Anemia is defined as a pathological process in which hemoglobin (Hb)
concentration in red cells is abnormally low, considering variations as
to age, gender, sea-level altitude, as a result of several situations
such as chronic infections, hereditary blood conditions, deficiency of
one or more essential nutrients that are necessary for the formation of
hemoglobin e.g.: folic acid, B12, B6 and C vitamins, and proteins(
Therefore, there is no doubt that iron deficiency is the cause of most
anemias. It is called iron deficiency anemia.
Some aspects about
There are two forms of iron: ferrous iron (Fe ++) and ferric iron (Fe+++).
The iron content in the human body is equivalent to 3 to 5g; part of it
is used for metabolic and oxidative functions (70% a 80%), and the rest
is stored as ferritin and hemosiderin in the liver, spleen and bone marrow
(20% a 30%).
Over 65% of the iron content is found in hemoglobin, whose major function
is to transport oxygen and carbon dioxide. In hemoglobin, an atom of divalent
iron is found at the center of the tetrapyrrole core (protoporphyrin IX),
forming the heme nucleus. Therefore, iron is essential for the formation
of hemoglobin( ).
In addition, iron is part of the composition of the myoglobin molecule
of muscle tissue and acts as an enzyme reaction cofactor in the Krebs
cycle, (responsible for the aerobic metabolism of tissues) and in the
synthesis of purines, carnitine, collagen and brain neurotransmitters.
Iron is also present in the composition of flavoproteins and heme proteins
catalase and peroxidase (found in erytrocytes and hepatocytes). These
enzymes are responsible for the reduction of the hydrogen peroxide produced
in the body ( ).
Today, iron is also involved in the conversion reactions of beta-carotene
into the active form of vitamin A, a fact that partly explains the important
interaction between these nutrients( )
Requirements and recommendations
Since iron is an important micronutrient, the body has a very efficient
mechanism to avoid its loss. This way, the iron content is maintained
within certain limits with the aim of adequating its use. Even the iron
that originates from red cells, taken from the circulatory system, whose
half life is 120 days, is reused. Daily iron losses are about 1 mg, mainly
due to cell desquamation. In addition, small quantities are lost through
urine, sweat and feces. Other situtations such as menstruation, lactation
and parasitosis may cause additional iron loss(
The intestinal tract plays a very important role in the recycling mechanism
of body iron, since absorption may change according to body needs, that
is, when reserves are low, there is a significant increase in absorption,
and when they are high, absorption is inhibited.
As body iron requirements are associated with different stages of life,
the rate of iron absorption by the intestinal tract is also related to
age group. For instance, a 12-month infant presents an absorption rate
four times higher than others in different age groups( ).
By considering these aspects, we may conclude that daily iron requirements
are low and vary according to the stage of life. Therefore, considering
an absorption rate of 10%, RDA (Recommended Dietary Allowances) ( )
preconizes a daily 10-mg intake of elementary iron for infants aged between
6 months and 3 years; 12 to 15mg, for male and female adolescents, respectively;
10 mg for male and female adults after they stop menstruating, and 15
mg for women at reproductive age and nurturers. Pregnant women need a
daily intake of 30 mg of iron.
Iron is found in several foods of animal origin (all kinds of meat,
milk, and eggs) and of vegetable origin (dark green vegetables, beans,
soy beans, among others). However, it is necessary to clarify the capacity
of the body of absorbing the available iron so that it can accomplish
several functions, which determines its bioavailability(
Absorption and transport
Duodenal iron absorption depends on the nature of the iron complex that
is present in the intestinal lumen, as well as on the presence of facilitating
and inhibitory factors in the diet, in addition to organic reserves.
Iron absorption can be classified as heme and nonheme absorption. The
iron linked to the heme comes from foods of animal origin (hemoglobin,
myoglobin and other heme proteins), which is well absorbed due to its
high bioavailability and, in addition to improving the absorption of nonheme
Nonheme iron is found in foods of vegetable origin under the form of ferric
complex, which is partially reduced to the ferrous form during digestion,
thus facilitating absorption, by the action of hydrochloric acid, bile
and pancreatic juice( ).
