Vitamin D for Premature Infants

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Baylor College of Medicine

Must not be taking: Diuretics

Disqualifiers: Bronchopulmonary dysplasia, Major congenital anomalies, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 18 weeks

39 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if participants must stop taking their current medications, but it does require that infants are no longer receiving mechanical ventilation or diuretics. If your infant is on these treatments, they may need to stop before joining the trial.

What data supports the effectiveness of the drug Vitamin D for premature infants?

Research shows that vitamin D supplementation in premature infants can increase their vitamin D levels to within the normal adult range, which is important for bone health. Studies also indicate that higher doses of vitamin D2 can lead to better mineral levels in the blood, which are crucial for healthy development. ^{1 2 3 4 5}

Is vitamin D safe for premature infants?

Vitamin D is generally safe for premature infants when given in appropriate doses, but high doses can lead to toxicity, causing high calcium levels in the blood. Monitoring vitamin D levels is important to avoid overdose, as excessive amounts can lead to serious health problems. ^{6 7 8 9 10}

How does vitamin D differ from other treatments for premature infants?

Vitamin D is unique for premature infants because it helps with calcium absorption and bone health, which is crucial for preventing rickets (a bone disorder) in these infants. Unlike other treatments, vitamin D can be given in different forms like drops or through maternal supplementation, and its dosage can vary to meet the specific needs of premature infants. ^{2 5 7 11 12}

What is the purpose of this trial?

Transitional formulas (22 kcal/oz) are recommended for infants less than 35 weeks gestation at birth. However, few data are available related to follow-up of infants receiving these formulas who were 28-34 weeks gestation at birth. Primary hypothesis: Provision of supplemental vitamin D to a transitional formula will lead to higher serum 25-hydroxyvitamin D (25-OHD) levels and no infant with a serum 25-OHD less than 20 ng/mL when assessed at approximately 52 weeks post-menstrual age (PMA).

Research Team

Amy h, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for preterm infants born between 28 and 34 weeks gestation, weighing 1000-2250g, who are now 34 to almost 39 weeks post-menstrual age. They should be transitioning to formula feeding and not on mechanical ventilation or diuretics. Infants with severe lung disease requiring daily diuretics, major birth defects, serious intestinal issues, or needing high-calorie formulas can't join.

Inclusion Criteria

I was born prematurely, between 28 and 34 weeks, weighing 1000-2250g.

I am not on a ventilator or taking water pills, but I may use a low flow nasal cannula.

I am between 34 and 38 weeks pregnant.

Exclusion Criteria

I have major birth defects, severe NEC (a serious gut condition) or can't tolerate feeding well.

I am pregnant with twins, not with triplets or more.

My baby needs daily diuretics and special formula due to BPD after 38 weeks PMA.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Infants receive vitamin D or placebo drops added to transitional formula daily from PMA 34-38 weeks until hospital discharge and at home until 52 weeks PMA

Approximately 18 weeks

Follow-up

Participants are monitored for serum 25-hydroxyvitamin D levels and bone status at 52 weeks PMA

4 weeks

Treatment Details

Interventions

• Placebo
• Vitamin D

Trial Overview The study tests if adding vitamin D to a transitional formula improves vitamin D levels in preterm infants without causing levels to drop below a certain threshold when checked around their first birthday after expected delivery (52 weeks PMA). Half will receive the supplement; the other half will get a placebo.

Participant Groups

Group I: Investigational Nutrition Experimental Treatment 1 Intervention

Starting between post menstrual age (PMA) 34 0/7 to 38 6/7 weeks, infants in the Investigational Nutrition group will receive vitamin D drops that are added to transitional formula daily through hospital discharge and at home until the outpatient follow-up visit at 52 weeks PMA.

Group II: Routine Nutrition Placebo Group 1 Intervention

Starting between post menstrual age (PMA) 34 0/7 to 38 6/7 weeks, infants in the Routine Nutrition group will receive placebo drops that are added to transitional formula daily through hospital discharge and at home until the outpatient follow-up visit at 52 weeks PMA.

Vitamin D is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Vitamin D for:

• Rickets
• Osteomalacia
• Osteoporosis
• Hypocalcemia
• Hyperparathyroidism
• Malabsorption states
• Cirrhosis
• Obesity

Approved in European Union as Vitamin D for:

• Rickets
• Osteomalacia
• Osteoporosis
• Hypocalcemia
• Hyperparathyroidism
• Malabsorption states
• Cirrhosis
• Obesity

Approved in Canada as Vitamin D for:

• Rickets
• Osteomalacia
• Osteoporosis
• Hypocalcemia
• Hyperparathyroidism
• Malabsorption states
• Cirrhosis
• Obesity

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Mead Johnson Nutrition

Industry Sponsor

Trials

80

Recruited

15,900+

The Children's Nutrition Research Center

Collaborator

Trials

2

Recruited

150+

Findings from Research

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 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]

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 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 60 healthy neonates, a single oral dose of 2.5 mg of cholecalciferol every 3 months effectively maintained adequate vitamin D levels without causing toxicity, making it a safe option for high-risk infants.

Higher doses of 15 mg led to prolonged vitamin D overload in 50% of infants, indicating that lower doses are preferable to avoid potential side effects while still preventing vitamin D deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D prophylaxis during infancy: comparison of the long-term effects of three intermittent doses (15, 5, or 2.5 mg) on 25-hydroxyvitamin D concentrations. Zeghoud, F., Ben-Mekhbi, H., Djeghri, N., et al.[2018]

Vitamin D is essential for calcium absorption and bone health in infants, with a recommended daily intake of 400 IU for both preterm and full-term infants to prevent conditions like rickets, although rickets in premature infants is primarily due to calcium and phosphorus deficiency rather than vitamin D deficiency.

There is no strong evidence supporting routine testing of vitamin D levels or the need for high serum vitamin D levels in healthy infants, and while vitamin D toxicity is rare, care should be taken to avoid excessive doses from supplements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D in Preterm and Full-Term Infants. Abrams, SA.[2021]

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]

References

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

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

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

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

3. 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]

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

Absorption, dosage, and effect on mineral homeostasis of 25-hydroxycholecalciferol in premature infants: comparison with 400 and 800 IU vitamin D2 supplementation. [2019]

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

Vitamin D prophylaxis during infancy: comparison of the long-term effects of three intermittent doses (15, 5, or 2.5 mg) on 25-hydroxyvitamin D concentrations. [2018]

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

Vitamin D in Preterm and Full-Term Infants. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

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

9. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Toxicology of Vitamin D in Pediatrics: A Review and Case Reports. [2023]

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

Vitamin D supplementation and risk of toxicity in pediatrics: a review of current literature. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

[The requirements of vitamin D (cholecalciferol) and of 25-hydrocalciferol (25HCC) in premature children during their early life (author's transl)]. [2013]

12. England pubmed.ncbi.nlm.nih.gov

Vitamin D metabolism in the premature newborn: A randomized trial. [2018]