Vitamin D Supplementation for Premature Birth

Overseen By Emily K Stephens, BSN, RNC-NIC

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: The University of Texas Health Science Center, Houston

Disqualifiers: Congenital anomaly, Nonbacterial infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

180 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications.

What data supports the effectiveness of the treatment 800 IU/day vitamin D supplementation for premature birth?

Research shows that early supplementation with 800 IU of vitamin D in very low birth weight infants is effective and safe, and it helps improve vitamin D levels in preterm infants, reducing the risk of vitamin D deficiency. ^{1 2 3 4 5}

Is vitamin D supplementation safe for premature infants?

Vitamin D supplementation in premature infants can be safe if monitored properly, as excessive amounts can lead to potentially toxic levels. In one study, 23% of infants on standard treatment had to stop due to high vitamin D levels, and two infants showed signs of vitamin D toxicity. Monitoring helps maintain safe levels and prevent overdose. ^{1 2 4 6 7}

How does the drug 800 IU/day vitamin D supplementation differ from other treatments for premature birth?

The 800 IU/day vitamin D supplementation is unique because it provides a higher dose than the typical maximum of 400 IU/day used in other studies, aiming to improve vitamin D status and potentially enhance bone mineral density in preterm infants. ^{8 9 10 11 12}

What is the purpose of this trial?

This trial is testing whether giving extremely premature infants a daily dose of vitamin D can improve their lung, bone, immune system, and brain health. The study focuses on babies born very early or with very low birth weight, who are at higher risk for health issues. Vitamin D supplementation has been studied extensively in preterm and low birth weight infants, showing improvements in growth and vitamin D status but mixed results on other health outcomes.

Research Team

Maria del Mar Romero López, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Eligibility Criteria

The ViDES Trial is for newborns born at less than 28 weeks gestational age or weighing under 1000 grams. It's not for babies with major birth defects, conditions like cystic fibrosis that affect vitamin D absorption, or those deemed too sick by their neonatologist. Babies over 32 weeks GA can't join regardless of weight.

Inclusion Criteria

Informed written consent in an Institutional Review Board (IRB)-approved manner

My baby was born before 28 weeks or weighed less than 1000 grams.

My condition is congenital.

Exclusion Criteria

My baby was born after 32 weeks of pregnancy.

Any major congenital anomaly

A known congenital nonbacterial infection

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Infants receive either placebo or vitamin D supplementation at 800 IU/day for the first 28 days after birth

4 weeks

Daily administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, including respiratory support and growth metrics

2 years

Long-term follow-up

Assessment of neurodevelopment and growth metrics at 2 years

2 years

Treatment Details

Interventions

• 800 IU/day vitamin D supplementation with feedings in the first 28 days after birth
• Placebo
• Usual Care

Trial Overview This trial tests if giving extremely premature infants an extra dose of vitamin D (800 IU/day) helps improve their bone health, lung function, immune system, and brain development compared to usual care during the first month after birth.

Participant Groups

Group I: Usual care plus vitamin D supplementation Experimental Treatment 2 Interventions

Infants will receive cholecalciferol 800 IU/day in the first 28 days after birth, given enterally four times per day (0.5mL per dose = 200 IU) until the infant is provided 400 IU/day (when feedings reach about 120 -160 mL/kg/day). At that point the study cholecalciferol will be reduced to 400 IU/day for a total supplementation of 800 IU/day.

Group II: Usual care plus placebo Active Control 2 Interventions

Infants will receive placebo (normal saline) in the first 28 days after birth. Care will be unaffected and provided based on the judgment of the attending neonatal faculty and NICU policies and routine practices. When the infant receives about 120 to 160 mL/kg/day of fortified milk at 24 kcal/ounce, the infant will receive supplementation with 400 IU/day of vitamin D as usual care.

800 IU/day vitamin D supplementation with feedings in the first 28 days after birth is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Cholecalciferol for:

• Prevention and treatment of vitamin D deficiency
• Rickets
• Osteomalacia

Approved in United States as Vitamin D3 for:

• Prevention and treatment of vitamin D deficiency
• Rickets
• Osteomalacia

Approved in Canada as Cholecalciferol for:

• Prevention and treatment of vitamin D deficiency
• Rickets
• Osteomalacia

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

The Gerber Foundation

Collaborator

Trials

45

Recruited

6,200+

Findings from Research

In a study of 96 preterm infants, daily supplementation of 800 IU of vitamin D3 significantly reduced the prevalence of vitamin D deficiency compared to 400 IU, with rates of deficiency at 38.1% versus 66.7% at 40 weeks' postmenstrual age.

