ORCID Profile
0000-0002-6226-7611
Current Organisation
Kings College London
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 28-12-2015
DOI: 10.1002/HEP.28265
Abstract: A challenge in obstetrics is to distinguish pathological symptoms from those associated with normal changes of pregnancy, typified by the need to differentiate whether gestational pruritus of the skin is an early symptom of intrahepatic cholestasis of pregnancy (ICP) or due to benign pruritus gravidarum. ICP is characterized by raised serum bile acids and complicated by spontaneous preterm labor and stillbirth. A biomarker for ICP would be invaluable for early diagnosis and treatment and to enable its differentiation from other maternal diseases. Three progesterone sulfate compounds, whose concentrations have not previously been studied, were newly synthesized and assayed in the serum of three groups of ICP patients and found to be significantly higher in ICP at 9‐15 weeks of gestation and prior to symptom onset (group 1 cases/s les: ICP n = 35/80, uncomplicated pregnancy = 29/100), demonstrating that all three progesterone sulfates are prognostic for ICP. Concentrations of progesterone sulfates were associated with itch severity and, in combination with autotaxin, distinguished pregnant women with itch that would subsequently develop ICP from pruritus gravidarum (group 2: ICP n = 41, pruritus gravidarum n = 14). In a third group of first‐trimester s les all progesterone sulfates were significantly elevated in serum from low‐risk asymptomatic women who subsequently developed ICP (ICP/uncomplicated pregnancy n = 54/51). Finally, we show mechanistically that progesterone sulfates mediate itch by evoking a Tgr5‐dependent scratch response in mice. Conclusion: Our discovery that sulfated progesterone metabolites are a prognostic indicator for ICP will help predict onset of ICP and distinguish it from benign pruritus gravidarum, enabling targeted obstetric care to a high‐risk population. Delineation of a progesterone sulfate‐TGR5 pruritus axis identifies a therapeutic target for itch management in ICP. (H epatology 2016 :1287–1298)
Publisher: Walter de Gruyter GmbH
Date: 06-08-2021
Abstract: Multicentre international trials relying on diagnoses derived from biochemical results may overlook the importance of assay standardisation from the participating laboratories. Here we describe a study protocol aimed at harmonising results from total bile acid determinations within the context of an international randomised controlled Trial of two treatments, URsodeoxycholic acid and RIF icin, for women with severe early onset Intrahepatic Cholestasis of pregnancy (TURRIFIC), referred to as the Bile Acid Comparison and Harmonisation (BACH) study, with the aims of reducing inter-laboratory heterogeneity in total bile acid assays. We have simulated laboratory data to determine the feasibility of total bile acid recalibration using a reference set of patient s les with a consensus value approach and subsequently used regression-based techniques to transform the data. From these simulations, we have demonstrated that mathematical recalibration of total bile acid results is plausible, with a high probability of successfully harmonising results across participating laboratories. Standardisation of bile acid results facilitates the commutability of laboratory results and collation for statistical analysis. It may provide the momentum for broader application of the described techniques in the setting of large-scale multinational clinical trials dependent on results from non-standardised assays.
