Introduction
Anemia is a global health problem; an estimated 300-million children
worldwide had anemia in 2011.1 Iron deficiency anemia
(IDA) is the most common cause of anemia in childhood. Thus, the WHO has
recommended an international anemia control guideline: all children and
women living in settings where the prevalence of anemia exceeds 20%
should receive supplemental iron.2 In Thailand, this
recommendation has been adopted by the Department of Health, Ministry of
Public Health (MOPH) and incorporated into our routine childcare. It is
fully subsidized by the Thai government through the National Health
Security Office (NHSO). The MOPH recommends a universal iron supplement
in Thai infants over 6 months old for IDA prevention when these babies
come for routine vaccination. Iron supplementation continues until 24
months of age, with 12.5 mg of elemental iron weekly.3This age group has been selected as infants over 6 months who have a
high prevalence of IDA, which can impair physical, behavioral, and
cognitive functions and result in persistent neurocognitive defects,
despite later iron therapy.4 However, local
practitioners, in particular pediatricians, are concerned about this
policy since there is a high prevalence of thalassemia and hemoglobin
disorders in Thailand (P. Surapolchai et al., manuscript in
preparation). It is widely accepted thalassemia disease could
significantly increase the risk of iron overload (IOL), leading to iron
toxicity in later life.5-6
Thalassemia (thal) is characterized by inherited mutations of α and β
globin genes causing decreased globin synthesis. At least 5.2% of the
world population carries one allele of globin gene variants (carrier or
trait).7 For α-thal, there are two types based on
molecular defects: α0-thal caused by deletions of two
linked α-globin genes in cis (–/αα) and
α+-thal caused by deletions of one α-globin gene
(-α/αα) or nucleotide mutations (αTα/αα or
αα/ααT). Coinheritance of two affected alleles (in
autosomal recessive mode) leads to chronic hemolytic anemia and
ineffective erythropoiesis known as thalassemia disease (thal
disease).8 Hemoglobinopathy, on the other hand, is
mainly caused by mutations of coding sequences, leads to qualitative
defects. Several hemoglobinopathies are innocuous and do not lead to any
clinical consequences.9 However, some mutations such
as hemoglobin E (Hb E) at codon 26 of the β-globin genes (GAG
>AAG) also have quantitative effects and interaction of Hb
E with β-thal mutations leads to Hb E/β-thalassemia (Hb E/β-thal)
syndrome with heterogeneous clinical severity. In Thailand, 30 to 40
percent of Thais possess thal carriers including α-thal, β-thal and Hb
E. Due to the high prevalence of all genotypes, it is not uncommon to
find individuals with combined α and β-globin
abnormalities.10-13 Collectively, these thal traits,
either simple or in combination, are asymptomatic and do not require
specific treatment; they are then classified as thalassemia minor (thal
minor). In addition, individuals with homozygous Hb E (Hb E/E), although
carry two defective β-globin genes, they are benign with milder forms of
anemia without hepatosplenomegaly or blood transfusion
required.14
Several previous studies have extensively examined iron status in thal
patients15-18, but little is known about thal minor in
comparison to normal populations19, particularly in
infants. Iron overload is one of the most common complications in thal
patients due to blood transfusions and increased iron
absorption5-6. Intestinal iron intake in thal has been
shown to be enhanced due to hepcidin suppression by the upregulation of
erythropoietic markers, such as GDF-11, GDF-15, and Erfe, in response to
chronic anemia and erythropoietin drive.20-22 Hepcidin
generally controls iron intake through duodenal enterocytes by limiting
the expression of ferroportin: an intestinal iron gateway into our
circulation. Recent studies have consistently shown hepcidin suppression
in thal patients.23,24 More recently, a study from Sri
Lanka has demonstrated β-thal carriers had mildly suppressed hepcidin
concentrations out of proportion to their iron stores. It has been
suggested that widespread distribution of iron supplementation could
possibly increase the risk of harmful iron overload in β-thal
carriers.25 In Thailand, there has been no data on the
iron status and hepcidin levels in the young Thai population with our
common thal traits; α-thal and Hb E and homozygous HbE, especially
infants who would receive supplementation through our national program.
Our main objective in this study was to determine the iron status in
infants aged 6 to 12 months at our Well Baby Clinic and identify the
prevalence of iron deficiency (ID) and IDA among those with or without
thal. In addition, we evaluated the clinical and laboratory
characteristics of each group to identify which factors, including
hepcidin levels, would significantly influence iron status. Our work
aimed to illustrate whether infants with thal are at similar or lower
risk of ID or IDA compared to the general population at this age and
supply evidence regarding safe universal iron supplementation for Thai
infants in the future.