Biomarkers of Inflammation and Redox Imbalance in Umbilical Cord in Pregnancies with and without Preeclampsia and Consequent Perinatal Outcomes

Abstract

Objective. To compare redox imbalance and inflammation biomarkers in umbilical cords from pregnancies with and without preeclampsia (PE) and to analyse their relationships with perinatal outcomes. Methods. A controlled cross-sectional study was conducted in Maceió, Alagoas, Brazil, that involved pregnant women with PE and a group of women without the disease, through the application of a standardized questionnaire. After delivery, umbilical cord samples were collected to measure antioxidant defense, products from oxidative damage, and inflammation biomarkers such as myeloperoxidase (MPO), interleukin- (IL-) 6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α). Statistical analyses were performed using Stata version 13.0 software and IBM Statistical Package for the Social Sciences (SPSS) 20.0, adopting a 95% confidence level ( α = 0.05 ), with the chi-square test, the Wilcoxon–Mann–Whitney test, and the multinomial and Poisson regression tests. Results. One hundred PE pregnant women and 50 women without the disease were studied. The umbilical cords from PE pregnancies showed higher levels of reduced glutathione (GSH) ( p ≤ 0.001 ), glutathione peroxidase (GPx) ( p = 0.016 ), and malondialdehyde (MDA) ( p = 0.028 ) and lower levels of IL-6 ( p = 0.030 ) and TNF-α ( p ≤ 0.001 ) than the other group, with some associations among these biomarkers with perinatal outcomes. Conclusion. The higher levels of GSH and GPx, in addition to the lower levels of IL-6 and TNF-α, found in the PE umbilical cord, may result from adaptive mechanisms to maintain the oxidative and inflammatory balance; however, despite these changes, the damage to the cell membranes was not minimized, as the MDA level was higher in women with PE than in women without the disease. This implies that a redox imbalance is present, confirming that other physiological and adaptive mechanisms are being activated to preserve foetal health. Therefore, the present work unveils an important role of the umbilical cord in controlling redox imbalance and inflammation in PE pregnancies. Our results reinforce the necessity for continuous research on GSH as a protective compound for the perinatal outcome, especially in PE women.

Exploration of shared gene signature with development of pre-eclampsia and cervical cancer

“…Moreover, oxidate stress, which was characterized by lipid peroxidation accumulation, also plays a crucial role in the pathogenesis of PE. Recently, Fragoso et al reported that the umbilical cords from PE pregnancies showed higher levels of antioxidants including glutathione peroxidase (GPx) and malondialdehyde (MDA) than pregnancies without PE diagnosis, indicating the defensive mechanism to maintain the oxidative balance ( Fragoso et al, 2021 ). Despite all these efforts, the mechanisms regulating the onset and progression of PE remain largely unknown, making it crucial to explore highly sensitive biomarkers to provide an early and intensive care for patients at risk ( Grill et al, 2009 ).…”

Endothelial dysfunction in preterm infants: The hidden legacy of uteroplacental pathologies

“…Hence, identifying, understanding, and quantifying the contribution of pre-and postnatal processes to endothelial dysfunction is challenging and requires an early endothelial evaluation to limit confounding factors (103). Although many fetal processes are not fully understood, the available endothelial biomarkers to perform this evaluation in NICU are numerous (76,103,152,175,260). They await further studies to validate their diagnostic and therapeutic potential.…”

“…Several studies investigated, through cord blood samples analysis, the oxidant and antioxidant state of newborns of preeclamptic women, with or without FGR, compared to newborns from physiological pregnancies (156,(174)(175)(176)(177)(178)(179)(180)(181)(182)(183). Different analytical methods and some biomarkers have been used to measure oxidative stress, such as direct detection of ROS (e.g., hydrogen peroxide, H 2 O 2 ), indirect research of the peroxidation products of lipids and proteins (e.g., malondialdehyde and protein carbonyl levels), and activity evaluation of antioxidant enzymes (e.g., glutathione peroxidase).…”

“…Different analytical methods and some biomarkers have been used to measure oxidative stress, such as direct detection of ROS (e.g., hydrogen peroxide, H 2 O 2 ), indirect research of the peroxidation products of lipids and proteins (e.g., malondialdehyde and protein carbonyl levels), and activity evaluation of antioxidant enzymes (e.g., glutathione peroxidase). Many studies found a cord blood profile comparable to the maternal one, with a higher level of ROS and lower antioxidant activity in the offspring of preeclamptic women, suggesting that the mother and fetus are subjected to a pro-oxidant environment (156,(174)(175)(176). Moreover, preclinical data from ewe's model support that chronic hypoxia exposure significantly increases fetal plasma urate concentration from oxidative stress (184).…”

Status of Oxidative Stress during Low-Risk Labour: Preliminary Data

“…During this time, vascular resistance decreases, and the diameter of placental vessels increases. This provides blood perfusion and protects the fetus against hypoxemia, and during delivery, against reduced uteroplacental blood flow [14,15].…”