Recommendations for the prevention and treatment of iron deficiency and iron deficiency anemia in children
I. Preface
Iron deficiency (ID) is the most common nutrient deficiency and a global health problem, and it is estimated that one-third of the world’s population is iron deficient. The prevalence of iron deficiency anemia (IDA) in children in developed countries in Europe and the United States has been significantly reduced due to health education and the widespread adoption of iron-fortified foods. According to WHO, the prevalence of anemia in children under 5 years old and 5-14 years old in developing countries is 39% and 48%, respectively, and more than half of them are IDA, while the prevalence of ID is at least twice as high as that of IDA.
The epidemiological survey of 16 provinces and cities in China in the early 1980s showed that the total prevalence of nutritional anemia in children aged 6 months-7 years was as high as 43%, and most of them were IDA. It was found that the total prevalence of ID in children aged 7 months-7 years was 40.3% and the prevalence of IDA was 7.8% in China. Although the prevalence of IDA has decreased significantly, iron deficiency (ID without anemia) is still serious, with the prevalence of iron deficiency and IDA in infants at 44.7% and 20.5%, respectively, significantly higher than that in toddlers and preschoolers, and the total prevalence of IDA in rural children at 12.3%, significantly higher than that in urban children (5.6%).
There is extensive research evidence that iron deficiency can affect a variety of functions in children, including growth and development, exercise, and immunity. Severe iron deficiency in infants and young children affects cognitive, learning ability and behavioral development, and cannot even be reversed by iron supplementation. Therefore, early diagnosis and timely intervention of ID are of great importance to prevent health impairment in children due to iron deficiency.
This recommendation has been drafted by the editorial committee of Chinese Journal of Pediatrics, the Hematology Group of the Pediatrics Branch of the Chinese Medical Association, and the Child Health Group of the Pediatrics Branch of the Chinese Medical Association with reference to relevant foreign prevention and treatment guidelines, and revised after extensive consultation with relevant experts, in the hope that it can play a positive role in the prevention and treatment of childhood ID and IDA in China.
II. Basic concepts and definitions
ID refers to the state of reduced total body iron content (TBI), including three developmental stages: iron reduction stage (ID), erythropoietic iron deficiency stage (IDE) and IDA, each with different iron metabolism characteristics.
IDA is a type of anemia caused by iron deficiency in the body, which eventually leads to a decrease in hemoglobin (Hb) synthesis, with small-cell hypochromic changes in red blood cells, characterized by abnormal iron metabolism such as decreased saturation of serum ferritin, serum iron and transferrin, and increased total iron binding capacity, and is the most serious stage of ID development.
The iron-reducing stage only reduces the body’s stored iron level, but erythropoiesis is not affected and there is no clinical anemia. In the erythropoietic iron deficiency phase, due to further decrease or depletion of stored iron, serum transferrin saturation decreases, serum iron transport to bone marrow Erythrocytes to participate in Hb synthesis decreases, and erythrocyte free protoporphyrin (FEP) level increases, but there is still no clinical anemia. The iron-reduced phase and the iron-deficient phase of erythropoiesis are therefore also collectively referred to as “iron deficiency without anemia”. For the sake of simplicity, it is proposed to name the iron-reducing phase and the erythropoietic iron deficiency phase as “iron deficiency”.
III. Causes of ID and high-risk groups
Under physiological conditions, the absorption and loss of iron are in dynamic balance. Therefore, from the pathophysiological point of view, the causes of ID can be classified as reduced absorption and increased loss. The main groups at risk for childhood ID are infants and adolescents between 6 and 24 months of age.
The main causes of ID in children include.
1. Insufficient congenital iron stores: the active transfer of iron from the pregnant mother to the fetus across the placenta against the concentration gradient during pregnancy, especially in the late gestational period when maternal-fetal iron transfer is greatest. Therefore, preterm birth, twin or multiple births, fetal blood loss and severe maternal iron deficiency can all lead to a decrease in fetal congenital iron stores. On the other hand, IDA in early pregnancy is closely related to preterm birth and low birth weight, and iron supplementation during pregnancy may reduce the incidence of preterm birth and low birth weight babies.
2. Inadequate iron intake: breast milk is low in iron despite high iron absorption; long-term exclusive breastfeeding without timely addition of iron-rich foods, or without the use of iron-fortified formula is an important cause of ID in children.
3. Intestinal iron absorption disorders: unreasonable diet and gastrointestinal diseases can affect the absorption of iron.
4. Growth and development, increased demand for iron: infants and adolescent children grow fast and have a high demand for iron, and failure to add iron-rich foods in a timely manner can easily lead to ID.
5. Increased iron loss: Long-term chronic blood loss in any part of the body can lead to iron deficiency, most commonly due to various clinical causes of gastrointestinal bleeding and increased menstruation in adolescent girls.
