The Benefit in Terms of Improvement in Haemoglobin Level at 6 Months in Premature Babies Receiving Alternate Iron Substitution 4 Times a Week Compared to a Daily Substitution (BienFER)

BienFer is a double-blinded randomized controlled trial about iron substitution and abdominal pain. Premature babies and low birth weight babies have lower iron stores than term newborns and are therefore at greater risk of iron deficiency and anemia. Iron deficiency could have consequences for cerebral development. Ferric substitution reduces the risk of iron deficiency and anemia. It is common to replace premature babies with iron substitution between 2 weeks and 6 months of life. In practice, the medical staff notice that newborn with iron substitution have abdominal pain and constipation. A study in the adult population shows that alternate iron supplementation versus daily supplementation improved iron absorption, with no difference in hemoglobin level and decrease abdominal pain. Studies in children shows that intermittent iron supplementation do not change hemoglobin and ferritin level and improve adherence. There is no data comparing daily versus alternate supplementation in premature babies.

The aim of the study is to evaluate if alternate (4 times/week) iron supplementation is equivalent to daily iron substitution for hemoglobin values in premature babies between 28 0/7 weeks amenorrhea (WA) and 34 6/7 WA, and if it reduces abdominal discomfort and inflammation, and if it improves compliance.

Study Overview

• Status: Recruiting
• Conditions: Premature Birth
• Intervention / Treatment: Drug: Iron Supplement

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Céline Ferraz; Phone Number: +41 79 553 84 54; Email: celine.ferraz@hcuge.ch
• Study Contact Backup: Name: Riccardo E Pfister, MD, PHD; Phone Number: +41 79 553 44 38; Email: riccardo.pfister@hug.ch

Study Locations

• Switzerland
  • GE
    • Geneva, GE, Switzerland, 1211
      • Recruiting
      • HUG
      • Contact: Riccardo E Pfister, PhD; Phone Number: +41795534438; Email: riccardo.pfister@hug.ch
      • Contact: Flavia Ferraro, MD; Phone Number: +41795536919; Email: flavia.ferraro@hug.ch
      • Sub-Investigator: Flavia Ferraro, MD
  • VD
    • Lausanne, VD, Switzerland, 1011
      • Recruiting
      • CHUV
      • Contact: Flavia Ferraro, MD; Phone Number: +41795536919; Email: flavia.ferraro@hug.ch
      • Contact: Anita Truttmann, MD; Phone Number: +41795561012; Email: anita.truttmann@chuv.ch
      • Sub-Investigator: Anita Truttmann, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Premature babies between 28 0/7WA and 34 6/7 WA
• Parental consent, postnatal
• Age of 2 weeks

Exclusion Criteria:

• anemia < 80g/l at 2 weeks of age
• Intraventricular Hemorrhage stage III and IV
• Necrotizing Enterocolitis
• Enteral feeding less than 100ml/kg/j after 2 weeks of life
• Congenital disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Alternate (4 times/week) iron supplementation; This arm will receive 2-3mg/kg/d of maltofer 4 times a day	Drug: Iron Supplement; The interventional group will receive 2-3mg/kg/day of iron supplementation 4 times per week and the sham comparator will receive 2-3mg/kg/day of iron supplementation 7 times per week
Sham Comparator: Daily iron substitution; This arm will receive 2-3mg/kg/d of maltofer 7 times per week.	Drug: Iron Supplement; The interventional group will receive 2-3mg/kg/day of iron supplementation 4 times per week and the sham comparator will receive 2-3mg/kg/day of iron supplementation 7 times per week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anemia at 6 months	Hemoglobin level	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anemia	Hemoglobin	at 2weeks, 1 month, 2-3 months
Anemia	Hematocrit level	at 2weeks, 1 month, 2-3 months
Ferritin	Ferritin	at 2 weeks, 1 month, 2-3 months and 6 months
Ret-Hb level	Ret-Hb level	at 2 weeks, 1 month, 2-3 months and 6 months
Transfusion	Number of patients needed a transfusion	at 1 month, 2-3 months and 6 months
Therapeutic level	Number of patients needed to increase the iron substitution to a therapeutic level	at 1 month, 2-3 months and 6 months
Evaluation of abdominal inflammation	Calprotectin level	at 2 weeks and 2-3 months
Evaluation of abdominal inflammation	Hepcidin level	at 2 weeks and 2-3 months
Evaluation of intestinal microbiota	Fecal sequencing	at 2-3 months
Comorbidities	Number of retinopathy of prematurity (ROP)	at 6 months
Comorbidities	Number of periventricular leukomalacia (PVL)	at 6 months
Comorbidities	Number of sepsis	at 6 months
Comorbidities	Number of intraventricular hemorrhage (IVH)	at 6 months
Comorbidities	Number of bronchopulmonary dysplasia (BPD)	at 6 months
Comorbidities	Number of necrotizing enterocolitis (NEC)	at 6 months
Evaluation of weight gain	Tracking weight in Kilograms	at 2 weeks, 1 month, 2-3 months and 6 months
Evaluation of height gain	Tracking height in Centimeters	at 2 weeks, 1 month, 2-3 months and 6 months
Evaluation of the growth's parameter	Tracking head circumference in Centimeters	at 2 weeks, 1 month, 2-3 months and 6 months
Evaluation of abdominal discomfort	Edin scale (0 (better outcome, no pain)-15 (worse outcome, pain))	3 times per week during hospitalization then 1 time per 2 weeks until 6 months
Evaluation of abdominal discomfort	Classify stools with Bristol scale (1 (severe constipation) -7 (severe diarrhea))	3 times per day during hospitalization then 1 time per 2 weeks until 6 months

Collaborators and Investigators

• Sponsor: Riccardo Pfister

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2024
• Primary Completion (Estimated): September 16, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: September 14, 2024
• First Submitted That Met QC Criteria: October 2, 2024
• First Posted (Actual): October 3, 2024

Study Record Updates

• Last Update Posted (Actual): May 25, 2025
• Last Update Submitted That Met QC Criteria: May 23, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Premature Birth
• Other Study ID Numbers: 2021-02374

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No