The role of methemoglobinemia in early and late complicated pregnancy.

The objective of this review was to direct attention about methemoglobin as a biomarker which has an important role in the detection of adverse effects of the oxidative stress, misbalanced production of ROS, RNS and RSS. According to our hypothesis, a pregnant woman continuously inhaling environmental toxics as fuel burning products, will traverse three, not two from current thought, distinct stages. The main difference among 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. Secondly, we also observed the utero-placental changes as "locus manifesting minoris resistentiae" in complicated pregnancy are not the causes but a consequence of increased systemic oxidative stress. Methemoglobin and hemolysis both occur as a result of oxidative stress, but the prevalent difference between them is that methemoglobin is a reversible phenomenon (oxidant-antioxidant balance) whereas hemolysis, which occurs as a result of oxidative stress on the erythrocyte membrane, is an irreversible event. Methemoglobinemia can additionally exacerbate an existing anemia, stimulating hypoxia that may be dangerous for both mother and fetus. Own prospective study of methemoglobin in pregnancy, revealed a significant rise in the level of methemoglobin >1.5 g/L (r=0.72, p<0.01) in the exposure period, which can be explained on the basis of an oxidant-antioxidant imbalance, resulting in methemoglobinemia. Methemoglobinemia and stillbirth recorded throughout 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). Results suggest that methemoglobin as individual indicator of oxidative stress is an early marker of the identification of women with a pregnancy risk. It has the advantage of being applicable some time before ultrasonic examination becomes feasible. Further support for this assumption will require further investigations that may lead to the supposition that increasing level of methemoglobin is related to environmental toxicities complicated pregnancy and IUGR, preeclampsia, and a high percentage of perinatal mortality and morbidity.