, et al
Effect of high-dose vs standard-dose vitamin D supplementation in pregnancy on bone mineralization in offspring until age 6 years: a prespecified secondary analysis of a double-blinded, randomized clinical trial
JAMA Pediatr.
; doi:

Investigators from the University of Copenhagen and Naestved Hospital, Denmark, conducted a double-blind randomized controlled trial to assess the effect of high- versus standard-dose vitamin D supplementation during pregnancy on anthropometrics and bone mineralization in children through age 6 years. Pregnant women at 24 weeks’ gestation and living in Zealand, Denmark, were eligible to participate. Participants were randomized 1:1 to receive a daily dose of 2,400 IU of cholecalciferol (vitD3) or matching placebo capsules from 24 weeks’ gestation until 1 week postpartum. All participants were encouraged to continue their daily intake of 400 IU of vitD3, so the study compared participants taking 2,800 IU (high dose) versus 400 IU of vitD3 (standard dose). Participant 25(OH)D levels were obtained prior to beginning study vitD3 supplementation and classified as insufficient (<30 ng/mL) or sufficient (≥30 ng/mL).

The primary outcomes were anthropometric and bone mineralization assessments in offspring through age 6 years. Anthropometric assessments included birth weight, birth length, and size for gestational age as obtained from the Danish Medical Birth Registry, as well as length, height, and BMI obtained via study visits at 1 week, 1 month, 3 months, 6 months, twice yearly until age 3 years, and yearly until age 6 years. Bone mineralization was assessed using dual-energy radiography absorptiometry (DXA) scans at ages 3 and 6 years. DXA scans provided data on whole-body and head bone mineral content (BMC) and bone mineral density (BMD). Investigators assessed the effect of allocation arm on longitudinal anthropometrics using a mixed-effects model and on bone mineralization using multivariable linear regression accounting for child anthropometrics and stratified by maternal pre-supplementation 25(OH)D levels and season of birth (May-November [summer] vs November-May [winter]).

There were 623 participants randomized and 584 children included in analysis (297 in the high-dose group and 287 in the standard-dose group). There was no difference between groups in birth anthropometrics or longitudinal anthropometrics through age 6 years. However, children born to participants in the high-dose (vs standard-dose) group had significantly higher whole-body BMC at ages 3 and 6 years and higher whole-body BMD as well as head BMD and BMC at age 6 years. These effects were most pronounced in children born to mothers with insufficient pre-supplementation 25(OH) D levels and among children born during the winter.

The authors conclude that high-dose (vs standard-dose) vitD3 supplementation in pregnancy improves bone mineralization in children by age 6 years.

Dr Fechner has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.

The American College of Obstetrics and Gynecology recommends screening only pregnant women at increased risk for vitamin D deficiency. If vitamin...

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