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What did the project achieve?
Our laboratory experiments suggest that by using gene therapy to boost the levels of antibacterial molecules in the cervix, we can help to improve the survival of newborns and reduce signs of inflammation and damage to the developing brain,” says Professor Donald Peebles of University College London. “This innovative approach now warrants further investigation as a potential new treatment to prevent preterm birth and its potential long-lasting impact on children’s lives.”
Around 55,000 babies are born prematurely in the UK every year – that’s around one in 13.1,2 Tragically, more than 1,000 babies die each year after being born too soon.3-5 Many others who survive a very early birth develop lifelong problems such as cerebral palsy, blindness and learning difficulties.
While the causes of preterm birth remain poorly understood, there is evidence to suggest that bacteria can pass from the vagina into the womb and trigger inflammation, causing early labour and damaging the baby’s developing brain.
Professor Peebles’ team is investigating whether it is possible to reduce the risk of brain damage in preterm babies – by using a new gene therapy designed to boost the levels of anti-bacterial molecules in the neck of the womb, protecting the womb from infection.
The researchers carried out experiments in a laboratory model to compare the effects of vaginal infection with two different types of E.coli bacteria during pregnancy. One type is linked with meningitis – an inflammation of the lining of the brain and spinal cord – while the other does not cause disease.
“We showed that only infection with the disease-causing bacteria caused early labour and reduced newborn survival,” says Professor Peebles. “We also found increased signs of brain inflammation, cell death and a reduction in the number of nerve cells one week after birth – in newborns that were exposed to these bacteria in the womb.”
The team then tested the effects of their new gene therapy at preventing preterm birth and protecting the brain from damage after exposure to the disease-causing bacteria.
“While our gene therapy did not prevent premature birth, the treatment improved newborn survival – both at birth and over the longer term,” says Professor Peebles. “Encouragingly, it also reduced signs of inflammation and damage in the developing fetal brain shortly after infection – and the treatment may also prevent cell death in the developing brain one week after birth.”
The researchers also carried out experiments using gene therapy with a different anti-bacterial molecule – with similarly promising results. Further research is now needed to explore whether this potential treatment for mothers at high risk of preterm labour could help improve the survival and quality of life of premature babies in the future.
References
- Office for National Statistics, Vital statistics in the UK: births, deaths and marriages - 2020 https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/vitalstatisticspopulationandhealthreferencetables [website accessed 16 February 2023]
- Birth characteristics in England and Wales: 2020 https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/livebirths/bulletins/birthcharacteristicsinenglandandwales/2020
- Office for National Statistics. Childhood mortality in England and Wales 2020. Table 17. http://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/datasets/childmortalitystatisticschildhoodinfantandperinatalchildhoodinfantandperinatalmortalityinenglandandwales [website accessed 16 February 2023]
- National Records for Scotland. Section 4: Stillbirths and Infant deaths: https://www.nrscotland.gov.uk/statistics-and-data/statistics/statistics-by-theme/vital-events/general-publications/births-deaths-and-other-vital-events-quarterly-figures/3rd-quarter-2022 [website accessed 16 February 2023]
- Northern Ireland Statistics and Research Agency. Registrar General Annual Report 2015 – Stillbirths and Infant Deaths: https://www.nisra.gov.uk/publications/registrar-general-annual-report-2015-tables-and-full-report [website accessed 16 February 2023]
This research was completed on
In the UK, around 61,000 babies are born prematurely each year and sadly, more than 1,000 will die.1-7 Children who survive can experience lifelong conditions such as cerebral palsy, learning difficulties, blindness and hearing loss. Evidence suggests that bacteria can pass into the womb and trigger inflammation, which can cause early labour and damage the baby’s developing brain. Professor Donald Peebles at University College London is developing an innovative new gene therapy that could help prevent preterm birth and protect the baby’s brain. He is now carrying out laboratory tests to investigate the effectiveness of this potential new treatment.
Action Medical Research and Borne are jointly funding this research.
How are children’s lives affected now?
Around one in every 13 babies in the UK will be born premature, before 37 weeks of pregnancy.1-8 And, despite extensive research over recent years, these numbers are not falling.9
Tragically, being born too soon is the biggest cause of newborn death.10 And premature birth is not just a fight for life. Many children, particularly those born before 32 weeks of pregnancy, will grow up experiencing serious, long-term consequences – including cerebral palsy, learning difficulties, blindness and hearing loss.