IV. Diagnostic criteria for iron deficiency
1. Risk factors leading to iron deficiency, such as improper feeding, rapid growth, gastrointestinal diseases and chronic blood loss.
2. Serum ferritin <15ug/L, with or without reduced serum transferrin saturation (<15%).
3. Normal Hb, and normal morphology of peripheral blood mature red blood cells.
V. IDA diagnostic criteria
1. Decreased Hb, in line with WHO diagnostic criteria for childhood anemia, i.e. 6 months-6 years <110g/L; 6-14 years <120g
Due to the effect of altitude on Hb value, Hb rises about 4% for every 1000m increase in altitude.
2. Peripheral blood erythrocytes showed small cell hypochromic changes: mean erythrocyte volume (MCV) <80fl, mean erythrocyte hemoglobin content (MCH) <27Pg, mean erythrocyte hemoglobin concentration (MCHC) <310g/L.
3. With a clear cause of iron deficiency: such as insufficient iron supply, impaired absorption, increased demand or chronic blood loss.
4. Iron therapy is effective: Hb should rise by more than 20g/L after 4 weeks of iron therapy.
5. Iron metabolism examination indicators meet the IDA diagnostic criteria: at least two of the following four items are satisfied, but it should be noted that serum iron and transferrin saturation are susceptible to factors such as infection and feeding, and there is a certain degree of diurnal variation.
(i) Decreased serum ferritin (SF) (<15ug/L), it is advisable to test serum CRP at the same time to exclude the effect of infection and inflammation on serum ferritin level as much as possible.
②Serum iron (SI) <10.7umol/L (60ug/dl).
③Total iron binding capacity (TIBC) > 62.7umol/L (350ug/dl).
④Transferrin saturation (TS) <15%.
6 bone marrow aspiration smear and iron staining: bone marrow stainable iron significantly reduced or even disappeared, bone marrow extracellular iron significantly reduced (0 ~ ±) (normal value: + + + + + +), the proportion of iron granulocytes < 15% is still considered the "gold standard" for the diagnosis of IDA; but because of the invasive test, generally do not need to carry out the test. For the diagnosis of difficult, or after the diagnosis of iron therapy is not satisfactory children, the conditions of the unit can be considered to clarify or exclude the diagnosis.
7. Exclusion of other microcytic hypochromic anemia: In particular, it should be differentiated from thalassemia minor, and attention should be paid to the differentiation of chronic disease anemia and pulmonary iron-containing hemoglobinopathy.
The diagnosis of IDA can be confirmed if the indicators of iron metabolism also meet the diagnostic criteria of IDA. primary units without relevant laboratory tests can start diagnostic treatment directly, and iron therapy can be diagnosed as IDA if it is effective. Bone marrow aspiration smear and iron staining are invasive tests and are not used as routine diagnostic tools for IDA, but can be considered in cases of diagnostic difficulties and ineffective treatment.
VI. Prevention of iron deficiency and IDA
1.Health education: guidance on reasonable feeding and diet.
2. Prevention during pregnancy: strengthen nutrition and intake of iron-rich foods. From the third month of pregnancy, oral iron supplementation at 60 mg/d of elemental iron, which can be continued until postpartum if necessary; supplementation with small doses of folic acid (400ug/d) and other vitamins and minerals.
3. Premature and low birth weight infants: Breastfeeding is advocated. Those who are exclusively breastfed should start iron supplementation from 2-4 weeks of age at a dose of 1-2mg/(kg.d) of elemental iron until 1 week of age. Infants who cannot be breastfed artificially should be fed with iron-fortified formula, which generally does not require additional iron supplementation. The iron content and absorption rate of cow’s milk is low, and it is not advisable to use simple cow’s milk feeding within 1 year of age.
Full-term infants: Because of the high bioavailability of iron in breast milk, breastfeeding should be done for 4-6 months as much as possible; thereafter, if exclusive breastfeeding continues, iron-rich foods should be added promptly; if necessary, iron supplementation can be done at a daily dose of 1 mg/kg of elemental iron. If breastfeeding is not adopted, breastfeeding is changed to mixed partial breastfeeding or artificial feeding of infants who cannot be breastfed, iron-enriched formula should be adopted and iron-rich food should be added in time. within 1 year of age, simple cow’s milk feeding should be avoided as much as possible.
5. Young children: pay attention to the balance of food and nutrition, correct anorexia and partial eating and other bad habits; encourage the intake of vegetables and fruits to promote intestinal iron absorption; try to use iron-fortified formula, not recommended to feed pure cow’s milk.
