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The co-primary objectives of this study are: 1) to investigate the effect adding a synbiotic (combination of a pre-and probiotic) to iron-fortified follow-up formula (FUF) on iron bioavailability, and 2) to investigate the effect adding Human Milk Oligosaccharides (HMOs) to iron-fortified FUF on iron bioavailability in 10-14 month-old Thai children.
Iron stores of healthy, full-term neonates are supposed to cover iron needs for the first 4-6 months of life. After 6 months of age, requirements for absorbed iron are high, as infants need to build body iron stores and triple their body weight before the first year of life. Iron concentrations in mature breastmilk are low (~0.3 mg/L) and cannot adequately cover the high iron requirements of children between 6 and 24 months of age. Follow-up formulas (FUF) are fortified milk-based products intended for infants above 6 months of age and young children aged 1-3 years, and are widely used as a liquid part of the weaning diet to supplement the diet of young children with macro- and micronutrients. Prebiotics and probiotics are increasingly added to foods for infants and young children due to emerging evidence on possible health benefits. We recently showed that the addition of prebiotic galacto-oligosaccharides (GOS) to an iron-containing micronutrient powder increased iron absorption in Kenyan infants. To our knowledge, the effect of the combination of pre- and probiotics (synbiotic) or human milk oligosaccharides (HMOs) on iron absorption from an iron-fortified FUF has not been investigated.
Thai children (10-14 months old) will be assigned to receive FUF fortified with isotopically labelled iron as FeSO4 1) with synbiotic, 2) HMO, and 3) without added prebiotics as a reference, in random order. Besides the iron source and synbiotic or HMO, the test FUF will be identical in terms of macro- and micronutrient composition. For the secondary objectives of this study, which will have a single-group, before-after design, each infant will receive the test FUF with added synbiotic for 25 days on gut comfort and quality of life outcomes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Test formula C | Experimental |
| |
| Test formula B | Experimental |
| |
| Test formula A | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Test formula A without added pre- and pro-biotic | Other | An identical formula as test formulas fortified with 2.20 mg iron as FeSO4-58 and 0.05 mg native iron per serving (235 ml), but without added pre- or probiotic. |
| Measure | Description | Time Frame |
|---|---|---|
| Fractional Iron Absorption (FIA) from an iron-fortified follow-up infant formula with and without the addition of a synbiotic | FIA from test formulas will be determined based on the shift of the iron isotope ratios in whole blood. | Measured 28 days after administration of last test formula |
| Fractional Iron Absorption (FIA) from an iron-fortified follow-up infant formula with and without the addition of a synbiotic | FIA from test formulas will be determined based on the shift of the iron isotope ratios in whole blood. | Measured 14 days after administration of last test formula |
| FIA from an iron-fortified follow-up formula with and without the addition of human oligosaccharides (HMOs) | FIA from test formulas will be determined based on the shift of the iron isotope ratios in whole blood. | Measured 28 days after administration of last test formula |
| FIA from an iron-fortified follow-up formula with and without the addition of human oligosaccharides (HMOs) | FIA from test formulas will be determined based on the shift of the iron isotope ratios in whole blood. | Measured 14 days after administration of last test formula |
| Measure | Description | Time Frame |
|---|---|---|
| Effects of feeding an iron-fortified FUF with added synbiotic (Formula B) for 25 days on Iron status (haemoglobin [Hb]) | Change in iron status biomarkers (Hb) from baseline until last study visit (day 40) | At baseline and last study visit (day 40) |
| Effects of feeding an iron-fortified FUF with added synbiotic (Formula B) for 25 days on Iron status (plasma ferritin [PF]) |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Amphawa Hospital | Samut Sakhon | Thailand |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39179207 | Derived | Scheuchzer P, Sinawat S, Donze AS, Zeder C, Sabatier M, Garcia-Garcera M, Ricci C, Kamontham T, Zimmermann MB, Baumgartner J. Iron Absorption from an Iron-Fortified Follow-Up Formula with and without the Addition of a Synbiotic or a Human-Identical Milk Oligosaccharide: A Randomized Crossover Stable Isotope Study in Young Thai Children. J Nutr. 2024 Oct;154(10):2988-2998. doi: 10.1016/j.tjnut.2024.08.016. Epub 2024 Aug 22. |
