Lieke Uijterschout

Iron intake and status of children aged 6-36 months in Europe: a systematic review.

Background: Iron deficiency is the most common nutritional disorder in the world. Young children are particularly vulnerable to the consequences of iron deficiency because of their rapidly developing brain. This review evaluates the prevalence of inadequate iron intake and iron deficiency (anaemia) in European children aged 6-36 months. Summary: Computerized searches for relevant articles were performed in November 2013. A total of 7,297 citations were screened and 44 studies conducted in 19 European countries were included in this review. In both infants (6-12 months) and young children (12-36 months), the mean value of iron intakes in most countries was close to the RDA. Nevertheless, proportions of inadequate intakes were considerable, ranging from about 10% in the Netherlands up to 50% in Austria, Finland and the United Kingdom. The prevalence of iron deficiency varied between studies and was influenced by childrens characteristics. Two to 25% of infants aged 6-12 months were found to be iron deficient, with a higher prevalence in those who were socially vulnerable and those who were drinking cows milk as a main type of drink in their first year of life. In children aged 12-36 months, prevalence rates of iron deficiency varied between 3 and 48%. Prevalence of iron deficiency anaemia in both age groups was high in Eastern Europe, as high as 50%, whereas the prevalence in Western Europe was generally below 5%. Key Messages: In most European countries, mean iron intakes of infants and children aged 6 to 36 months were found to be close to the RDA. Nevertheless, high proportions of inadequate intakes and high prevalence rates of iron deficiency were observed. Health programs should (keep) focus(ing) on iron malnutrition by educating parents on food choices for their children with iron-rich and iron-fortified foods, and encourage iron supplementation programmes where iron intakes are the lowest.

Prevalence and risk factors of iron deficiency in healthy young children in the southwestern Netherlands.

Objectives: Iron deficiency (ID) and iron deficiency anemia (IDA), during the first years of life, are associated with delayed motor and neurological development. Many studies evaluated iron status without an assessment of an acute-phase protein to identify infection. Because most indicators of iron status are influenced by infection, these data may underestimate the ID prevalence. A food consumption survey in the Netherlands showed that the mean iron intake of children ages 2 to 3 years was below the advised adequate intake of 7 mg/day. The aim of the study was to investigate iron status in a well-defined, healthy population of young children in the southwestern region of the Netherlands and to identify risk factors for ID. Methods: We conducted a multicenter, observational study in healthy children ages 0.5 to 3 years. We defined ID as ferritin <12 &mgr;g/L and IDA when, in addition, hemoglobin was <110 g/L. Children with elevated C-reactive protein levels (>5 mg/L) or underlying causes for anemia were excluded. Parents filled in a questionnaire to identify risk factors for ID. Results: We included 400 children in the study. ID and IDA were detected in 18.8% and 8.5% of the children, respectively. The present use of formula and the visit of preschool/day care were associated with a lower prevalence of ID, and a high intake of cows milk was associated with a higher prevalence of ID, after adjustment for age. Conclusions: ID is present in 18.8% of healthy children ages 0.5 to 3 years and living in the southwestern region of the Netherlands. The present visit of preschool/day care and the use of formula are associated with a reduced risk of ID, whereas a high intake of cows milk is associated with an increased risk of ID.

Iron deficiency occurs frequently in children with cystic fibrosis

In adult CF patients iron deficiency (ID) is common and primarily functional due to chronic inflammation. No recent data are available on the cause of ID and iron deficiency anemia (IDA) in children with CF. Over the last decades onset of inflammation and pulmonary disease in children with CF is delayed by improved nutritional status. We questioned whether ID occurs in the same extent among children with CF as in adult CF patients. We therefore conducted a study to investigate the iron status of children with CF and to determine whether ID and IDA are associated with dietary iron intake, lung disease severity and Pseudomonas aeruginosa (PA) infection.

Serum hepcidin measured by immunochemical and mass-spectrometric methods and their correlation with iron status indicators in healthy children aged 0.5-3 y.