6. Adolescent children: adolescent children, especially girls are often prone to iron deficiency and even IDA due to anorexia and increased menstruation; should pay attention to adolescent mental health and counseling, strengthen nutrition, a reasonable diet; encourage the consumption of vegetables and fruits, etc., to promote iron absorption. Generally no additional iron supplementation is needed, for adolescent girls to be diagnosed as iron deficiency or IDA, oral iron supplementation can be taken at a dose of 30-60mg/d elemental iron.
7. Screening: IDA is the most common type of anemia in infants and children, so Hb measurement is the simplest and easiest indicator to screen children for IDA and is widely used. The U.S. Preventive Services Task Force (USPSTF) survey concluded that there is no evidence to support screening for IDA in healthy children aged 6-12 months without anemia. Based on our current socioeconomic status, it is recommended that only children at high risk for iron deficiency be screened, including: preterm infants, low birth weight infants, infants who are still exclusively breastfed (without added iron-rich foods and without iron-fortified formula supplementation) for 4-6 months after birth, artificially fed infants who cannot be breastfed, and infants fed with cow’s milk alone. Hb testing is recommended at 3-6 months after birth for preterm and low birth weight infants, and at 9-12 months for other children. Hb testing is recommended once a year for young children with high risk factors for iron deficiency. Adolescent children, especially girls, should have Hb testing routinely and regularly.
VII. Treatment of iron deficiency and IDA
1. General treatment: strengthen care, avoid infection, reasonable feeding, give iron-rich food and pay attention to rest.
2. Etiological treatment: Find the cause of iron deficiency and underlying diseases as far as possible, and take appropriate measures to remove the cause. Such as correcting anorexia and partial eating and other poor eating habits, treating chronic blood loss diseases, etc.
3. Iron therapy: Give oral iron therapy as much as possible.
① In primary care units where iron metabolism testing is not available, if the child meets the diagnostic criteria for anemia, with typical small-cell hypochromic changes in red blood cell morphology and a clear cause of IDA, the diagnosis of IDA can be made and diagnostic iron supplementation therapy can be started. In conditional medical units, iron metabolism index examination should be carried out as far as possible to clarify the diagnosis.
② Oral iron therapy: ferrous iron preparations should be used for oral iron supplementation to facilitate the absorption of iron. A variety of ferrous preparations are available, and the decision of which preparation to use should be based on supply and other circumstances, but the dose of iron supplementation should be calculated according to elemental iron, that is, 2-6 mg/kg of elemental iron supplementation per day, taken between meals, 2-3 times per day. Vitamin C can be taken orally at the same time to promote iron absorption. Iron supplementation should be continued for 2 months after Hb normalization to restore the body’s stored iron level. If necessary, other vitamins and trace elements, such as folic acid and VitB12, can be supplemented at the same time. evidence-based medical data show that intermittent supplementation with elemental iron 1-2mg/(kg.times) 1-2 times a week or once a day can also achieve the effect of iron supplementation for a period of 2-3 months.
VIII. Efficacy standard
Reticulocytes start to rise after 3-4 days of iron supplementation, and reach the peak in 7-10 days, and then drop to normal in 2-3 weeks. The amount of hemoglobin starts to rise after 2 weeks of iron supplementation, and Hb should rise more than 20g/L after 4 weeks.
If the expected therapeutic effect does not appear after iron supplementation, it should be considered whether the diagnosis is correct, whether the child is taking the medication as prescribed, and whether there are reasons that affect iron absorption or cause continued iron loss, and further examination or referral to a specialist should be made.
Diagnostic criteria of anemia in children
Age
Hemoglobin
<1
<145g/L
1 month to 4 months
<90g/L
4 months～6 months
<100g/L
6 months～6 years
<110g/L
6 years～14 years
<120g/L
Iron deficiency anemia is easily absorbed by bivalent iron supplements, ferrous sulfate (containing 20% iron), iron fumarate (containing 33% iron), ferrous gluconate (containing 12% iron), ferrous succinate (trade name Sulifex, containing 35% iron), polysaccharide iron complex (trade name Liguaneng, containing 46% iron), and sodium iron chlorophyllate (trade name Shengbuning) are used according to elemental iron 1~2mg/kg, between meals. Orally, 2 to 3 times a day, until the anemia is corrected and then orally for about 2 months. When taking iron orally, avoid taking it with cow’s milk, tea and coffee, and adding vitamin C will help iron absorption. Antacids should also be avoided unless there is a peptic ulcer. The dose should be calculated according to the elemental iron contained, according to the experiment, it is appropriate to take 4-6mg/kg of iron orally in 3 doses per day, (equivalent to 0.03g/kg/day of ferrous sulfate; 0.02g/kg/day of iron fumarate; 1.2ml/kg.d of 2.5% ferrous sulfate combination)