Research into premature birth

Almost 50,000 babies are born prematurely each year in the UK and many suffer lifelong consequences as a result. This is one of the highest rates in Europe and it’s still rising, yet there is currently no accurate screening test available to identify women at risk. Tommy’s believes creating a test must be an absolute priority and much of our current research is devoted to this.

Our London and Manchester centres are searching for biological markers identifying women likely to have preterm babies. Both centres are participating in the international SCOPE study, which is investigating ways to predict various pregnancy probjems, including preterm birth. We have previously found that fetal fibronectin is a reliable indicator of preterm birth and we are now investigating the cost-effectiveness of a screening test based on this.

Our research into preterm birth is also focusing on strategies to prevent or delay early labour. At our centre in Edinburgh, Tommy’s Professor Jane Norman is leading a major new trial of 8,000 women (the OPPTIMUM trial) to see whether progesterone is effective in preventing preterm birth. We're also looking closely at ways to prevent the contractions that begin the labour process. There have been some exciting results in this area, as you'll see below.

Individual research projects

Making Pregnancy Safer (MAPS) – the UK arm of the international SCOPE study
Investigators: Manchester - Professor Philip Baker, Dr Jenny Myers, Suzanne Moody, Sarah Lawson; London - Annette Briley, Dr Lucy Chappell, Jenny Carter, Beth Steff, Professor Lucilla Poston, Professor Andrew Shennan, Paul Seed, Professor Robyn North
Funding: Part-funded by Tommy’s
Timescale: 2007–2011
Summary: The SCOPE study (known as MAPS in the UK) is a huge international study looking at how to predict and prevent the major diseases of late pregnancy: pre-eclampsia, preterm birth and fetal growth restriction. The project plans to recruit 10,000 pregnant women worldwide to test whether certain clinical and molecular markers (certain proteins, fats and small molecules in blood) can predict these complications. We already know that none of the candidate markers will work on their own, but combinations of markers are likely to result in clinically useful screening tests. The Tommy’s centres in both Manchester and London are participating in this major study.
Progress report: The MAPS study is part of a consortium made up of researchers in Manchester, London, Leeds, Cork, Auckland, Adelaide and, hopefully, the USA. Internationally, 4,500 first-time mothers are now participating. The Tommy’s Manchester centre has so far recruited over 250 women and aims to recruit 100 women per year until the end of the study. All research teams have access to the samples and data and after several years of recruitment the immense effort to establish the SCOPE cohort is now being rewarded. The data collected from the first 3,500 women participating in SCOPE has already been analysed by our collaborators in New Zealand and has produced some promising results.

Is progesterone a cost-effective way to prevent preterm birth? (the OPPTIMUM trial)
Investigators: Professor Jane Norman with co-investigators from around the UK including Professor Andrew Shennan (Tommy’s centre in London) and Professor Tina Lavender (Tommy’s centre in Manchester)
Funding: Tommy’s funds several of the doctors working on this project.
Timescale: 2008–2013
Summary: Spontaneous preterm birth is a pervasive and expensive health problem, with over 40,000 babies being born preterm (before 37 weeks) in the UK every year. Two studies have now suggested that progesterone reduces preterm delivery in high-risk women. This project, called the OPPTIMUM trial, will recruit over 8,000 women around the UK to test whether giving natural progesterone daily from 22 to 34 weeks of gestation is a cost-effective way to reduce the likelihood of preterm birth and the associated neonatal death and childhood disability that often accompanies it.
Progress report: Regulatory approval to start recruiting women to join the clinical trial was obtained in January 2009 and we now have 13 sites up and running, with a further 10 sites nearly ready to go.

Preventing the contractions that cause preterm birth
Investigators: Professor Jane Norman, Professor M Harnett, Professor I McInnes, Professor S Nelson, Professor W Martin, Dr Mei Yuan
Funding: Tommy’s funds several of the doctors working on this project.
Timescale: 2008–2010
Summary: This project will investigate how ‘danger receptors’ in the womb are involved in the process of labour. We believe that by blocking these receptors we might be able to block inappropriate contractions (preterm labour). Our study will examine this hypothesis by looking at muscle tissue from the womb in the laboratory.

Anti-inflammatory signals to prevent preterm labour
Investigators: Professor Jane Norman, Professor Henry Jabbour, Dr Fiona Denison, Dr David Maldonado Perez, Dr Ellie Golightly, Sara Rinaldi
Funding: Tommy’s funds several of the doctors working on this project.
Timescale: 2008–2011
Summary: In this study we will look at the role of signals made naturally in the body that stop inflammation. We believe that by increasing these signals we could stop the inflammation that occurs in preterm labour, and thus prevent both preterm birth and the damage to baby’s brains that can occur as a result of the inflammation in the womb in preterm labour.

A new drug therapy for preterm labour
Investigators: Professor Henry Jabbour, Dr Fiona Denison, Dr Roberto Catalano, Professor Jane Norman, Dr Marta Gorowiec, Dr Tamsin Lannagan
Funding: Tommy’s funds several of the doctors working on this project.
Timescale: 2009 –2011
Summary: In this study we are working with the Medical Research Council (MRC) Drug Discovery Group to develop a new treatment for preterm labour. We believe that the drug that we are developing will both stop the womb contracting and prevent the harmful effects of inflammation within the womb, thus improving the outcome for babies.

