UCL Institute for Women's Health (IfWH)

Maternal Medicine

Lead: Dr David Williams

Research Overview

There are two main research aims of the maternal medicine group at the Institute for Women’s Health.

1. To understand the patho-physiology of pre-eclampsia and to design an effective treatment. The purpose of this research is to translate scientific understanding into targeted clinical therapy.

2. To understand how the physiological changes of pregnancy act as a physical stress test for the mother that predicts her future health. The purpose of this research is to develop a postpartum assessment of pregnancy outcome that could be used for primary prevention of chronic disease.

Pre-eclampsia Research

Background to Pre-eclampsia Research

Pre-eclampsia is a multi-system syndrome of pregnancy characterized by gestational hypertension and proteinuria. Pre-eclampsia affects 3-5% of pregnancies and worldwide is associated with over 60,000 maternal deaths per year. Delivery remains the only cure, but premature delivery can be detrimental to neonatal health whilst delayed delivery exposes the mother to the escalating risks of an unpredictable multi-system disorder.

Utero-placental pathology from pregnancies affected by pre-term pre-eclampsia is similar to that found in pregnancies affected by fetal growth restriction (FGR). Late pre-eclampsia is often associated with a relatively large placenta and normal sized babies. Inadequate placental invasion and incomplete adaptation of maternal spiral arteries in early pregnancy, leads to placental ischaemia, reduced fetal growth and in vulnerable women to pre-eclampsia.

The mechanism by which the placenta invades the uterine placental bed and induces angiogenesis involves a delicately regulated interaction of immunological and angiogenic factors. Placental derived growth factors involved in placental angiogenesis have altered expression in pre-eclampsia and fetal growth restriction, which are also involved in cardiovascular disease.

Current Projects in Pre-eclampsia

1. A prospective analysis of maternal vascular, inflammatory and placental factors leading to pre-eclampsia. (Dr Muna Noori, clinical PhD student)
2. An investigation into the paternal phenotype of pregnancies complicated by fetal growth restriction and/or pre-eclampsia. (Dr Sara Manning, clinical PhD student)
3. The StAmP Trial: A Proof of Principle Randomised Placebo-Controlled Trial of Statins to Ameliorate Early Onset Pre-eclampsia. (An MRC funded trial in collaboration with Birmingham University)

Pregnancy: A Fitness Test For  Life

Background to Pregnancy as a Predictor for Women's Future Health

During pregnancy, almost every organ of the mother's body has to work harder in order to meet the demands of the developing fetus. Women with chronic disease struggle to fulfil these physiological demands. As a consequence, pregnancy outcome can be compromised and long-term maternal health may be threatened.

Gestational syndromes generally develop in the second half of pregnancy when the physiological burden of pregnancy is at its greatest. For example, the progressive insulin resistance of pregnancy acts as a stress-test that transiently unmasks carbohydrate intolerance which we term “gestational diabetes mellitus” in women who are predisposed to type-2 diabetes. Childbirth leads to remission of the maternal condition, but the disease returns in later life when the effects of aging and weight gain expose a persistent vulnerability to diabetes.

Current Projects in Future Maternal Health

1. Gestational hyperthyroidism and risk of future Graves’ disease (Elisa Filippi, Maryam Parisaei)
2. The Genetics of Gestational Diabetes Mellitus (A multi-centre resource collection)

Current Group Members

• Dr David Williams (Lead, consultant and honorary senior lecturer, maternal medicine)
• Dr Muna Noori (Clinical PhD student)
• Dr Sara Manning (Clinical PhD student)
• Dr Elisa Filippi (Honorary research fellow UCL)

