During the enrollment period, the consecutive medical records of 1708 pregnancies at our center were reviewed. Among them, 1582 pregnancies were excluded for not progressed into liver cirrhosis (Fig. 1) and 126 pregnancies were diagnosed with liver cirrhosis before or during pregnancy. 97 pregnancies continued the pregnancy were enrolled into group A and 29 pregnancies discontinued for the concerning of disease progression were enrolled into group B. The group A were matched with 194 patients (1:2 ratio) without liver diseases based on the registration numbers and assigned to group C. All patients who received cesarean section in group A were further assigned into group A1 if the intrauterine balloon was used to prevent the postpartum hemorrhage or group A2 if not. The patients who were screened and enrolled in the different study groups are shown in Fig 1.
The Outcomes of the patients with liver cirrhosis or not
The clinical characteristics of patients at screening in each group are shown in Table 1. When compared to patients without liver cirrhosis (group C), patients with liver cirrhosis have significantly lower level of platelet(123.51±66.66 vs. 239.60±54.70*109/L,P=4.34*10-40), hemoglobin(117.37±14.91 vs. 124.97±14.13 g/L,P=3.7*10-7 ), Prothrombin activity (96.79±17.27 vs. 105.87±11.14%, p=1.0*10-5) and higher level of ALT(43.38±60.49vs.20.74±21.42 IU/L, p=5.98*10-4 ), Total Bilirubin( 20.35±39.31 vs.11.00±6.78 umol/L, p=0.023 ), and Creatinine (45.72±7.49 vs.43.00±6.65 umol/L, p=2.25*10-3). There were no differences of the other baseline values between two groups, including the age (30.79±5.01 vs.31.38±4.13, p=0.322), ratio of primigravida (36.1% vs.40.2%), and multiple pregnancy times (33% vs.48.2%).
As shown in table 2, a significantly higher frequency of negative outcomes (71.1% [69/97] vs12.9% [25/194], p<0.05) was observed in group A than group C. In terms of obstetrical complications, higher incidence of cesarean section (73.6 %vs.49.5%, P<0.05), postpartum hemorrhage (13.8% vs 2.1%, p<0.05) and blood transfusion (28.9% vs 2.1%, p<0.05) were observed in group A than group C. In Group A, 17.2 % (15/87) patients received intrauterine balloon pressure and 1 patient received subtotal hysterectomy to prevent further postpartum hemorrhage. In group C, only 3.7% (7/88) patients received intrauterine balloon pressure and no one underwent hysterectomy.
Other obstetrical outcomes, for example, ectopic pregnancy (3.1% vs. 0%, P=0.065), pregnancy-induced hypertension (8.2 vs.2.7, P=0.065), gestational diabetes mellitus( 20.7 %vs. 14.4%, P=0.187), placenta previa(4.6% vs. 1.1%, P=0.155), poor wound healing( 3.4% vs. 0.5%, P=0.181) and less oligohydramnios ( 1.1% vs.6.4%, P=0.057) seemed to be occurred in group A than group C, however no statistical significance were found.
In terms of liver-related disease, the rates of bleeding gums(7.2 %vs. 1.0%, P<0.05), TBA elevation (18.6 %vs.3.1%, P<0.05), new ascites or aggravating ascites(6.2% vs.0%,p<0.05), MODS(7.2% vs.0.5%, P<0.05) and intensive care unit admissions(24.1% vs 1.1%,P<0.05) were found in group A than group C.10.3% infection (4 bacterial peritonitis, 1 chorioamnionitis, 1 fungi infection, 3 severe pneumonia and 1 intestinal infections) were observed in group A. However, only 1 case with upper tract infection were observed in group C(P<0.05). There were no cases of maternal deaths but 2 cases of variceal bleeding in our study. One case was a tubal ectopic pregnancy and received laparoscopic Salpingectomy. 1 day later she underwent variceal bleeding more than 1000ml. The other case underwent variceal bleeding during postpartum. 8 patients were diagnosed with esophageal varices before the third trimester and 5 patients received endoscopic treatment or pericardial devascularization before delivery. One patient developed progressive jaundice at 8 weeks, and progressive disturbance of consciousness after a fall at 22 weeks, MRI indicated subdural hematoma and subarachnoid hemorrhage. She was recovered and delivered after treatment.
In terms of fetal/infant complications, a significantly higher frequency of preterm delivery (30.7% vs. 4.2%, p=6.89*10-10), low birth weight infant (13.6% vs. 2.6%, P=3.88*10-4), asphyxia of newborn (10.2% vs. 1.1%, P=9.42*10-4), neonatal ICU admission (9.1% vs. 1.6%, P=0.008) and fetal/newborn death (4.5% vs.0%, P=0.016) in group A than in group C. The intrauterine fetal death were occurred at 31.29±6.02weeks.
The Outcomes of the patientswith liver cirrhosis continued pregnancy or not
The clinical characteristics of the liver cirrhosis patients who continued the pregnancy or not were summarized in suppl Table 1. Compared to the patients who chose to continue the pregnancy, patients who discontinued the pregnancy for concerning the disease deteriorated had more history of gravidity (89.6% vs. 63.9%) and multipara (79.3% vs. 33%). More women in group B had Hypersplenism (thrombocytopenia or anemia) than group B (54.6%vs.79.3%, P=0.017). The lower level of PLT (85.34±54.49 vs. 123.52±66.66,p=0.006), PTA(.89.56±11.50 vs.96.79±17.27, p=0.036) and a higher level of Albumin(41.81±5.00 vs.39.49±5.22,p=0.036) were found in group B than group A. Compared to women who chose to discontinue the pregnancy, women in group B had more severe negative outcomes (32.0 vs.3.4, P=0.002).
The predictors of severe negative outcomes in patients who had liver cirrhosis and progressed into the third trimester
To investigate the predictors of severe negative outcomes in this population, we performed multivariate classification logistic regression analysis to compare the baseline variables. Patients with severe negative outcomes had a higher CTP scores (OR= 2.128, 95% CI:[ 1.002, 4.521] ,p=0.049) . Besides, patients with liver cirrhosis caused by Wilson’s disease had a better prognosis than by HBV infection (OR= 0.009, 95% CI: [0, 0.763], p=0.038). No other predictors of negative maternal outcomes were found with a significant difference in baseline values (suppl Table 2).