Stretch: a signal for preterm labour?
Investigators: Dr Rachel Tribe, Fran Willey, Professor Mike Taggart (University of Newcastle)
Funding: Tommy’s part-funds this project.
Timescale: 2006¬–2010
Summary: Late in pregnancy, the uterus reaches its maximum size so the uterine muscle and fetal membranes have to stretch to accommodate the growing fetus. This stretching is part of the process that eventually leads to labour. This project aims to discover what causes the stretching and whether it can be stopped to prevent preterm labour.
Progress report: This project has already yielded some exciting results. We have identified key genes involved in the stretching process and demonstrated a link between the stretching of the womb and the immune system which suggests that we were correct in believing that uterine distension may ‘prime’ the uterus for labour. This should provide useful treatment targets for preventing preterm birth, particularly in cases of twins and triplets.

Genetic causes of preterm labour
Investigators: Dr Rachel Tribe, Dr Evonne Chin-¬Smith, Dr Mark Johnson (Imperial College London), Dr Philip Aaronson (KCL)
Funding: Tommy’s funded a pilot study for this project.
Timescale: 2007¬–2010
Summary: This project is trying to discover the method by which certain genes become activated, causing the muscles of the uterus to contract powerfully and bring on early labour. If we can identify this mechanism, we may be able to find methods to delay or prevent preterm labour.

Investigating the role of potassium channels in stopping preterm labour
Investigators: Dr Rachel Tribe, Dr Iain Greenwood (St George’s University of London), Dr Philip Aaronson (KCL), Laura McCallum
Funding: Part-funded by Tommy’s
Timescale: 2008¬–2010
Summary: Activation of contractions is involved in the initiation of both preterm and normal labour and we know that this is triggered by the amount of calcium entering the cell. This project examines whether the level of calcium may be limited by activating so-called ‘potassium channels.’ These are small pores on the cell membranes that allow potassium in and out. It is hoped that opening these channels will keep uterine muscle in a relaxed, non-contractile state, thus preventing preterm labour.
Progress report: We are looking at how some new drugs that target a specific family of potassium channels (KCNQ and KCNH) can stop uterine contractions. This study is providing comprehensive information on the contribution of these potassium channels to the control of uterine excitability during pregnancy. With drug companies very interested in potassium channels currently, this research could pave the way for a concrete treatment to help prevent preterm birth.

Do white blood cells play a role in preterm labour?
Investigators: Dr Sarah Hamilton, Dr Rebecca Jones, Dr Clare Tower, Dr Oksana Shynlova (University of Toronto), Professor John Challis (University of Toronto), Professor Stephen Lye (University of Toronto)
Funding: Tommy’s completely funds this project.
Timescale: 2008–2010
Summary: Recent studies suggest that labour is triggered when white blood cells (leukocytes) move from the blood into the inner lining of the uterus, called the decidua. So, blocking recruitment of leukocytes to the decidua might be used to block labour when it is in danger of happening prematurely. This project will identify which factors regulate leukocyte recruitment to the decidua during preterm and normal labour with the eventual aim of developing a treatment to prevent or delay preterm birth.

Developing a human tissue model for investigating uterine function
Investigators: Dr Rachel Tribe, Professor Mike Taggart (University of Newcastle)
Funding: Tommy’s part-funds this project.
Timescale: 2007¬–2010
Summary: The study of preterm labour has been hampered by the fact that most of the research to date has been on mice, and mice have a bicornuate uterus, which is totally different from most women. This project aims to develop a human uterine tissue model to gain more accurate results. This model will be extremely useful to other uterine physiologists and the wider research community, particularly those interested in disease associated with smooth muscle function (e.g. cardiovascular disease and asthma).

Are natural antimicrobial defences altered in women at high risk of preterm labour?
Investigators: Dr Rachel Tribe, Professor Andrew Shennan, Claire Foster, Dr Danielle Abbott
Funding: Tommy’s is funding this one-year pilot project.
Timescale: 2009–2010
Summary: In order to develop treatments to prevent or stop preterm labour, we have to understand more about the processes causing it. One potential cause is infection that spreads from the vagina into the uterus (womb), but why some women are more at risk/less able to mount an appropriate immune response to combat this is unknown. This project, an extension of a clinical study already successfully undertaken at KCL, aims to understand how a woman's body may protect itself from risk of preterm labour by producing natural antimicrobial substances (nature's antibiotics).

Investigating uterine artery widening in normal pregnancy
Investigators: Dr Lynda Harris, Professor John Aplin, Professor Philip Baker (in collaboration with Dr Judith Bulmer and Dr Gendie Lash at the University of Newcastle)
Funding: Study taking place in a Tommy’s funded centre
Timescale: 2009 onwards
Summary: During pregnancy, the baby must receive a constant supply of blood to provide it with the nutrients and oxygen it requires to develop properly. To make sure this happens, the structure of the blood vessels in the womb changes, making them much wider. If this process does not happen, it can cause the baby to be born too small or too early and can make the mother seriously ill. As the blood vessels begin to change their shape, white blood cells cluster around them. The aim of this project is to understand how the white blood cells aid the process of vessel widening.

Investigating problems with uterine artery widening
Investigators: Dr Lynda Harris, Samantha Smith, Dr Rebecca Jones, Professor John Aplin
Funding: Study taking place in a Tommy’s funded centre
Timescale: 2006 onwards
Summary: During pregnancy, the developing baby needs a constant and enlarged supply of blood, so elastic fibres in the blood vessels of the womb are broken down and the vessels are permanently widened. If this process does not happen, it can cause the baby to be born too small or too early and can make the mother seriously ill. Our aim is to identify the proteins that control breakdown of elastic fibres in the womb. We hope this will lead to development of a treatment to make blood vessels in the womb wider, if the process does not happen naturally.