Enteral Calcium or Phosphorus Supplementation in Preterm or Low Birth Weight Infants: a Systematic Review and Meta-analysis

Objectives: To assess effects of calcium or phosphorous supplementation compared with no supplementation in human milk-fed preterm or low birth weight infants.

Methods: Data sources include Cochrane Central Register of Controlled Trials, Medline and Embase. We included Randomized controlled trials (RCTs) and non-randomized trials (quasi-randomized).

Results: Three studies (4 reports; 162 infants) were included. At latest follow-up (38 weeks), there was reduction in osteopenia (3 studies, 159 participants, relative risk 0.68, 95% confidence interval [CI] 0.46-0.99). At latest follow-up (6 weeks), there was no effect on weight (1 study, 40 participants, mean difference [MD] 138.50 g, 95% CI -82.16 to 359.16); length (1 study, 40 participants, MD 0.77 cm, 95% CI -0.93 to 2.47); and head circumference (1 study, 40 participants, MD 0.33 cm, 95% CI -0.30 to 0.96). At latest follow-up, there was no effect on alkaline phosphatase (55 weeks) (2 studies, 122 participants, MD -126.11 IU/L, 95% CI -298.5 to 46.27, I2 = 73.4%); serum calcium (6 weeks) (1 study, 40 participants, MD 0.54 mg/dL, 95% CI -0.19 to 1.27); and serum phosphorus (6 weeks) (1 study, 40 participants, MD 0.07 mg/dL, 95% CI -0.22 to 0.36). The certainty of evidence ranged from very low to low. No studies reported on mortality and neurodevelopment outcomes.

Conclusions: The evidence is insufficient to determine whether enteral supplementation with calcium or phosphorus for preterm or low birth weight infants who are fed mother's own milk or donor human milk is associated with benefit or harm.