Antioxidants do not improve early childhooddevelopment in children with Down’ssyndromeEllis JM, Tan HK, Gilbert RE, Muller DP, Henley W, Moy R,et al. Supplementation with antioxidants and folinic acidfor children with Down’s syndrome: randomised controlledtrial. BMJ 2008;336:594-7.

Question Among children with Down’s syndrome, does sup-plementation with antioxidants, folinic acid, or both improvepsychomotor 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 monthswith trisomy 21.

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

Outcomes Griffiths developmental quotient and an adaptedMacArthur communicative development inventory adminis-tered 18 months after starting supplementation; biochemicalmarkers in blood and urine at age 12 months.

Main Results Children randomized to antioxidant supple-ments attained similar developmental outcomes to thosewithout antioxidants (mean Griffiths developmental quotient57.3 v 56.1; adjusted mean difference 1.2 points, 95% confi-dence interval �2.2 to 4.6). Comparison of children random-ized to folinic acid supplements or no folinic acid also showedno 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 numbersof words said or signed: for antioxidants versus none, the ratioof 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). Nosignificant differences were found between any of the groupsin the biochemical outcomes measured. Adjustment for po-tential confounders did not appreciably change the results.

Conclusions This study provides no evidence to support theuse of antioxidant or folinic acid supplements in children withDown’s syndrome.

Commentary Ellis et al supplemented infants with Down’ssyndrome aged less than 7 months with antioxidants (selenium,zinc, vitamins A, E, and C) � folinic acid versus placebo todetermine whether this might improve educational attainmentmeasured by the Griffiths developmental quotient and anadapted MacArthur communicative development inventory 18months after starting supplementation. Antioxidants were usedbecause of postmortem evidence of neuronal depletion and struc-tural brain abnormalities during late gestation/early postnatal life.The mechanism may be hydrogen peroxide overproduction by

superoxide dismutase and cystathionine �-synthase—2 enzymescoded for on chromosome 21. This study was well planned andexecuted. In particular, study recruitment was rapid—meaningthat changes in Down’s syndrome screening techniques, whichcould conceivably have influenced the educational potential ofthe children by detecting those fetuses most severely affectedwith Down’s syndrome, would be unlikely to affect the conclu-sion. The study found no significant benefit of supplementation,either with antioxidants or with folinic acid. This is perhaps notsurprising because differences between fetuses with Down’s syn-drome and unaffected fetuses can be identified after only 11weeks gestation, implying that by 7 months of age, any damagemay already have been done. Giving vitamins to 6-month-oldbabies with trisomy 21 does not improve their educationalachievement, and until evidence of any benefit of expensivevitamin supplements is available, they cannot be recommended.

Timothy Reynolds, MB ChB, MDQueen’s Hospital, Burton on Trent

Staffordshire, England

Non-pharmacologic therapy may be effectivefor infants with gastroesophageal refluxOrenstein SR, McGowan JD. Efficacy of conservative therapyas taught in the primary care setting for symptoms suggestinginfant gastroesophageal reflux. J Pediatr 2008;152:310-4.

Question Among infants with gastroesophageal reflux dis-ease (GERD), does nonpharmacologic conservative therapyresult in symptomatic improvement over time?

Design Observational cohort before a randomized trial.

Setting Five general pediatric outpatient practices in theUnited States.

Participants Of the first 50 screened infants, 40 (range 4 to 43weeks; median age, 13 weeks) met inclusion/exclusion criteriaincluding abnormal (�16/42) scores on the Infant Gastroesoph-ageal Reflux Questionnaire-Revised (I-GERQ-R).

Intervention Parents of the infants were taught conservativetherapy measures by each site’s study nurse: feeding modifi-cations, positioning, and tobacco smoke avoidance.

Outcomes I-GERQ-R scores and symptom response detailsbefore and 2 weeks after institution of these measures.

Main Results The median initial and final scores were 23(16-36) and 18 (7-34; P � .000001). The median scorechange was �5 (�6 to �16). Scores of 78% improved at all;59% improved at least the threshold of 5 points; 24% becamenormal. Scores for individual symptoms related to regurgita-tion, crying, and arching improved significantly.

Conclusions Two weeks of conservative therapy measurestaught in a primary care setting improved 59% beyond the5-point threshold and normalized 24% of infants with symp-tom severity diagnostic for GERD, as substantiated with aresponsiveness-validated instrument.

Clinical Research Abstracts for Pediatricians 441