After digestion, most of the iron forms an intraluminal deposit; therefore,
its absorption is determined by facilitating factors (ascorbic acid, all
kinds of meat, amino acids such as lysine, cysteine and histidine, citric
and succinic acids, and sugars such as fructose) or inhibitors (phytates,
found in cereals; phenolic compounds such as flavanoids, phenolic acids,
polyphenols and tannins, found in black tea and maté, coffee and
some soft drinks; calcium and phosphate salts, found in milk protein sources;
egg fibers and protein)( ).
Therefore, we should take into consideration that there are iron-rich
foods such as beans, which present low bioavailability due to the presence
of phytates and fibers. On the other hand, meats have much lower iron
contents, with high bioavailability. Milk is another interesting example
of bioavailability because mother's milk and cow's milk have basically
the same amount of iron; mother's milk, however, presents high absorption
rate while cow's milk presents low bioavailability due to its calcium
and phosphate salt contents( ).
The absorbed iron may be stored in the enterocyte cytoplasm in different
ways: as ferritin conjugate, protein linkers (mobilferrin) or nonprotein
linkers (AMP, ADP, amino acids), also in charge of transporting iron from
the enterocyte into the basolateral membrane. Part of the iron that is
stored this way may return to the intestinal lumen through desquamation.
Transferrin transports iron through the bloodstream. Each transferrin
molecule joins two Fe+++ ions. This way, the measurement of serum transferrin
saturation (% of serum iron ratio and the total capacity of iron linking)
is considered an important indicator of body iron content.
It is necessary to have specific receptors, which exist in great quantities
in the tissues that need iron more urgently (bone marrow, liver, placenta),
so that the body can use iron appropriately. Usually, about 70 to 90%
of the iron is absorbed by the bone marrow for the production of hemoglobin.
In the liver, spleen and bone marrow, iron may be deposited, bound to
ferritin and hemosiderine up to twenty times beyond its normal amount( ).
Iron reserves formed during pregnancy are extremely important for new-borns
as these reserves will form an important source of endogenous iron, which,
together with the exogenous iron from breastmilk, will meet iron requirements
up to 4-6 months of life.
This way, the dosage of serum ferritin is an important indicator of body
iron stores as it is directly proportional to the amount of body iron
Clinical signs and lab exams for the detection
of iron deficiency and anemia
Iron deficiency occurs at three stages. The first stage - iron depletion
- occurs when iron content is not enough to meet body requirements. At
the beginning, there is a reduction in iron deposition, characterized
by serum ferritin below 12 mg/l, without functional changes.
If the negative balance persists, the second stage begins - iron-deficient
erythropoiesis - characterized by a reduction in serum iron, transferrin
saturation below 16% and an increase in the free erythrocyte protoporphyrin
level. At this stage, work capacity may be reduced.
At the third stage - iron deficiency anemia - hemoglobin is below the
standards for age and gender. This stage is characterized by the development
of microcytosis and hypochromia.
Iron depletion at the initial stages is substantially higher than anemia
itself. The Panamerican Health Organization / World Health Organization
estimates that for each person with anemia there is at least another one
with iron deficiency. Thus, a population in which 50% of children suffer
from anemia - as is the case of Brazil, 100% actually have iron deficiency( ).
The operational definition of anemia, in terms of hemoglobin levels, was
established by the World Health Organization, adopting the level of 11.0
g/dl for children under the age of six and pregnant women. For children
aged between 6 and 14 years and nonpregnant adult women, the level was
12 g/dl, and 13 g/dl for adult men( ).
The clinical signs of anemia are not easily recognizable, and many times
go unnoticed. These signs include paleness, anorexia, apathy, irritability,
reduced attention and psychomotor deficiencies( ).
Etiology of iron deficiency anemia
Usually, anemia originates from blood loss and/or prolonged iron deficient
diet, especially in periods in which requirements are high, as in the
case of children and adolescents who have accelerated growth rate. In
addition, pregnancy and lactation are periods in which there is a lot
of iron requirement.
