Pregnancy is associated with progressive hypercholanemia, hypercholesterolemia, and hypertriglyceridemia, which can result in metabolic disease in susceptible women. Gut signals modify hepatic homeostatic pathways, linking intestinal content to metabolic activity. We sought to identify whether enteric endocrine signals contribute to raised serum bile acids observed in human and murine pregnancies, by measuring fibroblast growth factor (FGF) 19/15 protein and mRNA levels, and 7α‐hydroxy‐4‐cholesten‐3‐one. Terminal ileal farnesoid X receptor (FXR)‐mediated gene expression and apical sodium bile acid transporter (ASBT) protein concentration were measured by qPCR and western blotting. Shotgun whole‐genome sequencing and ultra‐performance liquid chromatography tandem mass spectrometry were used to determine the cecal microbiome and metabonome. Targeted and untargeted pathway analyses were performed to predict the systemic effects of the altered metagenome and metabolite profiles. Dietary CA supplementation was used to determine whether the observed alterations could be overcome by intestinal bile acids functioning as FXR agonists. Human and murine pregnancy were associated with reduced intestinal FXR signaling, with lower FGF19/15 and resultant increased hepatic bile acid synthesis. Terminal ileal ASBT protein was reduced in murine pregnancy. Cecal bile acid conjugation was reduced in pregnancy because of elevated bile salt hydrolase‐producing Bacteroidetes. CA supplementation induced intestinal FXR signaling, which was not abrogated by pregnancy, with strikingly similar changes to the microbiota and metabonome as identified in pregnancy. Conclusion: The altered intestinal microbiota of pregnancy enhance bile acid deconjugation, reducing ileal bile acid uptake and lowering FXR induction in enterocytes. This exacerbates the effects mediated by reduced bile acid uptake transporters in pregnancy. Thus, in pregnant women and mice, there is reduced FGF19/15‐mediated hepatic repression of hepatic bile acid synthesis, resulting in hypercholanemia.

Introduction: Intrahepatic cholestasis of pregnancy is characterised by pruritus and elevated serum bile acids. The pruritus can be severe, and pharmacological options achieve inconsistent symptomatic improvement. Raised bile acids are linearly associated with adverse fetal outcomes, with existing management of limited benefit. We hypothesised that therapeutic plasma exchange removes pruritogens and lowers total bile acid concentrations, and improves symptoms and biochemical abnormalities in severe cases that have not responded to other treatments.Methods: Four women with severe pruritus and hypercholanemia were managed with therapeutic plasma exchange. Serial blood biochemistry and visual analogue scores of itch severity were obtained. Blood and waste plasma samples were collected before and after exchange; individual bile acids and sulfated progesterone metabolites were measured with HPLC‐MS, autotaxin activity and cytokine profiles with enzymatic methods. Results were analysed using segmental linear regression to describe longitudinal trends, and ratio t tests.Results: Total bile acids and visual analogue itch scores demonstrated trends to transiently improve following plasma exchange, with temporary symptomatic benefit reported. Individual bile acids (excluding the drug ursodeoxycholic acid), and the sulfated metabolites of progesterone reduced following exchange (P = .03 and P = .04, respectively), whilst analysis of waste plasma demonstrated removal of autotaxin and cytokines.Conclusions: Therapeutic plasma exchange can lower potentially harmful bile acids and improve itch, likely secondary to the demonstrated removal of pruritogens. However, the limited current experience and potential complications, along with minimal sustained symptomatic benefit, restrict its current use to women with the most severe disease for whom other treatment options have been exhausted.

Vestibular migraine is a leading cause of vertigo in pregnancy and, although not a distinct migraine subtype, is an episodic syndrome associated with migraine. Vestibular migraine is associated with diverse symptoms such as vertigo, aura, allodynia, osmophobia, nausea, vomiting and tinnitus, many of which may be exacerbated by, masked or even dismissed in pregnancy. Vestibular migraine is likely an underdiagnosed and undertreated condition in pregnancy. The aetiology of vestibular migraine remains incompletely understood, although various theories have been proposed, including genetic predisposition, neurochemical dysregulation and pro-inflammatory mechanisms, all of which are derived from the pathophysiology of classical migraine. Physiologic changes to the endocrine, haematologic and vascular systems in pregnancy may affect pathophysiological processes in vestibular migraine, and can alter the course of symptoms experienced in pregnancy. These changes also predispose to secondary headache disorders, which may have similar presentations. There has been considerable progress in therapeutic advances in vestibular migraine prophylaxis and treatment outside of pregnancy. There is currently no significant evidence base for acute treatment or prophylaxis for pregnant patients, with treatment recommendations extrapolated from studies on classical migraine, and offered on a benefit versus risk basis. Challenges commonly encountered include difficulty establishing a diagnosis, in addition to recognising and treating neuropsychiatric and gestational co-morbidities. Anxiety, depression, hypertensive disorders and cardiovascular disease are closely associated with migraine, and important contributors to morbidity and mortality during pregnancy. Identifying and treating vestibular migraine during pregnancy offers a unique opportunity to impact future patient health through screening and early treatment of associated co-morbidities. There have been innovations in classical migraine therapy that may confer benefit in vestibular migraine in pregnancy, with emphasis on lifestyle modification, effective prophylaxis, abortive therapies, cognitive behaviour therapy and management of vestibular migraine-related comorbidities.

