Associate Director, Emory Global Health Institute Director, Global Health Office of Pediatrics Professor of Global Health, Rollins School of Public Health Professor of Pediatrics, Emory University School of Medicine
BRINDA: BIOMARKERS REFLECTING INFLAMMATION AND NUTRITIONAL DETERMINANTS OF ANEMIA
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In this study, the authors conducted a secondary analysis of data from the Optimizing Early Child Development Study (Toronto) with 745 healthy children. The authors note that the setting is from a high resource area with high maternal education.
In pediatric patients, 1-3 years, higher serum ferritin values were associated with higher cognitive function as measured by the Mullen Scales of Early Learning
Ferritin of 17 mcg/L or higher corresponded to maximum level of cognition
Based on this study, the authors recommend obtaining a ferritin level at 12 months of age at same time when a hemoglobin is recommended.
My take: The implication of this study is that iron deficiency, even in the absence of socioeconomic status, can have a detrimental effect on cognitive outcomes.
A recent retrospective study (G Aljomah et al. JPGN 2018; 67: 351-5) provides some useful information about anemia in the pediatric inflammatory bowel disease (IBD) population. This study included 153 patients, though the diagnostic tests varied considerably; for example, only 42 patients had a serum transferrin receptor (sTR) assay available at followup.
67.3% of patients had anemia at diagnosis. 38.5% had anemia of chronic disease (ACD) and the remainder had either iron deficiency anemia (IDA) or IDA in combination with ACD.
20.5% had anemia at followup approximately 1 year after diagnosis. 5.1% with ACD alone and 15.4% had IDA or IDA in combination with ACD.
In a subset of patients with more complete data, it was shown that anemia was much more common in patients with Crohn’s disease: 91.2% at diagnosis and 27.3% at followup compared with patients with ulcerative colitis with 40.0% at diagnosis and 7.7% at followup.
The authors used the sTR index (sTR/log ferritin index) to determine if ACD was present. “This index can differentiate IDA from ACD; however, it cannot separate IDA from the combination of IDA/ACD. IDA or IDA/ACD were considered to be present if the sTR index was greater than 1.03. An sTR index of <1.03 was taken to be indicative of the presence of ACD.”
Briefly noted: MR Serpico et al. JPGN 2018; 67: 341-5. This retrospective study examined the use of allopurinol to optimize thiopurine levels. 32 of 52 patients remained on the combination for 1 year. In this group, median alanine transaminase decreased to 19 from 77 (P<0.001) and median 6-TG levels increased to 322 from 166 (P<0.001). In addition, steroid-free remission rates improved to 82% (23 of 28). About 40% of the initial cohort of 52 patients were switched to antitumor necrosis factor therapy.
My take: The initial study shows that anemia is frequent in pediatric IBD, especially at diagnosis (67%). Even at followup, 20% of patients had ongoing anemia.
In brief: A recent cross-sectional study (KM Clark et al. J Pediatr 2017; 181: 56-61) showed that breastfeeding at 9 months of age in Chinese infants was associated with iron deficiency anemia.. Iron deficiency can contribute to neurodevelopmental delays in addition to anemia.
In Zhejiang (n=142), 27.5% of breastfed infants had iron deficiency anemia (IDA) compared with 0% of formula-fed infants.
In Hebei (n=813) , 44% of breastfed infants had IDA compared with 2.8% of formula-fed infants.
My take: In later infancy (after 6 months of age), breastfeeding infants are at increased risk for iron deficiency anemia.
A useful review of microcytic anemia (NEJM 2014; 371: 1324-31) discusses the most common causes, mechanisms and treatment of microcytic anemia.
Common causes discussed include thalassemia, iron deficiency anemia, and anemia of inflammation. With the latter, the authors review the pathophysiology: “the cause of this anemia is twofold. First, renal production of erythropoietin is suppressed by inflammatory cytokines, resulting in decreased red-cell production. Second, lack of iron availability for developing red cells can lead to microcytosis. The lack of iron is largely due to the protein hepcidin, an acute-phase reactant that leads to both reduced iron absorption and reduced release of iron from body stores.”
