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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether adding vitamin D to a special baby formula can help premature infants born between 28 to 34 weeks gestation achieve healthier vitamin D levels. The study compares two groups: one receives vitamin D drops with their formula, while the other receives placebo drops (a dummy treatment). Researchers aim to determine if the vitamin D group achieves better vitamin D levels by about one year after their original due date. This trial suits premature infants born at specific hospitals who have transitioned mostly to formula feeding and are no longer on mechanical ventilation.

As an unphased trial, this study provides a unique opportunity to contribute to important research that could improve health outcomes for premature infants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that giving vitamin D to infants, including those born early, is generally safe. Studies have found that vitamin D reduces the number of premature babies with low levels of this vitamin. Without extra vitamin D, many premature infants are born with deficiencies. Adding vitamin D significantly lowers these deficiency rates.

Some research has explored higher doses of vitamin D. These studies found that giving preterm infants 800 IU or more each day led to positive results, particularly for bone health. A review of high-dose vitamin D in young children found it to be generally safe.

Most health guidelines recommend that both preterm and full-term infants receive 400 IU of vitamin D daily to support healthy bones. This amount is considered safe and well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for premature infants focus on providing essential nutrients through standard formulas and supplements. However, this new approach uses vitamin D drops added directly to transitional formula, which might enhance bone health and immune function more effectively. Researchers are excited because vitamin D is crucial for development, and this method could offer a simple yet impactful way to support growth and health in premature infants, potentially leading to better long-term outcomes.

What evidence suggests that Vitamin D might be an effective treatment for premature infants?

Research has shown that giving vitamin D to premature babies can improve their health. For example, a high dose of vitamin D (800 IU/day or more) has been linked to better short-term growth in weight and length. Studies also indicate that more vitamin D can lower the risk of deficiency in these babies. One study suggested that higher doses of vitamin D are safe and may improve overall health outcomes for premature infants. In this trial, infants in the Investigational Nutrition group will receive vitamin D drops added to their formula, while those in the Routine Nutrition group will receive placebo drops. These findings support the idea that adding vitamin D to special formulas for premature babies could be beneficial. ^{2 6 7 8 9}

Who Is on the Research Team?

Amy h, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

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 was born between 28 and 34 weeks of pregnancy and weighed between 1000-2250g.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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 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]

Citations

1.

nature.com

nature.com/articles/s41372-025-02440-9

Short-term and long-term effects of vitamin D ...

High-dose (≥800 IU/day) vitamin D supplementation for preterm infants was associated with positive short-term outcomes, encompassing ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4925243/

A Comparison of Three Vitamin D Dosing Regimens in ...

It is plausible that higher doses of vitamin D may be well tolerated in premature infants, and in fact may improve clinical outcomes. The higher dose given ...

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S1875957224000731

Risk factors and outcomes of vitamin D deficiency in very ...

This study aimed to evaluate the prenatal and postnatal risk factors and clinical outcomes of VDD in VP infants.

4.

publications.aap.org

publications.aap.org/pediatrics/article/150/Supplement%201/e2022057092K/188647/Enteral-Vitamin-D-Supplementation-in-Preterm-or

Enteral Vitamin D Supplementation in Preterm or Low Birth ...

Our systematic review found moderate certainty evidence of increase in weight, length, and reduction in vitamin D deficiency during first 6 ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01600430?tab=table

Vitamin D Supplementation for Extremely Preterm Infants

Premature infants will be randomized to receive one of the 3 fixed doses of vitamin D: either placebo (zero dose), 200 IU/day, or 800 IU/day. The ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8537871/

Monitored Supplementation of Vitamin D in Preterm Infants

Earlier studies reported an incidence of VDD in preterm infants between 64–83% at birth which was reduced by vitamin D supplementation to 40–66% [32,33].

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9387322/

Vitamin D intakes and health outcomes in infants and ...

One RCT found participants who received 400 IU/d of vitamin D3 were at lower risk of developing asthma at 6 months, compared to those who ...

8.

jamanetwork.com

jamanetwork.com/journals/jamanetworkopen/fullarticle/2791031

Safety of High-Dose Vitamin D Supplementation Among ...

This systematic review and meta-analysis investigates the safety of high-dose vitamin D supplementation in children aged 0 to 6 years by ...

9.

karger.com

karger.com/anm/article/76/Suppl.%202/6/42589/Vitamin-D-in-Preterm-and-Full-Term-Infants

Vitamin D in Preterm and Full-Term Infants

Available research, as well as most guidelines, recommend an intake of 400 IU daily of vitamin D as adequate for bone health in preterm and full-term infants.