Objective: Establish whether pregnancies complicated by gestational diabetes mellitus (GDM) are associated with a fetal cardiac phenotype that predisposes to arrhythmia; utilising measurements derived from non‐invasive abdominal fetal ECG.Design: Prospective observational study.Setting: Three tertiary obstetric units, United Kingdom.Population: Women aged ≥ 16 years with either GDM or uncomplicated pregnancy (control) who were > 20 weeks gestational age.Methods: The MonicaAN24 non‐invasive abdominal fetal ECG monitor was fitted for overnight recording.Main Outcome Measure: Calculation of the fetal heart rate (FHR) and fetal heart rate variability (HRV) time domain metrics standard deviation of normal‐to‐normal intervals (SDNN), root mean square of successive differences (RMSSD) and the PR, QRS, QT intervals was performed. Groups were compared using linear regression models (stratified by sleep state) and adjusted for fetal sex and ethnicity.Results: Ninety‐six participants were included. For HRV in sleep state 1F, SDNN was higher for GDM than control participants 12.56 (10.45–16.62)ms versus 8.58 (5.83–9.73)ms [p = 0.01] [median (IQR)]. There were no differences in SDNN in sleep state 2F. No differences were identified in RMSSD in either sleep states or in the cardiac time intervals. We observed a negative correlation between HRV and body mass index/HbA1c and a positive correlation between FHR and body mass index/HbA1c in sleep states 1F/2F.Conclusions: Alterations of HRV and FHR rate may be associated with a diagnosis of GDM, likely secondary to altered autonomic function in utero.

Objective: Describe maternal/fetal outcomes of pregnant women with cirrhosis.Design: Prospective, national cohort study utilising the UK Obstetric Surveillance System between 1st June 2017 and 30th November 2020.Setting: UK.Population: Pregnant women with cirrhosis.Methods: Rates of adverse perinatal outcomes were compared with published rates for uncomplicated pregnancies. The prediction of adverse pregnancy outcomes by albumin‐bilirubin (ALBI) score was determined.Main Outcome Measures: Maternal and fetal outcomes.Results: 52 eligible cases were reported (denominators represent available data for each outcome). Commonest causes included autoimmune hepatitis (12/50 (24.0%)), cholestatic disease (9/50 (18.0%)) and viral disorders (8/50 (18.0%)). Maternal decompensation occurred in seven women. Worst ALBI score predicted decompensation and maternal ICU admission (AUROC 0.80 (p = 0.03) and 0.81 (p = 0.03), respectively). Untreated varices were associated with increased rates of variceal bleed (p = 0.01). No women died. There were 42 live births (51.2% preterm), one stillbirth, and two neonatal deaths. The worst ALBI score in pregnancy predicted pre‐term birth (AUROC 0.74 (p = 0.03)). Compared to a healthy population, women with cirrhosis were at increased risk of cholestasis in pregnancy (OR 29.4, 95% CI 13.8–61.6, p < 0.001), ICU admission (OR 42.5,95% CI 15.2–118.8, p < 0.001), pre‐term birth (OR 13.2, 95% CI 7.1–24.4, p < 0.001), and babies with low birth weight (OR 12.0, 95% CI 6.5–22.0, p < 0.001), neonatal intensive care unit admission (OR 4.4, 95% CI 2.4–8.2, p < 0.001) and perinatal mortality (OR 15.8, 95% CI 4.9–51.3, p < 0.001).Conclusion: Women with cirrhosis and their babies are at increased risk during pregnancy. The ALBI score predicts maternal decompensation, ICU admission, and pre‐term birth.

This primigravid pregnant woman had a new diagnosis of primary biliary cholangitis (PBC) that was treated with a combination of ursodeoxycholic acid (UDCA) and bezafibrate. Pregnancy may unmask underlying chronic hepatic disorders in susceptible women and, in some cases, the associated abnormalities of liver function or increased serum bile acids (hypercholanaemia) can result in significant fetal and maternal risk. Maternal pruritus, with associated sleep deprivation, may cause considerable distress. To our knowledge, this is the first reported case of a new diagnosis of PBC in pregnancy treated with a combination of both UDCA and a fibrate. The case demonstrates the importance of accurate and efficient diagnosis alongside effective multidisciplinary team working to initiate appropriate, timely treatment to minimise the risk to fetus and mother. Early assessment, risk stratification and cautious surveillance is paramount in managing evolving or coexisting pathology plus individualised delivery planning, aiming to optimise fetal and maternal outcomes.