Prevalence and associated factors of iron deficiency in Spanish children aged 1 to 11 years.

Iron deficiency (ID) is the most common nutritional deficiency affecting children worldwide. Most traditional laboratory parameters to assess ID can be altered by infections or other inflammatory states, including obesity. The aims of this study were to determine the prevalence of ID in healthy children and to analyse associated factors, avoiding potential confounding factors through the use of serum transferrin receptor (sTfR), reticulocyte haemoglobin content and sTfR/log ferritin index. A cross-sectional population-based study was conducted on 951 children aged 1 to 11 years in Almería (Spain). ID was detected in 7.7% of children and iron deficiency anaemia in 0.9%. Multivariate analysis identified the following as independent risk factors: age under 5 years (OR: 2.2, 95% CI: 1.35-3.6); excessive consumption of cow's milk and dairy products (OR: 1.87, 95% CI: 1.13-3.1); and insufficient consumption of vegetables (OR: 2.7, 95% CI: 1.2-6.1).Conclusions: Using a combination of iron status parameters with greater discriminatory power than classical measures, this study detected a considerable iron deficiency prevalence in Spanish children. Younger children and specific dietary habits exhibit a particular risk for ID, so special attention should be paid to this population. What is Known: • Iron deficiency remains the most prevalent nutritional deficit worldwide, and children aged under 3 years are the most vulnerable to this condition. • Accurate assessment of iron status, based on a combination of biochemical indicators, can often be complicated. What is New: • Iron deficiency continues to present a health problem in Spanish children aged 1 to 11 years, considering the serum transferrin receptor and reticulocyte haemoglobin content for diagnosis. • Excessive consumption of dairy products and low consumption of vegetables are independent risk factors for iron deficiency.

Status of folate in healthy children in Almeria.

The objective of this study is to establish reference values for folic acid in a healthy population of children aged 4-11 years and to examine related epidemiological, dietary and analytical factors. A cross-sectional study of 658 healthy children aged 4-11 years was made. Epidemiological, socioeconomic and dietary variables were analysed, the BMI Z-score was obtained, levels of serum folate and serum vitamin B12 were determined and haematological, iron status and erythropoietic activity parameters were examined. The study data were analysed by non-parametric tests and linear multiple regression. The mean folate value was 8.6 ± 4.6 ng/mL (95% reference interval: 2.8-20 ng/mL). A level < 3 ng/mL (5th percentile) was considered as folate deficiency (4.6% of subjects). No child reported symptoms related to this deficiency. Folate values were significantly lower with age (p < 0.01), low NSE and low parental educational level (p: 0.0001). No relationship was found between folates and the analytical variables. According to multivariate linear regression, the variables significantly associated with serum folate were age, socioeconomic level and vitamin B12.Conclusions: Serum folate levels in healthy school children are described. Age, socioeconomic level and serum vitamin B12 are factors associated with folate status. Specific cut-off values for a paediatric population should be defined. What is Known: • Folic acid is an essential micronutrient for optimal growth and development; its deficit is associated with adverse health effects. • The studies on their status and deficit are not comparable due to a lack of agreement on appropriate indicators and reference values. What is New: • This study reports the levels of serum folate in a large population of healthy schoolchildren, with strict inclusion criteria in a developed country and identifies the associated sociodemographic, dietary and analytical (vitamin B12, iron parameters and erythropoietic activity) factors, avoiding potential confusion.

The usefulness of reticulocyte haemoglobin content, serum transferrin receptor and the sTfR-ferritin index to identify iron deficiency in healthy children aged 1-16 years.