Publisher: Elsevier BV
Date: 04-2006
Publisher: Wiley
Date: 18-06-2010
Publisher: Elsevier BV
Date: 2017
Publisher: National Institute for Health and Care Research
Date: 12-2020
DOI: 10.3310/EME07090
Abstract: Intrahepatic cholestasis of pregnancy, characterised by maternal pruritus and raised 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, but without an adequate evidence base. We aimed to evaluate whether or not ursodeoxycholic acid reduces adverse perinatal outcomes in affected women. Multicentre, masked, randomised, placebo-controlled, two-arm, parallel-group trial. Thirty-three UK maternity units. Women with intrahepatic cholestasis of pregnancy aged ≥ 18 years, between 20 +0 and 40 +6 weeks’ gestation with a singleton or twin pregnancy and no known lethal fetal anomaly. Women were randomly assigned (1 : 1 allocation ratio) to take ursodeoxycholic acid tablets or matched placebo tablets, at an equivalent dose of 1000 mg daily, titrated as needed. The primary outcome was a composite of perinatal death (in utero fetal death after randomisation or known neonatal death up to 7 days) or preterm delivery ( 37 weeks’ gestation) or neonatal unit admission for at least 4 hours (from birth until hospital discharge). Each infant was counted once within this composite. Analyses were by intention to treat. Between 23 December 2015 and 7 August 2018, 605 women were randomised, with 305 women allocated to the ursodeoxycholic acid arm and 300 women to the placebo arm. There was no evidence of a significant difference in the incidence of the primary outcome between the groups: 23.0% (74 out of 322 infants) in the ursodeoxycholic acid group compared with 26.7% (85 out of 318 infants) in the placebo group adjusted risk ratio 0.85 (95% confidence interval 0.62 to 1.15). There was no evidence of a significant difference in total costs (maternal, infant and the cost of ursodeoxycholic acid) between the two trial groups. There were two serious adverse events in the ursodeoxycholic acid group and six in the placebo group. Limitations include a primary outcome event rate in the control group that was lower than that estimated for the s le size calculation, but the lack of evidence of effect in all analyses suggests that it is unlikely that the trial had insufficient power. In this clinical trial of ursodeoxycholic acid in women with intrahepatic cholestasis of pregnancy, there is no evidence that it is effective in reducing a composite of adverse perinatal outcomes. Future research should aim to elucidate the aetiology and pathophysiology of adverse perinatal outcomes, particularly stillbirth, in women with intrahepatic cholestasis of pregnancy to assist the development of an effective preventative treatment. Further exploratory analyses may identify groups of women who might respond to ursodeoxycholic acid treatment. Current Controlled Trials ISRCTN91918806. This project was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation Vol. 7, No. 9. See the NIHR Journals Library website for further project information.
Publisher: Wiley
Date: 12-07-2010
Publisher: Oxford University Press (OUP)
Date: 06-2010
Publisher: Springer Science and Business Media LLC
Date: 19-06-2017
DOI: 10.1038/NG.3895
Abstract: Preecl sia, which affects approximately 5% of pregnancies, is a leading cause of maternal and perinatal death. The causes of preecl sia remain unclear, but there is evidence for inherited susceptibility. Genome-wide association studies (GWAS) have not identified maternal sequence variants of genome-wide significance that replicate in independent data sets. We report the first GWAS of offspring from preecl tic pregnancies and discovery of the first genome-wide significant susceptibility locus (rs4769613 P = 5.4 × 10
Publisher: Springer Science and Business Media LLC
Date: 19-07-2016
Publisher: Springer Science and Business Media LLC
Date: 16-05-2009
Publisher: Springer Science and Business Media LLC
Date: 19-07-2022
DOI: 10.1186/S13063-022-06462-Y
Abstract: Each year in the UK, approximately 35,000 women develop gestational diabetes mellitus (GDM). The condition increases the risk of obstetric and neonatal complications for mother and child, including preecl sia, preterm birth, and large for gestational age babies. Biochemical consequences include maternal hyperglycemia, neonatal hypoglycemia, and dyslipidemia. Metformin is the most commonly used firstline pharmacological treatment. However, there are concerns about its widespread use during pregnancy, due to its limited efficacy and potential safety concerns. Therefore, there is a need for additional therapies that improve both maternal–fetal glucose and lipid metabolism. Ursodeoxycholic acid (UDCA) is not currently used for treatment for GDM. However, it can improve glucose control in type 2 diabetes, and it improves fetal lipid profiles in gestational cholestasis. Consequentially, it is hypothesized that treatment with UDCA for women with GDM may improve both maternal metabolism and neonatal outcomes. The primary outcome of this trial is to assess the efficacy of UDCA compared with metformin to improve glucose levels in women with GDM. The trial is a two-armed, open-label, multi-center, randomized controlled trial. Women are eligible if they have been diagnosed with GDM by an oral glucose tolerance test between 24 + 0 and 30 + 6 weeks’ gestation, and if they require pharmacological intervention. In total, 158 pregnant women will be recruited across seven NHS Trusts in England and Wales. Women who consent will be recruited and randomized to either metformin or UDCA, which will be taken daily until the birth of their baby. Maternal and neonatal blood s les will be taken to evaluate the impact of the treatments on maternal glucose control, and maternal and neonatal lipid metabolism. Maternal and fetal outcomes will be evaluated, and acceptability of UDCA compared with metformin will be assessed. This trial has the potential to identify a potential new treatment for women with GDM. If successful, a future large multi-center trial will be designed to investigate where decisions can be personalized to identify which women will respond more effectively to UDCA than alternatives to improve maternal and baby outcomes. ClinicalTrials.gov NCT04407650.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Catherine Williamson.