Iron Supplementation and Intestinal Microbiome
Iron Supplementation and Intestinal Microbiome
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.
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 1-2 weeks until normalized. Hematocrit and reticulocyte count will be
 monitored by the medical team.
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.