Correlation of direct and indirect bilirubin in fetus serum of normal and preeclamptic pregnancy

Introduction. It is known that in severe preeclampsia biochemical and pathohistological changes of hypoxic nature can occur due to changes that occur in the blood vessels as a whole, but also in the liver of the pregnant woman and the fetus. Determination of direct and indirect bilirubin in fetal blood in normal and preeclamptic pregnancies is of great importance to determine the health status of the fetus (newborn), as well as their prognosis, morbidity and mortality.
Purpose of the paper. It is to analyze the level and correlation of direct and indirect bilirubin in the blood of pregnant women and fetuses/newborns in normal and preeclamptic pregnancy.
Material and methods. The study included 80 pregnant women. In 40 pregnant women both pregnancy and fetal development flow in physiological form. While in 40 pregnant women we have selected pregnant women with preeclampsia and intrauterine growth retardation (IUGR - intrauterine growth retardation). The gestational age of pregnant women with normal flow was determined by the method of recent menstruation as well as by determining the biometrics of the fetus by ultrasonography. The processing of the results was done by statistical methods. Scattered, non-parametric numerical variables were analyzed using the Mann Whitney U test for independent samples. The Spearman correlation coefficient was used to calculate the data with normal distribution.
Results. They showed that there is no significant difference in the median of gestational weeks between pregnant women with physiological pregnancies and preeclamptic pregnancies [U = 1455.500, z=-1.827, p=0.068]. There is a very statistically significant difference between the median of newborn body weight between pregnant women with physiological pregnancy and preeclamptic pregnancy [U=489.500, z=-6.883, p <0.001]. Changes in patient age [1,817; 95% CI (-0.216; 3.849)] do not show statistical significance [t (118) =1.770, p=0.079].
The results have determined that the achieved values show that there is no statistically significant difference between the values of serum indirect bilirubin in pregnant women with physiological pregnancy and preeclamptic pregnancy [U=1430.500, z=-1.943, p=0.052]. There is also no statistically significant difference in direct bilirubin (µmol/L) values between pregnant women with physiological pregnancies and pregnant women with preeclamptic pregnancies [U=1537,000, z=-1.578, p=0.115]. The presented changes did not reach the threshold of statistical significance at the level α=0.05, so it can be concluded that there is no statistically significant difference in the values of indirect serum bilirubin between the fetus with increasing stagnation (IUGR) and the fetus with growth and normal development [U=1432.500, z=-1.929, p=0.054], while there is a statistically significant difference in the median values of direct bilirubin in the serum of stunted fetuses (IUGR) and fetuses with normal growth and development [U=1412.500, z=-2.037, p=0.042].
There is no statistically significant linear correlation between weeks of gestation and indirect serum bilirubin values in fetuses / newborns with normal development and growth (rs=-0.063; p> 0.05). There is a statistically significant linear correlation between the week of gestation and indirect serum bilirubin values in fetuses/newborns with increasing stagnation (rs = 0.666; p <0.001). There is a very significant positive linear statistical correlation between weeks of gestation and direct serum bilirubin in fetuses/newborns with increasing stagnation (rs=0.673; p<0.001).
Discussion. The increase in the level of bilirubin directly in the fetus with increasing stagnation (IUGR), is due to preeclampsia, as a consequence of hypoxia of the fetal liver. Due to the growing stagnation and hypoxia of the fetus, from the adrenal gland increases the synthesis of fetal cortizol which stimulates the synthesis of these enzymes uridin-diphosphate-glucuronyl-transferase as well as bilirubin-diglucuronyl-glucuronosyl-transferase which are found in hepatic fetuses. These enzymes conjugate indirect bilirubin to direct bilirubin as the case is followed by an increase in the level of direct bilirubin in the fetal blood with increasing stagnation. The increase in the level of direct bilirubin in fetuses with increasing stagnation is also explained by the fact that fetuses with increasing stagnation are in a state of stress which is caused by hypoxia. Hypoxia stimulates increased levels of prolactin, thyroid-stimulating hormone (TSH), which stimulate microsomes in liver cells to stimulate the synthesis of the enzyme glycuronyl transferase which makes the conjugation of indirect bilirubin to direct bilirubin.
The increase in the level of indirect bilirubin during the development of pregnancy in the fetus with increasing stagnation, is explained by the fact that due to hypoxia of the fetus with increasing stagnation, increases the synthesis of erythropoietin in the fetal kidneys which then stimulates erythropoiesis in the medulla (marrow) bone as the case follows the increase in the number of erythrocytes in relation to plasma as well as the increase in blood viscosity in the fetus with increasing stagnation (IUGR). In the fetus with increasing stagnation, the increase of indirect bilirubin in linear form follows also due to hypoxia and acidosis which exists in the growing stagnation of the fetus, in addition the increase of indirect bilirubin in linear form can also be caused due to hemolysis of erythrocytes as a consequence of oxytocin of fetal origin, which is synthesized in the fetal thymus with increasing stagnation. It has been proven that as the fetus grows, the level of fetal oxytocin also increases.
Conclusions. Based on the results we conclude that the level of direct serum bilirubune is significantly higher (p=0.042) in the fetus/newborn with increasing stagnation (IUGR) compared to the fetus/newborn with normal development. The results showed that there is a significant positive linear correlation (p<0.001) between the age of the fetus/newborn with stagnation (IUGR) and indirect bilirubin. In fetuses/neonates with increasing stagnation during intrauterine life, the level of indirect bilirubin increases with increasing fetal age during intrauterine life. The results also found that there is a positive linear correlation (p <0.001) between direct fetal/neonatal serum bilirubin with increasing stagnation during intrauterine life. Direct bilirubin levels increase significantly with the age of the fetus/neonates with increasing stagnation during intrauterine life.