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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
55
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))
Msambweni County Referral Hospital
Msambweni, Kwale County, Kenya
Fractional iron absorption in %
Fractional iron absorption (%), measured as erythrocyte incorporation of stable iron isotopes at day 19
Time frame: Day 19
Hemoglobin (Hb)
Iron status will be determined at baseline
Time frame: Baseline
Hemoglobin (Hb)
Iron status will be determined at day 19
Time frame: Day 19
Plasma Ferritin (PF)
Iron status will be determined at baseline
Time frame: Baseline
Plasma Ferritin (PF)
Iron status will be determined at day 19
Time frame: Day 19
Soluble Transferrin Receptor (sTfR)
Iron status will be determined at baseline
Time frame: Baseline
Soluble Transferrin Receptor (sTfR)
Iron status will be determined at day 19
Time frame: Day 19
C-reactive protein (CRP)
Inflammation status will be determined at baseline
Time frame: Baseline
C-reactive protein (CRP)
Inflammation status will be determined at day 19
Time frame: Day 19
Alpha-1-acid glycoprotein (AGP)
Inflammation status will be determined at baseline
Time frame: Baseline
Alpha-1-acid glycoprotein (AGP)
Inflammation status will be determined at day 19
Time frame: Day 19
Human Milk Oligosaccharides concentrations in breast milk
Human Milk Oligosaccharides concentrations in breast milk of the mothers of the participating infants will be measured at baseline to determine maternal secretor status.
Time frame: Baseline
Human Milk Oligosaccharides concentrations in breast milk
Human Milk Oligosaccharides concentrations in the breast milk of the mothers of the participating infants will be measured at Day 19 to determine maternal secretor status.
Time frame: Day 19
Anti-oligosaccharide immunoglobulins
Infant blood serum immunoglobulins toward mucosal oligosaccharide antigens and microbial carbohydrate antigens will be measured at baseline
Time frame: Baseline
Intestinal Fatty Acid Binding Protein (I-FABP) in infants diagnosed with iron deficiency anemia
I-FABP will be assessed in infants diagnosed with iron-deficiency anaemia and receiving supplementation with oral iron syrup as per local standard of care.
Time frame: Day 19
Fecal calprotectin in infants diagnosed with iron deficiency anemia
Fecal calprotectin will be assessed in infants diagnosed with iron-deficiency anaemia and receiving supplementation with oral iron syrup as per local standard of care. Fecal calprotectin will be measured 3 days before beginning of oral iron supplementation. The sampling period will last for 72 hours.
Time frame: 3 days before oral iron supplementation
Fecal calprotectin in infants diagnosed with iron deficiency anemia
Fecal calprotectin will be assessed in infants diagnosed with iron-deficiency anaemia and receiving supplementation with oral iron syrup as per local standard of care. Fecal calprotectin will be measured on day 4 of oral iron supplementation. The sampling period will last for 72 hours.
Time frame: Day 4 of oral iron supplementation
Fecal calprotectin in infants diagnosed with iron deficiency anemia
Fecal calprotectin will be assessed in infants diagnosed with iron-deficiency anaemia and receiving supplementation with oral iron syrup as per local standard of care. Fecal calprotectin will be measured on day 15 of oral iron supplementation. The sampling period will last for 72 hours.
Time frame: Day 15 of oral iron supplementation
Hemoglobin (Hb) in infants diagnosed with iron deficiency anemia
Iron status will be assessed in infants diagnosed with iron-deficiency anaemia and receiving supplementation with oral iron syrup as per local standard of care
Time frame: Day 18 of oral iron supplementation
Plasma Ferritin (PF) in infants diagnosed with iron deficiency anemia
Iron status will be assessed in infants diagnosed with iron-deficiency anaemia and receiving supplementation with oral iron syrup as per local standard of care
Time frame: Day 18 of oral iron supplementation
Soluble Transferrin Receptor (sTfR) in infants diagnosed with iron deficiency anemia
Iron status will be assessed in infants diagnosed with iron-deficiency anaemia and receiving supplementation with oral iron syrup as per local standard of care
Time frame: Day 18 of oral iron supplementation
C-reactive protein (CRP) in infants diagnosed with iron deficiency anemia
Inflammation status will be assessed in infants diagnosed with iron-deficiency anaemia and receiving supplementation with oral iron syrup as per local standard of care
Time frame: Day 18 of oral iron supplementation
Alpha-1-acid glycoprotein (AGP) in infants diagnosed with iron deficiency anemia
Inflammation status will be assessed in infants diagnosed with iron-deficiency anaemia and receiving supplementation with oral iron syrup as per local standard of care
Time frame: Day 18 of oral iron supplementation
Hemoglobin in stool from infants diagnosed with iron deficiency anemia
Hemoglobin concentration will be assessed in stools from infants diagnosed with iron-deficiency anaemia and receiving supplementation with oral iron syrup as per local standard of care. Hemoglobin concentration in stools will be measured 3 days before beginning of oral iron supplementation. The sampling period will last for 72 hours.
Time frame: 3 days before oral iron supplementation
Hemoglobin in stool from infants diagnosed with iron deficiency anemia
Hemoglobin concentration will be assessed in stools from infants diagnosed with iron-deficiency anaemia and receiving supplementation with oral iron syrup as per local standard of care. Hemoglobin concentration in stools will be measured on day 4 of oral iron supplementation. The sampling period will last for 72 hours.
Time frame: Day 4 of oral iron supplementation
Hemoglobin in stool from infants diagnosed with iron deficiency anemia
Hemoglobin concentration will be assessed in stools from infants diagnosed with iron-deficiency anaemia and receiving supplementation with oral iron syrup as per local standard of care. Hemoglobin concentration in stools will be measured on day 15 of oral iron supplementation. The sampling period will last for 72 hours.
Time frame: Day 15 of oral iron supplementation.
Intestinal Fatty Acid Binding Protein (I-FABP) in infants diagnosed with iron deficiency anemia
I-FABP will be assessed in infants diagnosed with iron-deficiency anaemia and receiving supplementation with oral iron syrup as per local standard of care.
Time frame: Day 18 of oral iron supplementation
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