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infants in the ursodeoxycholic acid group, and 300 women and 318 infants in the placebo group (consent to use data was withdrawn for 1 woman and 2 infants).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.

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HbA1c level ≥ 48 mmol/mol (≥ 6.5%) has reasonable sensitivity and high specificity in comparison to OGTT for early postpartum screening of diabetes in GDM. At 6(th) week postpartum screening, if FBG is normal and HbA1c < 44 mmol/mol OGTT is not recommended.

BACKGROUND Gestational diabetes mellitus (GDM) is a common metabolic derangement in pregnant women. In the women identified to be at high risk of GDM, a 75 g oral glucose tolerance test (OGTT) at 24-28 wk gestation is the recommended screening test in the United Kingdom as per National Institute for Health and Care Excellence (NICE). Hypoglycaemia following the glucose load is often encountered and the implication of this finding for the pregnancy, fetus and clinical care is unclear. AIM To determine the prevalence of hypoglycaemia at any time during the screening OGTT and explore its association with birth weight. METHODS All deliveries between 2009 and 2013 at the local maternity unit of the University hospital were reviewed. Of the total number of 24,154 women without pre-existing diabetes, those who had an OGTT for GDM screening based on NICE recommended risk stratification, who had a singleton delivery and had complete clinical and demographic data for analysis, were included for this study ( n = 3537). Blood samples for fasting plasma glucose (FPG), 2-hour plasma glucose (2-h PG) and HbA 1c had been obtained. Birth weight was categorised as low (≤ 2500 g), normal or Macrosomia (≥ 4500 g) and blood glucose ≤ 3.5 mmol/L was used to define hypoglycaemia. Binary logistic regression was used to determine the association of various independent factors with dichotomized variables; the differences between frequencies/proportions by χ 2 test and comparison between group means was by one-way ANOVA. RESULTS Amongst the study cohort (3537 deliveries), 96 (2.7%) women had babies with LBW (< 2500 g). Women who delivered a LBW baby had significantly lower FPG (4.3 ± 0.6 mmol/L, P = 0.001). The proportion of women who had a 2-h PG ≤ 3.5 mmol/L in the LBW cohort was significantly higher compared to the cohorts with normal and macrosomic babies (8.3% vs 2.8% vs 4.2%; P = 0.007). The factors which predicted LBW were FPG, Asian ethnicity and 2-h PG ≤ 3.5 mmol/L, whereas maternal age, 2-h PG ≥ 7.8 mmol/L and HbA 1c were not significant predictors. CONCLUSION A low FPG and 2-h PG ≤ 3.5 mmol/L on 75-gram OGTT are significantly associated with low birth weight in women identified as high risk for GDM. Women of ethnic backgrounds (Asians) appear to be more susceptible to this increased risk and may serve as a separate cohort in whom we should offer more intensive follow up and screening for complications. Cost implications and resources for follow up would need to be looked at in further detail to support these findings.