Early Iron Exposure on the Gut Microbiota in Young Infants

Study Overview
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Brief Summary
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This study will look at the amount of iron in infant formula and how that affects a child's gut development. The children of mothers who plan to formula feed their children will be randomized to receive either high iron or low iron formula from birth until 4 months of age. Infants will consume only the study provided formula during enrollment. Blood and stool samples will be collected at birth and end of study to measure the effects of the iron exposure. The overall object is to compare high iron versus low iron exposure in formula-fed infants during the first months of life. Aims include determining the types of bacteria that are present in the infants' fecal microbiome, determining the effect of high iron exposure on gut microbiome and sleep patterns, and comparing iron status and homeostasis between the low and high iron formula groups.

Detailed Description
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Disturbance of the gut microbial colonization during infancy may result in long-term programming impact of metabolism and disease risks of the host. The early gut microbial colonization coincides with the maturation of the infant's mucosal innate immune system and research showed that the gut microbial dysbiosis is associated with impaired innate immune development. Thus, ensuring proper microbial colonization early in life is critical to the maturation of the immune system and long-term health. Iron fortification can increase the abundance of pathogenic bacteria and induce inflammation in older infants. However, it is still not known what the effect of iron is on a more vulnerable population: the newborn infant, who has immature immune system. Infants 0-4 months are at a low risk for iron deficiency due to the iron endowment at birth, which is compatible with the very low iron content (<0.5mg Fe/L) in breastmilk. However, commercial infant formulas are all fortified with ≥12mg Fe/L. Whether this striking difference drives adverse health effects is unknown/unexamined, especially on early colonization and immune homeostasis. The overall objective is to determine the impact of high vs. low iron exposure in formula-fed infants during the early post-natal months on gut microbiome.

Official Title
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Different Iron Exposure on the Development of Gut Microbiota From Birth to Four Months

Conditions
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Infant Development

Intervention / Treatment
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* Other: Iron in infant formula


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy new born infants Exclusion Criteria: Newborn infants with conditions that prohibit cow-milk based formula consumption

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 4 Months

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized to one of the two groups with different amount of iron consumed.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard iron arm<br>Participants randomized to this arm will consume infant formula containing 12 mg/L of iron, equivalent to the standard iron content in U.S. infant formula | Other: Iron in infant formula<br>* Participants will receive the same low-iron (5 mg/L) infant formula. Infants in the standard iron group will add iron supplement to pre-made infant formula so the iron content will be 12 mg/L.<br>|
| Experimental: Low iron arm<br>Participants randomized to this arm will consume infant formula containing 5 mg/L of iron, equivalent to the standard iron content in European infant formula | Other: Iron in infant formula<br>* Participants will receive the same low-iron (5 mg/L) infant formula. Infants in the standard iron group will add iron supplement to pre-made infant formula so the iron content will be 12 mg/L.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gut microbiota | the gut microbial structure of the participants, by stool samples collected | birth to 4 months of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Iron status: soluble transferrin receptor | Soluble transferrin receptors are proteins found in blood that can be elevated with iron deficiency. | at baseline (birth) and end of intervention (4 months) | 
| Iron status: ferritin | A ferritin blood test shows how much iron is stored in your body. | at baseline (birth) and end of intervention (4 months) | 
| Iron status: hepcidin | Hepcidin is a regulator of iron metabolism. | at baseline (birth) and end of intervention (4 months) | 
| Inflammation: c-reactive protein | C-reactive protein (CRP) is a substance produced by the liver in response to inflammation. | at baseline (birth) and end of intervention (4 months) | 
| Immunity: soluble CD14 | biomarker of innate immunity | at baseline (birth) and end of intervention (4 months) | 
| Sleep patterns: duration | Participants will wear a device (Micro Motionlogger Watch version 734) to provide objective measurements of duration. | end of intervention (4 months) |