Active Collaborators

• Professor Asif Ahmed (Angiogenesis, Birmingham University)
• Professor Aroon Hingorani (Clinical Pharmacology and Genetics, UCL)
• Professor Ashley Moffett (Centre for Trophoblast Research, Cambridge University)
• Dr Aspasia Angelakopoulou (Epidemiology, LSHTM)
• Dr Leanne Bellamy (Clinician, Imperial College)
• Dr Juan-Pablo Casas (Epidemiology, LSHTM)
• Dr Anne Donald (Clinical Pharmacology, Kings College)
• Dr Mohammad Ibrahim (Clinical Immunology, Kings College)
• Dr James Leiper (Molecular Medicine, UCL)
• Dr Muna Noori (Obstetrics, Imperial College)

Recent Funding

2008-11: A proof of principle randomised placebo-controlled trial for use of statins to ameliorate early onset preeclampsia (2008-11) With Birmingham University
MRC; £499753

2008-10: Paternal phenotype of fathers of pre-eclamptic and fetal growth restricted pregnancies. UCLH/UCL CBRC. £78,000 and for equipment from EGA Trustees, £25,500 and UCL/UCLH CDRC, £26,007

Original Publications Since 2006

• Bellamy L, Casas JP, Hingoranin A, Williams DJ. Type 2 Diabetes mellitus after Gestational Diabetes: a meta-analysis and systematic review. Lancet 2009; 373: 1773-79
• Bachy VB, Williams DJ, Ibrahim M. Altered dendritic cell function in normal pregnancy. J. Reprod Immunol. 2008; 78: 11-21
• Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia and the risk of cardiovascular disease and cancer in later life: a systematic review and meta-analysis. BMJ 2007; 335: 974-77
• Ghaem-Maghami S, Cook HL, Bird AC, Williams DJ. Pathological myopia, pre-eclampsia and the progression of choroidal neovascularisation. BJOG 2006; 113: 608-09

Reviews, Chapters and Commentaries Since 2006

• Williams D and Davison J. Chronic Kidney Disease in Pregnancy. BMJ 2008; 336: 211-215.
• Heaney D, O’Brien P, Williams D. Neurological disorders in pregnancy. In Medical disorders in pregnancy. Eds Powrie R, Greene M. Blackwell Science. In press 2009
• Williams DJ. Physiological changes of normal pregnancy. In Oxford Textbook of Medicine (fifth edition). Eds, Warrell DA, Cox TM, Firth JD & Benz EJ. Oxford University Press, Oxford, 13.1, 383-385, (in press 2009).
• Williams DJ. Nutrition in Pregnancy. In Oxford Textbook of Medicine (fifth edition). Eds, Warrell DA, Cox TM, Firth JD & Benz EJ. Oxford University Press, Oxford, 13.2, 386-389 (in press 2009).
• Williams DJ. Medical management of normal pregnancy. In Oxford Textbook of Medicine (fifth edition). Eds, Warrell DA, Cox TM, Firth JD & Benz EJ. Oxford University Press, Oxford, 13.3, 390-395 (in press 2009).
• Williams DJ & Mayahi L. Maternal Medicines and the Fetus. In Rodeck & Whittle’s Fetal Medicine, 2nd Edition. Pp 158-180. Elsevier (2008)
• Williams DJ. Pregnancy with pre-existing renal disease. In Comprehensive Clinical Nephrology, 3rd Edition. Eds, John Feehally, Juergen Floege, Rick Johnson. Pub Mosby (2007); 42; 495-504.
• Williams DJ and de Swiet M. Cardiac disease in pregnancy. In The Textbook of Perinatal Medicine, 2nd edition. Ed in chief Asim Kurjak 195, 2076-2090; (2006).
• Williams DJ. Renal Disorders in Pregnancy. In High Risk Pregnancy. (Third Edition) Elsevier Saunders, Philadelphia, Pennsylvania. Eds James DK, Steer PJ, Weiner CP & Gonik B. pp 1098-1124 (2006).

Future Developments

Future work in pre-eclampsia research is focussed on proving whether our novel observations in early pregnancy have a causative role in mediating pre-eclampsia.

Future work in predicting a woman’s health following pregnancy is focussed on the consequences of other gestational syndromes and applying these observations to systems that can be used for primary prevention of disease.