800IU versus 400IU per day of vitamin D3 in term breastfed infants: a randomized controlled trial from an LMIC.

Abstract

This open-label, block-randomized controlled trial compared the effect of 800IU/day and 400IU/day of oral vitamin D3 supplementation in reducing vitamin D insufficiency (VDI) among healthy-term breastfed infants at 14weeks of postnatal age. All eligible infants were randomized to receive either 800 or 400IU/day of oral vitamin D3 (starting within the first week until 14weeks). The primary outcome was the proportion of infants with VDI (25-OH-D < 20ng/ml) at 14weeks. Secondary outcomes were vitamin D deficiency (VDD, < 12ng/ml), severe VDD (< 5ng/ml), anthropometry, biochemical or clinical rickets, and any adverse events related to vitamin D toxicity (VDT). Among 102 enrolled infants, the distribution of baseline variables (including cord 25-OH-D levels; 13.0 versus 14.2ng/ml) was similar in both groups. On intention-to-treat analysis, the proportions of infants with VDI at 14weeks were significantly lower in the 800IU group compared to those in the 400IU group [24% versus 55%; RR 0.44; 95% CI: 0.25-0.76]. The proportions of infants with elevated parathormone (6% versus 26.5%; p = 0.012) and severe VDD (0% versus 12.2%; p = 0.033) were significantly lower in the 800IU group. Clinical rickets developed in three (6.2%) infants in the 400IU group. No infant developed VDT. Conclusions: Daily oral supplementation with 800IU of vitamin D3 resulted in an almost 50% reduction in the proportion of infants with VDI and prevented the occurrence of severe VDD at 14weeks of age compared to 400IU with no evidence of vitamin D toxicity. Trial Registration: Clinical Trial Registry of India (CTRI/2019/02/017374). What is Known: •Breastfeeding is the ideal source of nutrition for healthy-term breastfed infants; however,vitamin D content of breastmilk is suboptimal. •AAP recommends daily oral supplementation of 400 IU of vitamin D to all healthy-term breastfed infants; however, trials from high-income countries support insufficiency of this dose in maintaining serum 25-OH-D levels >20 ng/ml with no such information from low-middle-income countries. What is New: •800 IU/day of oral vitamin D3 supplementation among term breastfed infants significantly reduces vitamin D insufficiency at 14 weeks' age as compared to the recommended dose of 400 IU/day. •This higher supplemental dose is safe with no evidence of vitamin D toxicity.