Vitamin D supplementation for prevention of vitamin D deficiency in preterm and low birth weight infants

Vitamin D supplementation for prevention of vitamin D deficiency in preterm and low birth weight infants

Pharande P et al. Vitamin D supplementation for prevention of vitamin D deficiency in preterm and low birth weight infants. The Cochrane database of systematic reviews, 2026. PubMed 42746921 · DOI

Design

Cochrane systematic review and meta-analysis of randomised, cluster- or quasi-randomised controlled trials. Included 34 studies, 5012 infants. Fixed-effect models used for RR, RD, NNTB/NNTH, mean difference or SMD with 95% CI. Risk of bias assessed with Cochrane RoB 1; GRADE used for certainty of evidence.

Population

Preterm infants (born before 37 weeks' gestational age) and term low birth weight infants. Studies enrolling infants with rickets were excluded. Eleven studies (1514 infants) and 25 studies (1546 infants) enrolled preterm infants; one study enrolled 2079 term low birth weight infants.

Intervention

Vitamin D supplementation versus no supplementation or placebo, and higher-dose versus lower-dose vitamin D supplementation.

Dose as studied

Daily cumulative dose ≥ 200 IU. Higher dose defined as ≥ 800 IU/day, lower dose as 200 to < 800 IU/day. One term LBW infant study used weekly vitamin D3 at 35 μg from age seven days to six months.

Comparator

No supplementation, placebo, or a lower dose of vitamin D.

Duration

Outcomes assessed up to discharge/term-corrected age in preterm infants; up to six months of age in the term low birth weight infant study.

Outcomes, as reported

• Vitamin D deficiency (<30 nmol/L), preterm, supplementation vs none RR 0.20, 95% CI 0.12 to 0.35; RD -0.28, 95% CI -0.36 to -0.21; NNTB 4, 95% CI 3 to 5; 4 studies, 385 infants; moderate-certainty evidence
• Vitamin D insufficiency or deficiency (≤50 nmol/L), preterm, supplementation vs none RR 0.46, 95% CI 0.38 to 0.58; RD -0.38, 95% CI -0.47 to -0.29; NNTB 3, 95% CI 2 to 4; 4 studies, 385 infants; low-certainty evidence
• Vitamin D deficiency, term LBW infants, supplementation vs placebo at 6 months RR 0.21, 95% CI 0.13 to 0.34; RD -0.30, 95% CI -0.38 to -0.23; NNTB 3, 95% CI 3 to 4; 453 infants; moderate-certainty evidence
• Vitamin D deficiency, preterm, higher-dose (≥800 IU/day) vs lower-dose (200 to <800 IU/day) RR 0.15, 95% CI 0.07 to 0.31; RD -0.13, 95% CI -0.17 to -0.09; NNTB 8, 95% CI 6 to 13; 11 studies, 672 infants; moderate-certainty evidence
• Vitamin D excess (≥250 nmol/L), preterm, higher-dose vs lower-dose RR 5.76, 95% CI 1.09 to 30.3; RD 0.04, 95% CI 0.01 to 0.08; NNTH 25, 95% CI 13 to 100; 5 studies, 395 infants; moderate-certainty evidence
• Radiological osteopenia of prematurity, higher-dose vs lower-dose RR 0.85, 95% CI 0.48 to 1.50; 7 studies, 447 infants; low-certainty evidence
• Bone mineral content, higher-dose vs lower-dose SMD 0.13, 95% CI -0.22 to 0.49; 4 studies, 124 infants; low-certainty evidence
• Secondary hyperparathyroidism, higher-dose vs lower-dose RR 0.46, 95% CI 0.31 to 0.67; I²=31%; RD -0.17, 95% CI -0.25 to -0.09; NNTB 6, 95% CI 4 to 11; 6 studies, 409 infants; moderate-certainty evidence
• Hypercalcaemia, higher-dose vs lower-dose RR 1.10, 95% CI 0.16 to 7.45; RD 0.00, 95% CI -0.03 to 0.03; 6 studies, 418 infants; very low-certainty evidence

Limitations stated by the authors · Most included studies were at high risk of bias, lowering evidence certainty to moderate or low, and some outcomes to very low. Many subgroup analyses were underpowered due to insufficient data. Radiological osteopenia, bone mineral content, and secondary hyperparathyroidism were not reported in the no-supplementation-vs-none comparisons.

Funding · This Cochrane review had no dedicated funding.