Fetal growth restriction: investigating the potential of a growth factor
This research was completed on 30 November 2013
Published on 29 January 2009
Unborn babies with fetal growth restriction can grow so dangerously slowly in the womb that they are at risk of death and disability. There is no way to boost the babies growth rates while they are in the womb, so parents can face a stark choice between risking continuing with the pregnancy and agreeing to have their baby prematurely. Researchers believe a growth factor called VEGF might boost an unborn baby’s growth rate by increasing maternal blood flow to the womb. They are investigating the potential of this exciting new therapy.
What's the problem and who does it affect?
A stark choice
Fetal growth restriction is a major problem, affecting up to 8% of all pregnancies.1 Some babies with fetal growth restriction grow so slowly in the womb that their health is put at risk. Sadly, some are stillborn. Even babies who are born alive can be so small – sometimes just 500g or 1lb 1oz – that they remain at risk of dying or developing lifelong disabilities, such as cerebral palsy and learning difficulties. They also have an increased chance of developing heart disease, diabetes and high blood pressure in adulthood.
No current treatment can help unborn babies with fetal growth restriction. Parents can face a stark choice between continuing with the pregnancy, knowing there is a strong likelihood their baby will die in the womb, and agreeing to deliver the baby very prematurely, which brings its own risks of death and disability.
Babies who are both premature and very small for their age often stay in hospital for months after birth, even if they eventually grow up to be healthy. This is stressful for parents and costly for the NHS.
What is the project trying to achieve?
An exciting potential treatment
An unborn baby needs a constant supply of oxygen, glucose and other nutrients from its mother. These nutrients pass from the mother’s blood, through the placenta, to the baby.
During pregnancy, a woman’s circulatory system changes, with large increases in the amount of blood flowing to the womb – particularly the area around the placenta. This ensures the unborn baby receives all the nutrients it needs to grow and develop. It’s thought that one cause of fetal growth restriction is the failure of this process – meaning there isn’t enough of the mother’s blood flowing to the womb.
The researchers have identified an exciting potential therapy for fetal growth restriction. They have shown that increasing the production of a special protein – a growth factor called VEGF – can increase the flow of maternal blood to the womb in an animal model.2 In this project, they are investigating whether this increased blood flow actually improves fetal growth and increases birthweight both in normal pregnancies, and in those affected by fetal growth restriction, using another animal model.
What are the researchers' credentials?
|Project Leader||Dr A David MB ChB MRCOG PhD|
|Location||Prenatal Cell and Gene Therapy Group, Institute for Women's Health and Centre for Cardiovascular Biology & Medicine, University College London|
|Grant awarded||29 October 2008|
|Start date||1 December 2008|
|End date||30 November 2013|
|Grant code||SP4409, GN1738|
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The project leader, Dr Anna David, leads the Prenatal Cell and Gene Therapy Group at University College London. The group aims to develop new treatments for unborn babies who are suffering from severe and life-threatening disorders, by devising gene and cellular therapies that can be used while the baby is still in the womb.
The team’s ground-breaking research is internationally competitive. The group has published widely and won many international prizes. Indeed, the group is the only one working in this area of research in the UK and there are only a handful of similar groups in the world.
Team members have wide-ranging expertise - from basic science know-how needed in the laboratory to clinical skills, such as fetal ultrasound, that help translate their findings into medical practice. As well as being a successful researcher, Dr David is also a consultant, with expertise in treating women who have complicated pregnancies, including those affected by fetal growth restriction.
Who stands to benefit from this research and how?
Working towards the first ever treatment
The researchers’ laboratory work will reveal whether treatment with the growth factor VEGF has the potential to improve the growth of babies in the womb and lower the rate of death and complications. More work would be needed before the treatment could be trialled in pregnant women but, if successful, the group’s work might lead to the first ever therapy for fetal growth restriction. The researchers believe it is possible that VEGF may also help in another related and serious complication of pregnancy called pre-eclampsia.
Currently, some babies with very severe growth restriction have to be delivered as much as 15 weeks early, after just 25 weeks of pregnancy. At this stage, even relatively small increases in the baby’s weight are associated with major improvements in their chances of surviving and being healthy. Between 23 and 26 weeks of pregnancy, an increase in birth weight of just 100g – that’s just 3½ ounces - reduces a baby’s chances of dying by 40%.3 It also reduces their chances of developing complications, such as cerebral palsy. Clearly, babies have a lot to gain from any new treatment that can improve their growth rate within the womb.
- Resnik R. Intrauterine Growth Restriction. Obstetrics and Gynaecology 2002; 99:490-496.
- David AL, Torondel B, Zachary I et al. Local delivery of VEGF adenovirus to the uterine artery increases vasorelaxation and uterine blood flow in the pregnant sheep. Gene Therapy 2008; 15:1344-1350.
- Tyson JE, Parikh NA, Langer J, Green C, Higgins RD. Intensive Care for Extreme Prematurity: Moving Beyond Gestational Age. New England Journal of Medicine 2008; 358:1672-1681.