While the higher dose effectively lowered deficiency rates, it did not improve bone mineral content or density, and there was a small risk of vitamin D excess in one infant (2.4%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trial of daily vitamin D supplementation in preterm infants. Natarajan, CK., Sankar, MJ., Agarwal, R., et al.[2014]

In a study of 66 very low birth weight (VLBW) infants, early supplementation with 800 IU of vitamin D starting at 2 weeks of age was found to be safe and effective, achieving an 88% probability of vitamin D sufficiency by 36 weeks for those with initial levels ≥10 ng/mL.

For infants with lower initial vitamin D levels (<10 ng/mL), the supplementation still showed promise, with a 65% probability of achieving sufficiency, indicating that vitamin D intake may significantly improve vitamin D status in vulnerable populations like VLBW infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of early supplementation with 800 IU of vitamin D in very preterm infants followed by underlying levels of vitamin D at birth. Cho, SY., Park, HK., Lee, HJ.[2022]

In a study of 59 preterm infants born with a gestational age of less than 34 weeks, a single-dose intramuscular injection of 10,000 IU/kg of vitamin D3 significantly increased serum 25-hydroxyvitamin D levels by day 28 after birth compared to those receiving oral vitamin D3 drops.

The injection also resulted in a lower prevalence of vitamin D deficiency among the infants, with no reported cases of overdose or poisoning, indicating that this method is both safe and effective for improving vitamin D status in preterm infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A comparative analysis of the efficacy of two vitamin D supplementation regimens in preterm infants: a prospective randomized controlled study]. Ma, L., Geng, LM., Zhou, XH.[2020]

In a study of 25 healthy premature infants, daily supplementation of 500 IU of vitamin D2 significantly increased their plasma 25-hydroxyvitamin D levels from 30.6 nmol/l at birth to 65.3 nmol/l after 37 days, indicating effective absorption and metabolism of vitamin D2.

The increase in vitamin D levels was primarily due to the D2 fraction, while levels of vitamin D3 remained unchanged, suggesting that vitamin D2 supplementation is effective for rapidly achieving adequate vitamin D status in premature infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D nutritional status of premature infants supplemented with 500 IU vitamin D2 per day. Markestad, T., Aksnes, L., Finne, PH., et al.[2019]

In a study of 120 preterm neonates, those receiving 1000 IU of vitamin D3 daily had a significantly lower prevalence of vitamin D insufficiency (2%) compared to those receiving 400 IU (64.6%) at 40 weeks of corrected gestational age.

While some infants on the higher dose experienced elevated vitamin D levels (9.8%), there were no signs of toxicity, suggesting that 1000 IU is a safe and effective supplementation level for reducing vitamin D insufficiency in preterm infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized double-blind controlled trial comparing two regimens of vitamin D supplementation in preterm neonates. Tergestina, M., Rebekah, G., Job, V., et al.[2022]

In a study of 111 preterm babies, 12.6% were found to be vitamin D insufficient at birth, but this number rose dramatically to 52.2% at 6 weeks despite daily supplementation of 400 IU of vitamin D.

The findings suggest that the current recommended daily dose of 400 IU is insufficient to prevent vitamin D insufficiency in preterm infants, indicating a need for further research into higher supplementation doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D status and adequacy of standard supplementation in preterm neonates from South India. Tergestina, M., Jose, A., Sridhar, S., et al.[2018]

In a study of 109 preterm infants, monitored vitamin D supplementation (800-1000 IU) resulted in safer vitamin D levels compared to standard therapy, with a higher percentage of infants maintaining safe levels at 52 weeks of post-conceptional age.

Standard therapy led to a 23% discontinuation rate due to potentially toxic vitamin D levels, highlighting the importance of monitoring to prevent both deficiency and overdose in vitamin D supplementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitored Supplementation of Vitamin D in Preterm Infants: A Randomized Controlled Trial. Kołodziejczyk-Nowotarska, A., Bokiniec, R., Seliga-Siwecka, J.[2021]

A study involving 39 preterm infants showed that a lower vitamin D dose of 200 IU/kg (up to 400 IU/day) is effective in maintaining normal vitamin D levels and achieving similar bone mineral density as the higher recommended dose of 960 IU/day.

