Maternal complications
We present only descriptive data on maternal complications since we could not conduct a meta-analysis for maternal complications, due to a lack of odds ratios in the published reports on this topic. Maternal death rate was reported by eight studies and ranged from 0 to 7.8%. In total, 25 events of maternal deaths in 2794 pregnancies of women with cirrhosis (0.89%) were recorded, compared to 0,010% in control pregnancies, which is an 80-fold increase in risk (OR 80.2 95% CI 27.3 - 235.1; p <0.0001) The total numbers of maternal deaths in recent studies (range 1982-2002) were lower than in older studies (range 2004-2016) (OR 2.9 95% CI 1.2-7.1; p = 0.02). This trend in decreasing maternal mortality over time is illustrated by the time sequenced plots of the incidences of included studies (Figure S2). The most common cause of maternal death was variceal hemorrhage (n=13), the majority of which occurred during vaginal delivery (n=9) and some occurred during pregnancy (n=2), during cesarean section (n=1) or in the postpartum period (n=1). Other causes of maternal mortality were sepsis (n=2), preeclampsia (n=1), hepatic decompensation (n=2), flare of autoimmune hepatitis (n=1) and unknown (n=6) (figure S3).
Variceal hemorrhage, either resulting in maternal death or not, occurred 113 times in 2858 pregnancies (4,0%) reported in ten studies. In most cases the occurrence of variceal hemorrhage during pregnancy was new and had not occurred preconceptionally. The rate of preconceptional esophageal varices was mentioned in none of the included studies. In total 12% of variceal hemorrhage ended in maternal death (n=13). The total numbers of variceal hemorrhage in recent studies (range 1982-2002) were lower than in older studies (range 2004-2016) (OR 2.7 95% CI 1.7-4.1; p <0.0001), as is illustrated in the time sequenced plot of incidences of variceal hemorrhage (figure S4). In the study of Rasheed et all. 47% of pregnancies were complicated by variceal hemorrhage. The remaining seven studies found lower percentages of variceal hemorrhage varying between 0 and 16%. Screening endoscopy for esophageal varices during pregnancy was reported in five recent studies with rates of 3, 17, 28, 35 and 60%. Accompanying endoscopic therapy for (non-bleeding) esophageal varices was reported in three studies with rates 5, 23 and 28%.
The incidence of decompensated liver cirrhosis varied between 2 and 21%, with an outlying incidence in the study of Rasheed et al., who reported 64%. Ascites prevalence was reported in five studies and ranged from 3 to 11%. Hepatic encephalopathy was also reported in five studies and ranged from 1 to 13%.