Subido por Gerardo Adolphs

efectos cognitivos de la anemia ferropenica

1. Klepper J, Leiendecker B. GLUT1 deficiency syndrome
– 2007 update. Dev Med Child Neurol 2007; 49: 707–
spective Norwegian study. Dev Med Child Neurol 2013;
4. Klepper J. GLUT1 deficiency syndrome in clinical practice. Epilepsy Res 2012; 100: 272–7.
55: 440–47.
3. Anheim M, Maillart E, Vuillaumier-Barrot S, et al. Excel-
2. Ramm-Pettersen A, Nakken KO, Skogseid IM, et al.
lent response to acetazolamide in a case of paroxysmal dy-
Good outcome in patients with early dietary treatment
skinesias due to GLUT1-deficiency. J Neurol 2011; 258:
of GLUT-1 deficiency syndrome: results from a retro-
What do we know about the long-term cognitive effects of
iron-deficiency anemia in infancy?
University of North Florida, Jacksonville, FL, USA.
doi: 10.1111/dmcn.12127
This commentary is on the original article by Algarın et al. on pages
453–458 of this issue.
The topic of iron deficiency and its impact during development is critical as it is thought to affect 20 to 25% of the
worldwide population.1 A 2001 review of existing research
concluded that iron deficiency has a negative impact on
cognition, behavior, and motor skills that can have long
term implications.2 When it comes to brain regions, it
impacts areas associated with spatial navigation, such as the
hippocampus.1 One concern is that this relationship can be
confounded by external factors, such as low socioeconomic background. The issue of the affect of iron deficiency is not without controversy. Some argue that its
potential long-term negative consequences on cognitive
impairment and motor skills are far from either causal or
conclusive, and could be largely motivated by a desire to
promote the use of supplements.2
The study by Algarın et al.3 brings the research upto-date by investigating whether having iron-deficiency
anemia (IDA) in infancy affects cognitive inhibition in the
long term. They recruited children who were healthy fullterm infants, with no perinatal complications, and no acute
or chronic illnesses, but were identified as either having
iron-deficiency anemia (IDA) or not at 6, 12, or
18 months. Participants were given an oral iron supplement for a minimum of 6 months and had normal venous
hemoglobin concentrations at the end of the study. They
were tested again for the present study when they were
aged 10 years. Less than 5% of the sample had IDA
(defined as low venous hemoglobin concentrations) and
were not included in the analyses. Crucially, the researchers ensured that there was no difference in socio-economic
status between groups, so that the findings would be relatively free from this influence.
The researchers focused primarily on inhibitory control,
which is a key aspect of cognition – associated with decision-making and addictive behavior.4 The results indicated
that despite receiving iron treatment in infancy and the
absence of IDA at 10 years old, children who had IDA
during infancy performed significantly worse in a test of
cognitive inhibition.
The present research also added to existing research by
identifying smaller a P300 amplitude during event-related
potentials recordings. This profile of the P300 is consistent
with research associating this area with working memory
performance.5 Working memory – the conscious processing of information – is increasingly recognized as one of
the most important aspects of intelligence. This fundamental cognitive skill is deeply connected to a great variety of
human experience – from our childhood, to our old age,
from our education, to our mental health as adults.6
The implications of the present research are that IDA
can contribute to long-term cognitive impairments that
may jeopardize the future success of children. There is
some evidence that iron supplementation can be useful in
improving cognitive performance in iron-deficient (but
non-anaemic) females, even during adolescence.7 However,
in those with IDA, perhaps a useful way forward is to utilize both supplementation, as well as cognitive/brain training for maximum support for their learning needs.8
1. Lozoff B, Jimenez E, Hagen J, Mollen E, Wolf A.
2. Grantham-McGregor S, Ani A. A review of studies on
Poorer behavioral and developmental outcome more
the effect of iron deficiency on cognitive development in
than 10 years after treatment for iron deficiency in
children. J Nutr 2001; 131: 649S–68S.
infancy. Pediatrics 2000; 105: E51.
3. Algarın C, Nelson CA, Peirano P, Westerlund A, Reyes
S, Lozoff B. Iron-deficiency anemia in infancy and
poorer cognitive inhibitory control at 10 years. Dev Med
Child Neurol 2013; 55: 453–58.
4. Bechara A. Decision-making, impulse control and loss
of willpower to resist drugs: a neurocognitive perspective. Nat Neurosci 2005; 8: 1458–63.
