Prevalence, risk factors and adverse perinatal outcomes for Chinese women with intrahepatic cholestasis of pregnancy: a large cross-sectional retrospective study

Abstract

Background Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-related liver disorder and may cause adverse perinatal outcomes. This large cross-sectional retrospective study aimed to evaluate the prevalence and related risk factors of ICP and determine the adverse perinatal outcomes. Methods This large cohort study from 1 January 2018 to 31 December 2019, included 39,742 eligible pregnant women. Data were extracted from the institutional electronic medical record database and analyzed using univariate and multivariate logistic regression models to determine the risk factors and adverse perinatal outcomes of ICP. Results The overall prevalence of ICP was 3.81%. It was significantly higher in hepatitis B surface antigen (HBsAg) positive than negative women in all age groups, and in women with pre-pregnancy BMI underweight and obesity aged <25 years and ≥35 years than the other age groups. Multivariate logistic regression models showed an increased risk of ICP associated with maternal age <25 years and ≥35 years, pre-pregnancy underweight and obesity, HBsAg positive status, twin pregnancies, low maternal education, inadequate gestational weight gain, multiparous, in vitro fertilization, caesarean section history and the number of abortions ≥2. The presence of ICP was associated with increased risk of maternal outcomes of caesarean section and preterm birth, and neonatal outcomes of low birth weight and neonatal unit admission in singleton and twin pregnancies. Conclusion This study identified the prevalence, possible risk factors, and associated adverse perinatal outcomes of ICP, which provides useful information for clinicians to identify, counsel, and provide timely management for women at risk. KEY MESSAGES Maternal age <25 and ≥35, pre-pregnancy BMI underweight and obesity, hepatitis B surface antigen-positive status, twin pregnancies, low maternal education, inadequate gestational weight gain, multiparous, in vitro fertilization, caesarean section history and the number of abortions ≥2 are associated with an increased risk of ICP. Further, pregnancies with ICP are associated with an increased risk of maternal outcomes of caesarean section and preterm birth and neonatal outcomes of low birth weight and neonatal unit admission in singleton and twin pregnancies.

Clinical Management Guidelines for Intrahepatic Cholestasis of Pregnancy

“…High-risk factors for ICP revealed in published clinical studies are not entirely consistent. A cohort study of 39,742 pregnant women showed that maternal age younger than 25 years or older than 35 years, low or high prepregnancy body mass index (BMI), being positive for hepatitis B surface antigen, multiple pregnancies, low maternal education level, insufficient pregnancy weight gain, in vitro fertilization, history of cesarean delivery, or history of two or more miscarriages were all associated with an increased risk of ICP 7 . In addition to these factors, a retrospective study of 39,244 pregnant women found that those with gestational hypertension, preeclampsia, thrombocytopenia, hyperlipidemia, and gestational diabetes mellitus (GDM) had a higher risk of ICP than others 8 .…”

The correlation between serum total bile acid and adverse perinatal outcomes in pregnant women with intrahepatic cholestasis of pregnancy (ICP) and non-ICP hypercholanemia of pregnancy

“…Several noteworthy clinical observations regarding liver disease with hypercholanemia warrant emphasis. Researchers have already looked at studies with hepatitis patients and found that HBsAg-positive ICP patients had much higher levels of serum TBA and a higher risk of bad outcomes during pregnancy [ 9 ]. However, these studies did not compare the risk of poor pregnancy outcomes at the same TBA levels between ICP and other hypercholanemias in pregnancy.…”

“…The presence of risk factors or co-morbidities can increase the risk of stillbirth in women with ICP, according to the ICP clinical guideline published in the British Journal of Obstetrics and Gynaecology (BJOG) in 2022 [ 18 ]. There is a lot of evidence that hepatitis increases oxidative stress during the development of hypercholanemia [ 33–35 ], which leads to higher levels of total TBA in the peripheral blood compared to ICP [ 9 , 30 , 36 ]. Therefore, in patients who have TBA ≥100µmol/L and also have liver disease, excessive TBA concentrations and liver disease could work together to cause oxidative stress, which raises the risk of perinatal death.…”

The Incidence of Intrahepatic Cholestasis of Pregnancy and its Maternal, Fetal, and Neonatal Adverse Outcomes: A Systematic Review and Meta‐Analysis

“…Every study included in this systematic review scored greater than 50% on the quality checklist. Seven of the studies synthesized in this systematic review and meta-analysis were of moderate quality, 22,24,29,33,32,34,37 and three were of good quality 30,35,36 (Table 1).…”