Effect of Timing of Micronutrient Powder Consumption on Iron Absorption in Infants
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
      by ensuring that the iron needs of infants and young children are met without changing their
      traditional diet. In order to optimize iron absorption timing of MNP consumption might as
      well be important. This is because hepcidin, a key regulator of systemic iron balance, shows
      a circadian increase that may influence morning versus afternoon iron absorption from the
      MNP. Furthermore, a single dose of iron can increase hepcidin levels and potentially inhibit
      iron absorption from a second dose, consumed close in time to the first dose.

      To determine the difference between i) morning versus afternoon iron absorption and ii)
      consecutive versus alternate day iron absorption, investigators will enrol 20 infants from
      Kwale County aged 6-14 months and conduct two studies. In study 1, infants will consume 2
      test meals consisting of maize porridge containing isotopically labelled Ferrous Sulphate in
      the morning and afternoon on 2 days. In study 2, infants will consume 3 test meals consisting
      of maize porridge containing isotopically labelled Ferrous Sulphate on two consecutive days
      and 1 alternate day. In both studies, fourteen days after the last 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. Hepcidin
      concentrations will be measured before the morning and afternoon meals (study 1) and after
      second consecutive meal (study 2).

      Knowing the effect of time on the expected iron absorption will inform decisions on the ideal
      timing of MNP to cover the infant's requirement for absorbed iron.
    

Detailed description: 
      20 infants will be recruited from the Msambweni County Referral Hospital in southern coastal
      Kenya to participate in both studies.

      Study 1:

      At baseline a morning blood sample will be collected from potential study participants for
      the determination of the following iron and inflammation status parameters: hemoglobin (Hb),
      hepcidin, 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.

      Infants will consume the 1st test meal the next day after enrolment in the morning (day1). On
      day 2 a 2nd blood sample (1ml) will be collected in the afternoon quantify afternoon
      concentration of hepcidin in plasma and then the infants will consume the 2nd meal on the 3rd
      day in the afternoon.

      The two isotopically labelled test meals will be fed to the infants by their caregivers under
      supervision of the research team. The morning test meal A will contain 12 mg of iron as
      ferrous sulfate given as 2 mg of 57Fe and 10mg of 56Fe. The afternoon test meal will contain
      12 mg of iron as ferrous sulfate given as 2 mg of 58Fe and 10 mg of 56Fe.

      The test meals will consist of maize porridge (5-10% dry weight) and mineral water (8ml) and
      will be randomly administered on the two alternate days (AB or BA). Overnight, only breast
      milk will be allowed to the infant before coming for the morning meal and no breast milk will
      be given at least 3 h before both morning and afternoon test meal administration. Infants
      will not be allowed to eat or drink for 2 h after the test meal. 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 health status
      will be assessed.

      Study 2:

      At baseline a blood sample will be collected from potential study participants for the
      determination of iron and inflammation status parameters: hemoglobin (Hb), hepcidin, 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.

      Infants will be randomized to consume the consecutive days or alternate day meal schedule on
      day 1. 1ml of blood will be collected after the second consecutive meal to determine hepcidin
      level.

      Test meal A will contain 12 mg of iron as ferrous sulfate given as 2 mg of 54Fe and 10mg of
      56Fe. Test meal B will contain 12 mg of iron as ferrous sulfate given as 2 mg of 57Fe and
      10mg of 56Fe. Test meal C will contain 12 mg of iron as ferrous sulfate given as 2 mg of 58Fe
      and 10mg of 56Fe. All test meals will be consumed in the morning.

      The test meals will consist of maize porridge (5-10% dry weight) and mineral water (8ml).
      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. Test meals plus mineral water will be consumed
      completely in the presence of the investigators, and the infant will not be allowed to eat or
      drink for 2 h after the test meal. Fourteen days after the third test meal, 3 ml of whole
      blood will be collected by venipuncture for iron and inflammation status, and iron analysis
      in red blood cells.
    

Intervention name(s): Fortified maize porridge (MNP and Iron); Fortified Maize porridge (MNP + Iron + GOS)
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Maize porridge fortified with MNP and labelled iron compound; Maize porridge fortified with MNP + GOS and labelled iron compound
Intervention MeSH terms: Iron
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: Iron absorption; Iron deficiency; Hepcidin; Stable isotopes; Anemia; Infants