Twin pregnancies with ICP had a higher risk of CS, PTB, fetal distress, and NICU admission than singleton pregnancies with ICP. Higher TBA levels were linked to a higher risk of these adverse perinatal outcomes. Furthermore, we discovered a significant positive correlation between maternal serum, amniotic fluid, and umbilical cord blood TBA levels. Similarly, maternal TBA levels were significantly correlated with umbilical cord blood TBA, TB, GLB, ALB, CRE, Cl, and Mg.
Elderly maternal age, a family history of ICP, ICP in a previous pregnancy, and multiple pregnancies have been linked to an elevated risk of ICP [10, 24, 25]. ART, such as IVF-ET and/or ICSI, is associated with an increased risk of PPROM and ICP in twin pregnancies [5, 26]. Similarly, in our study, we discovered that the incidence of a history of ICP and IVF-ET was higher in twin pregnancies than in singleton pregnancies with ICP.
ICP is associated with increased rates of adverse perinatal outcomes [27, 28]. The rates of perinatal mortality, MSAF, fetal distress, and spontaneous PTB were found to be 3.5-11%, 27-45%, 14-22%, and 30-44% in ICP, respectively [29]. Effective fetal surveillance that can lower the risk of adverse fetal outcomes is currently lacking, and few studies have examined twin pregnancy and ICP. In our research, we discovered that twin pregnancies with ICP had a greater rate of CS, PTB, fetal distress, and NICU admission than singleton pregnancies with ICP, implying that ICP is more severe in twin pregnancies than in singletons.
The most lethal adverse perinatal complication of ICP is sudden stillbirth [30]. Stillbirth risk was higher in all cases of ICP [9], especially in those with peak serum TBA ≥ 100 μmol/L [28]. Elevated TBA could cause vasoconstriction disorders in the placental chorionic vessels and umbilical vein [5, 8, 10], which could be a factor in the increased risk of fetal distress, asphyxia, and sudden stillbirth in ICP [3, 5, 31]. ICP with TBA ≥ 100 μmol/L causes 6.8% of prenatal deaths [32]. Most stillbirths of singletons with ICP occur after 37 weeks of pregnancy [33], whereas stillbirths occur at an earlier gestational age in twin pregnancies with ICP. Stillbirth occurs in approximately 3.9% of twin pregnancies with ICP, according to Liu et al. [34]. In our study, the rate of stillbirth in twin pregnancies with ICP was 0.4% (5/633). Our hospital’s aggressive perinatal care management strategies, which were implemented to prevent stillbirth, are responsible for the reduced incidence of stillbirth in twin pregnancies with ICP.
The main concern of ICP management is stillbirth. The perinatal management of twin pregnancies with ICP is challenging for the obstetrician. Given the higher risk of fetal death, different guidelines recommend active management, such as enhanced monitoring and early delivery, to reduce the risk of fetal complications [5], which in turn increases the incidence of iatrogenic PTB [28]. The increased rate of iatrogenic PTB, especially in twin pregnancies, may be due to the active management of ICP. Similarly, our findings corroborated similar conclusions. We discovered that the rate of stillbirth was 0.4% in twin pregnancies with ICP, while the rate of PTB was 82.6%.
In twin pregnancies, ICP is a risk factor for PTB. However, the optimal time of delivery for women with twin pregnancies and ICP has not yet been determined. The reduction in stillbirths needs to be balanced with with the morbidities of prematurity and other perinatal problems. Based on our center’s experience, close antenatal monitoring and active and individual perinatal management are needed. Moreover, the timing of delivery should be discussed on an individual basis according to the known perinatal risk and benefits of available management options.
Our findings also suggest that peak TBA levels may fluctuate throughout pregnancy and may rise rapidly near term, even with medication therapy. Maximum TBA levels were linked to an increased risk of stillbirth in both drug-treated and untreated ICP [28]. Hence, the close and regular monitoring of serum TBA levels is essential; additionally, once ICP is diagnosed, repeating the TBA test until delivery is recommended to help guide the perinatal management of ICP, particularly in severe cases such as twin pregnancies with ICP.
In ICP, UDCA has been shown to relieve maternal pruritus, lower serum TBA levels, and improve liver function [10, 24, 35]. UCDA treatment was provided to all study participants in ours study. Furthermore, we discovered that high TBA levels reverted to normal levels almost 1 to 5 weeks after birth and that liver function returned to normal 4 to 6 weeks thereafter.
Brouwers, L. et al. [22] discovered a positive correlation between maternal serum TBA levels at diagnosis and delivery and umbilical cord blood TBA levels, indicating that TBA can be transported across the placenta. Similarly, we explored the correlations between maternal serum, umbilical cord blood, and amniotic fluid TBA levels in twin pregnancies with ICP. Our findings revealed a strong positive correlation between maternal serum, amniotic fluid, and umbilical cord blood TBA levels. TBA levels in maternal serum, umbilical cord blood, and amniotic fluid have all been found to be higher, which could be due to maternal-fetal circulation. As a result, we hypothesize that TBA is transported through the placenta and is involved in the utero-placental-fetal circulation.
Changes in bile salt and electrolyte transport processes, as well as lipid structure, may be involved in the etiology of ICP, according to Reyes H, et al. [36]. However, the linked etiological mechanism has not been investigated since then. TBA, TB, ALB, GLB, CRE, Cl, and Mg levels in umbilical cord blood had a strong positive correlation with maternal serum TBA levels in our study. This finding may provide some scientific evidence and direction for the etiological mechanism study of bile salt and electrolyte transport pathways in ICP.
An advantage of the current study is that it was one of the largest cohort studies in China focusing on the effect of different categories of TBA levels on the perinatal outcomes of twin pregnancies with ICP. This cohort was studied using the modern active management strategy, as well as dynamic and continuous testing of liver function and TBA levels during pregnancy. Second, we were the first to investigate the link between maternal serum, umbilical cord blood, and amniotic fluid. Finally, we are the first to investigate the link between maternal serum TBA levels and umbilical cord blood electrolyte and bilirubin levels. Our findings point to new directions for research and a better understanding of the etiological mechanisms of bile salt and electrolyte transport pathways in ICP. However, because this work was a single-center retrospective study, it has limitations. A large-scale, multicenter cohort study is necessary in the future to investigate alternative diagnostic and therapeutic interventions in ICP.