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Recommendations Summary

VLBW: Protein Amount (2020)

Click here to see the explanation of recommendation ratings (Strong, Fair, Weak, Consensus, Insufficient Evidence) and labels (Imperative or Conditional). To see more detail on the evidence from which the following recommendations were drawn, use the hyperlinks in the Supporting Evidence Section below.

  • Recommendation(s)

    VLBW: Protein Amount

    Healthcare practitioners should provide 3.5g to 4.0g of protein per kg bodyweight via enteral nutrition to very low birthweight (less than or equal to 1, 500g) preterm infants. Protein intake at 3.5g to 4.0g per kg bodyweight supports superior growth and protein accretion compared to protein intake of less than 3.5g per kg bodyweight.

    Rating: Fair

    • Risks/Harms of Implementing This Recommendation

      No undesirable effects of the higher protein intake were provided in included studies. Evidence was not located to support or discourage protein intakes greater than 4g per kg per day in infants with birthweights less than or equal to 1, 500g.

    • Conditions of Application

      Providing adequate protein intake is feasible in most clinical situations. One barrier is the lack of information about the specific composition of human milk. Most clinicians do not have access to real-time, specific analysis of the human milk fed to patients. This results in the use of estimated, rather than actual, intake values.

    • Potential Costs Associated with Application

      The cost of providing adequate nutrition, including adequate protein intake, is relatively small compared to the overall cost of caring for very low birthweight (VLBW) infants. One potential cost that could be considerable, is the purchase of human milk analysis equipment. Multi-component human milk fortifiers are a common method to provide additional protein to human milk-fed VLBW preterm infants. 

      Implementation Considerations

      • Consider the protein composition of donor milk if provided by the vendor and of mothers’ own milk if an FDA-approved human milk analyzer is available. If protein composition cannot be obtained, use published average values for breastmilk composition (Gidrewicz DA, Fenton TR; Nakano, etal,  2017).
      • Encourage the development of a feeding protocol that is accepted and used by key stakeholders in the NICU and that specifies when a protein modular is indicated, how it is started and advanced and when it is stopped.
      • Evaluate commercially available protein modulars and consider stocking one or more to add to fortified human milk and/or infant formula.
      • Provide a suitable area and staff education for safe handling and preparation of enteral feedings (Pediatric Nutrition, Steele, Collins et al 2018).

    • Recommendation Narrative

      Very low birthweight (VLBW) preterm infants have the highest per kilogram protein requirements of any humans. Health practitioners are concerned that VLBW preterm infants are not growing well and one reason can be inadequate nutrition, especially protein. Human milk is the preferred feeding for nearly all newborns but it requires fortification to meet the nutritional needs of VLBW infants. Specifically, for VLBW infants, human milk is known to provide inadequate amounts of protein. However, human milk is one of the few evidence-informed strategies associated with decreased necrotizing enterocolitis in preterm infants. Providing adequate protein intake to VLBW preterm infants could help reduce health inequities because VLBW infants are disproportionately born to families of low socio-economic status.  

      Two separate systematic reviews were conducted on protein intake: Protein amount with isocaloric comparison groups; and protein-energy, in which comparison groups varied in both protein and energy. There was heterogeneity among studies in regard to amount of protein provided to formula-fed and human milk-fed VLBW preterm infants. There is moderate certainty about the positive impact of adequate protein intake (3.5g to 4g per kg per day compared with lower protein intakes) on weight gain; there is less certainty about the effect of adequate protein intake on length, head circumference, mid-arm circumference gain, necrotizing enterocolitis, gastrointestinal health, or bone mineral content. One small RCT found some improvement in behavior development with protein intakes within the range of 3.5g to 4g per kg per day, compared with less. No studies were identified that evaluated mortality, and no undesirable effects were found with higher protein intake (4.7g per kg per day) within included studies.  

      No studies were identified that evaluated less than instead of greater than 4g per kg per day of isocaloric protein intake by VLBW preterm infants.  Studies were identified that evaluated less than vs greater 4g per k per day of protein intake by VLBW preterm infants with concurrent changes in energy intakes, however, with both protein and energy varied, it was not possible to attribute noted difference in growth or other outcomes to the differences in protein intake. 

    • Recommendation Strength Rationale

      Protein Amount

      • Moderate certainty evidence (grade II):  Weight
      • Low certainty evidence (grade III):  Development, lenght, head circumference, skinfold thickness, mid-arm circumference, bone mineral content


      • Moderate certainty evidence (grade II):  Weight 
      • Low certainty evidence (grade III):  NEC, anemia, length, head circumference, skinfold measurement, fat mass, gastrointestinal health.

    • Minority Opinions

      Consensus reached.