Premature birth - does inflammation hold clues to delaying labour?
First published on 3 May 2011
Updated on 17 March 2017
What did the project achieve?
“We’ve made an exciting discovery that may one day help protect premature babies from brain damage,” says Dr Raheela Khan of the University of Nottingham.
Over 61,000 babies are born too soon each year in the UK.1-4 Sadly, over 1,000 of these babies lose their lives and those who survive are at risk of developing lifelong problems such as cerebral palsy, blindness and learning difficulties.5-7 Many of these problems result from changes in the brain.
In this project, the researchers set out to investigate links between premature labour and inflammation, focusing on the role of a naturally occurring protein called P2X7.
The researchers have found out more about the role P2X7 plays in inflammation. They had hoped that medicines that block the action of P2X7 might stop contractions if women go into labour too soon. Laboratory work suggests this approach would not work as originally anticipated.
However, the team has discovered that these medicines might have a different benefit. “One of the causes of brain damage in premature babies is maternal infection,” says Dr Khan. “Our laboratory work suggests medicines that block P2X7, if given to mothers during pregnancy, might protect premature babies from this form of brain damage. We hope to find out more about this ground-breaking discovery in future studies.”
1. National Institute for Health and Care Excellence (NICE). Preterm labour and birth final scope April 2013. http://www.nice.org.uk/guidance/gid-cgwave0660/resources/preterm-labour-... Website accessed 15 August 2016
2. Office for National Statistics. Statistical bulletin: Birth Summary Tables, England and Wales: 2015. Live births, stillbirths, and the intensity of childbearing measured by the total fertility rate. http://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarria... Website accessed 15 August 2016.
3. ISD Scotland Data Tables (2015 data). Maternity and Births. Table 5 - Live births (all, singleton and multiple) by birthweight and gestation. http://www.isdscotland.org/Health-Topics/Maternity-and-Births/Publicatio... Website accessed 15 August 2016.
4. Northern Ireland Statistics and Research Agency. Births. Live births 1887-2014. http://www.nisra.gov.uk/demography/default.asp8.htm Website accessed 15 August 2016.
5. Office for National Statistics. Childhood mortality in England and Wales 2014. Table 6. http://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarria... Website accessed 03 August 2016
6. Northern Ireland Statistics and Research agency. Registrar General Annual Report 2014 – Section 4 Stillbirths and Infant Deaths (Excel files) Table 4.5. http://www.nisra.gov.uk/demography/default.asp99.htm Website accessed 03 August 2016.
7. National Records for Scotland. Vital Events Reference Tables 2014. Section 4: Stillbirths and infant deaths. Table 4.5: Infant deaths, by sex and cause, Scotland, 2004 to 2014. http://www.nrscotland.gov.uk/statistics-and-data/statistics/statistics-b... Website accessed 03 August 2016
This research was completed on 30 September 2015
Each week in the UK, more than 25 babies die after being born prematurely.1-3,a,b Many others who survive a very early birth develop lifelong disabilities. Around 40 per cent of premature births happen when expectant mothers go into labour too soon, typically without warning.4 Researchers are investigating the link between inflammation and premature labour, with the longer term aim of finding ways to identify women who are at risk and stop their babies from being born too soon.
- What's the problem and who does it affect?
- What is the project trying to achieve?
- What are the researchers' credentials?
- Who stands to benefit from this research and how?
What's the problem and who does it affect?
Early births put babies in danger
Over 60,000 babies are born prematurely in the UK every year.5-8,c Tragically, around 1,500 of them die.1-3,a,b Premature birth is in fact the biggest killer of babies in the UK.1-3,a,b
Very premature babies who do survive can spend many weeks in hospital in intensive care. Sadly, they are at risk of developing serious disabilities, such as cerebral palsy, blindness, hearing loss and learning difficulties, which can bring a lifetime of suffering. The babies’ families can be profoundly affected by the stress of caring for them.
Around 40 per cent of premature births happen because the mother goes into labour too soon, often without warning – many parents are totally unprepared for the early arrival of their baby.4 Other premature births happen after the mothers’ waters break early or by planned caesarean sections, prompted by complications in the pregnancy.
Once a woman has gone into the final stages of early labour, it is not normally possible to stop her baby from being born too soon. Little is known about why some women go into labour prematurely and it is not always possible to identify those who are at risk.
What is the project trying to achieve?
Infection, inflammation and early births
Evidence suggests that premature labour can be triggered by inflammation. The researchers are finding out more about how this happens – at a molecular level.
Inflammation is the body’s natural way of fighting disease, particularly infection. It is normally tightly controlled. However, it can sometimes go awry. In fact, excessive and misdirected inflammation is known to underlie many diseases, including arthritis and asthma.
