Integration of cervicovaginal microbiota, metabolome and host response data provide useful insight into preterm birth risk stratification in an ethnically diverse cohort.
Obstetric cholestasis is a liver disorder unique to pregnancy, which typically presents with pruritus. However, pruritus is common in pregnancy and the diagnosis of obstetric cholestasis is confirmed by finding abnormal liver function. We report 10 cases in which pruritus occurred before any abnormality in liver function tests (including total serum bile acids) and discuss the implications of this for clinical practice.
Endothelial dysfunction is a key feature of diabetes mellitus and is thought to be the major cause of vascular complications associated with the disease. The vascular endothelium demonstrates impaired synthesis of vasodilators and increased release of procoagulants and vasoconstrictors, defects which theoretically could explain the increased incidence of atherosclerosis and hypertension found within this patient group. The pathways mediating endothelial cell layer dysfunction are unknown, although many candidates have been proposed. This review concentrates on the hypothesis that increased oxidative stress combined with abnormal plasma lipid composition leads to reduced synthesis of endothelial vasodilators and hence endothelial dysfunction. Free radical generation is undoubtedly raised in diabetes but the evidence for decreased antioxidant status is debatable. The role of antioxidant and lipid-lowering therapy is considered, but few studies have directly investigated the effect of treatment on vascular function. Concern arises from individual studies of vitamin E in diabetic animals which have proved deleterious. Current literature implies that a combination therapy of vitamin E and vitamin C may be beneficial, but this needs to be investigated further in both animal and human diabetes.
Background Ursodeoxycholic acid is commonly used to treat intrahepatic cholestasis of pregnancy, yet its largest trial detected minimal benefit for a composite outcome (stillbirth, preterm birth, and neonatal unit admission). We aimed to examine whether ursodeoxycholic acid affects specific adverse perinatal outcomes.Methods In this systematic review and individual participant data meta-analysis, we searched PubMed, Web of Science, Embase, MEDLINE, CINAHL, Global Health, MIDIRS, and Cochrane without language restrictions for relevant articles published between database inception, and Jan 1, 2020, using search terms referencing intrahepatic cholestasis of pregnancy, ursodeoxycholic acid, and perinatal outcomes. Eligible studies had 30 or more study participants and reported on at least one individual with intrahepatic cholestasis of pregnancy and bile acid concentrations of 40 µmol/L or more. We also included two unpublished cohort studies. Individual participant data were collected from the authors of selected studies. The primary outcome was the prevalence of stillbirth, for which we anticipated there would be insufficient data to achieve statistical power. Therefore, we included a composite of stillbirth and preterm birth as a main secondary outcome. A mixed-effects meta-analysis was done using multi-level modelling and adjusting for bile acid concentration, parity, and multifetal pregnancy. Individual participant data analyses were done for all studies and in different subgroups, which were produced by limiting analyses to randomised controlled trials only, singleton pregnancies only, or two-arm studies only. This study is registered with PROSPERO, CRD42019131495. FindingsThe authors of the 85 studies fulfilling our inclusion criteria were contacted. Individual participant data from 6974 women in 34 studies were included in the meta-analysis, of whom 4726 (67•8%) took ursodeoxycholic acid. Stillbirth occurred in 35 (0•7%) of 5097 fetuses among women with intrahepatic cholestasis of pregnancy treated with ursodeoxycholic acid and in 12 (0•6%) of 2038 fetuses among women with intrahepatic cholestasis of pregnancy not treated with ursodeoxycholic acid (adjusted odds ratio [aOR] 1•04, 95% CI 0•35-3•07; p=0•95). Ursodeoxycholic acid treatment also had no effect on the prevalence of stillbirth when considering only randomised controlled trials (aOR 0•29, 95% CI 0•04-2•42; p=0•25). Ursodeoxycholic acid treatment had no effect on the prevalence of the composite outcome in all studies (aOR 1•28, 95% CI 0•86-1•91; p=0•22), but was associated with a reduced composite outcome when considering only randomised controlled trials (0•60, 0•39-0•91; p=0•016).Interpretation Ursodeoxycholic acid treatment had no significant effect on the prevalence of stillbirth in women with intrahepatic cholestasis of pregnancy, but our analysis was probably limited by the low overall event rate. However, when considering only randomised controlled trials, ursodeoxycholic acid was associated with a reduction in stillbirth in combination with pr...
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