Evidence map›Paper›PMID 40473805›Full record

SynthesisPediatric research2025

Systematic review and meta-analysis of enteral protein intake effects on growth in preterm infants.

Maria Sanchez-Holgado, Mark J Johnson, Ariadna Witte Castro, Susana Criado Camargo, Chris H P van den Akker, Patricia Alvarez-García, Marta Cabrera-Lafuente, Miguel Ángel Jiménez Varas, Miguel Saenz de Pipaon

Abstract readSystematic ReviewMeta-Analysis
In one paragraph

Synthesis in Pediatric research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Trial
  2. Review
  3. Article
  4. Amino acids and lean mass accretion in preterm neonates.Current opinion in clinical nutrition and metabolic care · 2026
    Review
  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Maria Sanchez-HolgadoDepartment of Neonatology. La Paz University Hospital. Hospital La Paz Institute for Health Research-IdIPAZ, Madrid, Spain.
Mark J JohnsonFaculty of Medicine, University of Southampton, Southampton, UK. M.Johnson@soton.ac.uk.ORCID 0000-0003-1829-9912
Ariadna Witte CastroDepartment of Neonatology. La Paz University Hospital. Hospital La Paz Institute for Health Research-IdIPAZ, Madrid, Spain.
Susana Criado CamargoDepartment of Neonatology. La Paz University Hospital. Hospital La Paz Institute for Health Research-IdIPAZ, Madrid, Spain.
Chris H P van den AkkerDepartment of Pediatrics-Neonatology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Patricia Alvarez-GarcíaDepartment of Neonatology. La Paz University Hospital. Hospital La Paz Institute for Health Research-IdIPAZ, Madrid, Spain.
Marta Cabrera-LafuenteDepartment of Neonatology. La Paz University Hospital. Hospital La Paz Institute for Health Research-IdIPAZ, Madrid, Spain.
Miguel Ángel Jiménez VarasInformation specialist. La Paz University Hospital, Madrid, Spain.
Miguel Saenz de PipaonDepartment of Neonatology. La Paz University Hospital. Hospital La Paz Institute for Health Research-IdIPAZ, Madrid, Spain.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe optimal enteral protein intake for adequate growth in preterm infants remains unclear. This systematic review evaluates the impact of protein intake from fortified human milk on growth in very preterm infants.

methodsRandomized clinical trials from January 2005 to August 2024 were included. Eligible studies measured true enteral protein intake in preterm infants. Searches were conducted in PubMed, Embase, and Cochrane CENTRAL. Risk of bias was evaluated using the revised Cochrane Risk of Bias Tool.

resultsTen randomized clinical trials (n = 646) were included. Meta-regression revealed a significant linear relationship between protein intake and weight gain (5.73 g/kg/day weight gain for each gram of protein/kg/day, p = 0.001), but not with head circumference or length gain. After adjustment for energy intake, significant relationships were found between protein intake and both weight gain and length growth. In contrast, the forest plot meta-analysis comparing high versus low protein intake showed no significant differences in weight or head circumference gain. However, infants receiving higher protein intake had greater weight at discharge (SMD 0.35, 95% CI 0.12 to 0.57, n = 312, 4 studies, high certainty) and more length growth (SMD 0.5, 95% CI 0.08 to 0.92, n = 174, 3 studies, moderate certainty). DISCUSSION AND

conclusionModerate to high-certainty evidence suggests that increased enteral protein intake improves growth outcomes in very preterm infants. REGISTRATION: PROSPERO CRD42022287991. IMPACT: This systematic review is the first to evaluate the impact of enteral protein intake on growth in preterm infants <32 weeks, using studies that measured actual intake. A positive correlation was found between protein intake and weight gain. Meta-regression suggests most premature infants may require 4.0-4.5 g/kg/day to achieve in utero growth rates, rather than 3.5-4.0 g/kg/day. The meta-analysis indicates a positive relationship between protein intake, growth in length, and discharge weight. These findings underscore the critical role of adequate protein intake in growth outcomes and highlight the need to maintain appropriate energy: protein ratios.

Indexed as

Dietary ProteinsEnteral NutritionInfant, PrematureEnergy IntakeHumansInfant, NewbornInfant Nutritional Physiological PhenomenaMilk, HumanRandomized Controlled Trials as TopicWeight GainDietary Proteins

Identifiers

PMID40473805
PMCPMC12602309

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.