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| Test formula B with synbiotic | Other | Test formula fortified with 2.20 mg iron as FeSO4-57 and 0.05 mg native iron per serving (235 ml) and added synbiotic. |
|
| Test formula C with HMOs | Other | Test formula fortified with 2.20 mg iron as FeSO4-54 and 0.05 mg native iron per serving (235 ml) and added HMOs. |
|
Change in iron status biomarkers (PF) from baseline until last study visit (day 40) |
| At baseline and last study visit (day 40) |
| Effects of feeding an iron-fortified FUF with added synbiotic (Formula B) for 25 days on Iron status (soluble transferrin receptor [sTfR]) | Change in iron status biomarkers (sTfR) from baseline until last study visit (day 40) | At baseline and last study visit (day 40) |
| Effects of feeding an iron-fortified FUF with added synbiotic (Formula B) for 25 days on inflammation status ((C-reactive protein [CRP]) | Change in CRP from baseline until last study visit (day 40) | At baseline and last study visit (day 40) |
| Effects of feeding an iron-fortified FUF with added synbiotic (Formula B) for 25 days on inflammation status (alpha-1-acid glycoprotein [AGP])) | Change in AGP from baseline until last study visit (day 40) | At baseline and last study visit (day 40) |
| Effects of feeding an iron-fortified FUF with added synbiotic (Formula B) for 25 days on gastrointestinal (GI) tolerance | Change in GI tolerance based on caregiver-reported stool frequency (number of stools per day), consistency (on a scale from watery, runny, mushy soft, formed soft, hard, and difficult-to-pass stools (yes/no) from baseline until last study visit (day 40) | At baseline and last study visit (day 40) |
| Effects of feeding an iron-fortified FUF with added synbiotic (Formula B) for 25 days on gut comfort | Change in gut comfort based on Gut Comfort Questionnaire to assess overall GI burden and individual GI symptoms/GI-related behaviours from baseline until last study visit (day 40) | At baseline and last study visit (day 40) |
| Effects of feeding an iron-fortified FUF with added synbiotic (Formula B) for 25 days on health-related quality of life | Change in health-related quality of life, assessed by validated Infant and Toddler Quality of Life questionnaire from baseline until last study visit (day 40) | At baseline and last study visit (day 40) |
| Effect of feeding an iron-fortified FUF with added synbiotic (Formula B) for 25 days on gut microbiota composition and diversity | Change in gut microbiota composition and diversity between baseline and last study visit (day 40) | At baseline and last study visit (day 40) |
| Effect of feeding an iron-fortified FUF with added synbiotic (Formula B) for 25 days on fecal pH | Change in fecal pH between baseline and last study visit (day 40) | At baseline and last study visit (day 40) |
| Effect of feeding an iron-fortified FUF with added synbiotic (Formula B) for 25 days on gut inflammation | Change in gut inflammation marker (calprotectin) between baseline and last study visit (day 40) | At baseline and last study visit (day 40) |
| Effect of feeding an iron-fortified FUF with added synbiotic (Formula B) for 25 days on gut integrity | Change in gut integrity marker (serum intestinal fatty acid binding protein [I-FABP]) between baseline and last study visit (day 40) | At baseline and last study visit (day 40) |
| ID | Term |
|---|---|
| D058616 | Synbiotics |
| D006279 | Health Maintenance Organizations |
| ID | Term |
|---|---|
| D056692 | Prebiotics |
| D019587 | Dietary Supplements |
| D005502 | Food |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
| D019936 | Probiotics |
| D019602 | Food and Beverages |
| D008329 | Managed Care Programs |
| D007348 | Insurance, Health |
| D007341 | Insurance |
| D005381 | Financing, Organized |
| D004467 | Economics |
| D004472 | Health Care Economics and Organizations |
| D017061 | Prepaid Health Plans |
| D006123 | Group Practice |
| D011364 | Professional Practice |
| D009934 | Organization and Administration |
| D006298 | Health Services Administration |
| D003695 | Delivery of Health Care |
| D010346 | Patient Care Management |
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