title: The concentrations of bile acids and erythropoietin in pregnant women with intrahepatic cholestasis and the state of the fetus and newborn.
abstract: Intrahepatic cholestasis of pregnancy (ICP) is not a common complication of pregnancy, but may be a threat to fetal condition. The elevated level of bile acids defines ICP and determines its severity. Indicators of hepatocyte damage during ICP are elevated ALT and AST. The fetal condition in the ICP depends on the degree of liver damage. The most common complication is preterm delivery, but the risk of fetal death is currently around 3.5%. Erythropoietin is a peptide hormone produced mostly in the kidneys and liver due to tissue hypoxia. EPO concentration in the blood serum of pregnant women increases, because of its production in the placenta. Reducing the blood flow through the fetal-placental unit is the cause of fetal complications associated with ICP. The reason for blood flow the decrease is elevated TBA concentration. The hypothesis of the study assumed that in the course of ICP, elevated bile acids reduce blood flow through the fetal-placental unit, which causes placental hypoxia, and which can lead to the increased secretion of EPO in the placenta.
  
  
  OBJECTIVE
  of this study was to find a correlation between high levels of bile acids and concentration of erythropoietin in the serum of women with ICP without anemia and renal dysfunction and to evaluate the course and outcome of pregnancy in women with ICP.
  
  
  METHODS
  73 pregnant women from the Department of Obstetrics and Gynaecology, Institute of Mother and Child in Warsaw, were included in the study. 33 pregnant women with ICP were included in group I. Group II (control) consisted of 40 women with pregnancy without ICP. The inclusion criteria for the study in group I were as follows: TBA≥11 μmol/l; elevated liver enzymes: ALT>41 U/l and/ or AST>40 U/l; and the presence of pruritus (current or history). The exclusion criteria included: anemia (HGB<11 g/dl); viral hepatitis A, B, C; other abnormalities of the liver and of the biliary tract; alcohol and drug addiction; HIV infection; diseases of skin with itching and rash; acute and chronic kidney disease; bone disease; acute and chronic bleeding in pregnancy and preeclampsia. Laboratory analysis of the parameters of liver function, kidney function and blood counts was performed on the same day as the TBA and EPO concentration. The intensity of pruritus in patients with ICP was determined on the basis of a special 5-degree scale, proposed by the author. the conditions of fetuses were monitored during laboratory tests of the pregnant women and delivery with cardiotocography and ultrasound. Analysis of the newborns was based on the following data: gestational age at delivery, birth weight, 1-minute and 5-minute Apgar scores, blood gas parameters in the umbilical artery. The statistical analysis of clinical and laboratory parameters was performed using Statistica 5.5 PL package. The results were analyzed in order to find significant differences between them.
  
  
  RESULTS
  In the group of pregnant women with ICP mean gestational age at delivery was 35.97±1.86 weeks, in the control group 38.1±1.46 weeks (p<0.05). The percentage of preterm births (<37 weeks) in group I was 45.5%, in group II 15% (p<0.05). At the time of delivery in group I fetal hypoxia symptoms were observed in 9.8% of fetuses vs 17.4% in group II (p=ns.). In the group of women with ICP 36.6% of newborns had low birth weight (less than 2500 g), including 2.4% of extremely low birth weight (<1000 g). In group II, the percentage of infants with low birth weight was 10.9% (p<0.05). The average 1-minute and 5-minute Apgar scores were lower in group I compared to group II (p<0.05). The average TBA concentration was 22.82±14.78 μmol/L in group I vs 2.43±2.04 μmol/L in group II (p<0.05). The obtained data show that the intensity of pruritus was not directly related to the concentration of bile acids. The activity of liver enzymes in the group of women with ICP was significantly increased compared to controls. There were no cases of jaundice among the women examined. Among coagulation parameters in group I, significantly elevated concentration of fibrinogen (p<0,05) was found. Differences in the values of selected markers of renal function (urea, creatinine) and hematological parameters were not statistically significant. Erythropoietin concentrations in both groups were similar. In group I the mean value was 17.35±8.86 mU/ml and in the control group 18.12±9.48 mU/ml (p>0.05).
  
  
  CONCLUSIONS
  In the group of pregnant women with ICP there was no correlation between the concentration of bile acids and erythropoietin. Preterm delivery and worse neonatal outcome were more common in the ICP group, which indicates that perinatal care should be improved and further studies are needed.
authors.affiliation: Klinika Położnictwa i Ginekologii, Instytut Matki i Dziecka, Kasprzaka 17a, 01-211 Warszawa, anewak@gmail.com.
authors.forename: Anna
authors.initials: A
authors.lastname: Kowalska-Kańka
authors.forename: Tomasz
authors.initials: T
authors.lastname: Maciejewski
authors.forename: Krzysztof Tomasz
authors.initials: KT
authors.lastname: Niemiec
mesh_terms: D000328:Adult; D001034:Apgar Score; D001647:Bile Acids and Salts / Q000097:blood*; D001724:Birth Weight; D002780:Cholestasis, Intrahepatic / Q000097:blood*; D004921:Erythropoietin / Q000097:blood*; D005260:Female; D005313:Fetal Death / Q000453:epidemiology; D005865:Gestational Age; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D010920:Placenta / Q000098:blood supply; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood*; D011256:Pregnancy Outcome / Q000453:epidemiology*; D047928:Premature Birth / Q000453:epidemiology*; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*; D012039:Regional Blood Flow; D055815:Young Adult
chemical_list: D001647:Bile Acids and Salts; D004921:Erythropoietin