Microcytic anemia in children: parallel screening for iron deficiency and thalassemia provides a useful opportunity for thalassemia prevention in low- and middle-income countries

Abstract

Microcytic anemia in children is commonly attributed to iron deficiency without attempting to find the cause. Inadequate investigations to exclude hemoglobinopathies lead to missed opportunities for identification of thalassemia carriers. Here we aim to describe the relative contribution of iron deficiency and thalassemia to microcytic anemia in children. This hospital-based prospective study was conducted at the Colombo North Teaching Hospital, Ragama, Sri Lanka. All newly diagnosed patients with microcytic anemia were recruited and data were collected using an interviewer-administered questionnaire. Full blood count, blood film, serum ferritin, c-reactive protein, quantification of hemoglobin sub-types and α-globin genotype were performed using 4?ml of venous blood. A total of 104 children (Male- 60.5%) were recruited. Iron deficiency was the cause for anemia in 49% whilst 16% and 10% had α- and β-thalassemia trait respectively. Seven (6.7%) children had co-existing iron deficiency and thalassemia trait while two coinherited α- and β-thalassemia trait. Children with β-thalassemia trait had significantly higher red cell count and lower mean corpuscular volume compared to children with iron deficiency. However, none of the red cell parameters were significantly different between children with α-thalassemia trait and iron deficiency. Iron deficiency contributes only to half of children with microcytic anemia; one-fourth had thalassemia trait. Co-existence of iron deficiency and thalassemia trait or co-inheritance of α- and β-thalassemia trait were found in 9%. Parallel investigation of children with microcytic anemia to diagnose iron deficiency and thalassemia provides an opportunity to identify thalassemia carriers which is beneficial for thalassemia prevention.     

Excretion of iron in response to deferoxamine in sickle cell anemia

Iron chelation with deferoxamine was studied in ten patients with sickle cell anemia who had received 2 to 37 liters of red blood cells. Urinary excretion of iron in response to 1.5 gm of deferoxamine administered intravenously ranged from 5.9 to 28.7 mg/24 hours and was closely related to the amount of iron acquired from transfusions. Administration of ascorbic acid did not improve deferoxamine-induced excretion of iron. Urinary excretion of iron in response to 0.75 gm of DFO intramuscularly was 4.7 to 6.9 mg/24 hours in three patients who had received 15 to 37 liters of red cells. The data indicate that measurement of DFO-induced excretion of iron is of value in detecting increased iron stores in children with sickle cell anemia who have received repeated transfusions and that chelation therapy will retard the accumulation of iron.     

Iron deficiency among apparently healthy children aged 6 to 24 months in Ibadan,Nigeria

Iron deficiency remains a global public health challenge, with a higher burden in children in the tropics. When it occurs early in life, it may have long-term effects on neurodevelopment. The aims of this study were to assess the iron status of children aged 6–24 months, to determine the prevalence of iron deficiency and its associated factors in Ibadan, Nigeria. The authors conducted a cross-sectional study between March and June 2014. A total of 202 apparently healthy children aged between 6 and 24 months attending 2 major immunization clinics in Ibadan were included. A questionnaire was used to collect information on sociodemographic characteristics, pregnancy and birth history, and nutritional history. Physical examination was carried out on all the subjects, and serum ferritin level was determined using an enzyme-linked immunosorbent assay (ELISA) technique. Iron deficiency was defined using a cutoff value of <30 µg/L. Fifty-nine children (29.2%) had iron deficiency. No clinical features were found to be significantly associated with iron deficiency. Iron deficiency was associated with breastfeeding (P = .020) and younger age (P = .015) in the study population. One hundred and forty-three (70.8%) of the study participants had anemia, and 39 (19.3%) had iron deficiency anemia. The prevalence of iron deficiency among apparently healthy children aged 6–24 months in Ibadan, Nigeria, is high. There is the need for a national policy on routine screening for iron deficiency and iron supplementation for infants and young children as recommended by the World Health Organization.     

