Iron Supplementation and Intestinal Health

University of South Florida

Status and phase: Enrolling; Phase 4

Conditions: Very Low Birth Weight Infant; Anemia of Prematurity

Treatments: Drug: 6 mg/kg/day Iron Sulfate; Drug: 2mg/kg/day Iron Sulfate

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04497012

Pro00041470

Details and patient eligibility

About

This is a randomized double-blinded study of enteral iron supplementation in Very Low Birth Weight infants. The subjects will be randomized into low dose (2 mg/kg/day) and high dose (6 mg/kg/day) of daily iron supplementation. The primary outcomes are intestinal health including microbiome, inflammation, and barrier function.

Full description

Infants and mothers will be recruited at a single academic level III NICU at Tampa General Hospital, Tampa, FL. Inclusion criteria infants: <1500 g at birth, expected to live beyond 2 weeks, not yet started on oral iron supplementation (OIS), and parental consent. Exclusion criteria infants: congenital intestinal defects, history of intestinal infection or perforation before OIS. Infants who require epogen for religious reason to prevent them from getting blood transfusions will be excluded from the study.

Intervention: Participants will be randomized to either 6 mg/kg/day or 2 mg/kg/day total of elemental iron once a day when they are consuming 150-160 ml/kg/day of enteral feeds and are at least 14 days old. The total iron doses will be provided by fortification of feeds and liquid iron sulfate and will be weight adjusted once a week. The participants will receive the study OIS doses until 36 week corrected gestational age or discharge, whichever comes first.

Sample collection and testing:

1. Stool and urine collection: We will collect weekly stool and urine samples non-invasively starting at enrollment until study completion. Samples will be collected from soiled diapers.
2. Blood tests: We will collect C-reactive protein (CRP) and ferritin level at 4 weeks after birth at the same time as other routine labs (complete blood count, reticulocyte count, and liver function test).
3. Monaural auditory brainstem response (ABR): for each ear will be performed at 36 weeks corrected gestational age or at discharge under the supervision of an audiologist who is blinded to the infants assigned iron doses and test results (stool microbiome, blood and urine tests).

Monitoring: iron supplementation dose will be increased by 2 mg/kg/day if ferritin level <100 mg/dL and the dose will be held if ferritin level >400 mg/dL. Ferritin level will be rechecked every 2 weeks until normalized. Hematocrit and reticulocyte count will be monitored by the medical team.

Enrollment: 183 estimated patients

Sex: All

Ages: 1 day to 6 months old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• <1500 g at birth, expected to live beyond 2 weeks, not yet started on oral iron supplementation (OIS), with mother at least 18 years of age, and parental consent.

Exclusion criteria

• congenital intestinal defects, history of intestinal infection or perforation before OIS. Infants who require epogen for religious reason to prevent them from getting blood transfusions will be excluded from the study.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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183 participants in 2 patient groups

Low Iron Sulfate Supplementation

Active Comparator group

Description:

Participants will be given 2 mg/kg/day total of elemental iron once a day when they are consuming 150-160 ml/kg/day of enteral feeds and are at least 14 days old. The total iron doses will be provided by fortification of feeds and liquid iron sulfate and will be weight adjusted once a week. The participants will receive the study iron dose until 36 week corrected gestational age or discharge, whichever comes first.

Treatment:

Drug: 2mg/kg/day Iron Sulfate

High Iron Sulfate Supplementation

Active Comparator group

Description:

Participants will be given 6 mg/kg/day total of elemental iron once a day when they are consuming 150-160 ml/kg/day of enteral feeds and are at least 14 days old. The total iron doses will be provided by fortification of feeds and liquid iron sulfate and will be weight adjusted once a week. The participants will receive the study iron dose until 36 week corrected gestational age or discharge, whichever comes first.

Treatment:

Drug: 6 mg/kg/day Iron Sulfate