273. Adverse perinatal outcomes of intrahepatic cholestasis of pregnancy and association with biochemical markers: Results of aggregate and independent patient data meta-analyses

Abstract

Background Whilst intrahepatic cholestasis of pregnancy (ICP) is associated with adverse perinatal outcomes, the relationship between specific biochemical markers and individual pregnancy complications has not been established. Methods We performed a systematic review of the literature (PubMed, Web of Science, Embase databases from inception to August 2017, selecting studies reporting perinatal outcomes for women with ICP with serum bile acid concentrations reported. Random effects meta-analysis was performed to determine risk of adverse perinatal outcomes. Individual patient data (IPD) were collected to assess associations between biochemical markers and adverse outcomes using logistic and stepwise linear regression (PROSPERO: CRD42017069134). Findings 22 studies were included in the meta-analysis (5515 ICP cases, 165 081 controls), with IPD from 18 studies (4163 ICP cases). Stillbirth complicated 0.83% ICP and 0.32% control pregnancies (OR 1.46 (0.73–2.89)). Stillbirth was associated with maximum total bile acid concentration (ROC AUC 0.80 (0.69–0.90)) but not alanine transaminase (ROC AUC 0.46, 95% CI 0.35–0.58). Prevalence of stillbirths was 0.20% (0.05–0.50%) with serum total bile acids Interpretation The risk of stillbirth is increased in women with ICP, but not significantly greater than population rates until serum bile acids ⩾100 μmol/L. The clear bile acid threshold of 100 μmol/L beneath which stillbirth rates were not elevated is a novel and important finding in our study. As most women with ICP have bile acids below this level, they can be reassured, provided repeat bile acid testing is performed.