VLBW: Formula Enrichment (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.
VLBW: Formula Enrichment
When human milk is not available, healthcare practitioners should provide very low birthweight (less than or equal to 1, 500g) preterm infants with preterm infant formulas that provide higher nutrient density than standard infant formula. Nutrient-dense preterm formulas appear to more closely match the nutritional needs of very low birthweight preterm infants and long clinical experience with preterm formulas suggests that they support good growth, and both functional, and biochemical measures of nutritional adequacy.
Risks/Harms of Implementing This Recommendation
No undesirable effects were found which could be due to limited evidence.
Conditions of Application
This recommendation is limited to scenarios when human milk is not available in sufficient supply. This recommendation is in reference to preterm infant formulas that generally provide 68 kcal to 100 kcal per 100 ml, protein-enriched (2.0g to 3.0g per 100 ml) (2.9 to 3.3 /100 kcal) and enriched with minerals, vitamins, electrolytes, and trace elements (Young et al, 2012).
Practitioners should work with the multidisciplinary care team to ensure that preterm infant formulas within the hospital’s formulary meet Life Sciences Research Office (LSRO) criteria for protein, calcium and phosphorus content (Klein 2002; Klen 2005).
When mother’s own milk is not available health care practitioners should provide preterm formula to very low birthweight preterm infants until hospital discharge. The multidisciplinary care team should evaluate the infant’s gestational age, growth, nutritional status and overall nutrient intake prior to recommending continuation of preterm formula post-discharge. Infants on preterm infant formula with extended stays in the hospital who approach term age or size (more than three kilograms) should have an evaluation by the multidisciplinary care team to assure that nutrient intakes are not exceeding tolerable upper levels.
Potential Costs Associated with Application
Costs of preterm formula will vary upon location and health care policies.
Formula enrichment comparisons were evaluated in the very low birthweight (VLBW) preterm infant systematic reviews process. No randomized control trials that compared standard formulas to preterm infant formulas (as defined by organizations such as the Life Science Research Organization for preterm and standard term formulas) were identifed in the VLBW preterm infant formula enrichment systematic review.
The workgroup examined and compared reliable resources for nutrient recommendations for preterm infant formulas. The 2002 Life Sciences Research Office (LSRO), 2020 American Academy of Pediatricts (AAP), Nutritonal Care of Preterm Infants (Koletzko 2014), 2010 European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) recommendations were evaluated. The nutrient recommendations for these resources were also compared to the VLBW Peterm Infant Protein Systematic Review. Calcium and phosphorus were not included in the Pre-B VLBW Preterm Infants Systematic Reviews since no studies were identified from the scoping review that met the VLBW preterm infant inclusion criteria.
Calcium and Phosphorus
- Recommended calcium content for preterm formulas had the following range:109mg to 185mg per 100 kcal.
- Recommended phosphorus content for preterm formulas had the following range: 55mg to 109mg per 100 kcal.
- VLBW Preterm Infant systematic review recommends 3.5g to 4.0g per kg per day
- The LSRO protein recommendations for preterm formula is 2.5g to 3.6g per 100 kcal which at 120kcal per kg would provide a daily intake of 3.0g to 4.3g per kg per day. However, if infants are provided with the lower end of the AAP (110kcal to 130kcal per kg per day) and ESPGHAN (110kcal to 135kcal per day) ranges for energy, LSRO’s lower end of their protein recommendation is not likely to provide sufficient protein (110 x 2.5 = 2.8g per kg per day).
- Protein recommendations for preterm infants from AAP 2020 (3.2g to 4.1g per 100kcal; 4.1g per /100kcal, at 120kcal per kg would provide up to 4.9g per kg) exceed the Pre-B Preterm Recommendations.
Based on the above assessment, preterm formulas should contain 3.2g to 3.3g of protein per 100kcal.
Recommendation Strength Rationale
Formula enrichment systematic reviews conducted by the preterm team did not identify literature that compared standard vs. preterm formulas for VLBW preterm infants. The consensus statement is based on credible resources and experience from the preterm team.
- Risks/Harms of Implementing This Recommendation
The recommendations were created from the evidence analysis on the following questions. To see detail of the evidence analysis, click the blue hyperlinks below (recommendations rated consensus will not have supporting evidence linked).
In VLBW preterm infants (less than or equal to 1,500g at birth), what is the effect of protein amount via enteral nutrition on weight?
In VLBW preterm infants (less than or equal to 1,500g at birth), what is the effect of protein amount via enteral nutrition on length, head circumference, skinfold measurements and mid-arm circumference?
In VLBW preterm infants (less than or equal to 1,500g at birth), what is the effect of protein amount via enteral nutrition on development?
In VLBW preterm infants (less than or equal to 1,500g at birth), what is the effect of protein amount via enteral nutrition on bone mineral content or density?
References not graded in Academy of Nutrition and Dietetics Evidence Analysis Process
- American Academy of Pediatrics Committee on Nutiriton. Pediatric Nutrition. Itasca, IL: American Academy of Pediatrics; 2020.
- Agostoni C, Buonocore G, Carnielli VP, et al. Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition. J Pediatr Gastroenterol Nutr. 2010;50(1):85-91.
- Klein CJ, Life Sciences Research Office. Nutrient requirements for preterm infant formulas. J Nutr. 2002;132(6 Suppl 1):1395S-1577S.
- Klein CJ, Heird WC. Summary and Comparison of Recommendation for Nutrient Contents of Low-Birth-Weight Infant Formulas. In. Bethesda, MD: Life Sciences Research Office; 2005
- Koletzko B, Poindexter B, Uauy R. Recommended nutrient intake levels for stable, fully enterally fed very low birth weight infants. World Rev Nutr Diet. 2014;110:297-299.
- Young L, Embleton ND, McGuire W. Nutrient-enriched formula versus standard formula for preterm infants following hospital discharge. Cochrane Database Syst Rev. 2016;12:CD004696.