Supplementation with antioxidants and folinic acid for children with Down's syndrome: randomised controlled trial.
OBJECTIVE
To assess whether supplementation with antioxidants, folinic acid, or both improves the psychomotor and language development of children with Down's syndrome.


METHODS
Randomised controlled trial with two by two factorial design.


METHODS
Children living in the Midlands, Greater London, and the south west of England.


METHODS
156 infants aged under 7 months with trisomy 21.


METHODS
Daily oral supplementation with antioxidants (selenium 10 mug, zinc 5 mg, vitamin A 0.9 mg, vitamin E 100 mg, and vitamin C 50 mg), folinic acid (0.1 mg), antioxidants and folinic acid combined, or placebo.


METHODS
Griffiths developmental quotient and an adapted MacArthur communicative development inventory 18 months after starting supplementation; biochemical markers in blood and urine at age 12 months.


RESULTS
Children randomised to antioxidant supplements attained similar developmental outcomes to those without antioxidants (mean Griffiths developmental quotient 57.3 v 56.1; adjusted mean difference 1.2 points, 95% confidence interval -2.2 to 4.6). Comparison of children randomised to folinic acid supplements or no folinic acid also showed no significant differences in Griffiths developmental quotient (mean 57.6 v 55.9; adjusted mean difference 1.7, -1.7 to 5.1). No between group differences were seen in the mean numbers of words said or signed: for antioxidants versus none the ratio of means was 0.85 (95% confidence interval 0.6 to 1.2), and for folinic acid versus none it was 1.24 (0.87 to 1.77). No significant differences were found between any of the groups in the biochemical outcomes measured. Adjustment for potential confounders did not appreciably change the results.


CONCLUSIONS
This study provides no evidence to support the use of antioxidant or folinic acid supplements in children with Down's syndrome.


BACKGROUND
Clinical trials NCT00378456.
Ellis
Jill M
JM
Centre for Evidence-based Child Health, Centre for Paediatric Epidemiology and Biostatistics, UCL Institute of Child Health, London WC1N 1EH.
Tan
Hooi Kuan
HK
Gilbert
Ruth E
RE
Muller
David P R
DP
Henley
William
W
Moy
Robert
R
Pumphrey
Rachel
R
Ani
Cornelius
C
Davies
Sarah
S
Edwards
Vanessa
V
Green
Heather
H
Salt
Alison
A
Logan
Stuart
S
D000284:Administration, Oral; D000975:Antioxidants / Q000008:administration & dosage*; D002658:Developmental Disabilities / Q000178:diet therapy / Q000201:enzymology; D019587:Dietary Supplements; D004314:Down Syndrome / Q000178:diet therapy* / Q000201:enzymology; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D007223:Infant; D007806:Language Disorders / Q000178:diet therapy / Q000201:enzymology; D002955:Leucovorin / Q000008:administration & dosage*; D010349:Patient Compliance; D011596:Psychomotor Disorders / Q000178:diet therapy / Q000201:enzymology; D013482:Superoxide Dismutase / Q000378:metabolism; D016896:Treatment Outcome
D000975:Antioxidants; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D002955:Leucovorin