c. Diet. Iron stores in a newborn can be depleted over a period of 2-6 months due to rapid growth. During this period, a normally born child can absorb 0.4-0.6 mg/day from the diet. To achieve this level of absorption, iron intake must be at the dose of 1 mg/kg/day for normally born children and 2 mg/kg/day for preterm infants, with a maximum daily dose of 15 mg of iron. These amounts of iron cannot be reached without using supplemental iron in foods.
From the first year up to the age of 6 years, the recommended amount of iron is 15 mg/day, from the age of 6 years up to the age of 11 years it is recommended to be 10 mg/day, and during puberty 18 mg/day. Both mother's milk and cow's milk have a small amount of iron (about 1 mg/liter). Mother's milk is more valuable. 49% of the iron found in mother's milk is absorbed, compared to 10% of the iron in baby formula. Children who receive mother's milk in the first 6 months of life have a higher level of ferritin (iron stores) than those fed with cow's milk and consequently the possibility of developing anemia is smaller.
Currently, infant formulas containing additional iron are used. Some of these formulas contain 10-12 mg/liter of ferrous sulfate which is absorbed up to 4%. Iron-fortified cereals are another source of iron intake. These contain 0.45 mg/gr of iron that is absorbed at a rate of 45%. 3-6 tablespoons of such cereals provide 3-6 mg of iron, and two servings per day will meet the daily iron needs of most children.
Dependency on cow's milk without iron supplement is another cause of iron deficiency. Not only is cow's milk poor in iron, but it can also cause gastrointestinal blood loss. Some mothers allow the child to use the milk bottle as a toy and pacifier, and children become dependent (milkoholics). In children with diminished iron stores and receiving an inadequate diet, iron-deficiency anemia develops due to the iron deficiency.
d. Blood loss during childhood. Occult blood loss (invisible, without an apparent anatomical lesion) has been observed in a series of children who develop iron-deficiency anemia. The process is associated with diffuse involvement of the intestines, with protein-losing enteropathy and with decreased absorption of certain nutrients. Hypoproteinemia and hypocupremia (due to decreased ceruloplasmin) appear. Later, iron-deficiency anemia develops. It is still unknown whether this intestinal syndrome is a cause or a consequence of iron deficiency.
It is thought that the cause of the enteropathy is hypersensitivity to a heat-labile protein of cow's milk. The daily amount of blood loss is 1-4 ml when fresh cow's milk is used and these anomalies are eliminated when heat-treated cow's milk or soy-containing formula (processed milk) are used. In children who consume fresh cow's milk up to the age of 2 years, iron-deficiency anemia develops more frequently.
In some cases, iron-deficiency anemia is the first disorder with intestinal involvement as a secondary phenomenon. It is thought that iron deficiency is responsible for defects in local immune mechanisms (there is a reduction of IgA in the intestinal tract cavity). It has been observed that there is a reduction in mitoses in the lymphatic follicles of the intestinal mucosa, as well as a reduction in mitoses in the intestinal crypts. Replenishing iron stores eliminates these anomalies. In children, Meckel's diverticulum is also a cause for blood loss.
e. Anemia of prematurity. Both full-term infants and preterm infants have a rapid and progressive decrease in Hb concentration in the first 6-8 weeks of life. Compared to full-term children, this decline is of a greater magnitude and faster. In weeks 2-8, the Hb concentration drops by approximately 1 gr/dl per week. The smaller the preterm, the lower will be the eventual nadir. In children with a birth weight < 1500 gr, Hb values can be up to 7 gr/dl in the first 1-2 months of life. The faster the fall in Hb level, the shorter is the survival of RBC in preterm infants.
The low level of Hb between months 1-3 of life is referred to as anemia of prematurity. Whether this anemia is physiological or true anemia is a subject of various discussions. Given that the distribution of O2 is insufficient to satisfy the tissue O2 needs in preterm infants, the anemia probably cannot be called "physiological".
Studies using radioimmunological methods of erythropoietin have assessed the capacity of preterm infants to respond to anemia in a physiological manner. It has been seen that in very small preterm infants there is an increase in EPO production when the Hb concentration falls below 10-12 gr/dl. Thus, both in full-term children and adults, the level of EPO in the blood is inversely related to the Hb concentration, i.e., the higher the Hb concentration, the lower the EPO level, and vice versa.
It is important to emphasize that the response of EPO to the decrease in Hb concentration is quantitatively inferior. The blood EPO values in preterm infants are much lower for a given Hb value, compared with the EPO values in the blood of older children with the same Hb concentration. These values are 10-100 times lower than those of adults with the same Hb level. Meanwhile, it has been observed that the in vitro response of erythroid precursors to EPO is normal.
