Iron deficiency anemia treatement and incidence of febrile seizures
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Iron deficiency anemia is one of the most prevalent
micronutrient deficiencies in young children in
India and other parts of the world, and it is strongly
associated with persistent cognitive and motor
delays even after the anemia and iron deficit have been
repaired. Madan, et al. [1] reported recently that children
aged 6-23 months with moderate to severe iron deficiency
anemia had lower mental and psychomotor scores that
persisted to as long as 19 years of age. These children also
had lower scholastic achievement and needed more
special education assistance than iron sufficient children.
These impairments may be related to several effects of
iron deficiency in the developing brain including altered
development of neurons in the hippocampus that encodes
memories, impaired energy metabolism, delayed
maturation of myelin, and slowed visual and auditory
evoked potentials [2]. Iron deficiency has also been
associated with alterations in synaptic neurotransmitter
systems including norepinephrine, dopamine, serotonin,
glutamate and gamma-aminobutyric acid (GABA). In
addition, a paper by Kumari, et al. [3] in this issue of
Indian Pediatrics provides evidence that iron deficiency is
also a risk factor for febrile seizures in children 6 months
to three years of age. This carefully done case-control
study with a large sample size showed a highly significant
association between iron deficiency and febrile seizures.
As expected, a family history of febrile seizures or
epilepsy in first degree relatives was also linked to the
occurrence of febrile seizures in these children. The
findings are consistent with another recent case-control
study from Kenya of children 3-156 months of age, which
reported that iron deficiency is a risk factor for simple
febrile seizures but not for other types of acute seizures
[4]. An important practical lesson from this study is that
preventing iron deficiency may be an effective way to
reduce the incidence of febrile seizures.
These new data are also important because they
suggest that there may be a mechanistic link between
febrile seizures associated with iron deficiency and two
other disorders that cause enhanced brain excitability:
restless leg syndrome (RLS) and attention deficit
hyperactivity disorder (ADHD). RLS occurs in children
and adults and is characterized by an urge to move the legs,
usually associated with an unpleasant sensation while
lying down for sleep at night [5]. Family studies and
genome wide association studies suggest a genetic
contribution to RLS, but it is also strongly associated with
reduced serum ferritin levels, and magnetic resonance
imaging (MRI) has shown reduced iron stores in brain in
many patients. Altered metabolism of dopamine also
appears to play a role in enhanced neuronal excitability in
spinal motor and sensory nerves in RLS, and it usually
responds well to dopaminergic agonists along with
replenishment of iron. Iron deficiency has also been
implicated in the pathogenesis of ADHD. Juneja, et al. [6]
reported that there was a significant negative correlation
between serum ferritin levels and the Connors Rating
Scale for ADHD. Low iron levels have also been measured
in the thalamus of children with ADHD using MRI, and the
serum ferritin level has been shown to predict the optimal
dose of amphetamine needed to treat ADHD. Gilbert, et al.
[7] recently reported that children with ADHD have
impaired cortical inhibition in response to transcranial
magnetic stimulation that correlates with the severity of
ADHD. These three disorders, febrile seizures, RLS and
ADHD, may reflect different facets of altered brain
excitability that is enhanced by iron deficiency and also
influenced by genetic factors. Iron is clearly important for
brain development as well as for prevention of anemia, and
more study is warranted to understand its role in these
common neurodevelopmental disorders.