What question did this study set out to answer?

This protocol aims to review the effectiveness of oral macro- and micronutrients on post-natal growth in very low birth weight infants.

February 20, 2026Open Access

Effect of nutrient supplementation on somatic growth in very low birth weight infants: a protocol for a systematic review and network meta-analysis

Key Points

This protocol aims to review the effectiveness of oral macro- and micronutrients on post-natal growth in very low birth weight infants.
Conduct a systematic review and network meta-analysis of trials and studies from 2010 to 2024.
Search for randomized controlled trials and observational studies focused on nutrient supplementation in infants.
Assess full-text publications independently for eligibility using set criteria.
Utilize PRISMA for the selection process and GRADE for evidence certainty evaluation.
Employ a frequentist approach with random-effect models for data analysis.
The network meta-analysis will rank nutrient supplementation interventions based on effectiveness.
Comparative effectiveness of different supplementation will be reported in summary tables.
Findings will address gaps in neonatal nutrition practices regarding nutrient supplementation.

Abstract

Abstract Aim No consensus exists on the ideal nutrition for preterm infants. This leads to significant practice variation. Fortification of expressed breast milk (EBM) and nutrient supplementation of the preterm infant’s diet have become common practices to enhance growth. This systematic review aims to review the comparative effectiveness of oral macro- and micronutrient supplements in enhancing post-natal growth for preterm infants. Additionally, to identify critical gaps in the current recommendations for nutrient supplements. Methods We will conduct a systematic review and network meta-analysis (NMA). Websites and databases will be searched for randomised controlled trials and prospective observational studies investigating oral macro and micro-nutrient supplementation to improve in-hospital somatic growth for premature very low birth weight infants (VLBWIs, < 1500 g). Two review authors will assess full-text English publications between 2010–2024 for potentially relevant studies for inclusion, independently and in duplicate, utilising an eligibility form based on the inclusion criteria. The selection process will be demonstrated graphically utilising a PRISMA flow diagram. Details and characteristics of excluded studies will be provided. A network meta-analysis (NMA) will be done using a frequentist approach and multivariate meta‐analysis. Random-effect models will be employed to estimate all relative treatment effects. Stata will be used for data analysis. All possible comparisons, containing the effect size and 95% CIs, will be reported in tabular form. If the assumptions that preserve the validity of the NMA are not met, a pairwise meta-analysis will be done. If the criteria for pair-wise meta-analysis are not met, only direct comparisons will be made, and a narrative description of the findings will be presented employing the synthesis without meta-analysis guidelines. The GRADE approach will be used to review the certainty of the evidence. For each comparison, the overall certainty of evidence for the primary outcomes will be evaluated. Estimates of the direct and/or indirect evidence of the NMA will be provided. Results The NMA will generate comparative rankings of nutrient supplementation interventions and evaluate their effectiveness in improving in-hospital growth. Results will be presented as summary tables and SUCRA rankings. Conclusion This NMA will provide evidence-based guidance on optimal nutrient supplementation strategies to enhance postnatal growth in VLBWIs, addressing a critical knowledge gap in neonatal nutrition practices. Systematic review registration This protocol has been registered with PROSPERO. Registration number: CRD420250650341.

Mark Helpful

Bookmark

Relay

View Full Paper