Study to assess the prevalence and cause of obstetric cholestasis
Mr A Shennan et al.
Guy's, King's & St Thomas' Hospital, London

Many babies may be dying at birth or being born prematurely because of a condition called obstetric cholestasis (OC) which often goes unrecognised. This major project aims to assess how widespread OC is and what causes it. The condition, characterised by excessive itching all over the body in the last trimester of pregnancy, may account for as many as 5% of stillbirths in the UK. Because itching is common in pregnancy, many women are not aware they may have the condition and are therefore missing out on life-saving treatment.

OC is a disease of the liver. Although its exact cause is not yet known, the team believes it may be linked to raised bile acids. The project will examine the relationship between liver function tests, bile acid tests, and itching. There also appears to be a strong genetic predisposition to the disease as well as an underlying susceptibility to the hormone oestrogen. The latter may explain why the condition surfaces in pregnancy and why women who have had cholestatic symptoms on the pill are more likely to suffer. The knowledge gained by this work will allow appropriate strategies to be developed to identify women at risk and eventually prevent fetal distress and stillbirth in OC pregnancies.

Already this research has made the important discovery that itching occurs before bile acids increase; previously it was thought that bile acids cause the itching. The study has produced some very interesting data, suggesting that the diagnosis of OC is often missed because the symptoms are not rigorously investigated. The first two papers of the data from this study have been recognized as important and have been accepted for publication in the British Journal of Obstetrics and Gynecology.

Prevention of recurrent miscarriage by genetic diagnosis before embryo implantations
Prof J Delhanty et al.
University College London

Genes are the blueprint of life and they determine the characteristics that are passed on from parents to children. Each human cell contains 23 pairs of chromosomes which encode genes, so that each gene is represented twice. Sometimes breaks can occur in chromosomes and if this happens to two chromosomes at the same time, the broken pieces can swap and rejoin in the wrong place. This is called translocation and usually causes no harm to the cell. This project aims to develop a faster and more efficient way of testing embryos to discover which can develop into a healthy baby.

Research and development of a training mannequin for the management of shoulder dystocia
Dr T Draycott, Mr S Howard

Shoulder dystocia is a dangerous complication of childbirth, where the fetal shoulders become lodged behind the mother's pelvis. The condition presents during the second stage of labour and requires expert clinical management in order to avoid fractures to the baby's arm or damage to nerves and, in severe cases, death of the baby. The team of clinicians, professional model makers and engineers have developed a prototype training mannequin to enable junior doctors and midwives to receive 'hands-on' training of shoulder dystocia management. The mannequin consists of a simulation of the bone, musculature and fat of the birth canal as well as an accurate fetal model. Hopefully, the development and possible marketing of this mannequin will help to prevent some of the unnecessary deaths and injuries of babies in the UK.

A joint project to investigate the failure of the placenta in miscarriage
Dr J Bulmer & Dr F Lyall
University of Newcastle upon Tyne & University of Glasgow

The causes of many miscarriages are not known, but it is known that in normal pregnancy, cells from the placenta migrate into the wall of the womb, then grow into the mother's blood vessels there. The result of this is that the blood vessels increase the blood supply to the placenta and to the baby enabling it to grow. In some cases of miscarriage it is thought that this does not occur and thus the baby is not able to grow and is lost, but it is not known why.

The researchers have devised a safe method of taking samples of the wall of the womb immediately after the miscarriage. Their work should provide a clearer picture of the factors responsible for miscarriage. It is only by understanding why the placental cells do not migrate properly into the wall of the womb that we will be able to consider more rational therapies in the future.

Two main factors are thought to be important in the migration of these specific placental cells (trophoblasts). The first of these factors are cell adhesion molecules, so called because they normally help cells attach to neighbouring cells or tissues. The research will look at whether miscarriage could be caused by a failure of the molecules found on the surface of these cells to stick to the placenta. This project has demonstrated that some cases of miscarriage are associated with abnormal changes in the blood vessels of the womb, and although it is not yet clear why this association exists, some possibilities were ruled out through this research.

Study to show that too much oxygen in the placenta too soon may cause early miscarriage
Dr G Burton & Dr E Jauniaux
University of Cambridge & UCL

Oxygen is the essence of life, except, it seems, in early pregnancy where it may be a cause of miscarriage. This project predicts that too much oxygen rather than too little may act on the growing baby in a similarly damaging way as when food goes stale or fats turn rancid. It is thought that in the first three months of pregnancy the concentration of oxygen in the uterus is very low, and although it is not clear why this is the case it may be protecting the delicate developing embryo from the harmful effects of oxygen.

This team used new imaging techniques to examine early pregnancy and these have shown that in miscarriage there is an abnormally early blood flow in the uterus to the placenta. This could lead to too much oxygen being present too soon in pregnancy, which could damage the placenta and lead to the loss of the baby. The long-term aim of the study is to discover a treatment which may prevent some early miscarriages.

Early results from this project suggest that the high levels of oxygen that would be associated with excessive maternal blood flow in spontaneous miscarriage are detrimental to the placenta. These high oxygen levels may destroy key tissues that could cause the pregnancy to miscarry. It has been shown that in complicated pregnancies there is premature onset of blood flow and the normal pattern of the blood flow is disrupted in these cases.

The project has enabled a greater understanding of the way in which the maternal circulation is established both in normal and complicated pregnancies. For the maintenance of a normal pregnancy it is probably necessary for a coordinated sequence of events to occur including a wave of oxidative stress through the placenta in association with a change in maternal blood flow. In early miscarriage, onset of the blood flow is premature and widespread, so synctial stress is both more exaggerated and extensive. Loss of synctial function will lead to fetal death, but differentiation of the cytotrophoblast cells and regeneration may restore sufficient hormone output to maintain the pregnancy.

Abnormality of the mother's small blood vessels and subsequent impairment of the placenta
Dr S Stone & Prof L Poston
Guy's, King's & St Thomas' Hospital, London

There is growing evidence to suggest that a common cause of many problems in pregnancy is abnormalities of the mother's blood vessels. One group of women who we know suffer recurrent complications, such as miscarriage and pre-eclampsia, are those with high levels of the antiphospholipid antibody in the blood which can lead, indirectly, to blood vessel damage.

This study will be testing the theory that the antiphospholipid antibody 'attacks' the lining of the blood vessels (the endothelium) that supply blood to the placenta. This would lead to a reduced blood flow which would impair the development of the placenta and the baby. Researchers will be measuring 'markers' of damage to the lining of the blood vessels in certain pregnant women. This will help them understand better the reasons why the placenta fails to work properly and the baby suffers.

The project is testing the theory that an antibody (antiphospholipid antibody) attacks the lining of the blood vessels, which supply blood to the placenta in women suffering from antiphospholipid syndrome (APS). Women are currently being recruited to the study and the study is progressing with the analysis of results.

Research to improve the understanding and prevention of premature labour
Research on understanding and preventing stillbirth and miscarriage
Research to improve the understanding and prevention of pre-eclampsia
Research to prevent health problems in small or premature babies