Antioxidants do not improve early childhood development in children with Down's syndrome

Article Outline

• Ellis JM, Tan HK, Gilbert RE, Muller DP, Henley W, Moy R, et al. Supplementation with antioxidants and folinic acid for children with Down's syndrome: randomised controlled trial. BMJ 2008;336:594-7
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Ellis JM, Tan HK, Gilbert RE, Muller DP, Henley W, Moy R, et al. Supplementation with antioxidants and folinic acid for children with Down's syndrome: randomised controlled trial. BMJ 2008;336:594-7 

Question Among children with Down's syndrome, does supplementation with antioxidants, folinic acid, or both improve psychomotor and language development?

Design Randomized controlled trial.

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

Participants A total of 156 infants aged less than 7 months with trisomy 21.

Intervention Daily oral supplementation with antioxidants (selenium 10 μg, 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.

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

Main Results Children randomized 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 randomized 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.

Commentary Ellis et al supplemented infants with Down's syndrome aged less than 7 months with antioxidants (selenium, zinc, vitamins A, E, and C) ± folinic acid versus placebo to determine whether this might improve educational attainment measured by the Griffiths developmental quotient and an adapted MacArthur communicative development inventory 18 months after starting supplementation. Antioxidants were used because of postmortem evidence of neuronal depletion and structural brain abnormalities during late gestation/early postnatal life. The mechanism may be hydrogen peroxide overproduction by superoxide dismutase and cystathionine β-synthase—2 enzymes coded for on chromosome 21. This study was well planned and executed. In particular, study recruitment was rapid—meaning that changes in Down's syndrome screening techniques, which could conceivably have influenced the educational potential of the children by detecting those fetuses most severely affected with Down's syndrome, would be unlikely to affect the conclusion. The study found no significant benefit of supplementation, either with antioxidants or with folinic acid. This is perhaps not surprising because differences between fetuses with Down's syndrome and unaffected fetuses can be identified after only 11 weeks gestation, implying that by 7 months of age, any damage may already have been done. Giving vitamins to 6-month-old babies with trisomy 21 does not improve their educational achievement, and until evidence of any benefit of expensive vitamin supplements is available, they cannot be recommended.