What should I say to parents about vitamin D supplementation from infancy to adolescence?

PART A: EVIDENCE-BASED ANSWER AND SUMMARY

The apparent re-emergence of nutritional rickets (1) and reported bone (2) and extraskeletal (3) benefits of vitamin D supplementation in adults are leading Canadian physicians to face frequent questions about vitamin D. Therefore, it is instructive to review the evidence base that guides nutritional recommendations regarding vitamin D supplementation from infancy to adolescence.

A Cochrane Collaboration review updated in 2007 (4) found evidence that 400 IU/day of vitamin D for 12 months prevented nutritional rickets in children aged three to 36 months in rural Turkey, and that 300 IU/day of vitamin D for at least the first 12 months of life (a calcium supplement was also added from five months of age) reduced the risk of rickets by 24% in China. In newborns, 400 IU/day of vitamin D₃ has been shown to maintain the serum concentration of 25-hydroxyvitamin D (25[OH]D) above the range classically associated with rickets (5). However, a systematic review (2) commissioned by the Agency for Healthcare Research and Quality found inconsistent associations between infant 25(OH)D concentrations and either rickets or measures of bone mineral mass.

There is a lack of evidence to recommend supplemental vitamin D intake in older age groups. Randomized trials (6) have shown that vitamin D₃ supplementation at doses as low as 200 IU/day increased bone mineral density in adolescent girls. In the Agency for Healthcare Research and Quality review (2), ‘fair evidence’ was found to support an association between higher 25(OH)D concentrations and bone mineral indexes in older children and adolescents. Vitamin D₃ doses equivalent to 2000 IU/day have been shown to safely raise serum 25(OH)D concentrations among adolescents (7), but such doses have not yet been conclusively linked to improved health outcomes.

Conclusions

There is adequate evidence to support the current recommendation that 400 IU/day of vitamin D₃ be provided in early childhood to prevent rickets. There is insufficient evidence to guide specific vitamin D recommendations for older children or adolescents. No prospective controlled supplementation trials have reported the effect of vitamin D supplementation during childhood on extraskeletal child health outcomes (eg, atopy or autoimmune diseases).

PART B: CLINICAL COMMENTARY

Which infants should receive vitamin D supplements and how much should they be given?

Consistent with the evidence (Part A), Health Canada (8) and the American Academy of Pediatrics (AAP) (9) advise that breastfed infants receive a daily supplement containing 400 IU of vitamin D₃. There is no low-risk group in which vitamin D supplementation is not recommended, because rickets has been reported in fair-skinned Canadian infants (10). Factors such as season of birth, maternal diet or location of residence should not deter parents from adhering to Health Canada recommendations. Caregivers should be reassured of the safety of the recommended vitamin D dose, regardless of exposure to sunlight. Preterm infants do not require a different dose of vitamin D (11,12).

The Canadian Paediatric Society (CPS) guidelines (13) suggest a total vitamin D intake of 800 IU/day for infants during the winter in northern Canada, and for individuals with “risk factors for vitamin D deficiency”; however, the benefits of doses greater than 400 IU/day have not yet been demonstrated in infants or children. Clinicians working in northern regions may wish to consider a simpler universal message (eg, “all infants need 400 IU/day every day of the year”).

At what age should infant supplementation start, and when can it stop?

Health Canada (8) recommends that supplementation “begin at birth and continue until the infant’s diet includes at least 400 IU/day of vitamin D from other dietary sources or until the breastfed infant reaches one year of age”. Waiting several weeks before initiating supplementation is not justified. New AAP guidelines (9) suggest starting infant supplementation within “the first days of life” because many infants are born with poor vitamin D stores due to maternal deficiency.

Beyond infancy, the guidelines regarding routine vitamin D supplementation are less clear. Older children are advised to meet an ‘adequate intake’ of 200 IU/day (14) via consumption of foods that naturally contain vitamin D (eg, oily fish) or are vitamin D-fortified (eg, cow’s milk and soy beverages contain approximately 90 IU to 100 IU of vitamin D per 250 mL). Vitamin D supplementation can therefore be routinely stopped when the toddler meets the adequate intake (eg, approximately two cups of milk). However, the AAP now recommends an intake of 400 IU/day for all children, an amount unlikely to be obtained in a typical diet. The implication that most children and adolescents would require a daily vitamin D supplement (or multivitamin) (9) would be a major nutritional policy shift based on weak evidence, because it is unknown whether 400 IU/day is necessary or sufficient to optimize vitamin D-related health outcomes in children (Part A). Until the benefits of specific vitamin D intake levels are established, continuation of vitamin D supplementation beyond infancy is, at present, only strongly warranted for children who do not regularly consume any vitamin D-fortified foods.

How should supplemental vitamin D be given to infants?

Caregivers can choose from among a few supplements that contain only vitamin D₃ (cholecalciferol). The most widely available products contain 400 IU of vitamin D₃ per 1 mL of an oily solution. A new product available in Canada contains 400 IU of vitamin D₃ in a single drop, which can be placed on the mother’s nipple just before the infant breast-feeds. Parents should be aware that similar-appearing supplements with higher concentrations (eg, 1000 IU/drop) are not recommended for infants. All vitamin D formulations can be mixed with breast milk or food, and be administered at any time of day. Also, vitamin D supplements can be administered as larger doses at less frequent intervals; if a dose is missed, there is no harm in adding it to the following day’s dose. There is no current rationale for routinely using supplements that contain micronutrients other than vitamin D. Calcium supplementation is rarely necessary, but clinicians should be on the lookout for toddlers with atypical diets that may be nutritionally inadequate (eg, vegan diets, milk protein allergies), particularly following weaning. These children may be at risk of rickets even if they are not severely vitamin D deficient (15).

Do formula-fed infants require vitamin D supplementation?

Commercial human breast milk substitutes (infant formulas) in Canada contain 100 IU of vitamin D₃ per 250 mL, indicating that an infant must consume at least 1 L of formula per day to receive the 400 IU/day of vitamin D. Although formula-fed infants are at low risk of rickets (10), all infants who consume formula should receive 400 IU/day of vitamin D₃ as a supplement, at least until formula consumption reaches 1 L.

Can an infant be exposed to sunshine instead of using oral vitamin D supplements?

Balancing the promotion of safe sun habits and optimizing the most natural form of obtaining vitamin D is one of the most controversial vitamin D-related issues. The CPS (13) suggests that “to take advantage of cutaneous production of vitamin D, yet minimize possibility of skin damage, infants and children should be exposed to sunlight for short periods (probably less than 15 min/day)”. This conflicts with other CPS advice (16) and the position of Health Canada (“infants under one year should be kept out of direct sunlight due to the risk of skin cancer” [8]). Evidence of the long-term harms of ultraviolet radiation should bar the clinician from recommending intentional sun exposure of an infant. Moreover, all children and adolescents should be protected from casual sun exposure by using sunscreen, which diminishes vitamin D production if properly applied to the skin. While the debate goes on, the best option is for clinicians to support both conventional safe sun and vitamin D messages, which implies reliance on oral vitamin D supplementation.

Conclusions

Our understanding of the broad role of vitamin D in health is rapidly evolving. Canadian clinicians should expect nutritional guidelines related to vitamin D supplementation to change over the coming years. In fact, Health Canada and the Institute of Medicine (United States) have recently launched a review of dietary vitamin D recommendations to be released by May 2010. In the meantime, we should remain wary of altering current practices based on preliminary research findings or speculation.