Iron deficiency and cyanotic breath-holding spells: The effectiveness of iron therapy

Abstract

Aim: Frequent cyanotic breath holding spells cause fear and severe anxiety to parents. This study aimed to evaluate clinical, laboratory and treatment characteristics of children with cyanotic breath holding spells. Methods: Included were 180 children (mean age: 1.82?±?0.53 years) with cyanotic breath holding spells. They were divided into three groups: with iron deficiency, with iron deficiency anemia and without iron deficiency. Blood hemoglobin (HB), ferritin and iron concentrations were measured at baseline and after 3 and 6 months of iron treatment. Results: The mean spell frequency was 24.57?±?7.31/months, 83% had spells after the age of 1 year, 37% had daily spells, 16% had family history of spells, and 61% had Iron deficiency/Iron deficiency anemia (p?=?.001). No significant difference in the frequency of spells between children with iron deficiency and those with Iron deficiency anemia. Compared to patients without iron deficiency, there was significant reduction of spells frequency, increased hemoglobin, ferritin and iron levels after 3 and 6 months of iron therapy (p?=?.0001). Negative correlations were observed between spell frequency with hemoglobin (p?=?.001), ferritin (p?=?.0001) and iron (p?=?.001) levels. Conclusion: Not only Iron deficiency anemia but also iron deficiency alone without anemia is associated with a risk of high-frequency cyanotic breath holding spells. Iron therapy results in reduction in spells’ frequency which was correlated with increasing ferritin and iron levels.     

Iron absorption and iron deficiency in infants and children with gastrointestinal diseases.

Iron status, iron absorption, and intestinal blood loss were studied in 199 children undergoing diagnostic evaluation for suspected malabsorption. Evaluation of iron status included hematological indices, serum ferritin, and transferrin saturation. Iron absorption was assessed by the increment of serum iron after an oral iron load. Iron deficiency was common among patients affected by malabsorptive states, such as celiac disease (84%), cow's milk intolerance (76%), Crohn's disease (72%), and giardiasis (64%), whereas it was less common among patients with postinfectious enteritis (41%) and chronic nonspecific diarrhea (11%). Intestinal blood loss was seen only in patients with Crohn's disease and cow's milk intolerance, irrespective of iron nutritional status. On the other hand, iron malabsorption was very common, affecting 85-95% of the iron-deficient patients in all diagnostic groups, except in chronic nonspecific diarrhea. Iron malabsorption was less common among patients with adequate iron nutritional status than in those with iron deficiency. Iron malabsorption appears to play a major role in the pathogenesis of iron deficiency in patients with malabsorption. The iron absorption test shows greater sensitivity as a screening test for upper intestinal malabsorption than the D-xylose absorption test.     

Iron deficiency in infants. Study of risk factors

A study of iron deficiency was carried out in two districts in Paris among 207 children aged 10 months recruited from two well-baby out-patient clinics. The main results are as follows: 12% of children were anemic, ferritin was low in 21% and 40% had a borderline deficiency, as shown by a decrease in siderophilin saturation. The average daily milk intake was greater among the immigrants, but this group, being mainly fed whole cow milk with no iron supplementation, had a lower iron intake overall. A positive correlation was found between the percentage of ingested iron-supplemented formulas and the mean corpuscular volume or serum iron levels. Iron deficiency was more frequent in children born to multiparous mothers and in the absence of any iron supplement during pregnancy. Weight gain was inversely correlated to ferritin levels, suggesting a major role of fast growth on iron metabolism.     

Iron deficiency as a risk factor for first febrile seizure

We conducted this study to determine the role of iron deficiency as a risk factor for first febrile seizure in children. Fifty children between 6 months to 6 years with first febrile seizure (Cases) and 50 children with febrile illness but without convulsions (Controls) were enrolled from the pediatric ward of a tertiary care hospital. Iron deficiency was determined by estimation of hemoglobin, red blood cell indices and serum ferritin. The mean serum ferritin level (μg/L) was significantly low in Cases (31.9 ± 31.0) as compared to Controls (53.9 ± 56.5) with P = 0.003. Iron deficiency could be a potential risk factor for febrile seizure in children.     

Nocturnal enuresis in sickle cell haemoglobinopathies.

The prevalence of nocturnal enuresis (wet at least two nights a week) was investigated in children, aged 8, who were being followed up as part of a prospective cohort study. There were 175 children with homozygous sickle cell disease, 106 with sickle cell haemoglobin C disease, and 150 controls with a normal haemoglobin genotype. In homozygous sickle cell disease, 48 boys (52%) and 31 girls (38%) were enuretic, a significantly higher prevalence than in those with sickle cell haemoglobin C disease--five boys (10%) and 11 girls (20%)--or in normal children--16 boys (22%) and 13 girls (17%). There was no significant difference between children with sickle cell haemoglobin C disease and the normal genotype. Boys with homozygous sickle cell disease were significantly more likely to be enuretic if they came from large families; there was a similar trend for girls with homozygous sickle cell disease, although it did not reach significance. Enuresis was more common in boys with homozygous sickle cell disease who had low concentrations of fetal haemoglobin and in girls with sickle cell haemoglobin C disease who had high mean corpuscular haemoglobin concentrations. Similar associations were not shown for girls with homozygous sickle cell disease or boys with sickle cell haemoglobin C disease.     

