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

## TL;DR

This study will compare the effectiveness of different nutrient supplements in improving growth for very low birth weight preterm infants.

## Contribution

The study introduces a network meta-analysis protocol to evaluate and rank nutrient supplementation strategies for preterm infants.

## Key findings

- The study will generate comparative rankings of nutrient supplements for preterm infant growth.
- It will identify gaps in current nutrition recommendations for very low birth weight infants.
- Results will be presented using GRADE and SUCRA methods to assess evidence certainty and effectiveness.

## Abstract

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.

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.

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.

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.

This protocol has been registered with PROSPERO.

Registration number: CRD420250650341.

The online version contains supplementary material available at 10.1186/s13643-025-03027-3.