This cross-sectional study, conducted on a population-based representative sample, evaluates the usefulness of reticulocyte haemoglobin content (CHr), serum transferrin receptor (sTfR) and sTfR/log ferritin (sTfR-F index) to recognise iron deficiency (ID) without anaemia, provides specific cut-off points for age and gender, and proposes a new definition of ID. A total of 1239 healthy children and adolescents aged 1-16 years were included. Complete blood count, iron biomarkers, erythropoietin, C-reactive protein, CHr, sTfR, and sTfR-F index were determined. ROC curves were obtained and sensitivity, specificity, predictive values, likelihood ratios, and accuracy for each specific cut-off points were calculated. Seventy-three had ID without anaemia. Area under the curve for sTfR-F index, sTfR and CHr were 0.97 (CI95% 0.95-0.99), 0.87 (CI95% 0.82-0.92) and 0.68 (CI95% 0.61-0.74), respectively. The following cut-off points defined ID: sTfR-F Index > 1.5 (1-5 years and 12-16 years boys) and > 1.4 (6-11 years and 12-16 years girls); sTfR (mg/L) > 1.9 (1-5 years), > 1.8 (6-11 years), > 1.75 (12-16 years girls) and > 1.95 (12-16 years boys); and CHr (pg) < 27 (1-5 years) and < 28.5 (6-16 years).Conclusions: CHr, sTfR and the sTfR-F index are useful parameters to discriminate ID without anaemia in children and adolescents, and specific cut-off values have been established. The combination of these new markers offers an alternative definition of ID with suitable discriminatory power. What is Known: • In adults, reticulocyte haemoglobin content (CHr), serum transferrin receptor (sTfR) and sTfR/log ferritin index (sTfR-F index) have been evaluated and recognised as reliable indicators of iron deficiency (ID). • Clinical manifestations of ID may be present in stages prior to anaemia, and the diagnosis of ID without anaemia continues to pose problems. What is New: • CHr, sTfR and the sTfR-F index are useful parameters in diagnosis of ID in childhood and adolescence when anaemia is not present. • We propose a new strategy for the diagnosis of ID in childhood and adolescence, based on the combination of these measures, which offer greater discriminatory power than the classical parameters.

Reference Values of Reticulocyte Hemoglobin Content in Healthy Adolescents.

Assessing iron status in a pediatric population is not easy, as it is based on parameters that undergo physiological variations in childhood and adolescence. Analysis of the reticulocyte hemoglobin content (CHr) to screen for iron deficiency may increase the accuracy of diagnosis, but, to date, reference values in healthy adolescents have not been adequately determined. A cross-sectional study was conducted on a population-based representative sample in the city of Almería (Spain), with 253 healthy non-iron-deficient (ID) subjects, aged 12 to 16 years. The mean CHr value was 31.6±1.3 pg. The CHr 2.5 percentile was 28.7 pg. There were no significant differences as regards age or sex. In the multivariate linear regression analysis, sex did not influence the variability of CHr, but it was related to age. CHr was influenced by hemoglobin and the Mentzer index, as well as by functional iron indicators such as erythrocyte protoporphyrin and serum transferrin receptor. These independent variables predicted two thirds of the variability in healthy adolescents (R=0.55). This study provides CHr reference ranges in healthy adolescents for use in clinical practice for the early detection of ID states. In populations with similar sociodemographic characteristics, values above the 2.5 percentile rule out ID, as values under the 2.5 percentile could be suggestive of functional ID.

Reference Values of Reticulocyte Hemoglobin Content and Their Relation With Other Indicators of Iron Status in Healthy Children.

Reticulocyte hemoglobin content (CHr) is considered an indicator of functional iron deficiency, but is understudied in children. The goals of this study are to determine the reference intervals for CHr in healthy children, and their relation with iron parameters, erythropoiesis, and individual conditions. A total of 902 children without iron deficiency, aged 1 to 11 years were analyzed in a cross-sectional study. Besides a physical examination of the subjects and a questionnaire completed by their parents, the complete blood count, serum transferrin receptor, ferritin, transferrin saturation, erythrocyte protoporphyrin, serum erythropoietin, C-reactive protein, and CHr levels were measured. Changes in CHr, iron status, and erythropoiesis at different age intervals were analyzed and linear multiple regression was used to identify the factors that determine CHr variability. Mean value obtained for CHr was 30.9±1.8 pg (P2.5-P97.5: 26.9 to 34.3 pg), but the influence of age on CHr (the values increased with age) and on the iron parameters justified the establishment of different reference ranges. In addition to age, nutritional status, hematologic measurements, reticulocytes, transferrin saturation, and erythrocyte protoporphyrin accounted for 39% of CHr variability.

Reference values of serum transferrin receptor (sTfR) and sTfR/log ferritin index in healthy children.