What causes premature birth is often unknown. But evidence suggests that infection is involved in four out of 10 women who experience an unexpected early labour.11
“Bacteria, usually found inside the mother’s vagina, can sometimes get through the neck of the womb – the cervix – and into the womb where the baby is growing,” says Professor Peebles. “This is bad news, as this infection can trigger inflammation that may cause premature birth and damage to the developing baby’s brain.”
How could this research help?
“We are aiming to develop a new treatment that can help prevent bacteria getting into the womb,” says Professor Peebles. “Our hope is it could both reduce the numbers of premature births, as well as reduce the risk of brain damage and its long-lasting impact on children’s lives.”
Anti-bacterial molecules produced in the cervix help to stop bacteria from getting through. The team are developing a new gene therapy that is designed to boost these natural defences, helping to protect the womb from infection.
“We are now planning the next stage of our laboratory tests, to investigate if our innovative new approach can prevent bacterial damage to the developing fetal brain,” says Professor Peebles. “And importantly, we also need to confirm that it is safe for both mother and baby.”
“If our results continue to show promise, we aim to take this potential new treatment into clinical trials within the next five years,” says Professor Peebles.
References
- Office for National Statistics: https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/livebirths/bulletins/birthsummarytablesenglandandwales/2016 [website accessed 12 December 2017]
- National Records of Scotland: 2016 Births, Deaths and Other Vital Events - Preliminary Annual Figures: https://www.nrscotland.gov.uk/statistics-and-data/statistics/statistics-by-theme/vital-events/general-publications/births-deaths-and-other-vital-events-preliminary-annual-figures/2016 [website accessed 12 December 2017]
- Northern Ireland Statistics and Research Agency. Births. Live births 1887-2016. https://www.nisra.gov.uk/publications/monthly-births [website accessed 12 December 2017]
- National Institute for Clinical Excellence: Preterm labour and birth final scope April 2013 https://www.nice.org.uk/guidance/ng25/documents/preterm-labour-and-birth-final-scope2
- Office for National Statistics. Childhood mortality in England and Wales 2014. Table 6. http://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/datasets/childmortalitystatisticschildhoodinfantandperinatalchildhoodinfantandperinatalmortalityinenglandandwales [website accessed 12 December 2017]
- National Records for Scotland. Section 4: Stillbirths and Infant deaths: http://www.nrscotland.gov.uk/statistics-and-data/statistics/statistics-by-theme/vital-events/general-publications/vital-events-reference-tables/2014/section-4-stillbirths-and-infant-deaths [website accessed 12 December 2017]
- Northern Ireland Statistics and Research Agency. Registrar General Annual Report 2015 – Stillbirths and Infant Deaths: https://www.nisra.gov.uk/publications/registrar-general-annual-report-2015-tables-and-full-report [website accessed 12 December 2017]
- Bliss charity: https://www.bliss.org.uk/prematurity-statistics-in-the-uk [website accessed 06 December 2017]
- House of Commons Library; World Prematurity Day 2015, Debate Pack CDP 2015/104: http://bit.ly/2DAFt0Q
- Blencowe H et al. Born too soon: the global epidemiology of 15 million preterm birth. Reproductive Health 2013; 10 Suppl 1 S2
- Romero R et al. The role of infection in preterm labour and delivery. Paediatrics Perinatal Epidemiology 2001; 15 Suppl 2 41-56.
| Project Leader | Professor Donald M Peebles, MA MBBS MD FRCOG |
| Project Team | Dr Simon N Waddington, BSc MSc PhDDr Natalie Suff, BSc MBBCh MRCOGDr Ahad A Rahim, BSc PhD |
| Project Location | Department of Maternal and Fetal Medicine, Institute for Women’s Health, University College London |
| Project Location Other | School of Pharmacy, University College London |
| Project duration | Two years |
| Date awarded | 21 November 2017 |
| Project start date | 1 October 2018 |
| Project end date | 30 September 2022 |
| Grant amount | £141,949 |
| Grant code | GN2647 |
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