I. Preface
Iron deficiency (ID) is the most common nutrient deficiency and a global health problem, and it is estimated that 1/3 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 use of iron-fortified foods. According to the 1999-2000 national epidemiological survey in the United States, the prevalence of ID and IDA in children aged 1 to 2 years was 7% and 2%, respectively, and the prevalence of ID in Hispanic children was still as high as 17%. The situation of iron deficiency in children in developing countries is even more serious. According to WHO, the prevalence of anemia in children under 5 years of age and 5-14 years of age 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 in 16 provinces and cities in China in the early 1980s showed that the total prevalence of nutritional anemia in children aged 6 months to 7 years was as high as 43%, and most of them were IDA.
In 2001, a study on the epidemiology of iron deficiency in children in China found that the total prevalence of ID in children aged 7 months to 7 years was 40.3% and the prevalence of IDA was 7.8%. Although the prevalence of IDA has been significantly reduced, iron deficiency (ID without anemia) is still serious, with the prevalence of iron deficiency and IDA in infants being 44.7% and 20.5%, respectively, significantly higher than that in toddlers and preschoolers, while the total prevalence of IDA in rural children is 12.3%, significantly higher than that in urban children (5.6%). There is extensive research evidence that iron deficiency can affect various functions of children such as 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 (TBI), including iron depletion (ID), irondeficient erythropoiesis (IDE) and IDA 3 stages of development, each with different iron metabolic characteristics. IDA is a type of anemia caused by iron deficiency in the body, which eventually leads to a decrease in hemoglobin (Hb) synthesis and 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 level of stored iron in the body, but erythropoiesis is not affected and there is no clinical anemia. In the erythropoietic iron deficiency phase, due to the further decrease or depletion of iron stores, the saturation of serum transferrin decreases, the transport of serum iron to bone marrow young red blood cells to participate in Hb synthesis decreases, and the level of freeerythrocyte protoporphorin (FEP) 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 deficiency and erythropoietic iron deficiency 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 decreased 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. congenital iron storage deficiency: active transfer of iron from the pregnant mother to the fetus across the placenta against the concentration gradient during pregnancy. In particular, maternal-fetal iron transport is greatest in late gestation. Therefore, preterm birth, twin or multiple births, fetal blood loss and severe maternal iron deficiency can all lead to reduced 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 is likely to reduce the incidence of preterm birth and low birth weight babies.
2, insufficient iron intake: breast milk is low in iron content 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 dietary mix and gastrointestinal diseases can affect the absorption of iron.
4, vigorous 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, the most common clinical causes of gastrointestinal bleeding and increased menstruation in adolescent girls.
IV. Diagnostic criteria for iron deficiency
1, with risk factors leading to iron deficiency, such as improper feeding, excessive growth, gastrointestinal diseases and chronic blood loss, etc.
2.Serum ferritin <15ug/L with or without reduced serum transferrin saturation (<15%).
3, Hb is normal, and the morphology of peripheral blood mature red blood cells is normal.
V. IDA diagnostic criteria
1, Hb decreased, in line with the WHO diagnostic criteria for childhood anemia, that is, 6 months to 6 years <110 g / L; 6 to 14 years <120 g / L. Due to the effect of altitude on the Hb value, for every 1000 meters increase in altitude, Hb rises about 4%.
2. Peripheral blood erythrocytes showed small cell hypochromic changes: mean erythrocyte volume (MCV) <80 fl, mean erythrocyte hemoglobin content (MCH) <27 pg, mean erythrocyte hemoglobin concentration (MCHC) <0.31.
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 more than 20 g / 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 met, but it should be noted that serum iron and transferrin saturation is susceptible to factors such as infection and feeding, and there is a certain degree of diurnal variation.
(i) Decreased serum ferritin (SF) (<15 g/L). It is recommended that serum CRP be tested at the same time to rule out the effect of infection and inflammation on serum ferritin levels if possible.
(ii) serum iron (serum iron, SI) <10.7 umol/L (60ug/d1).