LOW SERUM CARNITINE CONCENTRATIONS IN HEALTHY CHILDREN WITH IRON DEFICIENCY ANEMIA

Carnitine is not only obtained from animal-derived foods but also synthesized in the body. It plays an important role in the energy metabolism of many tissues, including heart and skeletal muscles. Iron is known to be essential for the biosynthesis of carnitine. Although many conditions are well known to cause secondary carnitine deficiency, iron deficiency, which is a very common condition in children, is not well studied as a cause of secondary carnitine deficiency in humans. This study demonstrates the coexistence of iron deficiency and low carnitine levels in otherwise healthy children. The mean carnitine concentration of 18 otherwise healthy children with iron deficiency anemia was significantly lower compared to the mean carnitine concentration of healthy children without iron deficiency anemia. Based on the evidence about the effect of low iron on carnitine stores in experimental animals, we proposed that low serum carnitine levels in these children may be secondary to iron deficiency. However, further studies need to be done to further clarify this relationship.     

Diagnosing iron deficiency in cyanotic heart disease

Objective : To determine the incidence of iron deficiency in children with CCHD by noninvasive, inexpensive and easy laboratory methods.Methods : Forty four children with cyanotic congenital heart disease (CCHD), aged 6 to 48 months were included in this study. The patients were categorized as iron deficient (n:28) and iron sufficient group (n:16). Children with CCHD who had iron deficiency were treated with iron for 3 months.Result : Iron sufficient patients were followed during 3 months without giving iron preparation. Mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), red cell distribution width (RDW), serum iron (SI), total iron binding capacity (TIBC) and serum ferritin levels were measured in all patients at the beginning and at the end of the study.Conclusion : In children with CCHD, hemoglobin (Hb), hematocrit (Hct) and red blood cell (RBC) counts were not considered significant parameters in the diagnosis of iron deficiency. Determination of MCV, MCH, RDW values is relatively easy and inexpensive method requiring small amount of blood for the diagnosis of iron deficiency during the follow-up of patients with CCHD     

LOW SERUM CARNITINE CONCENTRATIONS IN HEALTHY CHILDREN WITH IRON DEFICIENCY ANEMIA

Carnitine is not only obtained from animal-derived foods but also synthesized in the body. It plays an important role in the energy metabolism of many tissues, including heart and skeletal muscles. Iron is known to be essential for the biosynthesis of carnitine. Although many conditions are well known to cause secondary carnitine deficiency, iron deficiency, which is a very common condition in children, is not well studied as a cause of secondary carnitine deficiency in humans. This study demonstrates the coexistence of iron deficiency and low carnitine levels in otherwise healthy children. The mean carnitine concentration of 18 otherwise healthy children with iron deficiency anemia was significantly lower compared to the mean carnitine concentration of healthy children without iron deficiency anemia. Based on the evidence about the effect of low iron on carnitine stores in experimental animals, we proposed that low serum carnitine levels in these children may be secondary to iron deficiency. However, further studies need to be done to further clarify this relationship.     

Ferritin and iron levels in children with autistic disorder

Iron has an important role on cognitive, behavioral, and motor development. High prevalence of iron deficiency has been reported in autism. The aim of this study was to investigate iron status in a group of children with autistic disorder. The sample was composed of 116 children between 3 and 16 years with a diagnosis of autistic disorder according to DSM-IV criteria. Serum ferritin, iron, hemoglobin, hematocrit, mean corpuscular volume, and red cell distribution width values were measured. We found that 24.1% of subjects had iron deficiency, and 15.5% had anemia. There was a significant positive correlation between age and ferritin and hematological measures. Results of this study confirmed that iron deficiency and anemia are common in children with autistic disorder. Conclusion: These findings suggest that ferritin levels should be measured in subjects with autism as a part of routine investigation.     