Background:The diagnostic use of hepcidin is limited by the absence of standardization and lack of age-specific reference ranges in children in particular. The aim of this study was to determine reference ranges of serum hepcidin in healthy children aged 0.5–3 y using mass spectometry (MS) and a commercial immunochemical (IC) assay, and to investigate its association with other indicators of iron status and inflammation.Methods:We included 400 healthy children aged 0.5–3 y. We constructed reference ranges for MS-hepcidin and IC-hepcidin concentrations using the median, P2.5, and P97.5 in a normative population of 219 children with no anemia, no infection and/or inflammation, and no iron deficiency.Results:Median concentrations (P2.5–P97.5) of MS-hepcidin and IC-hepcidin were 3.6 nmol/l (0.6–13.9 nmol/l) and 7.9 nmol/l (1.9–28.6 nmol/l), respectively. We found a good correlation between both methods. However, MS-hepcidin was consistently lower than IC-hepcidin. Hepcidin correlated with ferritin and C-reactive protein.Conclusion:We provide reference ranges for hepcidin for an MS and commercial IC method. Absolute values between assays differed significantly, but hepcidin concentrations obtained by MS and IC methods correlate with each other, and both correlate with ferritin and CRP.

The value of Ret-Hb and sTfR in the diagnosis of iron depletion in healthy, young children

Objectives:Reticulocyte hemoglobin (Ret-Hb) content and soluble transferrin receptor (sTfR) are described as promising biomarkers in the analysis of iron status. However, the value of Ret-Hb and sTfR in the early detection of iron depletion, as frequently observed in children in high-income countries, is unclear. We hypothesized that young children to iron depletion, using the WHO cutoff of ferritin <12 μg/l, would have lower Ret-Hb and higher sTfR concentrations compared to children with a ferritin ⩾level 12 μg/l.Subjects/Methods:In this cross-sectional study, we analyzed mean concentrations of Ret-Hb and sTfR in 351 healthy children aged 0.5–3 years in a high-income country. The Student’s t-test was used to compare Ret-Hb and sTfR concentrations between groups.Results:We showed that concentrations of Ret-Hb and sTfR are similar in children with and without iron depletion. A decrease in Ret-Hb concentration was present only when ferritin concentrations were <8 μg/l. sTfR concentrations were similar in children with ferritin concentrations <6 μg/l and ⩾12 μg/l.Conclusions:Our results showed that the discriminative value of Ret-Hb and sTfR for the detection of iron depletion is limited. Our findings suggest that ferritin is the most useful biomarker in the screening of iron depletion in healthy children in high-income countries. However, ideally, reference ranges of iron status biomarkers should be based on studies showing that children with concentrations outside reference ranges have poor neurodevelopmental outcomes.

The value of soluble transferrin receptor and hepcidin in the assessment of iron status in children with cystic fibrosis.

BACKGROUND The value of ferritin in the diagnosis of iron deficiency is limited in patients with CF since it increases in the presence of inflammation. We hypothesized that the soluble transferrin receptor (sTfR) and hepcidin may provide more information than ferritin in assessing iron status in children with CF. METHODS We analyzed sTfR and hepcidin in relation to conventional iron status indicators in 49 children with CF. RESULTS We found no differences in sTfR concentration between children with and those without ID. sTfR concentrations were within the normal range in all children. Hepcidin concentrations were low, and concentrations below the limit of detection were observed in 25% of the clinically stable children. CONCLUSION The sTfR is not useful to determine the iron status in this population, whereas hepcidin might serve as an early indicator of deficient iron stores in children with CF.

Iron deficiency in the first 6 months of age in infants born between 32 and 37 weeks of gestational age

Background/objectives:Preterm infants are at risk of iron deficiency (ID). In the Netherlands, preterm infants born after 32 weeks of gestational age (GA) do not receive iron supplementation on a routine basis. We hypothesized that dietary iron intake in these infants might not be sufficient to meet the high iron requirements during the first 6 months of life.Subjects/methods:In a prospective cohort study, we analyzed the prevalence and risk factors of ID in 143 infants born between 32+0 and 36+6 weeks GA who did not receive iron supplementation.Results:ID at the age of 4 and 6 months was present in 27 (18.9%) and 7 (4.9%) infants. Results of a multivariable logistic regression analysis showed that ID was associated with lower birth weight, a shorter duration of formula feeding, more weight gain in the first 6 months of life and lower ferritin concentrations at the age of 1 week.Conclusions:Preterm infants born after 32 weeks GA have an increased risk of ID compared with those born at term, supporting the need of iron supplementation. Our results suggests that measurement of ferritin at the age of 1 week might be useful to identify those infants at particular risk and could be used in populations without general supplementation programs. However, the efficacy and safety of individualized iron supplementation, based on ferritin concentrations at the age of 1 week, together with other predictors of ID, needs to be further investigated, preferably in a randomized controlled trial.

