Chronic Venous Disease during Pregnancy Causes a Systematic Increase in Maternal and Fetal Proinflammatory Markers

Abstract

Chronic venous disease (CVD) is a common vascular disorder characterized by increased venous hypertension and insufficient venous return from the lower limbs. Pregnancy is a high-risk situation for developing CVD. Approximately a third of the women will develop this condition during pregnancy, and similarly to arterial hypertensive disorders, previous evidence has described a plethora of alterations in placental structure and function in women with pregnancy-induced CVD. It is widely known that arterial-induced placenta dysfunction is accompanied by an important immune system alteration along with increased inflammatory markers, which may provide detrimental consequences for the women and their offspring. However, to our knowledge, there are still no data collected regarding cytokine profiling in women with pregnancy-induced CVD. Thus, the aim of the present work was to examine cytokine signatures in the serum of pregnant women (PW) with CVD and their newborns (NB). This study was conducted through a multiplex technique in 62 PW with pregnancy-induced CVD in comparison to 52 PW without CVD (HC) as well as their NB. Our results show significant alterations in a broad spectrum of inflammatory cytokines (IL-6, IL-12, TNF-α, IL-10, IL-13, IL-2, IL-7, IFN-γ, IL-4, IL-5, IL-21, IL-23, GM-CSF, chemokines (fractalkine), MIP-3α, and MIP-1β). Overall, we demonstrate that pregnancy-induced CVD is associated with a proinflammatory environment, therefore highlighting the potentially alarming consequences of this condition for maternal and fetal wellbeing.

Considering the Effects and Maternofoetal Implications of Vascular Disorders and the Umbilical Cord

“…Chronic venous disease (CVD) is a vascular disorder characterized by increased venous hypertension and insufficient venous return from the lower limbs [76]. The haemodynamic changes that occur during pregnancy, such as vasodilation, compression of iliac veins and venous stasis, favour its development [77][78][79][80].…”

“…The foetus and neonate are also participants in this proinflammatory state [95]. Some studies have shown that gestational CVD favours this proinflammatory state, as indicated by increases in the levels of proinflammatory cytokines (IL-6, IL-12, TNF-α, IL-10, IL-13, IL-2, IL-7, IFN-γ, IL-4, IL-5, IL-21, IL-23, GM-CSF, chemokines (fractalkine), MIP-3α and MIP-1β) in pregnant women with CVD and in the umbilical cord blood of their newborns [76]. At the foetal and neonatal levels, this proinflammatory profile has been related to multiple pathologies, such as preeclampsia, preterm delivery, and the development of bronchial hyperresponsiveness or overweight during the first years of life and therefore forms part of the so-called "foetal programming" [46,47].…”

“…Some studies have shown that gestational CVD favours this proinflammatory state, as indicated by increases in the levels of proinflammatory cytokines (IL-6, IL-12, TNF-α, IL-10, IL-13, IL-2, IL-7, IFN-γ, IL-4, IL-5, IL-21, IL-23, GM-CSF, chemokines (fractalkine), MIP-3α and MIP-1β). This proinflammatory profile has been related to multiple pathologies, such as preeclampsia, preterm delivery, and the development of bronchial hyperresponsiveness or overweight during the first years of life and therefore forms part of the so-called "foetal programming [46,47,76,85,87,88] Author Funding: This study (FIS-PI21/01244) has been supported by the Instituto de Salud Carlos III (Plan Estatal de I+D+i 2020-2027) and co-financed by the European Regional Development Fund "A Road to Europe" (ERDF) and P2022/BMD-7321 MITIC-CM, Halekulani S.L. and M.J.R.…”

Irregular Expression of Cellular Stress Response Markers in the Placenta of Women with Chronic Venous Disease

“…Likewise, pregnancy-associated CVD involves changes at angiogenesis, lymphangiogenesis, with several changes in the extracellular matrix compared with healthy controls (HC) with no history of CVD [ 17 , 18 ]. All in all, these factors could have a negative impact not only on the mother’s life—during and after childbirth—but also on the fetuses’ development [ 19 ].…”

Measuring the Quality of Life in Patients with Chronic Venous Disease before and Short Term after Surgical Treatment—A Comparison between Different Open Surgical Procedures

“…The prevalence of this condition remains underestimated, early evidence of CVD being frequently overlooked by general practitioners [ 1 ]. Clinical manifestations of CVD can range from mild to severe, such as telangiectasia, varicose veins (most notably), lipodermatosclerosis or venous ulceration, and pain is one of the most common symptoms [ 2 , 3 ]. It is well-known that CVD negatively impacts patient’s quality of life (QoL), both at the physical and the psychological levels [ 4 ].…”