ABSTARCT The aims of this study were to determine appropriate reference ranges for serum transferrin receptor (sTfR) and sTfR/log ferritin (sTfR-F index) in healthy children and their relationship with iron parameters, erythropoiesis, and other conditions presented by the subject. A total of 902 children with normal iron status, aged 1-11 years, were included in a cross-sectional study. A physical examination was conducted and z-score of body mass index (zBMI) obtained. Complete blood count, iron biomarkers, erythropoietin, C-reactive protein, sTfR, and sTfR/log ferritin were determined. Linear multiple regression was applied to identify the factors that determined sTfR and sTfR-F index variability. Mean values for sTfR and sTfR-F index were 1.22 ± 0.28 mg/L (95% confidence interval [CI]: 1.2-1.23) and 0.87 ± 0.25 (95% CI: 0.85-0.88). The reference intervals (2.5th to 97.5th percentiles [P2.5-P97.5]) were 0.78-1.9 mg/L and 0.49-1.46, respectively. sTfR and sTfR-F values decreased with age (P <.03 and P <.0001, respectively). No changes were observed with sex. Changes in sTfR and sTfR-F index were consistent with ferritin and erythropoietin variations. Iron biomarkers, erythropoietin, and zBMI predicted 19% and 18.1% of the sTfR and sTfR-F index variability. The results provide reference ranges for sTfR and sTfR-F index in healthy children for clinical use in the assessment of body iron status. Both biomarkers are predicted by iron parameters, erythropoietin, and zBMI.

Thyroid Function and Thyroid Autoimmunity in Relation to Weight Status and Cardiovascular Risk Factors in Children and Adolescents: A Population-Based Study.

OBJECTIVE: In obese subjects, slight increases have been observed in thyrotropin [thyroid-stimulating hormone (TSH)] levels, but data in children are scarce. The aim of this study was to evaluate whether thyroid function and autoimmunity vary with weight status in a healthy population of children and adolescents and to determine whether hyperthyrotropinemia is associated with any cardiovascular risk factor. METHODS: This cross-sectional epidemiological study was conducted in Almería (Spain) on a representative sample of 1317 healthy subjects aged 2-16 years. Thyroid function, thyroid autoimmunity and cardiovascular risk factors were measured. Chi-square test, analysis of variance and multiple linear regression were used in the statistical analyses. RESULTS: The obese children and adolescents had thyrotropin levels (mean ± standard deviation) of 3.12±2.44 mU/L. These levels were higher than those of overweight subjects (2.79±1.51 mU/L) and of normal weight subjects (2.73±1.30 mU/L) (p=0.02). Levels of free thyroxine and urinary iodine did not differ significantly between the groups. The prevalence (95% confidence interval) of thyroid autoimmunity was lower in the individuals with normal weight (2.9%; 2.0-4.2) than in the overweight (6.3%; 3.9-9.9) and obese subjects (5.6%, 2.5-11.3) (p=0.02). TSH levels were associated with obesity (ß=0.36; p<0.001) and thyroid autoimmunity (ß=1.10; p<0.001). They were not associated with any cardiovascular risk factor. CONCLUSION: Obese children and adolescents had higher levels of thyrotropin than those who were overweight and of normal weight. The differences among the groups were of very little clinical significance and could possibly be linked to the higher prevalence of thyroid autoimmunity in obese subjects. The hyperthyrotropinemia in these subjects was not associated with any cardiovascular risk factor.

Reference values of serum transferrin receptor and sTfR/log ferritin index in healthy adolescents.

Adolescence is a period of increased iron requirements, which impact on iron status. The purpose of this research is to determine the reference intervals for serum transferrin receptor (sTfR) and sTfR/log ferritin index (sTfR-F index) in healthy adolescents, and their relation with iron parameters and erythropoiesis. A total of 253 healthy adolescents without overweight, aged 12 to 16 years, were selected in a cross-sectional study. Hemoglobin, red cell indices, reticulocyte hemoglobin content (rHb), reticulocytes, ferritin, transferrin saturation, erythrocyte protoporphirin, erythropoietin, C-reactive protein, sTfR, and sTfR-F index were measured. Changes in erythropoiesis and iron status in the age interval were observed and analyzed, and linear multiple regression was applied to identify the factors that determine the variability of sTfR and sTfR-F index. Mean values for sTfR and sTfR-F index were 1.32 ± 0.3 mg/L (95% CI, 1.3-1.36) and 0.9 ± 0.25 (95% CI, 0.87-0.93). The reference intervals were 0.84 to 1.97 mg/L and 0.51 to 1.44, respectively. sTfR and sTfR-F index values were significantly higher in boys (1.39 ± 0.3 vs. 1.23 ± 0.26 mg/L, P<0.0001 and 0.93 ± 0.37 vs. 0.86 ± 0.22, P<0.04) and decreased with age (P<0.0001 and 0.04, respectively). No changes were recorded in erythropoietin. Age, sex, pubertal status, and ferritin predicted 24.1% of sTfR variability and age, sex, pubertal status, transferrin saturation, rHb, erythrocytes, and reticulocytes predicted 15% of sTfR-F index variability.