The importance of “first-blood circulation stage”, a new insight into the pathogenesis of clinical manifestations of preeclampsia

The tested hypothesis points out that exposure to environmental toxic substances originating from coal or other fossil fuels burning is the most decisive for the impacts of the metabolic synergy of nitrogen oxides as oxidants that cause hemoglobin oxidation to methemoglobin, and sulphur dioxide metabolites as inhibitors of antioxidants, in the bloodstream throughout the period of pregnancy. The main difference between the present three-stage hypothesis and other hypotheses is the assertion that, in the pathogenesis of early and late complicated pregnancy, methemoglobin takes on an important role. Methemoglobin by itself and from heme, redox-active ferric iron as a product of methemoglobin catabolism, has prooxidant properties and causes important structural and functional changes in the vascular endothelium, such as growth arrest, senescence, morphological alterations and cell apoptosis. Our own prospective study of methemoglobin in pregnancy revealed a significant rise and correlation between the ground level of SO2 and the level of methemoglobin: >1.5 g/L (r = 0.72, p < 0.01) and sulfhemoglobin (r = 0.53, p < 0.05) in the bloodstream of pregnant women which can be explained on the basis of an oxidant-antioxidant imbalance (nitrogen and sulphur synergy effects), resulting in methemoglobinemia. Methemoglobinemia and pregnancy complications like stillbirths recorded throughout the exposure period are significantly higher than those recorded in the control period (p = 0.0205), and the frequencies of reproductive loss were significantly lower in the control than in the exposure period (p < 0.05). We point out the importance of the “FirstBlood circulation stage” as a new insight into the pathogenesis of the multisystemic oxidative stress and the link between a poorly perfused placenta and clinical manifestations of preeclampsia. The results suggest that the level of methemoglobin concentration in the bloodstream of pregnant women correlate with the inhalation of substances generated from coal combustion (SO2, NOx, NO, NO2 and others) and that is an early biomarker of the identification of women with a pregnancy risk, and having an significant role upon adverse effects on mother and fetus health.