Vitamin D supplementation not associated with bone mass in infants

A higher dose of vitamin D supplementation is not associated with advantages in bone mass for infants born with 25-hydroxyvitamin D (25[OH]D) concentrations less than 50 nmol/L, according to a recent study.

Vitamin D status at birth is reflective of 25(OH)D, with concentrations of under 50 nmol/L in mothers associated with increased risk of vitamin D insufficiency in infants. The vitamin D supplied by human milk is not adequate for infant daily intake.

Public health policies in North America to suggest vitamin D supplementation be initialized in breastfed infants shortly after birth. However, it is unknown if infants born with low 25(OH)D have compromised bone mineral content (BMC), or if increased vitamin D dosage is needed for improved vitamin d stores and bone health.

To evaluate outcomes in infants with serum 25(OH)D concentrations below 50 nmol/L receiving vitamin D supplementation when aged 1 to 12 months, investigators conducted a secondary analysis of a double-blinded, parallel, randomized clinical trial from March 2016 to March 2019.

The primary outcome of the trial was lean body mass, and the secondary outcome was assessment of bone mass among the a priori. Participants included healthy term singleton infants with an appropriate weight for gestational age. Inclusion criteria included having a mother planning to breastfeed until aged at least 3 months. Recruitment occurred at birth.

A reference group consisted of infants with birth serum 25(OH)D concentrations equal to or over 50 nmol/L, while infants with birth serum 25(OH)D concentrations under 50 nmol/L were randomized into 2 trial groups. Infants in 1 trial group were given 400 IU of oral vitamin D3 supplementation daily, while those in the other trial group were given 1000 IU.

Vitamin D3 supplementation was given to infants from ages 1 to 12 months. Assessments occurred at ages 1, 3, 6, and 12 months. Whole-body (WB) and lumbar spine (LS) vertebrae L1 to L4 BMC and bone mineral density (BMD) were measured.

Blood samples were collected from infants and mothers, along with spot urine samples from the infants. An automated chemiluminescent immunoassay was used to measure serum total 25(OH)D concentrations. Assessments on maternal nutritional intake at baseline also occurred. Breastfeeding status was also analyzed during each study visit.

There were 139 infants included in the trial, 58.3% of which were male. The median gestational age at birth was 39.6 weeks. There were 49 infants receiving 1000 IU daily, 49 receiving 400 IU daily, and 41 in the reference group.

No differences in WB and LS vertebrae L1 to L4 BMC and BMD were observed between groups. Bone outcomes also did not differ between groups when baseline values were included as a covariate. 

The 1000 IU group had higher serum 25(OH)D3 concentrations than the 400 IU group at ages 3, 6, and 12 months. However, the proportion of infants with sufficient vitamin D status did not differ from baseline in both trial groups. This showed an absence of effects from vitamin D supplementation on bone mass in infants born with 25(OH)D concentrations under 50 nmol/L.

Reference

Gharibeh N, Razaghi M, Vanstone CA, et al. Effect of vitamin D supplementation on bone mass in infants with 25-hydroxyvitamin D concentrations less than 50 nmol/L: aprespecified secondary analysis of a randomized clinical trial. JAMA Pediatr. 2023. doi:10.1001/jamapediatrics.2022.5837