Prevention of Rickets and Vitamin D Deficiency in Infants, Children, and Adolescents

We would like to caution neonatal providers attempting to follow the Vitamin D dosing recommendations of Wagner, Greer, and the AAP Section on Breastfeeding and Committee on Nutrition.1 The potential for hyperosmolar stress on the premature gut from multiple vitamin preparations should be taken into consideration when initiating vitamin D supplementation in VLBW infants being fed breastmilk. The osmolality of Poly-Vi-Sol® is known to be approximately 11,000 mOsm/kg and that of Tri-Vi-Sol® is 7,000 mOsm/kg.2 When 1 mL of these supplements is added to a typical volume of breastmilk for a VLBW infant, the final osmolality of the milk can be significantly increased to beyond the 450 mOsm/kg safe limit set by the AAP for commercial formula.3 Ernst et al demonstrated many years ago that 1 mL of Poly-Vi-Sol® added to 30 mL of preterm formula increases the final osmolality of the feeding to 744 mOsm/kg.4 This high value will be even higher in ELBW infants receiving smaller volumes of feedings. For example, in a 1 kg infant receiving enteral breastmilk (295 mOsm/kg)2 at 18 mL per feeding every 3 hours (150 mL/kg day), 1 mL of Poly-Vi-Sol® added to the feedings would increase the calculated milk osmolality to 858 mOsm/kg.

Recently, a 720 gram birthweight, 24-week gestational age male neonate in our care experienced an acute gastrointestinal emergency consistent with modified Bell’s stage 1a necrotizing enterocolitis (NEC). Symptoms developed within 6 hours of initiating 1 mL of Poly-Vi-Sol® added to his feedings once daily. The child had a postnatal age of 21 days and was only receiving approximately half of his total fluids from gavage-fed breastmilk. In reviewing his disease history, we estimated that the osmolality of the feeding containing the Poly-Vi-Sol® was approximately 1,300 mOsm/kg. Hyperosmolar feedings was thus considered a likely contributor to his NEC.

Hyperosmolar stress has long been known to be a risk factor for NEC in premature infants.5 Among the Vitamin D preparations available in the U.S.,1 ergocalciferol drops have the highest osmolality (16,277 mOsm/kg) followed by Poly-Vi-Sol® and Tri-Vi-Sol®,3 However, the dosing volume of ergocalciferol is only 0.05 mL per 400 units. This means that the calculated osmolality after adding a dose of ergocalciferol to the same amount of breastmilk as in our case would only be 340 mOsm/kg. Ergocalciferol is thus the safest choice based on osmolality alone, but it is not without safety hazards. Wagner et al correctly identified the potential for overdosing with ergocalciferol due to its extremely small dosing volume.1 Multivitamin preparations are easier to prepare and to dose but should be avoided in VLBW babies until full feedings are achieved in order to avoid hyperosmolar GI stress. When they are initiated, we recommend that the 1 mL dose be divided twice daily. Tri-Vi-Sol® has a lower osmolality than Poly-Vi-Sol® and it may be preferred. We estimate that the minimum volume of unfortified breastmilk required to maintain an osmolality < 450 mOsm/kg after adding either 0.5 mL of Tri-Vi-Sol® or Poly-Vi-Sol® is 22 mL and 35 mL, respectively. An alternative strategy that requires further research is the possibility of circumventing the need for infant vitamin D supplementation by using high dose maternal supplementation of vitamin D (>= 2,000 IU daily) to meet the same nutritional goals by generating higher vitamin D levels in their milk.6

1. Wagner CL, Greer FR. Prevention of rickets and vitamin d deficiency in infants, children, and adolescents. Pediatrics. 2008;122(5):1142-1152. 2. Jew RK, Owen D, Kaufman D, Balmer D. Osmolality of commonly used medications and formulas in the neonatal intensive care unit. Nutr Clin Pract 1997;12(4):158-163. 3. Commentary on breast-feeding and infant formulas, including proposed standards for formulas. Pediatrics. 1976;57(2):278-285. 4. Ernst JA, Williams JM, Glick MR, Lemons JA. Osmolality of substances used in the intensive care nursery. Pediatrics. 1983;72(3):347-352. 5. Kliegman RM, Fanaroff AA. Necrotizing enterocolitis. N Engl J Med. 1984;310(17):1093-1103. 6. Taylor SN, Wagner CL, Hollis BW. Vitamin D supplementation during lactation to support infant and mother. Journal of the American College of Nutrition. 2008;27(6):690-701.

Conflict of Interest:

None declared