No abstract

Profound physiological changes in the maternal cardiovascular system occur shortly after conception. These changes may impact upon the investigation of healthy and complicated pregnancies. Additionally, concerns regarding fetal exposure to ionising radiation are important considerations in maternal testing. This manuscript reviews the important physiological changes pertinent to the investigation of maternal cardiovascular disease in pregnancy.

Summary 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 We also included two unpublished cohort studies.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. Findings The 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 consideri...

Gitelman syndrome (GS) is an autosomal recessive renal tubulopathy because of mutations in the gene for the thiazide-sensitive sodium chloride co-transporter in the distal convoluted tubule. GS is characterized by hypokalaemia, secondary hyperaldosteronism, hypocalciuria and hypomagnesaemia. Little is known about GS in pregnancy. Eplerenone is an aldosterone antagonist and potassium-sparing diuretic used to treat hypertension and cardiac failure. We report the use of eplerenone to treat GS in pregnancy with a successful outcome for mother and baby.A 21 years old nulliparous woman presented with longstanding lethargy, muscle cramps, nausea, thirst and nocturia. Serum potassium was 2.6 mmol/L, urine potassium was inappropriately high consistent with renal loss, there was mild hypomagnesaemia, hypocalcuria and secondary hyperaldosteronism. She denied diuretic use. She had otherwise been well with no significant past medical history. GS was confirmed by DNA sequence analysis revealing compound heterozygosity with pathogenic mutations in exon 18 (2186G > T) and exon 25 (2872A > T) in the SLC12A3 gene. She was intolerant of oral potassium and magnesium supplements, spironolactone and non-steroidal anti-inflammatory drugs because of nausea, and intolerant of amiloride because of tinnitus. Treatment with a combination of eplerenone 50 mg twice a day and perindopril 2.5 mg each morning resulted in resolution of her symptoms and a serum potassium at the lower end of the normal range. After preconception counselling her perindopril was ceased, and she elected to fall pregnant while continuing treatment with eplerenone. Other than intermittent vomiting in first trimester her confinement was uneventful, with her serum potassium ranging between 2.6 and 2.9 mmol/L, a healthy baby girl weighing 3630 g born by vaginal delivery at 39 weeks gestation. The babies' potassium was normal. Two years post delivery mother and baby are well.Twelve pregnancies to mothers with GS have been described previously, all with an uneventful pregnancy course and excellent outcome, despite inability to normalize maternal serum potassium and magnesium levels even with large doses of oral supplements. 1,2 The aim in pregnancy should be to give adequate therapy to prevent maternal symptoms. Spironolactone and amiloride have been used in pregnancies complicated by GS syndrome in addition to electrolyte supplementation. Amniotic fluid levels should be monitored as oligohydramnios was reported in 5 of the 12 pregnancies. Eplerenone was used in our mother because of her intolerance to spironolactone, amiloride and oral potassium and magnesium supplements. We are only aware of one previous report of eplerenone use in pregnancy, commenced at 32 weeks gestation in a 41 years old woman with diastolic heart failure. 3 A healthy newborn was delivered, the gestation was not stated. In animal studies the only noticeable risk of foetal abnormalities occurred when laboratory animals were given doses well over 1000 times the recommended daily dose of eplerenone. Epler...

Interpretation of laboratory investigations relies on reference intervals. Physiological changes in pregnancy may result in significant changes in normal values for many biochemical assays, and as such results may be misinterpreted as abnormal or mask a pathological state. The aims of this review are as follows: 1. To review the major physiological changes in biochemical tests in normal pregnancy. 2. To outline where these physiological changes are important in interpreting laboratory investigations in pregnancy. 3. To document the most common causes of abnormalities in biochemical tests in pregnancy, as well as important pregnancy-specific causes.

Sleep disordered breathing (SDB) which includes obstructive sleep apnoea (OSA) and upper airway resistance syndrome (UARS), has emerged as a risk factor for adverse maternal-foetal outcomes in pregnancy. Physiological changes of pregnancy predispose a woman 'at risk' towards developing SDB. The increasing incidence of OSA in pregnancy closely correlates with the population trends of obesity. Common screening tools validated in non-pregnant subjects including Epworth Sleepiness Scale (ESS) and Berlin Questionnaire (BQ) are poor predictors of SDB in pregnancy. Preeclampsia, gestational hypertension and gestational diabetes mellitus (GDM) are linked with SDB. Preeclampsia and OSA share common pathological associations. It is unclear if one predisposes the other. Foetal morbidity includes intrauterine growth restriction (IUGR), preterm delivery, low birth weight, neonatal intensive care unit (NICU) admission and Apgar score of less than seven at one minute. Continuous positive airway pressure (CPAP) is a well-documented treatment of SDB in pregnancy and has been shown to reverse some of the adverse events. It becomes imperative to diagnose and manage this condition as OSA causes substantial morbidity in the untreated pregnant patient and foetus. Three short clinical cases and a literature review on SDB on pregnancy are presented.

No abstract

Background Bile acid levels and liver function tests may be normal at presentation in women with intrahepatic cholestasis of pregnancy. The biochemical results of patients presenting with pruritus typical for intrahepatic cholestasis of pregnancy were reviewed. Methods A retrospective audit of women coded as having intrahepatic cholestasis of pregnancy over a three-year period. Results One hundred and ninety-three women (1.1% of the obstetric population) presented with pruritus typical of intrahepatic cholestasis of pregnancy. Forty (21%) of these women had normal biochemistry at presentation, half subsequently developing abnormal results. Women with a history of allergic reactions were more likely to develop intrahepatic cholestasis of pregnancy. Conclusions Normal biochemistry should not preclude a trial of ursodeoxycholic acid in women with distressing pruritus typical for intrahepatic cholestasis of pregnancy. Biochemical tests which are more sensitive and specific in the diagnosis of intrahepatic cholestasis of pregnancy would be valuable. Investigation of other populations with intrahepatic cholestasis of pregnancy regarding a possible association with atopy/allergy would be interesting.