Supplementation with antioxidants and folinic acid for children with Down’s syndrome: randomised controlled trial

BMJ : British Medical Journal
Feb 2008
Citations:92
Influential Citations:4
Interventional (Human) Studies
84
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Methods
Randomized, double-blind trial with a 2x2 factorial design. 156 infants with Down syndrome aged under 7 months at enrollment; multiple UK sites (Midlands, Greater London, Southwest England, etc.); primary outcome: Griffiths developmental quotient at 18 months; secondary outcomes included language and motor milestones; biochemical markers measured; adherence monitored; allocation concealment good; blinding maintained until final outcome.
Intervention
Daily oral supplementation for up to 18 months starting in infancy (enrolment under 7 months). Doses: antioxidants (selenium 10 μg, zinc 5 mg, vitamin A 0.9 mg, vitamin E 100 mg, vitamin C 50 mg) and folinic acid (0.1 mg); dosage increased by 30% after the first birthday; administered as powders mixed with food or drink; regimen included antioxidants with folinic acid, antioxidants alone, folinic acid alone, or placebo.
Results
No evidence that antioxidants or folinic acid improved psychomotor development or language by 18 months. Adjusted mean differences for Griffiths quotient were small and not statistically significant; milestone attainment times showed no meaningful advantage; oxidative-stress biochemical markers were similar across groups. Conclusion: routine use of antioxidant or folinic acid supplements in young children with Down syndrome is not supported; benefits are unproven and potential adverse effects and costs should be weighed. Some participants taking antioxidants stopped due to vomiting or distress.
Limitations
Smaller-than-planned sample size (156 randomized vs 200 planned); about 11% loss to follow-up; follow-up limited to 18 months; limited power to detect small effects; adherence variability and regional recruitment differences may affect generalizability.

Abstract

Objectives To assess whether supplementation with antioxidants, folinic acid, or both improves the psychomotor and language development of children with Down’s syndrome. Design Randomised controlled trial with two by two factorial design. Setting Chi...