The lower levels of EPO in preterm infants are a cause of anemia, and the oxygen supply to tissues is improved by activating other adaptive mechanisms such as the shift in the Hb dissociation curve with the decrease in HbF level and the increase in 2,3-DPG (while the Hb concentration drops by 50%, the amount of O2 distributed under physiological conditions doubles, and knowing that EPO production depends on tissue oxygenation, the blood EPO concentration depends not only on the Hb concentration but also on the position of the Hb dissociation curve). This fact explains the concept that preterm infants are not necessarily functionally anemic.
Other studies have shown that suboptimal EPO production is related to "available oxygen" levels. This last term is an expression of the blood's capacity to release oxygen into tissues and is calculated from the oxygen-carrying capacity and oxygen affinity of blood. Even at low levels of "available oxygen", anemic preterm infants cannot reach the normal EPO levels for nonanemic adults. These data have emerged from the fact that symptoms and signs of anemia in preterm infants appear when venous O2 tension is < 30 torr and with a decrease in "available oxygen".
Some authors suggest that "maturity" in the response of EPO production to hypoxia is related to a shift in the site of EPO production. During intrauterine life, the kidneys are not the site of EPO synthesis. Experimental animal studies have shown that extrarenally produced EPO responds less to hypoxia than EPO produced in the kidneys. And a reasonable hypothesis is that this hyporesponse of extrarenally produced EPO to hypoxia continues in preterm infants. The observation that the EPO response to the decrease in "available oxygen" is lower the more premature the child supports this reasoning.
Symptoms associated with anemia include poor feeding, lethargy, suboptimal weight gain. Since heart and respiratory rates are influenced by many causes, tachycardia and tachypnea are not reliable indicators of anemia. Generally, symptoms of anemia appear when the Hb concentration falls below 10.5 gr/dl. Hb concentration alone is a poor index of the infant's need for a greater oxygen transport capacity.
Symptoms and signs of anemia correlate more closely with "available oxygen", which is calculated, and with central venous oxygen tension. A nomogram to measure central venous oxygen tension has been prepared as an aid to identify children who would benefit from blood transfusion. Anemia in the absence of clinical signs does not require treatment. Since the erythroid progenitors of infants with anemia from prematurity are more sensitive to EPO, the use of EPO may be an alternative treatment to RBC transfusion. Studies have shown that EPO administration can correct or stabilize anemia of prematurity.
From the lack of iron in food. It is rarer than the above causes and it has been measured that it takes on average 8 years for a normal person who does not receive iron in food to develop anemia. More so, the lack of iron in food contributes to the development of anemia from the above causes.
Iron malabsorption. Prolonged achlorhydria can cause iron deficiency, as the acidic environment of the stomach is needed to release ferric iron from foods. Thus, iron will bind with mucins and other substances (amino acids, sugars, amides) to be soluble and valuable for absorption in the more alkaline duodenum.
Surgical removals of the stomach, the proximal part of the small intestine, or untreated chronic diseases (sprue or celiac syndrome) may decrease iron absorption. Rarely, patients with no history of malabsorption have AF and fail to respond to oral iron therapy. Before starting parenteral iron therapy, iron malabsorption should be evaluated using radioiron or by measuring serum iron concentration (sideremia) and repeating the test after ½ hour and 1 hour from the administration of an oral ferrous sulfate solution (50-60 mg of iron). Sideremia should increase by more than 50% from the initial value.
Starch and clay eating, cause iron malabsorption and AF. A detailed history should be taken because often patients do not voluntarily disclose this problem. Pica is the swallowing of unusual substances (dirt, ice, laundry starch) that can reduce iron absorption or reduce the intake of iron-containing foods. Pica is a manifestation of iron deficiency and is eliminated with the treatment of the deficiency.
Genetic disorders cause iron deficiency. Experimentally it has been seen in rodents (sex-linked anemia [sla] mice, microcytic anemia [mk] mice, Belgrade rat), but it has not been clearly seen in humans and if it truly exists, it is a very uncommon cause of AF.
Parasites are causes of the development of iron deficiency, especially Ancylostoma duodenale (Necator americanus). Each parasite in this case can cause a blood loss of 0.05 ml/day. In females, up to 100 parasites can develop (5 ml blood/day) and in males up to 250 (12.5 ml blood/day). Schistosomiasis (blood loss from the urinary tract or intestine) and trichuriasis are often associated with iron deficiency. Every living being needs iron, and parasites, for their very name (to develop their life cycle), need it and have no source other than from the host by damaging the integrity of the mucosa (and its blood vessels).