Predictive factors of iron depletion in late preterm infants at the postnatal age of 6 weeks

Background/Objectives:Late preterm infants (born ⩾32 weeks of gestation) are at risk for developing iron deficiency and iron deficiency anaemia, and this may lead to impaired neurodevelopment. In the Netherlands, there is no guideline for standardised iron supplementation in these infants. Individualised iron supplementation has been suggested (that is, treating those infants with the highest risk), but risk factors for deprived iron stores in this specific group of infants are not well documented.Subjects/Methods:In this prospective multi-centre study, we analysed the iron status at the postnatal age of 6 weeks of 68 infants born between 32 and 35 weeks of gestation in the Netherlands. Serum ferritin (SF) <70 μg/l in the absence of infection (C-reactive protein <5 mg/l) was defined as iron depletion and whenever in combination with a haemoglobin level <110 mg/dl as iron-depleted anaemia. Medical charts were reviewed to identify risk factors.Results:Iron depletion and iron-depleted anaemia were present in 38.2% and 30.9% of the infants, respectively. Infants with a birth weight <1830 g and a SF <155 μg/l in the first week of life had a 26.4 times higher risk to develop iron depletion (95% confidence interval 3.1–227.0, P=0.003). Multivariate regression analyses also showed that iron depletion was associated with a higher number of blood draws.Conclusions:Iron depletion is common in late preterm infants at the age of 6 weeks in a setting without standardised iron supplementation. One should consider early individualised iron supplementation for late preterm infants with a low birth weight (<1830 g), and a low SF in the first week of life (<155 μg/l), as they have a high risk to develop iron depletion.

The influences of factors associated with decreased iron supply to the fetus during pregnancy on iron status in healthy children aged 0.5 to 3 years.

Objective:To investigate whether maternal anemia, pregnancy-induced diabetes, hypertension and smoking contributed to the recently found high prevalence of iron deficiency in a population of otherwise healthy children.Study design:Iron status was assessed in 400 children aged 0.5 to 3 years. We obtained information on the mothers’ laboratory results, the presence of diabetes and hypertension, smoking habits and use of medication while pregnant.Result:We found no influence of maternal anemia, diabetes, hypertension or smoking during pregnancy on iron status in the children. Mean corpuscular volume (MCV) values of the children were positively correlated to maternal MCV values.Conclusion:In this population, iron status in children is not affected by maternal anemia or maternal factors that are associated with a decreased iron transport during pregnancy. The correlation between MCV values in mothers and their children might be explained by genetic and/or shared environmental factors.

Red Blood Cell Distribution Width and the Platelet Count in Iron-deficient Children Aged 0.5–3 Years

Early detection of iron deficiency (ID) and iron deficiency anemia (IDA) in young children is important to prevent impaired neurodevelopment. Unfortunately, many biomarkers of ID are influenced by infection, thus limiting their usefulness. The aim of this study was to investigate the value of red blood cell distribution width (RDW) and the platelet count for detecting ID(A) among otherwise healthy children. A multicenter prospective observational study was conducted in the Netherlands to investigate the prevalence of ID(A) in 400 healthy children aged 0.5–3 years. ID was defined as serum ferritin (SF) <12 μg/L in the absence of infection (C-reactive protein [CRP] <5 mg/L) and IDA as hemoglobin <110 g/L combined with ID. RDW (%) and the platelet count were determined in the complete blood cell count. RDW was inversely correlated with SF and not associated with CRP. Calculated cutoff values for RDW to detect ID and IDA gave a relatively low sensitivity (53.1% and 57.1%, respectively) and specificity (64.7% and 69.9%, respectively). Anemic children with a RDW >14.3% had a 2.7 higher odds (95% confidence interval [CI]: 1.2–6.3) to be iron deficient, compared with anemic children with a RDW <14.3%. The platelet count showed a large range in both ID and non-ID children. In conclusion, RDW can be helpful for identifying ID as the cause of anemia in 0.5- to 3-year-old children, but not as primary biomarker of ID(A). RDW values are not influenced by the presence of infection. There appears to be no role for the platelet count in diagnosing ID(A) in this group of children.