Abstract
OBJECTIVES: To determine the response of infant (≤ 1 year) circulating 25-hydroxyvitamin D (25(OH)D) to maternal postpartum or infant intermittent vitamin D supplementation in comparison to current recommendations of direct daily oral infant supplementation (400 IU/d). METHODS: MEDLINE, MEDLINE In-Process, Embase, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched up to December 4(th) 2018. A systematic search of online trial registries for unpublished, ongoing, or planned trials was also completed. Risk of bias was assessed using the Cochrane Risk Assessment Tool. Meta-analysis was limited to trials with a control group of infants receiving 400 IU vitamin D/d. A weighted mean difference (WMD) and 95% confidence interval (CI) was generated using infant 25(OH)D as a continuous outcome. Random-effects models accounted for within- and between-study variability. Statistical heterogeneity was quantified with the I(2) statistic. RESULTS: A total of 28 trials were included, representing data from all 6 World Health Organization world regions. Of the 25 trials that specified a calciferol form, the majority (88%) employed vitamin D(3). Six trials (21%) had an overall low risk of bias. Six trials qualified for meta-analysis, stratified by maternal (n = 4) and infant (n = 2) administration. Maternal supplementation resulted in a modestly lower infant vitamin D status than daily infant supplementation (WMD =-7.3 nmol/L; 95% CI: -14.0 to -0.6; I(2 )= 37%, P = 0.17). Comparison of infant intermittent bolus dosing to daily supplementation was limited by a small sample size and substantial heterogeneity, resulting in a wide CI (WMD = 10.2 nmol/L; 95% CI: -42.9 to 63.3; I(2 )= 96%, P < 0.001). Safety outcomes, including effects on calcium homeostasis, were inconsistently reported. Four ongoing trials were identified as potential contributors to future reviews. CONCLUSIONS: Evidence to support the use of specific alternative maternal or infant regimens to substitute for current daily infant vitamin D supplementation is weak and inconsistent. Dose-ranging, adequately powered trials are required to establish the efficacy and safety of feasible alternative strategies to prevent infant vitamin D deficiency FUNDING SOURCES: SickKids C-GCH Growth and Development Fellowship.