Early Iron Exposure on the Gut Microbiota in Young Infants (IF)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Infant Development
• Intervention / Treatment: Other: Iron in infant formula

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Minghua Tang, PhD; Phone Number: 7653377572; Email: minghua.tang@ucdenver.edu
• Study Contact Backup: Name: Julie Long, MS; Phone Number: 303-724-9377; Email: julie.long@ucdenver.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Anschutz Medical Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 4 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy new born infants

Exclusion Criteria:

• Newborn infants with conditions that prohibit cow-milk based formula consumption

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard iron arm; 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; 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.
Experimental: Low iron arm; 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; 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.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2021
• Primary Completion (Anticipated): May 1, 2023
• Study Completion (Anticipated): May 1, 2023

Study Registration Dates

• First Submitted: January 30, 2019
• First Submitted That Met QC Criteria: January 31, 2019
• First Posted (Actual): February 4, 2019

Study Record Updates

• Last Update Posted (Actual): October 7, 2021
• Last Update Submitted That Met QC Criteria: September 29, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: 18-1317

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: the gut microbiome sequencing data will be shared

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No