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Preventing neural tube defects

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What did the project achieve?

“Our results underline the importance of the mother’s dietary intake of a vitamin called inositol before and during pregnancy which could help prevent serious neural tube defects like spina bifida,” says Professor Nicholas Greene of UCL Great Ormond Street Institute of Child Health. “The findings of this study will inform the design of a clinical trial to further explore whether taking this inexpensive and readily available supplement could help protect more babies from these life-changing conditions than is currently possible, over and above folic acid supplementation.”

Neural tube defects (NTDs) are severe developmental abnormalities that affect a baby’s brain or spinal cord. Spina bifida is the most common and can cause wide-ranging symptoms, such as difficulties with walking, incontinence, spinal curvature and learning difficulties. Affected children usually need several operations and, while most grow up to become adults, their lives are often cut short. Taking folic acid before and during pregnancy can prevent some, but not all, NTDs.

Professor Greene’s team has previously carried out a small clinical trial in the UK to investigate whether using inositol supplements during early pregnancy can also, like folic acid, help protect babies from NTDs – with encouraging results. In this project, the researchers carried out laboratory experiments to gain a deeper understanding of the effects of inositol deficiency and supplementation on the developing embryo.

“In experimental models, we showed that a deficiency of inositol in the mother’s diet leads to lower concentrations of this vitamin in the developing embryo – and that insufficient levels in the embryo are linked with NTDs,” says Professor Greene. “We also uncovered new insights into the biological effects of supplementary inositol on the developing embryo, which will help inform its clinical use.”

These findings provide further evidence that some NTDs may be linked with inositol deficiency or uptake and could be prevented by the use of dietary supplements by women planning pregnancy.

“If the results of the next trial are positive, implementation of inositol supplementation for prevention for NTDs could begin within five years  – helping to further reduce the number of babies born with these life-changing conditions around the world,” says Professor Greene.

This research was completed on

Neural tube defects (NTDs) are severe developmental abnormalities that affect a baby’s brain, spine, or spinal column. They affect around one in 1,000 pregnancies, with 190 babies born alive with an NTD in the UK every year.1-4 Taking folic acid can help prevent NTDs, but it is not always effective. Professor Nicholas Greene at the UCL Great Ormond Street Institute of Child Health is investigating if giving women a vitamin called inositol can also help protect babies inside the womb. He hopes that this could lead to a cheap, effective new approach to help reduce the number of babies born with NTDs in the future.

How are children’s lives affected now?

In early pregnancy, a structure forms in the developing embryo called the neural tube that eventually develops into the baby’s brain and spinal cord. It closes about four weeks after conception, but when something goes wrong, this can result in a neural tube defect – or NTD.

The most common NTD is spina bifida. Children with this condition may experience a wide range of symptoms that include difficulties with walking, incontinence, and learning difficulties. They usually need several operations and while most grow up to become adults sadly, their lives are often cut short.

Most NTDs are due to a combination of genetic and environmental risk factors, with a mother’s diet before and during early pregnancy playing an important role.

“Thankfully, women in the UK who are trying to become pregnant are now routinely advised to take folic acid, which can reduce the risk of their baby having an NTD,” says Professor Greene. “But this is not completely effective, so we need new approaches to protect more babies from these serious conditions.”

How could this research help?

“Our ultimate goal is to use a vitamin – called inositol – to reduce the risk of NTDs,” says Professor Greene. “As a cheap and readily available supplement, we’re excited about its potential to deliver benefits quickly.”

The team have already carried out a small clinical trial in the UK, with encouraging results. They now plan to find out more about the biological impact of inositol on the developing embryo – to understand how it works, how to use it most effectively, and identify any other unexpected effects.

Their results will help shape the design of a larger clinical trial to test whether the vitamin can truly help prevent babies from developing NTDs.

“Our hope is that one day taking inositol will mean fewer parents receiving heart-breaking news about their baby,” says Professor Greene. “And, as our knowledge about the genetic risk factors for NTDs improves, understanding how inositol and other nutrients help prevent these conditions could even pave the way towards personalised supplements for women planning a pregnancy.”

References

1.Morris JK. et al. Prevention of neural tube defects in the UK: a missed opportunity. Archives of Disease in Childhood. 2016; 101(7): 604-607. http://adc.bmj.com/content/101/7/604

2.Office for National Statistics: https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarri... [website accessed 12 December 2017]

3.National Records of Scotland: 2016 Births, Deaths and Other Vital Events - Preliminary Annual Figures: https://www.nrscotland.gov.uk/statistics-and-data/statistics/statistics-... [website accessed 12 December 2017]

4.Northern Ireland Statistics and Research Agency. Births. Live births 1887-2016. https://www.nisra.gov.uk/publications/monthly-births [website accessed 12 December 2017]

 

 

 

 

Project Leader Professor Nicholas D E Greene, MA PhD
Project Team Professor Andrew J Copp, DPhil MBBS, FMedSci, FRCPath, FRSB
Project Location Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, University College London
Project duration 28 months
Date awarded 20 November 2017
Project start date 1 June 2018
Project end date 30 September 2021
Grant amount £189,516
Grant code GN2656

 

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