New Standard? Vitamin D 800 IU/day for Preventing Osteopenia in Preterm Infants

Vitamin D is not only about “bones and calcium.” It helps the intestines absorb calcium and phosphorus, affects the work of osteoblasts (cells that build bone), immunity, and even muscle tone. In a full-term baby, part of the reserves comes “for future use” during pregnancy. In a premature baby, there is less time for accumulation, plus there are often difficulties with nutrition, long-term parenteral nutrition, and drug interactions. All this puts them in a high-risk group for vitamin D deficiency and osteopenia of prematurity.

What exactly did you study?

The focus is on two common supplementation regimens in very low birth weight (VLBW, <1500 g) infants:

• 400 IU/day (classic “American” starting dose),
• 800 IU/day (a dose often recommended by European protocols for risk groups).

The study was retrospective (i.e., they analyzed the data already accumulated by the department after the protocol change): one cohort had a dose of 400 IU, the next - 800 IU. Supplements began at about the 2nd week of life and continued until 36 weeks of postmenstrual age. At the time of discharge, everyone had a DEXA scan to assess mineralization (BMAD - "bone mineral density" adjusted for body size in babies).

The key advantage of such a design is the "real clinic": these are not the ideal conditions of an RCT, but the daily practice of the department. The disadvantage is that the groups could differ in some way (weight, nutrition, severity of the condition), and for this, statistics cannot correct everything.

Main result

Children receiving 800 IU/day had higher BMAD at discharge than children receiving 400 IU/day. The difference persisted even after adjusting for potential confounding factors (e.g., birth weight and duration of parenteral nutrition). The advantage of the high dose was also evident in specific skeletal areas (e.g., hip area).

Translation: Doubling the dose of vitamin D in VLBW babies was associated with “stronger” bones at discharge.

And how does this fit into the recommendations?

• A number of European guides allow 800–1000 IU/day for high-risk groups.
• In the US, 400 IU/day has been the “base” for many years.

New research suggests that for very low birth weight infants, 400 IU may not be enough if the goal is to significantly accelerate bone mineralization by the time of discharge.

Important Disclaimers

• This is not a randomized controlled trial (RCT). It is a before-and-after comparison at a single center. Yes, the authors adjusted for differences statistically, but residual bias is possible.
• Safety at higher doses is a fundamental issue. In real practice, it is necessary to monitor the level of 25(OH)D, calcium/phosphorus, alkaline phosphatase, take into account the total intake of vitamin D from formulas, breast milk fortifiers, etc.
• DEXA at discharge is a good proxy, but we are also interested in function (fractures, tone, motor development) and long-term consequences. For this, RCTs and longer observations are needed.

What does this mean for neonatal teams and families?

1. If your department often sees osteopenia in premature babies, and at 400 IU/day children consistently come out with low mineralization, it would be logical to discuss a protocol with increasing the dose to 800 IU/day with mandatory monitoring of vitamin D status and mineral metabolism.
2. It is important to calculate the total dose: drops + mixture/fortifier.
3. Individualization is everything: for the smallest and most “fragile” children, the benefits of 800 IU may outweigh the risks, but biochemical monitoring is mandatory.

Who will benefit most from this work?

• To neonatologists and nutritionists who formulate local protocols for VLBW/ELBW.
• For parents of premature babies - as a basis for discussion with a doctor about dosage and monitoring.
• For researchers - as an argument for launching randomized trials of high vs. standard dose with functional outcomes.

Frequently asked questions

Is this "proof" that everyone needs 800 IU?
No. It is a strong signal from real-world practice. But the gold standard remains the RCT with long-term follow-up.

Isn't it dangerous to take more vitamin D?
The danger is in an uncontrolled increase. With proper monitoring (25(OH)D, calcium/phosphorus, alkaline phosphatase; taking into account the total intake from food), the risk of toxicity is minimal. That is why the dose is changed at the level of department protocols, and not "a little more for everyone."

Why is DEXA important?
In preterm infants, bone is small and growing rapidly; simple radiographic signs are delayed. DEXA provides an early and quantitative view of mineralization—a useful marker of intervention effectiveness.

The study is published in the journal Frontiers in Endocrinology.