Iron Absorption From a Micronutrient Powder Containing Galacto-oligosaccharides (GOS)
Condition: Anemia, Iron-Deficiency
MeSH terms: Anemia, Iron-Deficiency; Iron Deficiencies
Study type: Interventional

Summary: 
      Infants and young children in sub-Saharan Africa have high rates of iron deficiency anemia
      (IDA), which adversely affects their growth and cognitive development. In-home iron
      fortification of complementary foods using micronutrient powders (MNPs) reduces risk for IDA.
      However, in areas with a high burden of infectious diseases iron may increase the risk of
      unfavorable gut microbiota composition possibly influencing diarrhea prevalence. Thus, there
      is an urgent need to find safer formulations of iron fortification for African infants. The
      investigators recently finished a randomized, double blind controlled intervention trial in
      Kenya where the investigators tested whether the addition of galacto-oligosaccharides (GOS)
      in a MNP containing 5 mg of iron protects against the adverse effects of the iron on the
      infant gut microbiome and gut inflammation (ClincalTrails.gov Identifier: NCT02118402).
      Prebiotics are also potential enhancers of colonic iron absorption. Therefore, to complement
      the intervention study, the present study will compare iron absorption from the combination
      of sodium iron EDTA (NaFeEDTA) and ferrous fumarate (FeFum) with and without prior
      consumption GOS or 3 weeks. The investigators will enroll 80 Kenyan infants from Kwale
      County, aged 6-14 months of whom 40 infants will consume maize porridge blended with MNP
      containing iron and 40 infants will receive a porridge mixed with MNP containing iron+GOS.
      After 3 weeks of MNP consumption, two test meals will be fed on two consecutive mornings, and
      will consist of maize porridge containing isotopically labeled FeFum and NaFeEDTA or
      isotopically labeled ferrous sulfate (FeSO₄), respectively. Fourteen days after the second
      test meal administration, a whole blood sample will be collected by venipuncture for iron
      isotopic analysis. Iron and inflammation status parameter will be determined at baseline and
      endpoint. A stool sample will be collected at baseline and on the first test meal day. The
      gut microbiome, fecal pH and fecal SCFAs profile will be analyzed. Knowing the expected iron
      absorption from the iron and GOS containing MNP will inform decisions on type of iron
      compound and dosing regimens for MNPs to allow the lowest iron dose to be used but still
      cover the infant requirement for absorbed iron.
    

Detailed description: 
      Iron absorption from two iron-fortified maize-based test meals will be measured in two groups
      of 40 infants (total N=80). Infants will be recruited at Msambweni District Hospital and
      communities served by Msambweni District Hospital in southern coastal Kenya. In group 1, iron
      absorption is measured after 3 weeks of MNP consumption containing 5 mg iron in form of
      NaFeEDTA (2.5 g) and FeFum (2.5 g) but no GOS. In group 2, iron absorption is measured after
      3 weeks of MNP consumption containing 5 mg iron in form of NaFeEDTA (2.5 g) and FeFum (2.5 g)
      and 7.5 g GOS. Iron absorption is measured as the incorporation of stable isotopes into
      erythrocytes at least 14 days after the test meal administration.

      At baseline, a blood sample will be collected from potential study participants for the
      determination of the following iron and inflammation status parameters: hemoglobin (Hb),
      plasma ferritin (PF), soluble transferrin receptor (sTfR), zinc protoporphyrin (ZnPP),
      C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP). Anthropometrics (height, weight,
      mid-upper arm and head circumference) will be measured, and demographics, the medical history
      and the feeding habits will be assessed using a questionnaire. On day 1, infants will be
      enrolled and randomized into the two groups, and then start the intervention. The infants
      will consume 1 MNP sachet added to maize porridge per day for a total of 5 weeks. A stool
      sample will be collected on day 1 for the determination of gut microbiota composition, fecal
      pH and fecal SCFAs. After 3 weeks of MNP consumption, the two isotopically labelled test
      meals will be fed to the infants by their caregivers under supervision of the research team
      on two consecutive mornings between 7 and 8 am. Test meal A will contain 2.5 mg 57Fe in form
      of FeFum and 2.5 mg iron as NaFeEDTA (given as 1.5 mg 56Fe and 1 mg 58Fe). Test meal B will
      contain 5 mg iron in form of FeSO₄ (3 mg of 56Fe and 2 mg of 54Fe). The test meals will
      consist of maize porridge (5-10% dry weight) and mineral water (30 ml) and will be randomly
      administered on the two consecutive days (AB or BA). Overnight, only breast milk will be
      allowed to the infant and no breast milk will be given at least 3 h before test meal
      administration. Infants will not be allowed to eat or drink for 2 h after the test meal. On
      the day of the first test meal, a stool sample will be collected and analyzed for gut
      microbiota composition, fecal pH and fecal SCFAs. Fourteen days after the second test meal
      administration, 3 ml of whole blood will be collected by venipuncture for iron isotopic
      analysis and iron and inflammation status. Anthropometrics and the baseline questionnaire
      will be repeated. Compliance of MNP consumption and adverse event reporting (morbidity
      monitoring) will be done during weekly visits of the infants.

      In a follow-on study, iron absorption from the two above described mentioned iron-fortified
      maize-based test meals will be measured in 24 infants aged 6-12 months without pre-feeding of
      GOS. All procedures will be done identical as described above.
    

Intervention name(s): Fortified maize porridge (MNP+iron); Fortified maize porridge (MNP+iron+GOS)
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Maize porridge will be home-fortified with the MNP + iron. Maize porridge for the test meal will be fortified with labelled iron compounds; Maize porridge will be home-fortified with the MNP + iron + GOS. Maize porridge for the test meal will be fortified with labelled iron compounds
Intervention MeSH terms: Iron
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: Iron fortification; Anemia; Iron Deficiency; Iron Absorption; Prebiotics; Stable isotopes