Vitamins & Minerals for children with Down’s syndrome

(Concluded in 2006. Results released February 2008 in the BMJ.)

A randomised controlled trial of the effects of antioxidant and folinic acid supplementation on the mental development, growth and health of children with Down’s Syndrome

Research Team: Stuart Logan, Ruth Gilbert, Jill Ellis, Alison Salt, Carole Cummins, Robert Moy, Sally Grantham-McGregor, David Muller, Cornelius Ani, Tim Cole, Sally Riggs, Rachel Miles

This study is a joint initiative between researchers from the Institutes of Child Health in London and Birmingham, the Down’s Syndrome Association, the Down’s Syndrome Research Foundation and the Research Unit of the Royal College of Paediatrics and Child Health.

Summary: This trial aims to examine the effects of supplementation with antioxidants and folinic acid on the health, growth and psychomotor development of children with Down’s syndrome. 200 children with Down’s syndrome, less than 6 months of age will be recruited in London and the West Midlands and randomised into four groups who will receive antioxidants, folinic acid, a combination of antioxidants and folinic acid or a placebo.

Background: Down’s syndrome (DS) is a genetic condition caused by the presence of an extra chromosome 211. It is the commonest genetic cause of learning disability in the UK 2. People with DS are also at increased risk of poor growth 3 and a number of health problems 2,4. The link between the chromosomal abnormality and these problems is not well understood. However there is good evidence that there are biochemical differences in individuals with DS 5. People with DS seem to be more susceptible to damage by certain naturally occurring chemicals (called free radicals) 6, and have also been shown to have increased folic acid metabolism 7.

In an attempt to rectify these biochemical differences it has been suggested that children with DS may benefit from supplementation with either antioxidant medication or folinic acid or both. It is argued that treating the biochemical problems may improve the child’s development and health. However there is very little evidence about the effects of supplementation in children with DS. A recent review on the subject 5 found that previous trials have been small and poorly conducted.

Given the biochemical arguments and the increasing interest from parents, there is a clear need for a good quality trial of supplementation.

Down Syndrome Research Network (DSRN)

As part of this study the Royal College of Paediatrics and Child Health Research Unit have agreed to help to establish the Down Syndrome Research Network of Paediatricians in London and the West Midlands. Initially the members of this network will help to organise the trial and make sure that parents of young children with Down’s syndrome in their area are offered a chance to take part. In the future, it is hoped that DSRN will provide a forum for improving the management of children with this condition and be able to support other potential research projects in the field.

Outline of the study

Participants: Children with Down’s syndrome who are under 6 months old and live inside the M25 or in the West Midlands will be invited to take part. Children will be excluded if their parents do not speak English or if they have serious medical problems, such as severe heart defects.

Allocation: After agreement to participate, children will be allocated by chance to receive one of the following:

1/ Antioxidants –A combination of Selenium, Zinc and the vitamins A, E & C.

2/ Folinic acid

3/ A combination of 1 and 2 above

4/ A placebo/ dummy medicine

Neither researchers nor families will be aware of which group each child is in.

Intervention: Parents will be asked to give the medicines to their children once a day.  Throughout the trial all participating families will be visited on a regular basis by the trial research assistants.

Outcome Measures: Children will have their height and weight measured on three occasions. Blood, which is usually taken routinely on children with DS for clinical tests, will be sent for additional biochemical assays. At the end of the study the child’s general development and speech will be assessed and we will also ask parents to fill in a health questionnaire.

Dissemination of results: Results of the trial will be presented first to the sponsoring organisations and to members of DSRN. Thereafter they will be published in appropriate medical journals. After publication a report will also be made available to all members of the sponsoring organisations and posted on the trial website.

Ethical approval: Ethical approval has been obtained from the London Multi-Centre Research Ethics Committee (MREC) and all relevant local Ethics Committees have been informed. Written consent will be obtained from all parents.

 

References

1. Hernandez D,.Fisher EM. Down syndrome genetics: unravelling a multifactorial disorder. Hum.Mol.Genet. 1996;5 Spec No:1411-6.

2. Epstein CJ. Down syndrome (Trisomy 21). In Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease. Volume 1., pp 749-94. New York: McGraw Hill., 1995.

3. Cronk C, Crocker AC, Pueschel SM, Shea AM, Zackai E, Pickens G et al. Growth charts for children with Down syndrome: 1 month to 18 years of age. Pediat 1988;81:102-10.

4. Marder, E. and Dennis, J. Medical management of children with Down's syndrome. Current Paediatrics. 7, 1-7. 1997.

5. Ani, C., Grantham McGregor, S., and Muller, D. P. Nutritional supplementation in Downs Syndrome:  Theoretical considerations and current status. Developmental Medicine and Child Neurology.  2000;42:207-213.

6. Brooksbank BW, Balazs R. Superoxide dismutase, glutathione peroxidase and lipoperoxidation in Down's syndrome fetal brain. Brain Res. 1984;318:37-44.

7. Regland B,.Gottfries CG. Slowed synthesis of DNA and methionine is a pathogenetic mechanism common to dementia in Down's syndrome, AIDS and Alzheimer's disease? Med.Hypotheses 1992;38:11-9.