Clinical Study On The Association Of Serum Total Bile Acid Levels In Pregnant Women With Intrahepatic Cholestasis Of Pregnancy With Adverse Outcomes In Mothers And Their Infants

Aims: To investigate the impacts of TBA levels in serum of pregnant women with ICP on clinical pregnancy outcome and neonatal disease.Methods: A case-control study was used to retrospectively analyze the clinical data of 224 pregnant patients with ICP and their perinatal infants admitted to the first affiliated hospital of Jinan university from January 2010 to December 2018.The TBA levels were divided into mild group(10~40 ?mol/L),severe group(40~100 ?mol/L),extremely severe group(?100 ?mol/L)and normal pregnant women at the same time were randomly selected as the control group.The data of pregnancy laboratory test results,pregnancy adverse outcomes in mothers and their babies were collected.Correlation analysis of serum TBA levels in patients with ICP during pregnancy and pregnancy adverse outcomes and neonatal development markers at birth were analyzed by statistical methods such as analysis of variance,chi-square test and non-parametric tests.Results: In this study,a screening was performed in 38968 pregnant women who had delivery at the hospital,and 248 pregnant women with ICP were found.The incidence rate of ICP in our hospital was 0.63%.224 eligible ICP pregnant women and 129 normal pregnant women had taken part in this study and analyzed as follows.There were significant differences in the incidence rate of preterm birth among the four groups(P=0.000).The incidence rate of preterm birth in the mild group was higher than that in the control group(P=0.004).The incidence rate of preterm birth in the severe and extremely severe group were significantly higher than that in the control group and mild group(P=0.000).There were statistically significant differences in incidence rate of low birth weight infant among the four groups(P=0.022).The proportion of low birth weight infant in the severe group was higher than that in the control group(P=0.006).There were statistically significant differences between the four groups of pregnant women with CHB during pregnancy(P=0.001).The multiple comparison results between multiple sample rates showed that the proportion of pregnant women in severe group and extremely severe group with CHB were higher compared with control group(P=0.001;P=0.000).The results of Kruskal-Wallis H test comparing multiple independent samples showed that there were statistical differences in HBV DNA quantification among the four groups of pregnant women(P=0.021).The HBV DNA viral level was higher compared with the extremely severe group and lower in the control group(P=0.017).The HBe Ag positive rate of pregnant women in mild group,severe group and extremely severe group were higher than that in control group(P=0.002).There were significant differences in ALT and AST before delivery among pregnant women in the mild,severe,extremely severe and control groups(P=0.000;P=0.000).The ALT and AST of pregnant women in severe group(P=0.024)and control group(P=0.005)were significantly lower than those in extremely severe group.There was a significant statistical difference in the neonatal hospitalization rate among the four groups(P=0.000).The neonatal admission rate in the mild(P=0.004),severe(P=0.000)and extremely severe groups(P=0.000)were higher than the control group,and the differences were statistically significant.Furthermore,the hospitalization rate of neonates in the severe and extremely severe groups were significantly higher than that in the control group(P=0.000).There was also a statistically significant difference in neonatal hospitalization rates between the mild and the extremely severe groups(P=0.001).There were statistical differences in the diagnosis of neonatal infection,myocardial damage,neonatal pneumonia,hypofibrinogenemia,respiratory distress syndrome,sepsis,neonatal anemia,hypocalcemia and hypoalbuminemia in the four groups of newborns(P<0.05).Multiple linear regression showed that the birth head circumference of the newborn was related to the TBA level: the birth head circumference of the severe group was smaller than the control group(P=0.001);the birth head circumference of the extremely severe group was smaller than the control group(P=0.000).The head circumference of neonates that mothers with preeclampsia during pregnancy became smaller(P=0.000).The birth weight of the newborn is related to the TBA level: the birth weight of the newborn in the severe group is lower than the control group(P=0.012);the birth weight of the newborn in the extremely severe group is lower than the control group(P=0.002).The birth weight of neonates that mothers during pregnancy with preeclampsia became smaller(P=0.000).In addition,the greater the weight of pregnant women before delivery,the greater the birth weight of the newborn(P=0.003).Binary logistic regression analysis showed that high TBA level in the severe group was a risk factor for preterm birth,low birth weight infants,amniotic fluid fecal infection and neonatal hospitalization.Odds ratio(OR)values were 16.76(95% CI: 0.02~0.15),6.36(95% CI: 0.05~0.49),3.03(95% CI: 0.15~0.72)and 2.82(95% CI: 0.18~0.68).High TBA level in the extremely severe group was a risk factor for premature birth,low birth weight infants and neonatal hospitalization,with OR values of 25.13(95% CI: 0.01~0.18),10.59(95% CI: 0.02~0.50),9.78(95% CI: 0.03~0.42).Pregnant women with CHB and preeclampsia were risk factors for premature delivery(OR=5.05,95% CI: 0.05~0.81;OR=30.81,95% CI: 0.00~0.21).Pregnant women with preeclampsia was a risk factor for low-birth-weight babies(OR=30.81,95% CI: 0.00~0.24).Pregnant women HBs Ag positive and HBe Ag positive were risk factors for amniotic fluid fecal infection,OR values were 4.84(95% CI: 1.35-17.34)and 6.90(95% CI: 0.03~0.68).Cesarean section and gestational diabetes were risk factors for neonatal hospitalization,with OR values of 2.71(95% CI: 0.20~0.69)and 2.88(95% CI: 0.17~0.69),respectively.Conclusion: TBA levels in pregnant women with ICP are associated with preterm birth,low birth weight infant,amniotic fluid stool,neonatal admission rate and neonatal complications.CHB is a risk factor for affecting the TBA levels of pregnant women with ICP,which can easily lead to a sharp deterioration of the liver function and have the increased risk of adverse outcomes in mothers and their infants.Multivariate regression analysis showed that the higher TBA levels in pregnant women with severe and extremely severe groups should be at the increased risk for smaller neonatal head circumference and lower birth weight.High TBA levels in the severe and extremely severe groups are risk factors for premature birth,low birth weight infants and neonatal hospitalization.