Effect of weekly vitamin D supplements on mortality, morbidity, and growth of low birthweight term infants in India up to age 6 months: randomised controlled trial

Randomized controlled trial in singleton term infants with low birthweight enrolled within 48 hours of birth from Safdarjung Hospital in New Delhi, India, an urban low-income setting. The vitamin D arm included 1,039 infants and the placebo arm included 1,040 infants.

Infants in the active arm received 35 µg (1400 IU) of granulated vitamin D3 (cholecalciferol) orally once weekly, dissolved in a small amount of expressed breast milk. Supplementation began at 7 days of age and continued for 6 months, for a maximum of 25 doses; the comparator was placebo.

Weekly vitamin D improved vitamin D status and modestly improved growth, but it did not reduce death or severe morbidity compared with placebo. The primary outcome of hospital admission or death by 6 months was not significant: adjusted rate ratio 0.93 (0.68 to 1.27), P=0.64. Deaths were similar (20 vs 19), and severe morbidity was also not significantly different (adjusted P=0.12). At 6 months, severe vitamin D deficiency was less common in the vitamin D group (18 [8] vs 92 [39]), while adequate vitamin D status was more common (122 [57] vs 63 [27]). Adjusted anthropometric differences favored vitamin D for weight 0.12 (0.01 to 0.22), length 0.12 (0.02 to 0.21), and arm circumference 0.11 (0.01 to 0.21).

The intervention did not improve the main clinical endpoints of mortality or severe morbidity, so the clinical significance of the biological and growth benefits is limited. Follow-up was only 6 months, and the findings come from low-birthweight term infants in one urban hospital setting in India, which may limit generalizability. The growth effects were modest, and head circumference did not change significantly.