Objective: To explore the relationship between total bile acid (TBA) concentration and fetal pulmonary surfactant in intrahepatic cholestasis of pregnancy (ICP).
Methods: Fifty five patients with ICP (ICP group) who received cesarean section from April 2008 to February 2010 in Second Xiangya Hospital, Central South University, were recruited. The general conditions of the neonates within 7 days after birth in ICP group were recorded. Those with fetal distress, neonatal asphyxia, or neonatal respiratory distress syndrome were referred as pathological neonates, others were referred as normal neonates. Over the same period, 23 healthy gravidas were recruited as control group. Enzymatic method was used to detect the TBA concentrations in maternal blood, cord blood and amniotic fluid. ELISA was employed to measure the urfactant protein A (SP-A) concentration in cord blood. High performance liquid chromatography system was used to detect the concentrations of phosphatidylcholine (PC), phosphatidylinositol (PI), lysophosphatidylcholine (LPC), and sphingomyelin (SM) in amniotic fluid.
Results: (1) The concentrations of TBA in maternal blood, cord blood and amniotic fluid were (30.1 ± 7.9), (9.3 ± 3.3) and (4.4 ± 1.5) mmol/L in ICP group, (4.8 ± 2.2), (4.9 ± 0.9) and (1.4 ± 1.1) mmol/L in control group, respectively. The differences between the two groups were significant (P < 0.05). (2) The SP-A concentration in cord blood in ICP group was (29.5 ± 6.4) µg/L, significantly higher than that in control group, which was (22.6 ± 7.4) µg/L (P < 0.05). (3) There were 20 pathological neonates and 35 normal neonates in ICP group. In pathological neonates, the concentrations of TBA and SP-A in cord blood were (10.9 ± 2.2) mmol/L, (37.0 ± 5.9) µg/L, respectively; and were (8.0 ± 2.8) mmol/L, (26.7 ± 4.8) µg/L in normal neonates. The differences were significant (P < 0.05). (4) There was a positive correlation between TBA concentration in cord blood and in maternal blood (r(1) = 0.706, P < 0.05). The TBA concentration in cord blood was positively correlated with SP-A concentration as well (r(3) = 0.494, P < 0.05). (5) The PC and PI concentrations in amniotic fluid were (65.4 ± 7.2) mg/L and (3.8 ± 0.6) mg/L in ICP group, (69.7 ± 3.7) mg/L and (4.3 ± 0.7) mg/L in control group, respectively. The differences were significant (P < 0.05). The concentration of LPC in amniotic fluid in ICP group was (4.8 ± 0.9) mg/L, significantly higher than that in control group (P < 0.05), which was (4.2 ± 0.6) mg/L. The concentration of SM in amniotic fluid was (3.5 ± 0.8) mg/L in ICP group, (4.0 ± 0.5) mg/L in control group, with no significant difference (P > 0.05). (6)The ratio of PC/LPC in ICP group (14.2 ± 3.2) was significantly lower than that in control group (16.9 ± 2.5) (P < 0.05). (7)The TBA concentration in cord blood was negatively correlated with PC and PI concentrations (r(1) = -0.561, r(2) = -0.407, P < 0.05), and had no correlation with LPC concentration (r(3) = 0.260, P > 0.05).
Conclusions: (1) The fetal TBA concentrations in both cord blood and amniotic fluid of patients with ICP was higher than those of healthy gravidas, they were also positively correlated with maternal TBA concentration. (2) ICP resulted in the change of fetal pulmonary surfactant and this change was associated with TBA concentrations in both cord blood and amniotic fluid.