5. Patel SH, Azzam PN. Characterization of N200 and
7. Bruner AB, Joffe A, Duggan AK, Casella J, Brandt J.
8. Alloway TP, Bibile V, Lau G. Computerized working
P300: selected studies of the Event-Related Potential.
Randomised study of cognitive effects of iron supple-
memory training: can it lead to gains in cognitive skills
Int J Med Sci 2005; 2: 147–54.
mentation in non-anaemic iron-deficient adolescent
in 2 students? Comput Hum Behav 2013; 29: 632–638.
6. Alloway TP, Alloway RG. Working Memory: The Con-
girls. Lancet 1996; 348: 992–6.
nected Intelligence. New York: Psychology Press, 2012.
Proper stratification of survival curves by level of gross motor
Mortality Research and Consulting Inc., Newport Beach, CA, USA.
doi: 10.1111/dmcn.12136
This commentary is on the original article by Touyama et al. on pages
459–463 of this issue.
Touyama et al. report on long-term survival of cerebral
palsy (CP) in Okinawa, Japan.1 The authors stratified
Kaplan-Meier survival curves by Gross Motor Function
Classification System (GMFCS) level.2 Stratification by
GMFCS level is valuable for two reasons: (1) level of
gross motor function is a strong predictor of long-term
survival in CP; and (2) the GMFCS is a validated and
widely employed measure of gross motor functioning in
CP. Proper stratification by GMFCS level could allow
for more meaningful between-study comparisons of survival.
Unfortunately, the method of stratification in various
studies may make comparisons of survival curves problematic. In Touyama et al.1 GMFCS level was ascertained
‘as closely as possible to the follow-up termination date’
of their study, whereas follow-up began at age 2. If
GMFCS level is determined at an older age and then
groups are formed at age 2 on this basis, a bias in the
Kaplan-Meier survival analysis may result. It is not clear
in which direction this bias may work. I will consider
two extreme (hypothetical) possibilities to illustrate the
First, suppose that every 2-year-old child with CP who
lives long enough eventually is at GMFCS level V and
remains so thereafter. In this case, late ascertainment of
GMFCS level would bias survival estimates for 2-year-olds
at GMFCS level V toward longer survival. This is because
children of all GMFCS levels (at age 2) would be included
in the analysis, and survival is undoubtedly better for
2-year-olds at a GMFCS lower than level V. Furthermore,
children who died before reaching GMFCS level V would
be excluded from the analysis. Thus, not only would
higher functioning children be included in the analysis, but
many who died would be excluded.
402 Developmental Medicine & Child Neurology 2013, 55: 397–404
Another extreme possibility is that all children at
GMFCS level V who live long enough eventually improve
to one of levels I to IV. In this case, late ascertainment of
GMFCS level would bias results for 2-year-olds at
GMFCS level V toward shorter survival: only children
who died before improving or who never improved during
the follow-up period would contribute to the analysis.
A third possibility is that GMFCS level is stable over a
child’s lifespan. In this case, the timing of ascertainment of
GMFCS level would not matter. The truth lies somewhere
between the two extremes: over time, some 2-year-olds at
GMFCS levels I to IV will decline to level V, and some
initially at GMFCS level V will improve.3
Touyama et al.,1 in a communication to the editors of
the journal, have clarified that all children at GMFCS level
V at first ascertainment remained at level V throughout the
study period; eight children changed from GMFCS level
IV at first ascertainment to level V at last ascertainment, all
of whom were alive at the termination of the study; and no
children at GMFCS levels I to III at first ascertainment
become level V at last ascertainment. My interpretation is
that GMFCS level was fairly stable for this study, and thus
the impact of late ascertainment on the survival curves was
not likely to be dramatic. (Note: A DMCN statistical advisor rightly pointed out that the foregoing issues of possible
bias apply when the question at hand is: what impact does
GMFCS level now have on long-term survival in the future.
If GMFCS level is understood to change over time, a different question is: what impact does level of GMFCS at
any time have on survival at that moment? For this question, modeling methods that handle time-varying
covariates, e.g. Cox proportional hazards or logistic regression, could be used to estimate the impact.)
Brooks et al.4 compared survival in CP at GMFCS level
V in California and in Sweden. The 16-year Kaplan-Meier
survival was 67% in California and 63% in Sweden, a
result the authors suggested was, ‘a significant additional
piece of evidence that survival probabilities are remarkably
similar for children with severe disability in developed
countries.’ Now in Touyama et al. we find 74% 16-year
survival (from 2 to 18y) for GMFCS level V.
Neither Brooks et al. nor the authors of the original
Swedish study by Westbom et al.5 make clear how or