Evaluation of the Effects of Routine Iron Supplementation in Children on Gastrointestinal Iron Losses
Condition: Iron Deficiency Anemia; Gastro Intestinal Bleeding; Iron-deficiency
MeSH terms: Gastrointestinal Hemorrhage; Anemia, Iron-Deficiency; Iron Deficiencies
Study type: Interventional

Summary: 
      Iron deficiency anaemia (IDA) is common among infants and young children in sub-Saharan
      Africa.Oral iron administration is usually recom-mended as cost effective measure to prevent
      and treat iron deficiency (ID) and IDA during childhood. In Kenya, national nutrition
      policies for anaemia prevention recommend a daily dose of 3-6 mg ele-mental iron per kg body
      weight if a child is diagnosed with anaemia.

      Using a novel technology, recent research found increased iron losses during iron
      supplementation. In an explorative analysis of stool samples collected from Gambian toddlers
      (Speich et al., 2020), an increase in faecal iron losses during iron supplementation was
      reported. The present study is aiming to analyse a relationship between routine iron
      supplementation and increased faecal occult blood losses in 24 Kenyan children with anaemia
      and iron deficiency in a more structured manner.

      Secondary objectives of the study are to measure and monitor iron and inflammatory status
      during the course of the study and to quantify long-term iron absorption and iron losses
      during a 12-weeks iron supplementation period, in order to put iron balance into relationship
      to occurring faecal occult blood losses during such an intervention.
    

Detailed description: 
      Infants and young children in sub-Saharan Africa have high rates of iron deficiency anaemia
      (IDA), which adversely affects their growth and cognitive development. WHO recommends daily
      administration of 3 mg elemental iron per kg body weight in form of drops or syrup in 6-23
      month-old ID or anaemic infants. In settings where anaemia prevalence in this age group is
      >40%, WHO further recommends daily administration of 10-12.5 mg elemental iron for prevention
      of ID and anaemia. The Kenyan Ministry of Health adopted the WHO strategy to treat IDA in its
      "Basic Paediatric Protocols" released in 2016, and specified a dose of 3-6 mg elemental Fe
      per kg body weight and day.

      WHO guidelines for anaemia prevention and control in infants aged 6-23 months are based on a
      systematic review and meta-analysis of randomized controlled trials investigating the effect
      of daily iron supplementation on health in infants. The review reported a significantly lower
      risk of iron-deficiency anaemia in infants when supplemented. However, iron supplements and
      iron-containing micronutrient powders (MNPs) do not always show efficacy; for example, in a
      recent large intervention trial in Pakistan, there was no significant effect of 12 months of
      iron supplementation on haemoglobin status.

      Among the many potential factors contributing to the limited success of health and nutrition
      policies in reducing the prevalence of iron deficiency, increased iron losses during iron
      supplementation have not been considered. In a recent study in Gambian toddlers, a 3.4-fold
      increase in iron losses was detected, specifically from 0.22 (0.19;0.29) mg/d to 0.75
      (0.55;0.87) mg/d, during a 12-week iron intervention with daily consumption of 12 mg iron as
      ferrous fumarate in MNPs routinely distributed by the United Nations Children's Fund and the
      World Food Program. Furthermore, the administered iron dose significantly correlated with
      faecal haemoglobin concentration in the Gambian toddlers. In a recent iron supplementation
      pilot study in Kenyan toddlers, the investigators measured a significant increase in faecal
      haemoglobin concentration during iron supplementation. Increased basal iron losses during
      iron supplementation could also be detected in 10 Swiss women. Several endoscopy studies have
      suggested iron supplementation may cause irritation/inflammation of the gut mucosa,
      potentially leading to gastrointestinal blood losses.

      To explore a potential relationship between iron supplementation with common iron supplements
      and increased faecal occult (small traces of blood, not visible in stool) blood losses, this
      study will measure haemoglobin and porphyrin content in stool samples collected before and
      throughout a 91-day iron supplementation intervention. Intervention product will be 6 mg iron
      / kg body weight as ferric ammonium citrate and ferrous fumarate syrup (Ranbaxy Ranferon-12
      Syrup, Ranbaxy Laboratories, Gurgaon, India) administered daily. Faecal occult blood losses
      will also be compared to absolute iron losses determined by the recently developed dilution
      of stable iron isotopes methodology. The study population will consist of 24 anaemic 2-years
      old children in Kwale County of southern coastal Kenya. The hypothesis of the investigators
      is that iron status will improve, but faecal occult blood losses will increase. The data from
      this project may provide valuable information towards the development of safer and more
      effective iron supplementation regimens.
    

Intervention name(s): Ferric ammonium citrate and ferrous fumarate syrup (Ranbaxy Ranferon-12 Syrup, Ranbaxy Laboratories, Gurgaon, India)
Intervention type(s): Dietary Supplement
Intervention description(s): Daily supplementation with iron syrup for 13 weeks. The dosage will be calculated based on body weight and adjusted after 4 and 8 weeks of intervention
Intervention MeSH terms: Ferrous fumarate
Intervention model: Single Group Assignment
Intervention model description: Prospective intervention study
Masking: None (Open Label)
Primary purpose: Prevention