SummaryBackgroundIntrahepatic cholestasis of pregnancy, characterised by maternal pruritus and increased serum bile acid concentrations, is associated with increased rates of stillbirth, preterm birth, and neonatal unit admission. Ursodeoxycholic acid is widely used as a treatment without an adequate evidence base. We aimed to evaluate whether ursodeoxycholic acid reduces adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy.MethodsWe did a double-blind, multicentre, randomised placebo-controlled trial at 33 hospital maternity units in England and Wales. We recruited women with intrahepatic cholestasis of pregnancy, who were aged 18 years or older and with a gestational age between 20 weeks and 40 weeks and 6 days, with a singleton or twin pregnancy and no known lethal fetal anomaly. Participants were randomly assigned 1:1 to ursodeoxycholic acid or placebo, given as two oral tablets a day at an equivalent dose of 500 mg twice a day. The dose could be increased or decreased at the clinician's discretion, to a maximum of four tablets and a minimum of one tablet a day. We recommended that treatment should be continued from enrolment until the infant's birth. The primary outcome was a composite of perinatal death (in-utero fetal death after randomisation or known neonatal death up to 7 days after birth), preterm delivery (<37 weeks' gestation), or neonatal unit admission for at least 4 h (from birth until hospital discharge). Each infant was counted once within this composite. All analyses were done according to the intention-to-treat principle. The trial was prospectively registered with the ISRCTN registry, number 91918806.FindingsBetween Dec 23, 2015, and Aug 7, 2018, 605 women were enrolled and randomly allocated to receive ursodeoxycholic acid (n=305) or placebo (n=300). The primary outcome analysis included 304 women and 322 infants in the ursodeoxycholic acid group, and 300 women and 318 infants in the placebo group (consent to use data was withdrawn for 1 woman and 2 infants). The primary composite outcome occurred in 74 (23%) of 322 infants in the ursodeoxycholic acid group and 85 (27%) of 318 infants in the placebo group (adjusted risk ratio 0·85 [95% CI 0·62–1·15]). Two serious adverse events were reported in the ursodeoxycholic acid group and six serious adverse events were reported in the placebo group; no serious adverse events were regarded as being related to treatment.InterpretationTreatment with ursodeoxycholic acid does not reduce adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy. Therefore, its routine use for this condition should be reconsidered.FundingNational Institute for Health Research Efficacy and Mechanism Evaluation Programme.

Primary hyperparathyroidism is rare during pregnancy. Recognition may be challenging as symptoms overlap with those of other common disorders of pregnancy. Furthermore, physiological changes of pregnancy affecting calcium homoeostasis mean awareness of the condition and careful interpretation of results in the light of pregnancy are essential for diagnosis. Maternal complications of primary hyperparathyroidism include nephrolithiasis, pancreatitis, cardiac arrhythmias, hypertension and peptic ulcers. At its most severe, hypercalcaemic crisis may occur, presenting with acute neurological disturbance. Most commonly, the underlying aetiology is a solitary parathyroid adenoma whereby parathyroidectomy is the only cure. A 30-year-old Caucasian woman booked under Consultant care presented at 32 weeks gestation with vomiting and right-sided loin pain. Following presentation, she was diagnosed with renal calculi. She was delivered by caesarean section (CS) due to deterioration in renal function. Post-CS, she had a grand mal seizure. She was found to have hypercalcaemia with underlying hyperparathyroidism.

Total laparoscopic hysterectomy and bilateral salpingo-oophorectomy (TLH) offers an alternative and potentially more favourable procedure for women with early endometrial neoplasia. This cohort review presents the first 66 consecutive cases of TLH for endometrial neoplasia from one surgical team in a large teaching hospital. Data were collected for all women undergoing hysterectomy for suspected endometrial cancer, grade 1-2 adenocarcinoma, carcinoma in situ or severe atypical hyperplasia over 4 years using a prospectively kept theatre database. A total of 95 hysterectomies were identified, 66 (69%) underwent TLH, 18 (19%) underwent laparoscopically assisted vaginal hysterectomy (LAVH) and 11 (12%) had total abdominal hysterectomy (TAH) procedures. The mean age and body mass index of the patients in each group were similar, and average blood loss was lower in the TLH group (129 ml) compared to LAVH (185 ml) or TAH (247 ml). Total theatre time for TLH (113 min) was similar to LAVH (112 min) and less than the TAH group (127 min). Conversion rate from TLH to TAH was 0%. There were no major complications in the TLH group. These data report our early experience with a TLH and demonstrate a satisfactory record during its introduction. This new procedure offers a safe alternative to TAH for many women with no increased morbidity in agreement with recent literature. Although this paper reports a non-randomised series, we hope that it will serve to show that these techniques can be adopted safely by a new unit.