Iron deficiency in proteinuric children with nephrotic syndrome: A cross-sectional pilot study

Massive proteinuria in nephrotic syndrome causes depletion of various proteins. Iron deficiency can occur due to urinary loss of iron, transferrin, and soluble transferrin receptors. We conducted this cross-sectional study of 52 children with proteinuric nephrotic syndrome, aged 1–12 years (mean 7.1 ± 2.7 years). Hemoglobin (Hb), RBC indices (MCV, MCH, MCHC), percentage of hypochromic RBCs (Hypo-He), reticulocyte hemoglobin content (Ret-He), and serum ferritin were examined. Seven (13%) patients had iron deficiency anemia and another 10 (19%) exhibited iron deficiency. A higher proportion of children with steroid-resistant disease had anemia than did steroid-sensitive children (P = 0.076). Thus, children with nephrotic syndrome may have iron deficiency (32.7%), which needs to be screened.     

Sickle cell syndromes. II. The sickle cell anemia-alpha-thalassemia syndrome

Five American black patients, ages 1 to 16 years, with the sickle cell anemia-alpha-thalassemia syndrome are described. Each patient had persistent microcytosis not explained by iron deficiency, and in each family the presence of alpha-thalassemia in combination with sickle cell trait was demonstrated in one of the parents. In one patient, in whom the diagnosis of sickle cell anemia was established at birth, an elevated level of Barts (gamma4) hemoglobin was also found. In these patients levels of alkali-resistant hemoglobin and reticulocyte counts were similar to those of sickle cell anemia patients of comparable age; however, stained smears of their peripheral blood rarely showed the presence of irreversibly sickled cells. No major ameliorative effect of the alpha-thalassemia on the clinical expression of the sickle cell disease of these patients was evident.     

儿童缺铁性贫血诊疗进展

缺铁性贫血(iron deficiency anemia,IDA)是因体内铁缺乏致使血红蛋白合成减少而引起的贫血。喂养不当、消化系统疾病、微量元素及维生素缺乏等仍然是导致儿童 IDA 的高危因素,高热惊厥与儿童 IDA 的关系尚有争议。研究表明,婴幼儿时期铁缺乏能够导致认知抑制控制功能不可逆减退,延迟结扎脐带等措施则可以有效预防儿童 IDA。间断补充铁剂等方法在治疗儿童 IDA 过程中亦能达到良好效果。     

The incidence, treatment, and follow-up of iron deficiency in a tertiary care pediatric clinic

To assess the incidence, treatment, and follow-up of iron deficiency in children seen in a tertiary hospital, a retrospective chart review was performed in 2002 of 364 consecutive children screened for iron deficiency with free erythrocyte protoporphyrin and hemoglobin. Sixty-five of the 352 children studied (18.5%) were iron-deficient and 19 patients (5.4%) were anemic. Eighty percent of the affected children were treated with iron, and only 25% had follow-up blood testing done. Iron deficiency is common in children younger than 2 years of age. Whether or not the children had anemia, treatment and follow-up were less than optimal.     

Effect of G-6 PD deficiency on sickle cell disease in Saudi Arabia

High incidence of G6PD deficiency has been reported in areas of the eastern province of Saudi Arabia where sickle cell gene is also prevalent. This study was conducted to assess the co-incidence of this enzymopathy with Hb S and its influence upon the clinical and hematological expression of sickle cell disease. Eighty three children with SS disease, 145 patients with sickle cell trait and 100 random cord blood as samples with normal Hb AF, and an FS electrophoretic pattern respectively were examined. The frequency of interaction of G6PD deficiency with Hb S was found significantly increased but no effect of this enzyme defect was discerned on the clinical and hematological status of homozygous sickle cell disease.     

Iron intakes and status of 2‐year‐old children in the Cork BASELINE Birth Cohort Study