The causes of iron deficiency anemia and iron deficiency may have their
onset in the intrauterine life. Physiological reserves of iron (0.5g/kg
in full-term new-borns) are formed during the last three months of pregnancy,
and together with the iron found in breastmilk, meet the demands of breast-fed
infants until their sixth month of life. Therefore, we may conclude that
prematurity, due to lack of time, and low weight at birth, due to reduced
reserve, associated with early interruption of exclusive breast-feeding,
are the most common causes that contribute to iron depletion in breast-fed
infants. During the first childhood, the problem is aggravated by incorrect
feeding, especially at weaning, when breastmilk is usually replaced with
iron-deficient foods. Cow's milk is a good example, because, although
it has the same iron content as breastmilk, its bioavailability is too
low, and more often than not, mothers replace a meal with bottle feeding.
Other aspects that aggravate and most times determine insufficient iron
deposition have to be considered. These aspects include low socioeconomic
and cultural level, poor sanitation conditions and difficult access to
health services, and poor mother/child relationship( ).
Acute or chronic blood loss depletes body iron reserves and may cause
pathologies such as gastroesophageal reflux, intolerance to cow's milk
protein and intestinal parasitoses( ).
Parasites such as Ancylostoma duodenale or Necator americanus may cause
considerable iron loss, either through the blood sucked by the parasite
or through the bleeding caused by the lesion to the intestinal mucosa,
also caused by the parasite. Other parasites like Ascaris lumbricoides
and Giardia lamblia cause bleeding as they compete for food. In general,
the incidence of these parasites occurs in children who are older than
Prevalence of iron deficiency anemia
Iron deficiency and iron deficiency anemia are considered the major
public health problems and the most common nutritional deficiency around
due to their high prevalence, effects on development and growth, rersistance
to infections and association with the mortality of infants younger than
Iron deficiency anemia is universally distributed. There is an estimate
that 25% of the world population are affected by iron deficiency; the
population groups which are most affected are infants aged between 4 and
24 months, school-age children, female adolescents, pregnant women and
nurturing mothers( ).
Iron deficiency anemia affects 43% of preschool children all over the
world, especially in developing countries, which present prevalence rates
four times higher than those found in industrialized countries. This high
prevalence is associated with poor sanitation conditions, low socioeconomic
conditions and high morbidity among infants( ).
In Americas, approximately 94 million people are believed to suffer from
iron deficiency or iron deficiency anemia, especially in the Caribbean
and in the Andes, having affected around 60% of pregnant women in 1997( ).
A meeting held in Buenos Aires in 1992 presented the results of different
studies carried out in several Latin American countries (Argentina, Bolivia,
Brazil, Chile, Paraguay, Peru, Uruguay, Costa Rica, Cuba, El Salvador,
Venezuela, Haiti and countries in the Caribbean ). The prevalence of anemia
for pregnant women ranged between 13 and 61%; and 18 and 45% in preschool
According to a national study carried out in Ecuador, iron deficiency
anemia affected 70% of infants between 6 and 12 months and 45% of infants
between 12 and 24 months( ).
In Brazil, there are no national data on the prevalence of iron deficiency
anemia. However, punctual studies carried out in the last few decades
in several regions of the country have shown a significant increase in
the prevalence and severity of iron deficiency in risk groups, regardless
of their economic level. In the age group comprising infants younger than
2 years, the prevalence of iron deficiency anemia is between 50% and 83%( ).
In the city of São Paulo, the prevalence of iron deficiency anemia
has been increasing. In 1974, anemia was present in 23% of infants aged
between 6 and 60 months, in a representative sample of the city's population( )
. In 1984, another study registered a rate of 36% ( ),
in which the highest prevalence rates were found among infants aged 6
to 11 months (54%) and 12 and 24 months (58%).
The Public Sector Basic Units attends to people with low socioeconomic
level, which are at greater risk for nutritional problems. In Recife,
85% of infants aged between 6 and 11 months, and 82% of infants aged 12
and 23 months were found to suffer from anemia( ).
In a sample of 2992 infants aged between 6 and 23 months, who were attended
on spontaneous demand at 160 Basic Health Units, in 63 municipalities
of the state of São Paulo, 59% presented hemoglobin rates below
11.0 g/dl. and, 25%, rates below 9.5 g/dl( ).
