Can Early Vitamin D Supplementation Help Preemies Breathe Easier?

For babies born extremely early—before 28 weeks of pregnancy—every drop of nutrition counts. Their underdeveloped lungs, fragile bones, and increased risk for complications make early life a high-stakes balancing act in neonatal intensive care units (NICUs). One nutrient that’s drawn increasing attention is vitamin D, essential for healthy bone development and potentially critical in supporting lung function too. But can a short early course of vitamin D supplementation make a difference?

Our new randomized controlled trial, just completed in 2024, set out to answer that question. We investigated whether giving a higher dose of vitamin D during the first two weeks after birth could improve respiratory outcomes and bone health in extremely preterm (EPT) infants who were fed human milk.

The trial included 126 infants born before 28 weeks of gestation. Within the first 72 hours after birth, half of the infants were randomly assigned to receive 800 IU/day of vitamin D mixed into their breast milk feedings for the first 14 days. The other half received the standard care without this added vitamin D. Importantly, the trial was “masked,” meaning that caregivers and researchers didn’t know which infants were in which group—helping ensure unbiased results.

We looked at several outcomes, including:

- The severity of bronchopulmonary dysplasia (BPD), a chronic lung disease common in preterm infants.

- Lung function at 36 weeks postmenstrual age, using impulse oscillometry to measure airway resistance and reactance (R7-19 and AX, respectively).

- Metabolic bone disease, assessed through lab markers like alkaline phosphatase and phosphorus.

What Did We Find?

First, the good news:

The intervention clearly worked to raise vitamin D levels. After two weeks, infants who received the supplement had 25-hydroxy vitamin D3 levels nearly 30 ng/mL higher than those who didn’t. And there were no serious side effects.

As for the main goal—reducing BPD severity? That’s where things get more interwined. The rate and severity of BPD were similar between groups. Likewise, lung function measures (AX and R7-19) showed no statistically significant differences.

Still, there were some interesting trends:

- Infants who got early vitamin D showed lower rates of metabolic bone disease by day 28 (9% vs 20%), although the difference didn't quite reach statistical significance (p=0.08)

- Their lower ponderal index (PI) at 36 weeks may point to better linear growth—a potential indicator of improved skeletal health (p=0.07).

Why This Clinical Trial Still Matters

Although we didn’t prove that early vitamin D improves lung outcomes, this study offers several important takeaways:

1. It’s safe. High-dose vitamin D (800 IU/day) given early, through breast milk, raised blood levels effectively without causing harm.

2. It adds depth. By using sophisticated lung function tests, we moved beyond binary outcomes (like “BPD: yes or no”) and added detail to how preemies’ lungs actually function.

3. It shows potential for bone health. The drop in metabolic bone disease and the associated growth improvements are promising, even if the results weren’t statistically definitive.

4. It’s realistic. The method of mixing vitamin D into feeds rather than giving it directly reflects how care is actually delivered in many NICUs—and could influence future protocols.

What’s Next?

This study doesn’t close the book on vitamin D in preterm infants. Instead, it raises new questions: Would a longer course or higher cumulative dose yield clearer benefits? Would infants with more severe vitamin D deficiency see greater improvements? Could better tailoring of lung function metrics—adjusted for infant size and sex—help reveal meaningful differences?

The answers will take time. But for now, this trial adds a valuable piece to the puzzle of how to best support the smallest, most vulnerable patients from day one.

Bottom Line:

Early high-dose vitamin D raised blood levels and showed potential benefits for bone health in extremely preterm infants—but didn’t significantly change respiratory outcomes by 36 weeks. Still, the findings support safe early use and open the door for more research into optimizing vitamin D in neonatal care.

Read the full-text article published in The Journal of Pediatrics here