Over half of the women who go into labour prematurely have signs of inflammation within the womb.9 In this project, the researchers are investigating how inflammation might trigger premature labour. They are studying the role of a protein called P2X7, which is present in the walls of white blood cells – cells that play a key role in inflammation.
The researchers suspect that infection, or the activation of other ‘danger signals’ in a woman’s body, might switch on P2X7 and initiate a series of events that stimulate inflammation and trigger labour. They also believe that drugs that block the action of P2X7 might have the ability to delay premature labour. They are investigating their theories in detail in the laboratory, using samples donated by around 300 pregnant women and a laboratory model.
What are the researchers' credentials?
|Project Leader||Dr Raheela N Khan PhD|
|Location||Academic Division of Obstetrics and Gynaecology, Graduate Entry Medical School, University of Nottingham in conjunction with the Centre for Integrative Physiology, University of Edinburgh|
|Grant awarded||19 November 2010|
|Start date||8 August 2011|
|End date||30 September 2015|
|Grant code||SP4601 GN1783|
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The researchers together have an internationally recognised track record in the field of pregnancy and inflammation, with over 30 years of combined expertise. They are acclaimed experts in the molecular mechanisms that control contractions during labour, with a programme of research that is well established. They have complementary skills and experience.
The studies are being carried out in two state-of-the-art laboratories – one at Nottingham University’s Graduate Entry Medical School, which is based at the Royal Derby Hospital, and the other at the University of Edinburgh’s Centre for Integrative Physiology. The team is perfectly placed to succeed in this important investigation of how inflammation triggers labour.
Who stands to benefit from this research and how?
Tackling premature birth
The researchers aim to help pregnant women who are at risk of going into labour prematurely. At the moment, it is not possible to identify all of these women or stop their babies from being born too soon.
The researchers are in the early stages of their work. They hope to boost our understanding of how inflammation within the womb might trigger early labour, by focusing on the possible role of a naturally occurring protein called P2X7. They are also investigating whether blocking the action of P2X7 with a drug can delay birth in a laboratory model.
Longer term, the researchers’ work might enable them to develop a new way to identify women who are at risk of going into labour early – possibly by developing a blood test that detects specific signs of inflammation. The researchers’ findings might also help guide the development of new treatments for women who are at risk of giving birth early.
Premature birth is a major cause of death and disability in babies.1-3,a,b Economic costs are staggering. Finding new ways to prevent premature birth could bring profound benefits to the babies, their families and society as a whole.
- Office for National Statistics. (2009) Child Mortality Statistics in England and Wales, 2009 (Table 6) [Online]. Available from http://www.statistics.gov.uk/downloads/theme_health/child-mortality/chil... [Accessed 22 March 2011]
- Northern Ireland Registrar. (2009) General Annual Report 2009 (Section 4: Stillbirths and Infant Deaths) [Online]. Available from http://www.nisra.gov.uk/demography/default.asp76.htm [Accessed on 22 March 2011]
- General Register Office for Scotland. (2009) Vital Events Reference Tables 2009 (Section 4: Stillbirths and Infant Deaths) [Online]. Available from http://www.gro-scotland.gov.uk/statistics/theme/vital-events/general/ref... [Accessed on 22 March 2011]
- Goldenberg RL. The management of preterm labor. Obstet Gynecol 2002; 100:1020-37.
- Office of National Statistics. (2010) Birth Summary Tables, England and Wales 2009: 21/07/10 (Table 1)[Online]. Available from http://www.statistics.gov.uk/statbase/Product.asp?vlnk=14408. [Accessed: 22 March 2011]
- Northern Ireland Registrar General. (2009) Annual Report 2009 (Section 3 Births, Table 3.1)[Online]. Available from http://www.nisra.gov.uk/demography/default.asp76.htm [Accessed: 22 March 2011]
- General Register Office for Scotland. (2009) Vital Events Reference Tables 2009 (Section 3 Births; Table 3.1) [Online]. Available from http://www.gro-scotland.gov.uk/statistics/theme/vital-events/general/ref... [Accessed 22 March 2011]
- Office of National Statistics News Release (May 2007). 1 in 13 live births in England and Wales are born preterm. [Online] Available from http://www.statistics.gov.uk/pdfdir/preterm0507.pdf [Accessed 22 March 2011]
Hagberg H et al. Role of cytokines in preterm labour and brain injury Br J Obstet Gynecol 2005 112, S1 16-18
- a. For England and Wales, deaths listed as due to “immaturity related conditions”
- b. For Scotland and Northern Ireland, deaths listed as due to “disorders related to length of gestation and fetal growth”
- c. Calculation made by Action Medical Research based on figures in references 5-8 for the number of births a year in the UK and the number of preterm deliveries in England, respectively. Estimate assumes incidence of premature birth is the same for the UK overall as it is for England.