③Total iron binding capacity (TIBC) >62.7 umol/L/L (350 ug/d1).
④transferrin saturation (transferrin saturation, TS) <15%.
6, bone marrow aspiration smear and iron staining: bone marrow can stain iron significantly reduced or even disappeared, bone marrow extracellular iron significantly reduced (0-+) (normal value: + to ++++), iron granulocyte ratio < 15% is still considered the "gold standard" for the diagnosis of IDA; but because of the invasive test. In general, this test is not required. For children with diagnostic difficulties, or the diagnosis of iron therapy is not satisfactory, 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 differentiate chronic disease anemia and pulmonary iron-containing hemoglobinosis. 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 where diagnosis is difficult and treatment is ineffective.
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 according to elemental iron 60 ms / d, if necessary, can be extended to the postpartum period; supplementation with small doses of folic acid (400 mgd) and other vitamins and minerals.
3, premature and low birth weight infants: promote breastfeeding. Those who are exclusively breastfed should start iron supplementation from 2 to 4 weeks of age at a dose of 1~2 mg/(kg?d) of elemental iron until the age of 1 week. 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, within 1 year of age should not be fed with cow’s milk alone.
4, full-term infants: due to the high bioavailability of iron in breast milk, breastfeeding should be done for 4-6 months as much as possible; thereafter, if you continue to exclusively breastfeed, iron-rich foods should be added in a timely manner; if necessary, iron can be supplemented at a daily dose of 1 mg/kg of elemental iron. If breastfeeding is not used, breastfeeding is changed to mixed partial breastfeeding or artificial feeding of infants who cannot be breastfed, iron-enriched formula should be used 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 partiality and other bad habits; encourage the intake of vegetables and fruits to promote intestinal iron absorption; try to use iron-fortified formula, and do not recommend simple cow’s milk feeding.
6, adolescent children: adolescent children, especially girls are often prone to iron deficiency and even IDA due to anorexia and increased menstruation; should focus on adolescent mental health and counseling, strengthen nutrition, a reasonable diet; encourage the consumption of vegetables and fruits, etc., to promote the absorption of iron. Generally no additional iron supplements, for adolescent girls to be diagnosed as iron deficiency or IDA, oral supplemental iron 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 Service Task Force (USPSTF) survey concluded that there is no evidence to support screening for IDA in healthy children aged 6 to 12 months without anemia. Based on the current socioeconomic situation in China, 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 iron-rich foods or iron-fortified formula supplementation) for 4 to 6 months after birth, artificially fed infants who cannot be breastfed, and infants who are fed with cow’s milk alone. Hb testing is recommended at 3-6 months of life for preterm and low birth weight infants, and other children can be tested for Hb at 9-12 months of age [1tl cited. In young children with risk factors for iron deficiency, Hb screening is recommended once a year. Adolescent children, especially girls, should be routinely and regularly tested for Hb.
VII. Treatment of iron deficiency and IDA
1, general treatment: strengthen care, avoid infection, reasonable feeding, give iron-rich food, 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 bad eating habits, treating chronic blood loss diseases, etc.
3.Iron therapy: Give oral treatment of iron 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 has a clear cause of IDA, it can be diagnosed as IDA and start diagnostic iron supplementation therapy. 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 the supply and other circumstances, but the dose of iron supplementation should be calculated according to elemental iron, i.e., 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 1~2 ms/(kg?) once or twice a week or once a day can also achieve the effect of iron supplementation for 2~3 months.
Efficacy criteria
The reticulocytes start to rise after 3~4 d of iron supplementation, reaching a peak in 7~10 d, and dropping to normal after 2~3 w. The amount of hemoglobin starts to rise after 2 weeks of iron supplementation, and Hb should rise more than 20 g/L after 4 weeks. If the expected therapeutic effect does not occur after iron supplementation, it should be considered whether the diagnosis is correct, whether the child is taking the medication as prescribed, whether there are reasons affecting iron absorption or causing continued iron loss, and further examination or referral to a specialist.