Prevention of Hypertensive Disorders of Pregnancy—Is There a Place for Metformin?

Abstract

The possibility of prophylaxis of hypertensive disorders of pregnancy (HDPs) such as preeclampsia (PE) and pregnancy-induced hypertension is of interest due to the unpredictable course of these diseases and the risks they carry for both mother and fetus. It has been proven that their development is associated with the presence of the placenta, and the processes that initiate it begin at the time of the abnormal invasion of the trophoblast in early pregnancy. The ideal HDP prophylaxis should alleviate the influence of risk factors and, at the same time, promote physiological trophoblast invasion and maintain the physiologic endothelium function without any harm to both mother and fetus. So far, aspirin is the only effective and recommended pharmacological agent for the prevention of HDPs in high-risk groups. Metformin is a hypoglycemic drug with a proven protective effect on the cardiovascular system. Respecting the anti-inflammatory properties of metformin and its favorable impact on the endothelium, it seems to be an interesting option for HDP prophylaxis. The results of previous studies on such use of metformin are ambiguous, although they indicate that in a certain group of pregnant women, it might be effective in preventing hypertensive complications. The aim of this study is to present the possibility of metformin in the prevention of hypertensive disorders of pregnancy with respect to its impact on the pathogenic elements of development

Supraphysiological Role of Melatonin Over Vascular Dysfunction of Pregnancy, a New Therapeutic Agent?

“…Impaired placentation is the principal cause of complications in pregnancy. It causes several negative outputs, including hypertension, and their severe expression occurs in about 2% and induces about 16% of all maternal deaths suggesting the relevance of prevention of hypertension and preeclampsia (Romero et al, 2011;Poniedziałek-Czajkowska et al, 2021). Preeclampsia involves the vasculature due to the impaired transformation of the spiral arteries and the reduced perfusion to the fetus and the placenta, with an elevation of oxidative and endoplasmic reticulum stress and finally, inducing a fetal growth restriction.…”

“…Impaired placentation is the principal cause of complications in pregnancy. It causes several negative outputs, including hypertension, and their severe expression occurs in about 2% and induces about 16% of all maternal deaths suggesting the relevance of prevention of hypertension and preeclampsia ( Romero et al, 2011 ; Poniedziałek-Czajkowska et al, 2021 ).…”

“…Preeclampsia involves the vasculature due to the impaired transformation of the spiral arteries and the reduced perfusion to the fetus and the placenta, with an elevation of oxidative and endoplasmic reticulum stress and finally, inducing a fetal growth restriction. The systemic stress shoddy remodeling of the uteroplacental spiral arteries release placental factors to maternal circulation, increasing the maternal inflammatory response and oxidative stress such as high production of proinflammatory cytokines/chemokines such as IL-1β, IL-6, and IL-8 ( Nunes et al, 2019 ; Valencia-Ortega et al, 2019 ; Poniedziałek-Czajkowska et al, 2021 ; Spence et al, 2021 ). Moreover, the impaired invasion of the uterine wall by trophoblast induce hypoxia, and produce a modification of placental secretion of critical angiogenic and antiangiogenic factors such as vascular endothelial growth factor (VEGF) ( Frigato et al, 2009 ) and Placental lactogen (PL-II) member of the prolactin gene family.…”

“…These vascular factors and their impaired secretion have been proposed to predict risk during pregnancy ( Wang and Zhao, 2010 ; Valenzuela et al, 2012 ; Lenke et al, 2019 ). Besides, VEGF and placental growth factor (PlGF) induce placental angiogenesis via activation of VEGFR-1/Flt-1 and VEGFR-2/KDR, and both factors increase endothelial cell adhesion, chemotaxis and increase angiogenesis ( Helske et al, 2001 ; Poniedziałek-Czajkowska et al, 2021 ).…”

“…Another antiangiogenic factor secreted during Preeclampsia is soluble Endoglin (sEng), which reduces the proangiogenic and vasodilator effects of Endoglin. Finally, the elevated production of sFlt-1 and sEng and the decrease of VEGF and PIGF secretion induce an impairment of endothelial function, causing preeclampsia ( De Oliveira et al, 2013 ; Shah and Khalil, 2015 ; Poniedziałek-Czajkowska et al, 2021 ).…”