Treatment of iron deficiency anemia –pointers:
Ferrous sulfate (325 mg [65 mg of elemental iron] orally three times a day -considered first line for adults. Ferrous gluconate at a daily dose of 325 mg [35 mg elemental] is an alternative.
“Several trials suggest that lower doses of iron, such as 15 to 20 mg of elemental iron daily can be as effective as higher doses and have fewer side effects.”
“There are many oral iron preparations, but no one compound appears to be superior to another.”
In those with an inadequate response to oral iron therapy, parenteral iron can be helpful. The authors note that low-molecular-weight iron dextran (INFeD) is “associated with an incidence of reactions that is similar to that with the newer products but allows for higher doses of iron replacement.” Typical dosing for adults: 25 mg test dose, and if tolerated for 1 hr, can give 975 mg (1000 mg total) over 4-6 hours. The low-molecular-weight iron dextran should not be used in patients with previous iron dextran hypersensitivity reactions.
Alternative IV iron products: Ferric gluconate [Ferrlecit] 125 mg adult dose over 1 hour -given weekly (8 doses = 1000 mg) or Iron Sucrose [Venofer] 200 mg adult dose over 15-60 min, 300 mg over 1.5 hr, or 500 mg over 4 hr; can repeat in subsequent sessions until total dose of 1000 mg.
Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.
The title of this entry is not particularly surprising. A recent study (JPGN 2013; 57: 722-27) showed that among 263 children (1.5-6 years in age) in Jerusalem, that anemia was present in 11.2%, iron deficiency in 22%, and iron-deficiency anemia in 3.7%.
Children with extremely low red meat consumption had 4-fold higher rates of iron deficiency than those who consumed ≥2 servings per week. Poultry intake was not protective.
Bottomline: As more families choose a ‘health-conscious diet,’ iron deficiency may become more frequent.
In some patients with inflammatory bowel disease (IBD), treatment of anemia associated with IBD sometimes results in more symptomatic benefit than treatment of the IBD. Yet, anemia remains common in IBD, both in children and adults (Inflamm Bowel Dis 2012; 18: 513-19).
Using a cross-sectional observational study design, a tertiary adult and pediatric IBD center reviewed consecutive clinic patients in April 2009. The prevalence of anemia was 70% (41/59) children, 42% (24/54) adolescents, and 40% (49/124) adult. In addition, iron deficiency anemia was more common in the pediatric population: 36/41 children and 20/23 adolescents. In the adults with anemia, only 55% (27/49) were iron deficient. One of the key determinants of anemia was disease activity.
Interestingly, among patients with iron deficiency, younger age was inversely associated with treatment with iron therapy: 13% of children, 30% of adolescents, and 48% of adults.
Other important aspects of anemia in IBD:
Anemic patients can have quality of life scores as poor as those seen in malignancy
Almost all IBD patients will respond to either oral or parenteral iron. Erythropoetin reserved for patients who do not respond to parenteral iron.
-NEJM 2005; 352: 1011. Anemia algorithm. If transferrin saturation <16%, check ferritin. If ferritin less than 30, then patient with Fe-deficiency; if >100, anemia of chronic disease. If 30-100, could check soluble transferrin receptor (level of sTranReceptor/log ferritin < 1 is c/w anemia of chronic disease whereas when > 2, c/w combined Fe-def anemia and anemia of chronic disease)
-JPGN 2010; 51: 708. 25-50% still anemic 1yr post IBD diagnosis.
-IBD 2007; 13: 1545-53. Guidelines for anemia mgt w IBD. Max oral absorption is 10-20mg/day; thus IV iron often needed. Goal for iron Rx is transferrin saturation of 15-50% and ferritin > 30 mcg/L (>100 if active inflammation). Anemia of chronic disease likely if TS <16% and ferritin > 100. Rec IV iron Rx prior to use of Epo. IV iron effective alone in 70-80%. Epo if no response to IV iron & Hgb <10. Consider folic acid & B12 deficiency if high MCV. AZA/6MP usually associated with pancytopenia not isolated anemia.
-Gastroenterology 2011; 141: 846. Ferric carboxymaltose better than iron sucrose (Ferrlecit/Venofer) b/c can use higher dose & give more rapidly.