Comparative effectiveness of low-dose versus high-dose vitamin D on bone metabolic markers in preterm infants: a retrospective cohort study.

Background: Vitamin D (VD) supplementation is routinely used in preterm infants to support bone mineralization, but recommended doses vary across guidelines and clinical practice. In infants born at less than 32 weeks' gestation, evidence comparing commonly used regimens remains limited, particularly for early biochemical outcomes during the first postnatal month. This study aimed to compare 500 versus 900 IU/day VD supplementation for serum 25-hydroxyvitamin D [25(OH)D] and bone metabolic markers in this population. Methods: This single-center retrospective cohort study included preterm infants with a gestational age of less than 32 weeks who were discharged from the Neonatal Intensive Care Unit of the Women's Hospital, Zhejiang University School of Medicine between April 1, 2024 and May 31, 2025. Infants received either 500 IU/day (n=124) or 900 IU/day (n=115) of VD starting during postnatal days 5 to 8. Eligible infants had no prior VD supplementation and available 4-week outcome data; infants with major congenital anomalies, severe hepatic or renal dysfunction, major metabolic disorders, or protocol non-adherence were excluded. Serum 25-hydroxyvitamin D [25(OH)D] was measured by liquid chromatography-tandem mass spectrometry. Calcium, phosphorus, and alkaline phosphatase (ALP) were assessed within the first week after birth and again at 4 weeks of postnatal age. Major neonatal complications were also recorded. Results: Baseline characteristics were similar between groups, including gestational age, birth weight, parenteral nutrition duration, and first-week calcium, phosphorus, and ALP concentrations (all P>0.05). At 4 weeks of postnatal age, serum 25(OH)D concentrations were similar between the 500 IU/day and 900 IU/day groups (median (interquartile range), 31.46 (26.18-39.52) ng/mL versus 32.52 (24.94-38.57) ng/mL; P=0.771), and VD status distribution did not differ significantly. In gestational-age-stratified analysis, ALP was higher in the 900 IU/day group among infants born at 28+0 to 31+6 weeks' gestation, whereas no clear between-group difference was observed in infants born at less than 28 weeks' gestation. Calcium and phosphorus concentrations, as well as the incidences of major neonatal complications, did not differ significantly between groups. Conclusions: In preterm infants born at less than 32 weeks' gestation, 500 IU/day and 900 IU/day VD supplementation were associated with similar serum 25(OH)D concentrations and broadly comparable calcium-phosphorus biochemical findings by 4 weeks of postnatal age. The 900 IU/day regimen was associated with higher ALP in some analyses, particularly in infants born at 28+0 to 31+6 weeks' gestation. These findings are limited to the first month after birth.