Folic Acid Supplementation to Reduce Anemia in Extremely Preterm Infants (FASCINATE)

Folic Acid Supplementation to Reduce the Severity of Anemia and Blood Transfusions in Extremely Preterm Infants

Anemia of Prematurity (AOP) is very common in extremely preterm infants and often leads to blood transfusions. Folic acid, essential for growth and DNA synthesis, is deficient in premature infants. Despite the adoption of folic acid supplementation, evidence supporting its effectiveness in preventing AOP remains scarce. Recommendations for folic acid intake exceed what's naturally found in breast milk, particularly for extremely low birthweight infants. Practices regarding folic acid supplementation vary widely, prompting the need for research. The FACINATE trial aims to determine if additional folic acid supplementation improves hemoglobin levels and reduces late blood transfusions in extremely preterm infants, a question not addressed in current literature.

Study Overview

• Status: Not yet recruiting
• Conditions: Extreme Prematurity; Anemia of Prematurity
• Intervention / Treatment: Dietary supplement: Folic acid

Detailed Description

Anemia of prematurity (AOP) affects nearly all extremely preterm or extremely low birthweight (ELBW; birthweight <1000 g) infants. AOP's development involves various factors such as exacerbation of newborn physiological anemia, reduced response to erythropoietin after birth, frequent blood sampling, short lifespan of red blood cells, and rapid blood volume increase during growth.

To manage this anemia, most infants receive packed red blood cell transfusions, often based on specific hemoglobin thresholds. Despite efforts to minimize transfusion needs in ELBW infants, over 80% still require transfusions during their initial hospital stay. However, these transfusions come with potential adverse effects like infections, immune imbalances, lung and gut injuries, bronchopulmonary dysplasia, and retinopathy of prematurity.

Folic acid is crucial for fetal and postnatal development, playing a central role in DNA synthesis and supporting cell division. Its deficiency can hinder DNA synthesis, cause erythroblast apoptosis, and lead to anemia due to ineffective erythropoiesis. Preterm infants often lack sufficient folic acid, even more so in unfortified breast milk, which contains lower levels than recommended for adequate intake.

Supplementing folic acid for preterm infants began in the early 1990s based on limited studies on low-birth-weight (LBW) infants, primarily formula-fed and weighing >1000 grams. Despite its widespread use, there's insufficient robust evidence specifying the ideal dosage or confirming its effectiveness in preventing AOP or improving hemoglobin levels.

Unfortified breast milk's folic acid content falls short of recommended levels, especially for ELBW infants due to limited hepatic stores and rapid growth. Fortified breast milk or preterm formulas provide varying amounts of folic acid but might still be insufficient, especially for infants on restricted fluid intake due to lung injury.

The FACINATE trial aims to investigate whether additional supplementation of 50 mcg/day of folic acid improves hemoglobin levels and reduces late (>14 days of age) blood transfusions in extremely preterm infants, a specific question not yet explored in existing literature.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Belal Alshaikh, MD, MSc; Phone Number: (403) 956 1588; Email: belal.alshaikh@ahs.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N2T9
      • Foothills Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Infants born at <29 weeks of gestational age admitted to Foothill Medical Centre.
• Postnatal age 14 days.
• On minimum enteral feeding of 100 mL/kg/day

Exclusion Criteria:

• Infants with major congenital or chromosomal anomalies
• Infants with ongoing pulmonary or gastroenterology hemorrhage by 14 days of life.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; Oral folic acid 50 mcg daily starts at 14 days of age	Dietary supplement: Folic acid; Infants allocated to the intervention group will receive folic acid (50 mcg flat dose/day) starting at 14 days of age.
No Intervention: Control; No additional folic acid supplementation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin level	The difference in hemoglobin levels between the two groups	At 34-36 weeks corrected gestational age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Red blood cell transfusion	Number of required red blood cell transfusions	After 14 days of age and until 36 weeks corrected gestational age

Collaborators and Investigators

• Sponsor: University of Calgary
• Investigators: Principal Investigator: Belal Alshaikh, MD, MSc, University of Calgary

Study record dates

Study Major Dates

• Study Start (Estimated): March 11, 2024
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2028

Study Registration Dates

• First Submitted: January 10, 2024
• First Submitted That Met QC Criteria: January 22, 2024
• First Posted (Actual): January 24, 2024

Study Record Updates

• Last Update Posted (Actual): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: folic acid deficiency; extreme preterm; anemia of prematurity; neonatal blood transfusion
• Additional Relevant MeSH Terms: Hematologic Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Premature Birth; Anemia; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Hematinics; Folic Acid
• Other Study ID Numbers: REB23-1665

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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