Angiogenic imbalance, inflammation, and oxidative stress in patients with fetal growth restriction: A case-control study

Mehwish Iftikhar, Sumaira Sharif, Sawar Khan, Iftikhar Ali, Madeeha Shahzad Lodhi, Syed Imran Ali Shah, Malik Ihsan Ullah Khan

Abstract

Fetal growth restriction (FGR) is a critical condition linked to various etiologies, increasing the risk of fetal complications and mortality. The study investigated the expression levels of angiogenic factors and inflammatory cytokines in peripheral blood mononuclear cells (PBMCs) from normal pregnancies and those affected by FGR. It also examined their association with maternal oxidative stress markers. messenger RNA (mRNA) expression was analyzed using real-time PCR in PBMCs, while oxidative stress (OS) markers were assessed via spectrophotometric assays and ELISA in the maternal blood of 75 cases of FGR and 75 healthy pregnancies. FGR cases exhibited disrupted angiogenic signaling, elevated oxidative and inflammatory responses, indicating a pathological interplay among these systems. Results showed significantly reduced vascular endothelial growth factor (VEGF) along with increased soluble FMS-like tyrosine kinase-1 (sFlt-1) and nuclear factor-kappa B (NF-κB) expression in FGR cases. A notable inverse relationship of sFlt-1 existed with both VEGF and placental growth factor (PlGF), while sFlt-1 positively correlated with OS markers like Malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Additionally, NF-κB expression was strongly linked to MDA, tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). This understanding highlights the potential for targeted interventions, such as antioxidant therapies or strategies to modulate inflammatory pathways, to improve outcomes in FGR.

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