The Effect of Human Milk Oligosaccharides and Galacto-oligosaccharides on Iron Absorption in Kenyan Infants
Condition: Anemia, Iron-deficiency
MeSH terms: Anemia, Iron-Deficiency; Iron Deficiencies
Study type: Interventional

Summary: 
      Effective and safe strategies to deliver iron to infants and young children in Sub-Saharan
      Africa are urgently needed. One potential strategy to improve safety of iron fortification is
      to limit the total amount of unabsorbed iron entering the colon by lowering the daily iron
      dose but at the same time ensure efficacy by maximizing absorption from this lower dose. In
      Kenyan infants, the investigators have recently shown that consumption of 7.5 g of the
      prebiotic galacto-oligosaccharides (GOS) compared to no GOS consumption increased iron
      absorption from an iron containing micronutrient powder by ≈60%. It is uncertain whether a
      lower dose of GOS can also enhance iron absorption. Another question is whether HMOs,
      'natural prebiotics' found in high concentration in human breast milk, can also increase iron
      absorption similar to GOS. Therefore, the aim of this study is to measure fractional iron
      absorption from a maize-based porridge fortified with A) iron as ferrous fumarate, B) iron as
      ferrous fumarate and GOS and C) iron ferrous fumarate and HMOs, using an established stable
      iron isotope technique in 55 infants aged 8-12 months living in Msambweni and surrounding
      rural communities, Kwale County of southern coastal Kenya. Assessing the effect of a low dose
      of GOS and of HMOs on iron absorption will provide valuable information towards the
      development of new, highly bioavailable iron formulations for African infants.

      As per the local standard of care, the participants who will be iron-deficient anemic at the
      end of the study will be treated with oral iron supplements. To evaluate the effects of iron
      supplementation on iron and anemia status and to estimate obligatory iron losses in the
      gastrointestinal tract, blood and fecal samples will be collected before, during and fourteen
      days after the beginning of the treatment with oral iron supplements. Data about the efficacy
      of current supplementation strategies in iron-deficient anemic children and obligatory iron
      losses would provide additional evidence for the optimization of iron supplementation
      regimens.
    

Detailed description: 
      Iron absorption from differently labelled iron-fortified maize-based test meals will be
      measured in 55 infants. At baseline a venipuncture blood sample will be collected from all
      infants for the determination of the following iron and inflammation status parameters:
      hemoglobin (Hb), plasma ferritin (PF), soluble transferrin receptor (sTfR), C-reactive
      protein (CRP) and alpha-1-acid glycoprotein (AGP), and anti-oligosaccharide immunoglobulins.
      Anthropometrics will be measured; demographics, the medical history and the feeding habits
      will be assessed using a questionnaire. A breast milk sample from all mothers will be
      collected for determination of HMO profile and maternal secretor status. After baseline, 30
      infants will consume three different test meals on alternate days (day 1, day 3, and day 5)
      and 25 infants will consume two different test meals on alternate test meal days (day 1, day
      3 and day 5). The order of consumption of the three test meals will be randomly assigned.
      Test meal A will contain 5 mg of iron as ferrous fumarate given as 2.5 mg Fe-56 and 2.5 mg
      Fe-54 (control test meal). Test meal B will contain 5 mg of iron as ferrous fumarate given as
      2.5 mg Fe-56 and 2.5 mg Fe-58 and 4 g of GOS-75 (≈ 3 g GOS) (GOS test meal).Test meal C will
      contain 5 mg of iron as ferrous fumarate given as 2.5 mg Fe-56 and 2.5 mg Fe-57 and 2.0 g
      2'-fucosyllactose (2'-FL) and 1.0 g lacto-N-neotetraose (LNnT) (HMO test meal). The test
      meals will be based on maize porridge, consisting of refined maize flour, sugar and mineral
      water, and will be administered between 0700 and 0900. Overnight, only breast milk will be
      allowed to the infant and no breast milk and no other food 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 administration (day 17 and 19,
      respectively) a whole blood sample will be collected by venipuncture for analysis of the
      ratios of the different molecular weight iron incorporation into red blood cells and
      determination of iron and inflammation status (Hb, PF, sTfR, CRP and AGP). Furthermore,
      anthropometrics and some parts of the baseline questionnaire will be repeated.

      At endpoint (day 17 and 19, respectively), if the infant will be diagnosed with
      iron-deficiency anemia (Hb concentration below 110 g/l and low red blood cells mean
      corpuscular volume), the caregiver will be instructed to give the infant 4mg/kg iron in the
      form of oral syrup, daily. Compliance during the follow-up will be assessed by weighting the
      iron syrup containers before and after 14 days of treatment with the iron syrup. Collection
      of fecal samples will be performed over 3 time periods of 72h each. The first time period
      will start the 3 days prior of beginning of oral iron supplementation, the second will take
      place on day 4, 5 and 6 of oral iron supplementation and the last on day 15, 16 and 17 of
      oral iron supplementation. A venepuncture blood sample will be collected in the morning after
      the last day of fecal sample collection (day 18 of oral iron supplementation). Furthermore,
      some parts of the baseline questionnaire will be repeated. Adverse events (AEs) will be
      assessed throughout the entire study period.
    

Intervention name(s): ferrous fumarate; ferrous fumarate + GOS; ferrous fumarate + HMOs
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): Maize-based porridge fortified with iron (5mg) in form of ferrous fumarate; Maize-based porridge fortified with iron (5mg) in form of ferrous fumarate and GOS (3g); Maize-based porridge fortified with iron (5mg) in form of ferrous fumarate and HMOs (2'-FL (2g) + LNnT(1g))
Intervention MeSH terms: Ferrous fumarate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: Anemia; Iron-deficiency; Iron absorption; Prebiotic; Galacto-oligosaccharides; Human milk oligosaccharides; Infants; Kenya