Giving antioxidants to infants with Down’s syndrome
Authors: Tim Reynolds
Journal: BMJ (2008)

In their accompanying randomised controlled trial, Ellis and colleagues assess whether supplementation with antioxidants or folinic acid (or both) improves the psychomotor and language development of children under 7 months old who have Down’s syndrome. The trial compared 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 and found no significant difference in outcomes at 18 months.1

Antioxidants, vitamins, and miscellaneous food supplements are often believed to cure all manner of ills. In many cases, however, belief in food supplements flies in the face of the evidence.2 Vitamins have been tested as a preventive measure for cardiovascular disease, but the heart protection study (vitamin E, vitamin C, s carotene, 20 mg/d), the Norwegian vitamin trial (folic acid, vitamin B12), and a meta-analysis of the effects of fish oils on cardiovascular disease have failed to show benefit.3 4 5 Trials continue into prevention of prostate cancer (the SELECT trial; selenium and vitamin E), Alzheimer’s disease (the PREADVISE trial; selenium and vitamin E), and many other clinical conditions.6 7

The food supplement industry can use beliefs in the benefits of their products to support a profitable business. Understandably, parents will try any potentially effective treatment in an attempt to improve the health of their child with Down’s syndrome. They may also feel pressured and guilty about not being able to afford expensive treatments.

Clinical trials are based on sound theoretical expectations that benefits should accrue, but often theory does not translate into clinical benefit. In theory, the genetic defects in Down’s syndrome could act through excess oxidant stress that causes neurodevelopmental damage. It is therefore logical to investigate whether antioxidants could alleviate these defects.

One difficulty with researching infants with Down’s syndrome is that the birth prevalence of the disease is decreasing as a result of antenatal screening and termination of pregnancy. Antenatal screening may identify the most severely affected fetuses, so the average IQ of infants with Down’s syndrome who are not identified by screening may be higher than that of an unselected cohort. If the study had taken a long time to recruit, improvements in the NHS antenatal Down’s screening programme might therefore have caused a false improvement in IQ. However, the study by Ellis and colleagues took a relatively short time to recruit the number of infants needed. Not all children could tolerate the treatment but for those who could compliance was good. Despite this no significant biochemical or psychomotor differences were seen between the groups. The findings are consistent with previous research.8

The NHS fetal anomaly screening programme is currently working hard to increase the efficiency of antenatal Down’s syndrome screening by increasing the detection rate and decreasing the screen positive rate, which may encourage uptake of screening.9 Screening programmes can do more harm than good, and ethical guidelines for screening include the concept that screening should only be carried out if an effective treatment is available.10 When screening for Down’s syndrome, the treatment is currently termination of pregnancy, which may be an effective treatment from one viewpoint, but may not be an acceptable treatment from the position of the fetus with Down’s syndrome.

Antenatal screening for Down’s syndrome identifies differences between fetuses with and without trisomy 21, as early as 10 weeks’ gestation. This in itself indicates that postnatal supplementation would be unlikely to work. Folic acid supplements given before conception reduce the incidence of neural tube defects.11 Perhaps supplementation with antioxidants before conception could reduce the neurobiological development damage caused by excess gene dosage in trisomy 21. 

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.