The results indicate that the lower dose is sufficient for bone health, suggesting that excessive vitamin D should be avoided in preterm infants due to potential risks, as both doses resulted in comparable bone mineral content and density.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised controlled trial of vitamin D supplementation on bone density and biochemical indices in preterm infants. Backström, MC., Mäki, R., Kuusela, AL., et al.[2019]

In a study of 301 preterm infants, about 80% had deficient or insufficient vitamin D levels at 4 weeks of age, highlighting a common issue among very low birth weight (VLBW) and extremely low birth weight (ELBW) infants.

Vitamin D supplementation significantly improved 25-hydroxy vitamin D levels in VLBW infants by 8 and 12 weeks, while ELBW infants showed slower improvement, indicating that while supplementation is effective, monitoring is essential to prevent excessively high vitamin D levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum 25 Hydroxy Vitamin D Levels in Very Low Birth Weight Infants Receiving Oral Vitamin D Supplementation. Munshi, UK., Graziano, PD., Meunier, K., et al.[2019]

In a study of 32 preterm infants receiving either 400 or 800 IU/day of vitamin D3 for 4 weeks, those on the higher dose showed a significant increase in serum 25(OH)D3 levels, indicating better vitamin D status.

Infants receiving 400 IU/day were more likely to have low bone density, suggesting that an 800 IU/day dose may be more beneficial for improving bone health and overall growth in preterm infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized trial of two doses of vitamin D3 in preterm infants Anderson-Berry, A., Thoene, M., Wagner, J., et al.[2018]

A study of 378 preterm infants in a neonatal intensive care unit showed that monitoring daily Vitamin D intake significantly improved the amount of Vitamin D these infants received.

The improvement in Vitamin D intake was observed in both extremely low birth weight infants (less than 1000 g) and very low birth weight infants (1000-1500 g), highlighting the importance of monitoring for ensuring adequate nutrient intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D Intake in Very Low Birth Weight Infants in Neonatal Intensive Care Unit. Munshi, UK., Graziano, PD., Meunier, K., et al.[2018]

In a study of 10 preterm infants, it was found that they can produce high levels of 1.25-dihydroxyvitamin D, with concentrations significantly higher than those in adults, indicating their ability to metabolize vitamin D effectively despite their premature birth.

No signs of rickets were observed in these infants, suggesting that the daily intake of about 400 I.U. of vitamin D3 through total parenteral nutrition and enteral feeding is sufficient to maintain healthy vitamin D levels during early development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma 1.25-dihydroxyvitamin D concentrations in preterm infants. Fetter, WP., Mettau, JW., Degenhart, HJ., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Trial of daily vitamin D supplementation in preterm infants. [2014]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of early supplementation with 800 IU of vitamin D in very preterm infants followed by underlying levels of vitamin D at birth. [2022]

3. China pubmed.ncbi.nlm.nih.gov

[A comparative analysis of the efficacy of two vitamin D supplementation regimens in preterm infants: a prospective randomized controlled study]. [2020]

4. Sweden pubmed.ncbi.nlm.nih.gov

Vitamin D nutritional status of premature infants supplemented with 500 IU vitamin D2 per day. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

A randomized double-blind controlled trial comparing two regimens of vitamin D supplementation in preterm neonates. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Vitamin D status and adequacy of standard supplementation in preterm neonates from South India. [2018]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Monitored Supplementation of Vitamin D in Preterm Infants: A Randomized Controlled Trial. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Randomised controlled trial of vitamin D supplementation on bone density and biochemical indices in preterm infants. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Serum 25 Hydroxy Vitamin D Levels in Very Low Birth Weight Infants Receiving Oral Vitamin D Supplementation. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Randomized trial of two doses of vitamin D3 in preterm infants [2018]

11. United States pubmed.ncbi.nlm.nih.gov

Vitamin D Intake in Very Low Birth Weight Infants in Neonatal Intensive Care Unit. [2018]

12. Sweden pubmed.ncbi.nlm.nih.gov

Plasma 1.25-dihydroxyvitamin D concentrations in preterm infants. [2019]