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Giving antioxidants to infants with Down's syndrome
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Giving antioxidants to infants with
Down's syndrome
DOI 10.1136/bmj.39475.655058.80
Giving antioxidants
to infants with Down's syndrome
Tim Reynolds
consultant chemical pathologist
Clinical Chemistry
Department, Queen's Hospital, Burton on Trent, Staffordshire DE13
0RB
tim.reynolds@burtonh-tr.wmids.nhs.uk
Does not improve
psychomotor development
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 ?g, 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, ß 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.
Competing interests: TR is
currently director of prenatal screening for the Sheffield sub-regional
Down's syndrome screening programme and has been paid to speak at
conferences on screening for Down's syndrome. He has also received
consulting fees from several manufacturers of analytical reagents.
Provenance and peer review:
Commissioned; not externally peer reviewed.
Ellis
JM, Tan HK, Gilbert RE, Muller DPR, Henley W, Moy R, et al. Supplementation
with antioxidants and folinic acid for children with Down's syndrome:
randomised controlled trial. BMJ 2008 doi: 10.1136/bmj.39465.544028.AE.
Tatsioni
A, Bonitsis NG, Ioannidis JPA. Persistence of contradicted claims in
the literature. JAMA 2007;298:2517-26.
Heart
Protection Study Collaborative Group (Collins R, Armitage J, Parish
S, Sleight P, Peto R). MRC/BHF heart protection study of antioxidant
vitamin supplementation in 20<thin>563 high-risk individuals:
a randomised-controlled trial. Lancet
2002;360:23-33.
Bønaa
KH, Njølstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, et al;
for the NORVIT Trial Investigators. Homocysteine lowering and cardiovascular
events after acute myocardial infarction. N
Engl J Med 2006;354:1578-88.
Hooper
L, Thompson RL, Harrison RA, Summerbell CD, Ness AR, Moore HJ, et al.
Risks and benefits of omega 3 fats for mortality, cardiovascular disease,
and cancer: systematic review. BMJ
2006;332:752-60.
National
Cancer Institute, US National Institute for Health. SELECT trial. <a href=http://www.crab.org/select/www.crab.org/select/.
US
National Institute on Aging. PREADVISE trial. <a href=http://www.mc.uky.edu/preadvise/www.mc.uky.edu/preadvise/.
Salman
M. Systematic review of the effect of therapeutic dietary supplements
and drugs on cognitive function in subjects with Down syndrome. Eur
J Paediatr Neurol 2002;6:213-9.
National
Health Service. Fetal anomaly screening programme (FASP). <a href=http://nscfa.web.its.manchester.ac.uk/http://nscfa.web.its.manchester.ac.uk/.
Mant
D, Fowler D. Mass screening: theory and ethics. BMJ 1990;300:916-8.
Lumley
J, Watson L, Watson M, Bower C. Periconceptional supplementation with
folate and/or multivitamins for preventing neural tube defects. Cochrane
Database Syst Rev 2001;(3):CD001056.
Giving antioxidants to infants with
Down's syndrome
DOI 10.1136/bmj.39475.655058.80
Giving antioxidants
to infants with Down's syndrome
Tim Reynolds
consultant chemical pathologist
Clinical Chemistry
Department, Queen's Hospital, Burton on Trent, Staffordshire DE13
0RB
tim.reynolds@burtonh-tr.wmids.nhs.uk
Does not improve
psychomotor development
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 ?g, 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, ß 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.
Competing interests: TR is
currently director of prenatal screening for the Sheffield sub-regional
Down's syndrome screening programme and has been paid to speak at
conferences on screening for Down's syndrome. He has also received
consulting fees from several manufacturers of analytical reagents.
Provenance and peer review:
Commissioned; not externally peer reviewed.
Ellis
JM, Tan HK, Gilbert RE, Muller DPR, Henley W, Moy R, et al. Supplementation
with antioxidants and folinic acid for children with Down's syndrome:
randomised controlled trial. BMJ 2008 doi: 10.1136/bmj.39465.544028.AE.
Tatsioni
A, Bonitsis NG, Ioannidis JPA. Persistence of contradicted claims in
the literature. JAMA 2007;298:2517-26.
Heart
Protection Study Collaborative Group (Collins R, Armitage J, Parish
S, Sleight P, Peto R). MRC/BHF heart protection study of antioxidant
vitamin supplementation in 20<thin>563 high-risk individuals:
a randomised-controlled trial. Lancet
2002;360:23-33.
Bønaa
KH, Njølstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, et al;
for the NORVIT Trial Investigators. Homocysteine lowering and cardiovascular
events after acute myocardial infarction. N
Engl J Med 2006;354:1578-88.
Hooper
L, Thompson RL, Harrison RA, Summerbell CD, Ness AR, Moore HJ, et al.
Risks and benefits of omega 3 fats for mortality, cardiovascular disease,
and cancer: systematic review. BMJ
2006;332:752-60.
National
Cancer Institute, US National Institute for Health. SELECT trial. <a href=http://www.crab.org/select/www.crab.org/select/.
US
National Institute on Aging. PREADVISE trial. <a href=http://www.mc.uky.edu/preadvise/www.mc.uky.edu/preadvise/.
Salman
M. Systematic review of the effect of therapeutic dietary supplements
and drugs on cognitive function in subjects with Down syndrome. Eur
J Paediatr Neurol 2002;6:213-9.
National
Health Service. Fetal anomaly screening programme (FASP). <a href=http://nscfa.web.its.manchester.ac.uk/http://nscfa.web.its.manchester.ac.uk/.
Mant
D, Fowler D. Mass screening: theory and ethics. BMJ 1990;300:916-8.
Lumley
J, Watson L, Watson M, Bower C. Periconceptional supplementation with
folate and/or multivitamins for preventing neural tube defects. Cochrane
Database Syst Rev 2001;(3):CD001056.