Safety Aspects of a Randomized Clinical Trial of Maternal and Infant Vitamin D Supplementation by Feeding Type Through 7 Months Postpartum.

Background: The safety of higher dose vitamin D (vitD) supplementation in women who change from exclusive or full breastfeeding to combination feeding or who continue supplementation after cessation of breastfeeding is unknown. Objective: Compare vitD supplementation safety of 6,400 to 400 IU/day and 2,400 IU/day using specific laboratory parameters in postpartum women and their infants through 7 months postpartum by feeding type. Design: In this randomized controlled trial, mothers (exclusively breastfeeding or formula-feeding) were randomized at 4-6 weeks' postpartum to 400, 2,400, or 6,400 IU vitD3 (cholecalciferol)/day for 6 months. Breastfeeding infants in 400 IU group received oral 400 IU vitD3/day; infants in 2,400 and 6,400 IU groups received placebo. Maternal safety parameters (serum vitD, 25-hydroxy-vitamin D [25(OH)D; calcidiol], calcium, phosphorus, intact PTH; urinary calcium/creatinine ratios; and feeding type/changes) were measured monthly; infant parameters were measured at months 1, 4, and 7. Sufficiency was defined as 25(OH)D >50 nmol/L. Feeding type was defined as exclusive/full, combination, or formula-feeding. Data were analyzed using SAS 9.4. Results: Four hundred nineteen mother-infant pairs were randomized into the three treatment groups and followed: 346 breastfeeding and 73 formula-feeding pairs. A dose of 6400 IU/day safely and significantly increased maternal vitD and 25(OH)D from baseline in all mothers regardless of feeding type (p < 0.0001) and was superior to the 400 and 2,400 IU groups in achieving vitD sufficiency with no other differences in safety parameters by treatment or feeding type. Infants in the 2,400 IU group were more likely vitD-deficient than the other groups; otherwise, there were no infant safety parameter differences. Conclusions: While 6,400 IU/day was more effective than 400 or 2,400 IU/day in achieving maternal vitD sufficiency in all feeding groups, the groups did not differ on other safety parameters. Similarly, infant safety parameters did not differ by treatment group or feeding status. Clinical Trial Registration: FDA IND Number: 66,346; ClinicalTrials.gov Number: NCT00412074.