Folic Acid Supplementation to Reduce Anemia in Extremely Preterm Infants

Extreme Prematurity Clinical Trial

— FASCINATE  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06220461
• Other study ID #: REB23-1665
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 1, 2024
• Est. completion date: July 31, 2028

Study information

• Verified date: November 2023
• Source: University of Calgary
• Contact: Belal Alshaikh, MD, MSc
• Phone: (403) 956 1588
• Email: belal.alshaikh[@]ahs.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 90
• Est. completion date: July 31, 2028
• Est. primary completion date: July 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Anemia
• Anemia of Prematurity
• Extreme Prematurity
• Premature Birth

Intervention

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.

Locations

Country	Name	City	State
Canada	Foothills Medical Centre	Calgary	Alberta

Sponsors (1)

Lead Sponsor	Collaborator
University of Calgary

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hemoglobin level	The difference in hemoglobin levels between the two groups	At 34-36 weeks corrected gestational age
Secondary	Red blood cell transfusion	Number of required red blood cell transfusions	After 14 days of age and until 36 weeks corrected gestational age