Effect of Enteral Protein Amount on Growth and Health Outcomes in Very-Low-Birth-Weight Preterm Infants: Phase II of the Pre-B Project and an Evidence Analysis Center Systematic Review

Published:December 22, 2020DOI:


      Adequate protein intake by very-low-birth-weight preterm infants (≤1,500 g at birth) is essential to optimize growth and development. The estimated needs for this population are the highest of all humans, however, the recommended intake has varied greatly over the past several years. A literature search was conducted in PubMed, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Cochrane Central databases to identify randomized controlled trials evaluating the effect of prescribed protein intake and identified outcomes. Articles were screened by 2 reviewers, risk of bias was assessed, data were synthesized quantitatively and narratively, and each outcome was separately graded for certainty of evidence. The literature search retrieved 25,384 articles and 2 trials were included in final analysis. No trials were identified that evaluated effect of protein amount on morbidities or mortality. Moderate certainty evidence found a significant difference in weight gain when protein intake of greater than 3.5 g/kg/day from preterm infant formula was compared with lower intakes. Low-certainty evidence found no evidence of effect of protein intake of 2.6 vs 3.1 vs 3.8 g/kg/day on length, head circumference, skinfold measurements, or mid-arm circumference. Low-certainty evidence found some improvement in development measures when higher protein intake of 3.8 vs 3.1 vs 2.6 g/kg/day were compared. Low-certainty evidence found no significant difference in bone mineral content when these protein intakes were compared. No studies were identified that compared protein intake greater than 4.0 g/kg/day. This systematic review found that protein intake between 3.5 and 4.0 g/kg/day promotes weight gain and improved development.
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      T. R. Fenton is a professor, Community Health Sciences, Institute of Public Health, Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada, and Professor, Canada Nutrition Services, Alberta Health Services, Calgary, Alberta, Canada.


      S. Groh-Wargo is a senior nutritionist and professor, Departments of Nutrition and Pediatrics, Case Western Reserve University at MetroHealth Medical Center, Cleveland, OH.


      K. Gura is a manager, Clinical Research Program, Department of Pharmacy, Boston Children’s Hospital, Boston, MA.


      C. R. Martin is an associate professor of pediatrics, Harvard Medical School, Boston, MA, associate director, Neonatal Intensive Care Unit, Department of Neonatology, and director for cross-disciplinary research partnerships, Division of Translational Research, Beth Israel Deaconess Medical Center, Boston, MA


      S. N. Taylor is director of clinical research, Division of Neonatology, and associate professor, Department of Pediatrics, Yale School of Medicine, New Haven, CT.


      I. J. Griffin is director, Clinical and Translational Research, Biomedical Research Institute of New Jersey, Cedar Knolls, NJ, and Neonatologist, Department of Pediatrics, Morristown Medical Center, Morristown, NJ.


      M. Rozga is a nutrition researcher, Academy of Nutrition and Dietetics, Evidence Analysis Center, Chicago, IL.


      L. Moloney is a nutrition researcher, Academy of Nutrition and Dietetics, Evidence Analysis Center, Chicago, IL.