Iron Deficiency Anemia, Iron Supplementation and Genomic Stability in Infants

Study Overview
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Brief Summary
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This study compares weekly versus daily administration of iron for prevention of anemia in 6 months old infants. One third of the infants that are exclusively breast fed will not receive iron, the second third will receive iron weekly and the last third will receive iron daily. Half of the infants that take infant formula will receive iron weekly and the other half will receive iron daily.

Detailed Description
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Iron deficiency is the most prevalent nutritional deficiency and the main cause of anemia. It's estimated that 43% of pre-school children worldwide are anemic, in Argentina a national survey carried out in 2007 (last survey), showed that 34.5% of children less than 2 years old were anemic and that 50.8% of children 6 to 9 months old were anemic. Although there is a consensus on iron supplementation as a preventive strategy for anemia in infants, there is a poor adherence due mainly to mild gastrointestinal adverse effects and low prescription rates from pediatricians. On the other hand, the excess of iron can lead to genomic instability with structural and functional alterations on proteins, lipids and DNA. Weekly administration of iron has been proposed as an alternative of similar efficacy and higher effectiveness in older children and pregnant women, but sufficient evidence for infants is lacking.

Official Title
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Effectiveness of Weekly and Daily Iron Supplementation for the Prevention of Iron-deficiency Anemia in Infants. Impact on Genomic Stability

Conditions
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Anemia, Iron-deficiency

Intervention / Treatment
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* Drug: Weekly Ferrous Sulfate
* Drug: Daily Ferrous Sulfate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 3 months old infants, clinically healthy, born to term (>37 weeks), that weighted at birth between 2500 and 4000 g, that have normal prenatal records. Exclusion Criteria: anemic or iron deficient infants, or that have a chronic pathology, or that have undergone an acute pathology in the previous 15 days. Children that are receiving antibiotics or vitamin supplements.

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 3 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two main arms: weekly vs daily iron supplementation. Infants who are exclusively breast fed will be randomized into three groups: no iron supplementation, weekly iron supplementation and daily iron supplementation. Infants that are partially fed with infant formula will be randomized into two groups: weekly iron supplementation and daily iron supplementation.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Weekly Iron<br>Weekly ferrous sulfate: one dose (4mg/kg/week). | Drug: Weekly Ferrous Sulfate<br>* Drops<br>* Other names: Fer-in-sol;|
| Active Comparator: Daily Iron<br>Daily ferrous sulfate: one dose (1 mg/kg/day). Maximum daily dose: 40 mg | Drug: Daily Ferrous Sulfate<br>* Drops<br>* Other names: Fer-in-sol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anemia | Hemoglobin <11.0 g/dL in 6 months old infants. | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Iron deficiency | Serum Ferritin <12 ng/ml in 6 months old infants. If C-reactive protein > 5 mg/L, Iron deficiency is redefined as Serum Ferritin <30 ng/ml. | 7 days | 
| Adverse effects | Frequency of at least one of the following during the three months intervention: rejection of food intake, constipation, vomiting, diarrhea, abdominal pain. | Through study completion, an average of 1 year | 
| Genomic Instability | One of the following indicators is altered. Genomic damage: Comet assay: damage index (ID) over 200 cells. 8-oxo-dGuanosine. Oxidative Stress: catalase activity, superoxide dismutase activity, Tbars. | 15 days | 
| Adherence | Low adherence: 1. Less than 50% of the drug was given to the infant (according to the remaining volume of the drug in its recipient) 2. Less tha 50% of the allocated intakes (according to care-taker registration on an almanaq) | Through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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infant, primary prevention