492 Ursodeoxycholic acid and perinatal outcomes in intrahepatic cholestasis of pregnancy: an individual patient data meta-analysis

Abstract

Ursodeoxycholic acid (UDCA) is a commonly used pharmacological treatment for intrahepatic cholestasis of pregnancy (ICP), yet the largest clinical trial of its use detected minimal benefit for a composite perinatal outcome (stillbirth, preterm birth and neonatal unit admission), and evidence for perinatal benefit was not concluded in the 2020 Cochrane review. We aimed to determine whether UDCA affects adverse fetal and maternal outcomes for singleton pregnancies using an individual patient data meta-analysis of participants of randomized controlled trials (RCTs). Following a systematic review of the literature, authors were invited to submit individual patient data. We performed a fixed-effects meta-analysis using multilevel modelling, adjusting for bile acid concentration at randomization and parity. Analyses were performed in STATA version 16.0; this was part of a study registered in PROSPERO: CRD42019131495. Data were provided for 755 women from four RCTs, of whom 388 (51%) took UDCA. UDCA treatment was not associated with a difference in stillbirth (adjusted odds ratio 0.40, 95% confidence interval 0.04 to 4.68, p=0.469). However, UDCA was associated with a reduced composite of stillbirth and preterm birth (aOR 0.51, 95% CI 0.33 to 0.78, p=0.002), with reduced overall preterm birth for women randomized to UDCA (aOR 0.52, 95% CI 0.34 to 0.80, p=0.003). This was predominantly due to reduced spontaneous preterm birth (aOR 0.46, 95% CI 0.25 to 0.86, p=0.015) as iatrogenic preterm birth was not affected by UDCA treatment (aOR 0.63, 95% CI 0.37 to 1.10, p=0.114). The number needed to treat to prevent one composite outcome was 13.5 (95%CI 8.0 to 41.4), and for spontaneous preterm birth was 24.4 (95% CI 13.0 to 193.2). By using individual patient data, we revealed that spontaneous preterm birth was reduced for women with ICP taking UDCA in singleton pregnancies, as was a composite outcome of stillbirth and preterm birth. This abstract is presented on behalf of an International Study Collaborative.