Bio-equivalency Study of the Effects of Vitamin D2 and Vitamin D3 Supplements on 25-hydroxyvitamin D Levels in Exclusively Breast Fed Canadian Infants

Vitamin D is important to develop strong bones and teeth as well as to prevent rickets, a childhood bone disease in which the bones get very soft and bend. the investigators know that vitamin D can be produced by cells in our skin during sunny months of the year but there is a concern about the safety of sun exposure in infants. As well breast milk contains very little vitamin D. It is for this reason that Health Canada recommends all breast fed babies should receive 400 IU of vitamin D per day. There are two different types of vitamin D - vitamin D3 (animal source) and vitamin D2 (plant source). Standard infant preparations in Canada tend to be in the vitamin D3 form. To date, there is insufficient information to judge the equivalency of 400 IU of vitamin D2 and D3 given daily in very young Canadian infants. In view of over 1 million Canadian families practicing vegetarianism, this would appear to be an important and not yet answered question. The investigators cannot extrapolate from the adult data because the infant physiology is immature relative to adults and absorption, especially of fat soluble vitamins differs. This area needs to be better evaluated to emphasize the optimal isoform of vitamin D during infancy necessary for the development of adequate bone mass.

This study aims to compare the relative ability of equal daily intakes of vitamin D2 and D3, amounts (400 IU/d) currently recommended by Health Canada, to support circulating 25(OH)D concentrations after 3 months of supplementation in breastfed newborns. In particular, whether both supplements are equally effective in their ability to achieve and sustain optimal plasma 25(OH)D concentrations, defined as 25(OH)D values between 75-225 nmol/L.

Design: Randomized clinical trial in which 48, 1 month old infants, will be randomized to either the vitamin D2 or D3 isoform at the standard of care dosage (400 IU daily) for 3 months; a sufficient time to observe a change of vitamin D status ascribed to the supplement. Infant physiology is immature and evolving and the time to stabilize 25-hydroxy vitamin D (25(OH)D) is approximately 3 weeks (half-life). Supplements will be double blinded to participants, investigators and all staff.

Recruitment: Infants will be recruited from 1 large primary care center located in the greater Montreal area. The goal is for infants to begin the study at 4 weeks of age but a range of +/- 2 weeks. Rolling recruitment over a 9 months period with a 3 month follow-up for all beginning in May 2010. This covers both the synthesizing and non synthesizing periods of vitamin D. This age group has been selected (first month of life) since vitamin D stores transferred from the mother begin to decrease owing to the 15 to 30 day half life of 25(OH)D. After this point, infants need a source of vitamin D other than breast milk or sunshine. Because the majority of Canadian infants are now breastfed for at least 3-6 months of age the first 4 months of life appear to be an important time frame to examine the relative potency of the 2 isoforms.

Frequency and duration of follow up: Infants will be followed for 3 months with 2 visits, at baseline (~1 month) and the end of the study (~4 months). Visits will include anthropometric assessment and blood collection for the assessment of 25(OH)D and parathyroid hormone (PTH) concentrations. Bottles of supplement will be weighed upon receipt and return for compliance. As well, parents will be asked to self-report compliance at each visit. In order to encourage continued supplementation during the 3 month intervention, the investigators plan to a schedule a reminder phone call at approximately 1½ months post the baseline visit. Vitamin D supplementation of infants prior to the initial visit (birth to visit 1) will be documented, but considered as systematic error. Maternal baseline information will be collected at the first visit including demographics, ethnicity, pregnancy history and sun exposure during pregnancy. This data will be used to characterize the study population. At each visit, the health status and sun exposure and sunscreen use of the infants will be assessed. A computerized narrow band reflectometer will be utilized to measure skin pigmentation on unexposed skin of the inner upper arm and forehead. Procedures will be performed using guidelines established by the European Society of Contact Dermatitis. This test estimates melanin content of the skin which influences vitamin D status.