Young children are at risk of iron deficiency and subsequent anaemia, resulting in long‐term consequences for cognitive, motor and behavioural development. This study aimed to describe the iron intakes, status and determinants of status in 2‐year‐old children. Data were collected prospectively in the mother–child Cork BASELINE Birth Cohort Study from 15 weeks' gestation throughout early childhood. At the 24‐month assessment, serum ferritin, haemoglobin and mean corpuscular volume were measured, and food/nutrient intake data were collected using a 2‐day weighed food diary. Iron status was assessed in 729 children (median [IQR] age: 2.1 [2.1, 2.2] years) and 468 completed a food diary. From the food diary, mean (SD) iron intakes were 6.8 (2.6) mg/day and 30% had intakes < UK Estimated Average Requirement (5.3 mg/day). Using WHO definitions, iron deficiency was observed in 4.6% (n = 31) and iron deficiency anaemia in five children (1.0%). Following an iron series workup, five more children were diagnosed with iron deficiency anaemia. Twenty‐one per cent had ferritin concentrations <15 µg/L. Inadequate iron intakes (OR [95% CI]: 1.94 [1.09, 3.48]) and unmodified cows' milk intakes ≥ 400 mL/day (1.95 [1.07, 3.56]) increased the risk of low iron status. Iron‐fortified formula consumption was associated with decreased risk (0.21 [0.11, 0.41] P < 0.05). In this, the largest study in toddlers in Europe, a lower prevalence of low iron status was observed than in previous reports. Compliance with dietary recommendations to limit cows' milk intakes in young children and consumption of iron‐fortified products appears to have contributed to improved iron status at two years.     

Risk factors for iron deficiency in a hospitalized urban New Zealand population

OBJECTIVE: To determine which dietary practices and sociodemographic factors are associated with iron deficiency anaemia (IDA) and iron deficiency (ID) in hospitalized New Zealand children. METHODOLOGY: A prospective study of children 8-23 months of age hospitalized with an acute illness from 1997 to 1999. Iron deficiency was defined as abnormal values for two out of three of serum ferritin (< 10 micro g/L), serum iron saturation (< 10%) and red cell distribution width (> 14.5%). Iron deficiency anaemia (IDA) was defined as ID + serum haemoglobin concentration <110 g/L. Those with IDA or ID were compared separately with those who were not iron deficient. RESULTS: Three hundred and ninety-one children were enrolled. Two hundred and twenty had IDA, 73 had ID and 98 were not iron deficient. In a multivariate analysis, those children who had a diagnosis of pneumonia (odds ratio 4.43, 95% CI 1.49, 13.13) were Pacific (odds ratio 6.31, 95% CI 2.14, 18.63), were currently drinking breast milk (odds ratio 10.22, 95% CI 2.95, 35.42), had a mother who restricted her meat intake during pregnancy (odds ratio 4.40, 95% CI 1.53, 12.64) or lived in a household with more than three children (odds ratio 7.42, 95% CI 1.88, 29.34) were at increased risk of IDA. Those children who were Pacific (odds ratio 5.44, 95% CI 1.37, 21.65) or who drank tea (odds ratio 7.88, 95% CI 1.10, 56.33) were at increased risk of ID. Those with a diagnosis of gastroenteritis (odds ratio 0.16, 95% CI 0.03, 0.75) were at decreased risk of ID. CONCLUSIONS: Both dietary and non-dietary factors are associated with an increased risk of IDA and ID in New Zealand children. In this hospitalized sample, more non-dietary than dietary factors were associated with poor iron status.     

The prevalence of coeliac disease as detected by screening in children with iron deficiency anaemia

AIM: Iron deficiency anaemia is a frequent finding seen in coeliac disease, which can be diagnosed alone or with other findings. In this study, our aim was to determine the prevalence of coeliac disease in children with iron deficiency anaemia without significant gastrointestinal symptoms. METHODS: There were 135 children with iron deficiency anaemia in the patient group (group 1), and 223 healthy children without iron deficiency anaemia in the control group (group 2) in this study. Antiendomysial antibody (EMA) IgA test was given to both groups. Antiendomysial antibody-positive patients underwent small intestine biopsy. RESULTS: The mean age was 7.2+/-4.6 (2-16) y in the patient group (group 1) and 8.2+/-3.8 (2-16) y in the control group (group 2), and no significant difference between the two groups was detected. In terms of gender, there was a significant difference between groups 1 and 2 (M/F: 74/61 and 98/125, respectively) ( p<0.05). EMA was positive in six cases in group 1 (4.4%), and villous atrophy and/or inflammation in the lamina propria with increased intraepithelial lymphocytes was seen on small intestine biopsy in these patients. In the control group, EMA was negative in all children. In detailed histories of patients with coeliac disease diagnosis, recurrent iron deficiency anaemia/pica was found in four patients (66.7%) and occasionally foul-smelling or watery stool attacks were seen in four patients (66.7%). Three of these six patients (50%) had short stature. CONCLUSION: The prevalence of coeliac disease was high in patients with iron deficiency anaemia; therefore, gastrointestinal findings should be further examined for coeliac disease, and the possibility of coeliac disease should be investigated in patients with recurrent iron deficiency anaemia and short stature.