Higher Dose of Vitamin D Supplementation Does Not Improve Infant Bone Health

Infants given higher doses of vitamin D supplementation did not experience an improvement in overall bone health.

Bone health in infants did not improve with higher doses of vitamin D supplementation, according to study results published in the JAMA Pediatrics.

Infants born to mothers who are deficient in 25-hydroxyvitamin D (25[OH]D) are at an increased risk for vitamin D deficiency rickets. Due to the low amount of vitamin D in human milk necessary for bone mineralization, it is recommended that breastfed infants begin vitamin D supplementation shortly after birth. The researchers assessed whether or not an increased dosage of vitamin D supplementation in deficient infants would improve bone mineral density and accretion over time compared with infants who received standard of care. 

Researchers conducted a secondary analysis of a randomized double-blinded clinical trial conducted from March 2016 to March 2019 to assess bone mineralization and accretion rates over the first year of life. Infants of mothers intended to breastfeed until at least 3 months of age and who had serum 25(OH)D concentrations less than 50 nmol/L at birth were included. The researchers excluded infants of mothers with maternal comorbidities, or who were preterm, or from multiple births.

Of the 139 infants included in the study, a reference group of infants (n=41) with sufficient 25(OH)D concentrations (>50 nmol/L) was created and the researchers randomly assigned the cohort to receive either 400 IU (n=49) or 1000 IU (n=49) a day from age 1 month to 12 months. The researchers measured whole body and lumbar spine vertebrae L1 to L4 bone mineral content and bone mineral density using dual-energy x-ray absorptiometry (DEXA) at different accretion rates (ages 1 month to 3 months, 3 months to 6 months, and 6 months to 12 months).

The 1000 IU per day dosage of vitamin D supplementation did not lead to measurable improvements in bone health outcomes.

The researchers found serum 25(OH)D3 and 24,25(H)D2 concentrations in the 1000 IU group were higher at age 3 months, 6 months, and 12 months compared to the 400 IU group. The infants whole body bone mineral content, lumbar spine bone mineral content, and accretion rates of whole body and lumbar spine bone mineral content did not show any appreciable difference. Secondary markers of bone formation and resorption, which included parathyroid hormone (PTH) and urinary calcium to creatinine and phosphate to creatinine ratios, were also shown to not vary between the 2 dosage dependent groups. The increased vitamin D dosage did not significantly improve bone health.

Limitations include overrepresentation of minority groups, as 44.6% of the cohort identified as racial and ethnic minority group, and a possible underestimation of 25(OH)D concentrations.

The researchers concluded “[t]he 1000 IU per day dosage of vitamin D supplementation did not lead to measurable improvements in bone health outcomes. Evidence from this Montreal-based study suggests that the standard of care of 400 IU per day is enough to support bone health of breastfed infants born with serum 25(OH)D concentrations less than 50 nmol/L”. 

References:

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: a prespecified secondary analysis of a randomized clinical trial. JAMA Pediatrics. Published online February 13, 2023. doi:10.1001/jamapediatrics.2022.5837