Objective To determine the optimal total serum bile acid (TSBA) threshold and sampling time for accurate intrahepatic cholestasis of pregnancy (ICP) diagnosis. Design Case–control, retrospective cohort studies. Setting Antenatal clinics, clinical research facilities. Population Women with ICP or uncomplicated pregnancies. Methods Serial TSBA measurements were performed pre‐/postprandially in 42 women with ICP or uncomplicated pregnancy. Third‐trimester non‐fasting TSBA reference ranges were calculated from 561 women of black, south Asian and white ethnicity. Rates of adverse perinatal outcomes for women with ICP but peak non‐fasting TSBA below the upper reference range limit were compared with those in healthy populations. Main outcome measures Sensitivity and specificity of common TSBA thresholds for ICP diagnosis, using fasting and postprandial TSBA. Calculation of normal reference ranges of non‐fasting TSBA. Results Concentrations of TSBA increased markedly postprandially in all groups, with overlap between healthy pregnancy and mild ICP (TSBA <40 μmol/l). The specificity of ICP diagnosis was higher when fasting, but corresponded to <30% sensitivity for diagnosis of mild disease. Using TSBA ≥40 μmol/l to define severe ICP, fasting measurements identified 9% (1/11), whereas non‐fasting measurements detected over 91% with severe ICP. The highest upper limit of the non‐fasting TSBA reference range was 18.3 µmol/l (95% confidence interval: 15.0–35.6 μmol/l). A re‐evaluation of published ICP meta‐analysis data demonstrated no increase in spontaneous preterm birth or stillbirth in women with TSBA <19 µmol/l. Conclusions Postprandial TSBA levels are required to identify high‐risk ICP pregnancies (TSBA ≥40 μmol/l). The postprandial rise in TSBA in normal pregnancy indicates that a non‐fasting threshold of ≥19 µmol/l would improve diagnostic accuracy. Tweetable abstract Non‐fasting bile acids improve the diagnostic accuracy of intrahepatic cholestasis of pregnancy diagnosis.

Cardiac fibrosis occurs in a wide range of cardiac diseases and is characterised by the transdifferentiation of cardiac fibroblasts (FB) into myofibroblasts (MFB). Myofibroblasts produce large quantities of extracellular matrix proteins, resulting in myocardial scar. The antifibrotic effect of the bile acid ursodeoxycholic acid (UDCA) is established in cases of liver fibrosis but not the adult myocardium.Our hypothesis is: UDCA is antifibrotic in the adult heart, mediated by the membrane bile acid receptor Takeda G protein-coupled receptor 5 (TGR5).We constructed a predictive network of fibrosis using RNA-seq datasets. We found that UDCA and it’s analogue INT-777, both reduced MFB markers in rat and human FBs and living myocardial slices (LMS). Utilising a knock-out mouse model, we show that the antifibrotic effect of UDCA is mediated by TGR5. Finally, we performed RNA-seq upon UDCA-treated human FB and integrated with our network of fibrosis, establishing the mechanism of TGR5 agonists.

Linked article: This is a mini commentary on, Huri et al., pp. 1887–1896 in this issue. To view this article visit https://doi.org/10.1111/1471‐0528.17174

Essential fatty acids (EFAs) and their derivatives, the long and very long chain polyunsaturated fatty acids (LC-PUFAs), are preferentially transported by the mother to the fetus. Failure to supply EFAs is strongly linked with stillbirth, fetal growth restriction, and impaired neurodevelopmental outcomes. However, dietary supplementation during pregnancy is unable to simply reverse these outcomes, suggesting imperfectly understood interactions between dietary EFA intake and the molecular mechanisms of maternal supply. Here we combine untargeted lipidomics with transcriptional profiling of healthy and genetically-manipulated murine models to understand the maternal adaptations required to provide LC-PUFAs to the developing fetus. We discovered a late pregnancy-specific, selective activation of the Liver X Receptor signalling pathway which dramatically increases maternal supply of LC-PUFAs within circulating phospholipids. Crucially, genetic ablation of this pathway in the mother reduced LC-PUFA accumulation by the fetus. Overall our work suggests new molecular strategies for improving maternal-fetal transfer of these important lipids.