Maternal and Fetal Disease
The Maternal and Fetal Disease Group is based at the Guy’s site of King’s College London. The group has a programme of research that focuses on the aetiology of metabolic diseases of pregnancy, including intrahepatic cholestasis of pregnancy, gestational diabetes mellitus and dyslipidaemia. The group uses a combination of approaches to understand disease mechanisms and evaluate treatments to improve maternal and child health outcomes. These include collection of a large biobank of clinical specimens from pregnant women, use of in vitro and in vivo models to explain the endocrine signals that cause altered bile acid, glucose and lipid metabolism in pregnancy, and their relationship to disease and clinical trials. The group is also interested in the complications of cholestatic pregnancy during pregnancy and in the later life of the offspring, and is planning life course research with our colleagues in neonatology and paediatrics.
Endocrine signals that underlie the alterations in metabolism from early to late pregnancy
Aetiology of maternal cholestasis in pregnancy
- Reproductive hormone effects on bile acid and lipid metabolism.
- Influence of gestational increases in progesterone sulphates on nuclear receptor function.
- Role of circadian clock in gestational metabolic disease.
- Changes in white and brown adipose tissue in pregnancy.
Aetiology of gestational diabetes mellitus
- Genomic studies of rare penetrant mutations and common population susceptibility alleles in susceptibility to intrahepatic cholestasis of pregnancy.
- Whole genome sequencing (severe cholestasis, NIHR BioResource Rare Diseases).
- Gestational endocrine signals that influence bile acid pathways.
- The role of specific metabolites in gestational pruritus.
- Role of the gut microbiome and enterocyte bile acid signalling.
Influence of intrauterine environment on the subsequent health of the offspring
- Relationship between cholestasis and susceptibility to gestational diabetes mellitus.
- Enteroacinar signalling and susceptibility to cholestasis.
- Gut microbiome (16s and shotgun metagenomics) and luminal metabolite signals that influence glucose homeostasis
Mechanisms underlying unexplained stillbirth and preterm labour in metabolic diseases of pregnancy
- Mechanisms underlying increased susceptibility of offspring of cholestatic pregnancy to subsequent metabolic syndrome.
- Therapeutic interventions to prevent obesity, NAFLD and diabetes in the offspring of cholestatic pregnancy.
- Influence of paternal liver disease (cholestasis) on offspring health.
Clinical trial to establish whether ursodeoxycholic acid (UDCA) treatment prevents adverse pregnancy outcome
- Influence of bile acids on cardiac rhythm in models of the fetal heart.
- The role of ursodeoxycholic acid in preventing fetal arrhythmia.
- Influence of bile acids and related steroids on myometrial function.
Influence of paternal liver disease (cholestasis) on offspring health
- Randomised, controlled trial of UDCA vs placebo to establish whether UDCA protects against ICP-associated adverse pregnancy outcome (PITCHES trial).
- Investigations of mechanisms by which paternal disease influences subsequent health of offspring
- Evaluation of UDCA treatment to prevent paternal cholestasis influencing offspring metabolic health
Clinical Trials Co-ordinator
- Charlotte Mungeam
- Julie Wade
- Jenny Chambers
- Marta Vasquez Lopez (Imperial College)
- Mavis Machirori (Imperial College)
PA to Professor Catherine Williamson
| Postdoctoral scientists
A Phase III trial in IntrahepaTic CHolestasis of pregnancy to evaluate urSodeoxycholic acid (UDCA) in improving perinatal outcomes.