel-Nuñez

et al. 2023

IJMS

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Preterm birth (PB) is a leading cause of perinatal morbidity and mortality. PB prediction is performed by measuring cervical length, with a detection rate of around 70%. Although it is known that a cytokine-mediated inflammatory process is involved in the pathophysiology of PB, none screening method implemented in clinical practice includes cytokine levels as a predictor variable. Here, we quantified cytokines in cervical-vaginal mucus of pregnant women (18–23.6 weeks of gestation) with high or low risk for PB determined by cervical length, also collecting relevant obstetric information. IL-2, IL-6, IFN-γ, IL-4, and IL-10 were significantly higher in the high-risk group, while IL-1ra was lower. Two different models for PB prediction were created using the Random Forest machine-learning algorithm: a full model with 12 clinical variables and cytokine values and the adjusted model, including the most relevant variables-maternal age, IL-2, and cervical length- (detection rate 66 vs. 87%, false positive rate 12 vs. 3.33%, false negative rate 28 vs. 6.66%, and area under the curve 0.722 vs. 0.875, respectively). The adjusted model that incorporate cytokines showed a detection rate eight points higher than the gold standard calculator, which may allow us to identify the risk PB risk more accurately and implement strategies for preventive interventions.

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Cytokine see‐saw across pregnancy, its related complexities and consequences

Cited by 12 publications

References 97 publications

Case report: Complex evaluation of coagulation, fibrinolysis and inflammatory cytokines in a SARS-CoV-2 infected pregnant woman with fetal loss

Case report: Complex evaluation of coagulation, fibrinolysis and inflammatory cytokines in a SARS-CoV-2 infected pregnant woman with fetal loss

Histopathological and immunological characteristics of placentas infected with chikungunya virus

A Novel Predictive Machine Learning Model Integrating Cytokines in Cervical-Vaginal Mucus Increases the Prediction Rate for Preterm Birth

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