Iron deficiency anemia prevention should be established through the following
four approaches: nutritional education and improvement of diet quality,
including breast-feeding incentive, medicine supplementation, food fortification
and control of infections.
When recommending a diet for infants, some aspects should be dealt with
carefully, guaranteeing better body iron content; this includes maintenance
of exclusive breast-feeding up to the 4th - 6th month of life and initiation
of complementary feeding with iron-rich foods , which facilitate iron
absorption (all kinds of meat, citrus fruits). On the other hand, inhibitory
agents such as black tea, maté, coffee and soft drinks should be
avoided during meals. Ideally, meat should be cooked instead of fried;
the broth should be used too.
Therefore, the adequate choice of complementary foods is of paramount
importance, since children's diet should be diversified, balanced and
rich in high-bioavailability iron.
Medicine supplementation is very efficient in preventing and controlling
anemia. However, some studies have already shown that this kind of intervention
presents a drawback that significantly reduces the impact over the hematological
conditions of the infants who were followed up, namely lack of mother/child
relationship, regardless of nutritional status. Thus, as the mother does
not interact satisfactorily with her child, she does not realize how severe
the disease is and, consequently, she does not give her child the medication
.Therefore, only the preconization of medicine supplementation with ferrous
sulphate is not enough to assure health professionals that the child is
really receiving the supplementation.
The Brazilian Society of Pediatrics ( )
preconizes the profilactic iron supplementation as follows:
1) Full-term new-borns, with adequate weight for gestational age:
During breast-feeding period, after the 6th month, or when weaning is
initiated (weaning is when the infant is fed any other kind of food besides
breastmilk), up to the 24th month of life, should be given 1 mg of elementary
iron / kg of weight/day, or a weekly dosis of 45 mg, except for infants
who are receiving iron-fortified formulas.
2. )Low-weight preterm and new-born infants : after the 30th day of life,
2 mg/kg of weight/day, during 2 months. After that, use the same recommendation
for full-term new-borns with adequate weight for their gestational age.
In public health services such as day care centers and schools, the weekly
proposal has shown better results than the daily regimen since its administration
The use of fortified foods has been an alternative that is preferred by
industrialized countries for over 50 years, presenting excellent results.
The great advantage of fortified foods is that mothers do not have to
agree to the proposal; this way, when the food is ingested, we know for
sure that the iron was ingested too. When choosing the foods to be fortified,
it is important to remember that foods should be easily accessible, have
a low cost and belong to the usual eating habits of the region, without
having their taste or aspect changed; compounds with good bioavailability
should be used.
The Group for International Counseling on Nutrition-based Anemias suggests
the following recommendations for the control and prevention of nutrition-based
a) Nutritional education that motivates the consumption of iron-rich foods,
respecting the population's eating habits, associated with breast-feeding
b) Improvement of basic sanitation systems and medical assitance to all,
with control over intestinal parasitosis;
c) Design of iron supplementation programs in profilactic doses for risk
groups, with supervision and follow-up.
d) Design and incentive to food fortification programs, currently regarded
as the best preventive measure on the long run, with lower costs.
The use of milk-based formulas and milk fortified with ferrous sulphate,
chelate iron, and elementary iron presents rewarding results for infants
younger than 2 years( , ).
In Ribeirão Preto, in the interior of the state of São Paulo,
21 low-income families and a total of 88 infants between 1 and 6 years
were analyzed. These infants were fed water fortified with ferrous sulphate
at a concentration of 10mg of elementary iron per liter of solution. The
fortified water had good acceptance and improved Hb levels. ( )
Milk powder fortified with ferrous sulphate and vitamin C was used as
an experiment against iron deficiency anemia that assessed 107 infants/children
at 13 day care centers in the metropolitan area of São Paulo and
228 infants/children who received medical care at a Health Basic Unit.
The milk powder contained 9 mg of iron and 65 mg of vitamin C per 100
g of powder, and was fed to the children during 6 months. In this research,
the initial levels of anemia were respectively 66% and 73%; whereas at
the day care centers and basic health units, the prevalence rates dropped
respectively to 21% and 18% after fortified milk was used; in addition,
nutritional status was improved( , ).
