Effect of Infant Formula With Bovine Lactoferrin and Low Iron Concentration on Infant Health and Immune Function

Study Overview
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Brief Summary
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Breast milk is the gold standard of early infant nutrition and breastfed infants have advantages in several short and long term outcomes compared to those formula-fed. The first aim of this study is to evaluate the effect of adding bovine lactoferrin to infant formula. The general hypothesis is that bovine lactoferrin reduces some of the previously observed differences between formula-fed and breast-fed infants with regard to health and development. The main outcome studied is the effect on immune function. The second aim is to study the effects of lower iron concentration in infant formula and to test the hypothesis that iron can be lowered without negative effects on health and development. The main outcome studied here is iron status. Other outcomes in this trial are microbiota composition, metabolomics, growth, body composition and cognitive development. To test the lactoferrin hypothesis, formula-fed infants will be recruited and fed a low iron (2 mg/L) control formula, or the same formula supplemented with bovine lactoferrin. To test the iron hypothesis, a third group will be fed the same formula (no lactoferrin) with higher iron concentration (8 mg/L). Group allocation for all formula-fed infants will be double-blind randomized. Additionally, breast-fed infants will be recruited and used as a reference group (gold standard).

Official Title
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Effect of Infant Formula With Bovine Lactoferrin and Low Iron Concentration on Infant Health and Immune Function

Conditions
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Health of Formula-fed Children, Infant Infections in Formula-fed Children, Iron Status of Formula-fed Children

Intervention / Treatment
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* Dietary Supplement: Formula with low iron concentration (2 mg/L) supplemented with bovine lactoferrin
* Dietary Supplement: Formula with low iron concentration (2mg/L) without lactoferrin
* Dietary Supplement: Formula with normal iron concentration (8 mg/L) without lactoferrin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Formula-fed healthy infants at 6 +/- 2 weeks of age with: birth weight 2500-4500 g gestational age at birth ≥ 37 completed weeks no chronic disease or neonatal diagnoses believed to affect any outcome no given blood transfusions or iron supplements Exclusion Criteria: -

Ages Eligible for Study
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Minimum Age: 4 Weeks
Maximum Age: 8 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Low iron, with lactoferrin<br>Low iron, with lactoferrin | Dietary Supplement: Formula with low iron concentration (2 mg/L) supplemented with bovine lactoferrin<br> <br> |
| Active Comparator: Low iron, no lactoferrin<br>Low iron, no lactoferrin | Dietary Supplement: Formula with low iron concentration (2mg/L) without lactoferrin<br> <br> |
| Placebo Comparator: Normal iron, no lactoferrin<br>Normal iron, no lactoferrin | Dietary Supplement: Formula with normal iron concentration (8 mg/L) without lactoferrin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of infections | Morbidity journal, Health questionnaire | Up to 12 months of age | 
| Cytokine levels | IL-2, TNF-alpha | At 6 months of age | 
| Iron status | s-ferritin, s-transferrin, s-iron, s-transferrin receptor concentration, reticulocyte Hb | At 6 months of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dietary intake | Dietary journal | At baseline, 3, 4, 5, 6 and 12 months of age | 
| Growth | Anthropometric data, Body Composition (PeaPod) | At baseline, 4, 6, 12 months of age and 6 years of age | 
| Bloodpressure |  | At baseline, 4, 6, 12 months of age and 6 years of age | 
| Antibody response to vaccines | s-levels of specific antibodies to vaccines (DTP, Hib, PC) | At baseline, 4, 6 and 12 months of age | 
| Gut microbiota | Stool samples | At baseline, 4, 6, 12 months of age and 6 years of age | 
| Saliva proteins | Saliva total protein content, lactoferrin, saliva-peroxidase, IgA and amylase | At 4 months of age | 
| Inflammatory markers | s-hsCRP, s-calprotectin | At baseline, 4, 6 and 12 months of age and 6 years age | 
| Cognitive development and behavior | Bayley III, Wechsler Intelligence Scale for Children (WISC), Behavioral questionnaire | At 1 and 6 years of age | 
| s-hepcidin |  | At baseline, 4, 6, 12 months of age and 6 years of age | 
| Metabolomics | Analyzed in urine and serum samples | At baseline, 4, 6, 12 months of age and 6 years of age | 
| Amino acids | p-amino acids | At 4 and 6 months of age | 
| Blood urea nitrogen | p-urea nitrogen | At 4 and 6 months of age | 
| Cytokine levels | IL-2 and TNF alpha at baseline, 4 and 12 months of age and 6 years of age. Six additional cytokines at baseline, 4, 6 and 12 months of age and 6 years of age. | At baseline, 4, 6, 12 months of age and 6 years of age | 
| Iron status | s-ferritin, s-transferrin, s-iron, s-transferrin saturation, s-transferrin receptor concentration, retuiculocyte Hb | At baseline, 4 and 12 months of age and 6 years of age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lactoferrin, Infant formula, Iron