Summary:
Vitamin D plays an important role in bone development, calcium regulation, and immune function. Preterm infants are at high risk of deficiency because they miss the transfer of vitamin D from the mother that normally occurs in late pregnancy. This deficiency can contribute to metabolic bone disease and has also been linked to respiratory complications. Despite this, there is no clear agreement on how much vitamin D preterm infants should receive, with guidelines varying widely, leading to inconsistent clinical practice. This study is a prospective cohort study that investigated vitamin D levels in very preterm infants and how these levels change over time with routine supplementation. Infants born before 32 weeks gestation or with low birth weight were included and grouped based on their total vitamin D intake in the first four weeks of life. Blood vitamin D levels were measured at birth, 4 weeks, and 8 weeks, alongside other clinical markers. The results showed that nearly all infants were deficient at birth. By 4 weeks, deficiency rates were lower in those receiving moderate or higher supplementation, although small numbers of infants in both groups had excessively high levels. By 8 weeks, most infants across all intake groups had reached normal vitamin D levels. However, higher supplementation was associated with a greater proportion of infants developing excessive levels, while clinical markers remained largely stable and only one infant developed metabolic bone disease. Overall, the findings indicate that vitamin D deficiency is very common in preterm infants at birth, but standard supplementation can correct this over time. Lower daily doses appeared sufficient to achieve normal levels while reducing the risk of excessive vitamin D, whereas higher doses did not show clear additional benefit and increased the likelihood of elevated levels.
Abstract:
Background: Very preterm infants are at high risk of vitamin D deficiency (VDD), which contributes to metabolic bone disease (MBD) and other morbidities. Despite guidelines, optimal dosing remains uncertain. We determined VDD incidence and evaluated 25-hydroxyvitamin D [25(OH)D] responses to varying vitamin D intakes during the first 8 weeks of life. Methods: This prospective cohort enrolled infants born at <32 weeks’ gestation or birth weight <1500 g. Vitamin D supplementation followed institutional policy. Infants were categorized by total intake (parenteral plus enteral) during weeks 0–4: <400, 400–700, or >700 IU/kg/day. Serum 25(OH)D was measured at birth, 4, and 8 weeks. Biochemical markers and MBD screening were performed. VDD was defined as 25(OH)D < 20 ng/mL and excess (VDE) as >100 ng/mL. Results: Among 126 infants (gestational age 30 [27, 31] weeks; birth weight 1230 [950, 1570] g), 94.3% had VDD at birth. At 4 weeks, VDD persisted in 17.8% receiving <400 IU/kg/day and 6.5% receiving 400–700 IU/kg/day; vitamin D excess (VDE) occurred in 3.3% and 3.2%, respectively. At 8 weeks, normal 25(OH)D was achieved in 90.1% receiving <400 IU/kg/day and 77.4% receiving 400–700 IU/kg/day, while VDE increased to 8.6% and 22.6%, respectively. Biochemical markers remained normal; only one infant developed MBD. Conclusions: VDD is highly prevalent at birth in very preterm infants. Daily intake <400 IU/kg generally normalizes vitamin D status by 8 weeks while minimizing risk of excessive vitamin D. Higher doses may provide no additional benefit and increase risk of exceeding 25(OH)D levels.
Article Publication Date: 14/04/2026
DOI: 10.1038/s41430-026-01746-x
