Our study findings indicate that the concentrations of DBIL, TBA, ALT, AST, ALP, GGT, and LDH in the MCDA group were significantly higher than those in the DCDA group. Additionally, TBA level > 40 µmol/l was a risk factor only in monochorionic twin pregnancies after controlling for maternal age, prepregnancy BMI, gravidity, parity and conception method. In dichorionic twin pregnancies, TBIL level>17.1 µmol/l, AST level >200 U/L, and ALP level >400 U/L were associated with a higher risk of adverse neonatal outcomes after controlling for possible confounding factors.
Interpretation of Study Findings and Comparison with Published Literature
In comparison with singleton pregnancies, twin pregnancies tend to have an increased risk of maternal mortality and pregnancy-associated complications, such as GDM, HDP and PPH, with an earlier disease presentation and higher levels of maternal serum total bile acids[7]. Importantly, twin gestations have also been identified as being linked to the development of ICP[13], and adverse maternal and foetal outcomes were strongly associated with ICP in twin patients[10], which may be explained by elevated sex hormone levels; however, perinatal outcomes between MC and DC twin gestations complicated by ICP have rarely been reported.
Interestingly, the concentrations of DBIL, TBA, ALT, AST, ALP, GGT, and LDH in the MC group were significantly higher than those in the DC group, and we have not yet found other corresponding research to explain these intriguing findings. However, it was noteworthy that neonatal pneumonia and LBGI occurred more frequently in MC twins than in DC twins and that twin offspring delivered from monochorionic pregnancies had a lower mean birth weight and higher proportion of deliveries occurring between 34 and 37 weeks of gestation than those born from dichorionic pregnancies. This may be relevant to the higher prenatal maternal liver function biochemical parameters resulting in iatrogenic premature delivery in MC twin pregnancies. Xu’s study also reported that most of the foetuses of twin pregnancies with ICP were born before 37 weeks[9]. Mei’s retrospective study provided evidence that for women with MC twin pregnancy with ICP, TBA>40 μmol/L was associated with adverse perinatal outcomes[12], which was similar to what we found. The severity of hypercholanaemia is associated with adverse foetal outcomes, such as stillbirth, when maternal TBA concentrations exceed 40 μmol/L, and the association is markedly evident at ≥100 μmol/L[4,5]. TBA can be transported through the placenta and is involved in uterine-placental foetal circulation[14]. Studies have demonstrated an association between higher maternal bile acid levels and increased rates of foetal complications, particularly when serum bile acids are raised above 40 μmol/L[6]. Elevated TBA could increase oxytocin sensitivity of uterine muscle and cause vasoconstriction disorders in the placental chorionic vessels and umbilical vein, which could be a factor in the increased risk of foetal distress, asphyxia and stillbirth in ICP[15-17], especially when a placenta is shared in a MC twin pregnancy. It has been reported that bile acids are a key factor in the disruption of the structure of pulmonary surfactant in neonates from ICP pregnancies, and this has important implications for neonatal respiratory failure[18].
In addition, Mei's team also found that after adjusting for confounders, AST levels >200 U/L and ALP levels >400 U/L were associated with adverse perinatal outcomes in DC twin pregnancy complicated by ICP[8]. Our study had similar results to previous studies. Our study also indicated that TBIL levels exceeding 17.1 μmol/l were related to a higher risk of adverse neonatal outcomes in DC twin pregnancies, but we did not find similar results in MC twin pregnancies with ICP. Serum TBIL can reflect the early stage of intrahepatic cholestasis in pregnant women. TBIL is the combination of direct and indirect bilirubin. A sharp increase in the DBIL level often indicates the occurrence of obstructive jaundice so that it cannot be discharged from the biliary tract smoothly and can only enter the blood circulation, causing the serum TBIL to be at a high level. Elevated bilirubin can inhibit oxidative phosphorylation in nerve cells, reduce ATP production and increase the cytotoxicity of bile acids. However, data on the relationship between elevated total bilirubin levels and perinatal outcomes are inadequate in the previous literature. Although the mechanism is unclear, DC twin pregnancies with elevated AST, ALP and TBIL require intensified surveillance and management based on our results.
Clinical and Research Implications
ICP affected foetal outcomes, and when chorionicity was taken into consideration, although there was no difference in the incidence of neonatal stillbirth between the two groups, TBA>40 μmol/L was an independent risk factor for adverse perinatal outcomes in MC pregnancies, while TBIL level>17.1 µmol/l, AST level >200 U/L and ALP level >400 U/L were associated with a higher risk of adverse neonatal outcomes in dichorionic pregnancies. In addition, the serum biochemistry concentrations of DBIL, TBA, ALT, AST, ALP, GGT, and LDH in the MC group seemed to be apparently higher than those in the DC group. Evidence in previous literature is very limited regarding comparing the neonatal outcomes of monochorionic and dichorionic twin pregnancies complicated by ICP. Our findings indicated that monitoring predelivery liver function biochemical indexes in pregnant women according to chorionicity might facilitate personalized antenatal management to balance the iatrogenic prematurity risk and improve neonatal outcomes.
Strengths and Limitations
To our knowledge, this study is the first to compare the neonatal outcomes of monochorionic and dichorionic twin pregnancies complicated by ICP. The main strength was that we analysed the predictors of adverse outcomes in different chorionic twins. This result may help providers when they make delivery plans for patients with ICP in monochorionic and dichorionic twin pregnancies. In addition, we excluded twin pregnancies complicated by TTTS, TAPS and TRAPS to reduce bias in the assessment of neonatal outcomes. Several limitations of this study should be mentioned. First, this study was a single-centre study, and because it was not entirely population based nationally, the findings do not have reference value for populations in other regions. The data should therefore be interpreted with care because a selection bias may have been introduced due to regional divergence, and multicentre studies with adequate power remain warranted. Second, our study was retrospective, and medical records rather than direct patient interviews were used to obtain the data. Several maternal variables were not fully documented.