In an innovative experiment using chelate amino acid iron in a town in
the interior of the state of São Paulo, 9 mg of iron and 2000 IU
of vitamin A per liter of milk were fed to the children who participated
in the antianemia program. With an initial prevalence of 76%, this town
presents, today, rates that are compatible with those of industrialized
countries, that is, a prevalence of 4% for assisted children( ).
These results confirm that the anemia status can be easily reversed provided
that health professionals are properly aware of and involved in their
tasks. At the same time, political decisions should be taken.
The objective of the iron deficiency anemia treatment is to correct
the rate of circulating hemoglobin and restore iron deposition into the
tissues where it is stored.
It is recommended that iron salts be used, preferably by means of oral
administration. Iron salts (sulphate, fumarate, gluconate, succinate,
citrate, etc) are inexpensive and quickly absorbed; however, they produce
more side effects - nausea, vomiting, epigastric pain, diarrhea, intestinal
obstipation, dark feces and, on the long run, the development of dark
spots on teeth. Absorption is higher when iron salts are ingested one
hour before meals.
Salts contain different iron content. The suggested posology is 3 to 5
mg of elementary iron per kilo of weight per day, divided into 2 to 3
doses. ( )
The medication should be ingested together with fruit juice rich in vitamin
C, if possible, since this facilitates iron absorption.
Another recommendation is that medication cannot be administered together
with polyvitamin and mineral supplements. There are interactions of iron
with calcium, phosphate, zinc and other elements, thus reducing iron bioavailability.
Other factors that inhibit iron absorption such as black or maté
tea, coffee and antacids should be avoided during or after the ingestion
It is essential that the diet followed during treatment be balanced so
that erythropoiesis can be restored, assuring enough nutrients, especially
proteins in order to guarantee the supply of amino acids that are essential
to the production of hemoglobin; calories, to prevent these amino acids
from being used as source of energy; and foods rich in vitamin C, to increase
iron bioavailability in the diet.
Treatment response is fast and duration of treatment depends on the severity
of the disease. Absorption of iron ions is higher during the first weeks
of treatment. There is an estimated iron absorption of 14% during the
first week of treatment, 7% after 3 weeks and 2% after 4 months. The first
month of therapy is crucial for a successful treatment. A positive response
may be measured by the daily increment of 0.1 g/dl in the concentration
of hemoglobin after the fourth day of treatment. A maximum increase in
reticulocitose is observed between the 5th and 10th day of treatment,
and a substantial increase in the concentration of hemoglobin is observed
around the third week.
Medication should be continued for about 6 weeks after hemoglobin reaches
normal concentration so that iron organic reserves can be restored.
Blood transfusion is only recommended for infants whose hemoglobin concentration
is less than 5 g/dl or who present signs of heart discompensation. In
these cases, it is advisable to use 10 ml/kg of concentrated red blood
cells, in slow venoclise and monitoring of vital signs.
Therefore, it is necessary that the problem with the treatment of iron
deficiency anemia be approached globally. This way, measures that go beyond
the isolated view of iron deficiency anemia treatment can be adopted.
The reviewed literature has clearly shown that there are a great number
of alternatives for controling iron deficiency anemia. It is also clear
that whatever measure is adopted (medication supplements, food fortification
and/or nutritional education), the response is always positive, although
presenting variations as to response time, in lower or higher proportions.
In Brazil, however, iron deficiency anemia is a public health issue that
is, unfortunately, a far cry from a definite solution despite all the
knowledge that has been available on the subject and, consequently, on
the measures that could be used for its control. Nevertheless, what is
not well established yet, and is decisive in making any changes in the
critical status of the disease in our country is an effective and clearly
defined public health policy adopted by federal, state and municipal governments.
Obviously, the responsibility of health professionals cannot be overlooked
since the lack of commitment, which is easily noticeable throughout the
years, can aggravate the situation of our people. This easygoing behavior
must be changed. There is much to be done in the health sector for the
well-being of children, who should not wait longer for their right: life
at full potential.