Red blood cell distribution width is not a reliable biomarker for low iron stores in children with cystic fibrosis.

Low iron stores in children, absolute iron deficiency (AID), can lead to impaired neurodevelopment and requires iron therapy. In the presence of infection/inflammation, like in cystic fibrosis (CF), serum ferritin (SF) is not a reliable biomarker for AID. Red blood cell distribution width (RDW) is a promising alternative reported not to be influenced by infection in healthy children. Currently, there are no data on the diagnostic capacity of RDW to detect AID in pediatric CF patients. This was a prospective observational study that investigated iron status biomarkers in 53 Dutch pediatric CF patients. AID was defined using World Health Organization criteria for SF in stable patients (no recent pulmonary exacerbation) and C-reactive protein (CRP) ≤10 mg/l. Patients with AID had higher RDW levels than patients without AID (p = 0.019). An RDW ≥13.2% showed the following test statistics: sensitivity 100%; specificity 39.4%; positive predictive value 20%; and negative predictive value 100%. Furthermore, we found a correlation between RDW and CRP in the total group that originated from the stable patients (r = 0.308; p = 0.042). In conclusion, the diagnostic capacity of RDW for detecting AID in pediatric CF patients seems limited because RDW levels might also be influenced by chronic infection/inflammation in these patients.

Zinc protoporphyrin/heme ratio as parameter of iron status in moderately preterm infants: natural course and associations in the first 4 months.

OBJECTIVE: To determine the natural course of zinc protoporphyrin/heme ratio (ZnPP/H) and its role in the detection of iron deficiency (ID) and iron-deficiency anemia (IDA) in the first 4 months of life in moderately preterm infants. STUDY DESIGN: ZnPP/H was measured at 1 week, 6 weeks and 4 months postnatal age in a prospective cohort of 161 Dutch infants born at a gestational age of 32+0 to 36+6 weeks who did not receive an erythrocyte transfusion or iron supplementation. RESULTS: ZnPP/H levels decreased in the first 6 weeks and increased thereafter. At 4 months postnatal age, ZnPP/H was higher in the 11 (8.5%) infants with IDA (mean (s.d.): 260.8 (16.1)) but not in the 27 (21.3%) infants with ID (mean (s.d.): 177.0 (15.1)) compared with normal infants (mean (s.d.): 157.3 (12.5)). CONCLUSION: In moderately preterm infants, ZnPP/H can be of additional value to detect infants at risk for IDA due to iron-deficient erythropoiesis at 4 months of age.

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.

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.

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.

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 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.