||Consideration of the goals for nutritional management of low birth weight preterm infants includes not only meeting the recommended intake of nutrients, but also ensuring that growth, neurodevelopment, and long-term health outcomes are optimized. Achieving these goals requires an understanding of the intrauterine growth rate to be targeted and of the nutrient requirements of extremely premature infants. The tension between the goals of optimizing growth outcomes with the prevention of necrotizing enterocolitis (NEC) or treatment of morbidities such as bronchopulmonary dysplasia (BPD) can be a difficult balance. |
The association between growth, nutrition, and neurodevelopmental outcomes in premature infants has been well described, primarily through observational studies. Provision of maternal milk is associated with decreased in-hospital morbidity in premature infants, including lower rates of NEC, late-onset sepsis, BPD, and severe retinopathy of prematurity1,2 as well as with improved neurodevelopment at 18 and 30 months corrected age.3,4 Despite these tremendous benefits of human milk, observational studies have also shown that premature infants fed human milk have lower growth rates than infants fed term or preterm infant formula. Human milk – whether maternal or donor – provides insufficient quantities of protein, sodium, phosphorus, calcium and other nutrients to meet the estimated needs of the preterm infant.
Standardized feeding guidelines for preterm infants improve growth outcomes, decrease duration of parenteral nutrition, and decrease time to reach full enteral nutrition. As the research by Gephart and colleagues (reviewed in this issue) notes, feeding protocols also reduce the incidence of NEC. An intriguing finding is the fact that the use of any standardized feeding protocol – regardless of the specific details such as the rate of feeding advancement – is better than having no protocol at all. Not surprisingly, there have been no randomized controlled trials of different feeding protocols or regimens.
Every NICU should develop efforts to not only encourage but also actively support mothers in their efforts to initiate and maintain a supply of human milk. The composition of preterm milk is inherently different than term milk. As highlighted by Groh-Wargo, the composition of human milk is highly variable, and the nutrient content cannot be assumed to be identical in all mothers. Although the use of donor human milk is a reasonable alternative if mother's milk is not available, donor human milk is typically pooled from women who not only delivered at term but also who are many months into lactation. The lower protein and energy content of donor human milk must be considered in the development of fortification strategies to optimize growth.
While human milk is the indisputably optimal source of nutrition for premature infants, it is clear that fortification is needed to meet recommended macronutrient intake and improve growth outcomes. The growing number of studies evaluating the composition of pooled donor milk challenges the common assumption that all human milk contains 20 kcal/oz. In addition, these analyses demonstrating much lower than anticipated concentrations of protein in pooled donor milk should prompt a change in the mindset of how we use commercial human milk fortifiers (HMF). For example, the manufacturers of commercial HMF assume a static protein content of 1.4–1.6 g/dL in human milk and do not account for the natural decrease in protein over time with lactation. Clearly these assumptions for the macronutrient content of human milk do not apply when donor human milk is used, and our recipes and strategies for fortification must be updated if reasonable growth outcomes are to be achieved. Delays in fortification of human milk further compound the issue of suboptimal protein and energy intake with unfortified donor milk.
Improved growth outcomes were recently found in a large cohort of VLBW infants who were managed with a strategy to optimize early nutritional support according to recent recommendations.5 Based on these findings, recommendations to begin fortification of human milk before enteral intake reaches 100 mL/kg/day have been made. In the standardized feeding protocol synthesized by Gephart et al, fortification of human milk is delayed until the infant is tolerating 100 mL/kg/day. With advancement in enteral volume of 10-20 mL/kg/day, fortification may not take place until the infant is 10-14 days of age. In the prospective observational study conducted by Hair et al that evaluated an exclusive human milk diet, fortification was introduced when the infant was receiving 60 mL/kg/day of enteral nutrition. On the other hand, the approach used by Colaizy and colleagues in Iowa occurs much sooner (at 25 mL/d) and minimizes protein and energy deficits that can easily accrue with a delay in human milk fortification. The pilot study conducted by Tillman et al demonstrates the feasibility of fortification at the time of the very first enteral feed. Further studies are needed to determine the optimal strategy for fortification of human milk. Indeed, a fortifier that can deliver more protein and energy without diluting the volume of human milk is ideal.
Lapillonne et al provide an excellent summary of the role that long-chain polyunsaturated fatty acids (LCPUFA) play in normal growth, neurodevelopment, and health. The mean level of docosahexanoic acid (DHA) in donor human milk is significantly less than in maternal milk or preterm infant formula (and the content is highly variable from different milk banks).6 In addition, nonnutritive components of human milk such as bile salt-stimulated lipase (which improves the bioavailability of LCPUFAs) are inactivated by pasteurization, raising other considerations for differences in nutritional properties between donor and maternal human milk.
Studies such as those conducted by Rochow et al have shown that it is possible to individualize fortification to meet the nutritional needs of premature infants. However, this process is labor-intensive, and near- and midinfrared milk analyzers have not yet been approved by the FDA for clinical use.
Nutritional strategies to optimize outcomes in premature infants include human milk, careful monitoring of growth (weight, length, and head circumference), a combined strategy of early parenteral and enteral nutrition to ensure adequate protein and energy delivery to minimize deficits, and standardized feeding guidelines. Given the inherent differences in the composition of donor and preterm human milk, further studies are needed to identify fortification strategies that account for variations in the composition of maternal and donor human milk to achieve the best growth outcomes possible for premature infants while minimizing the risk of morbidities such as NEC.
1. Heller CD, O'Shea M, Yao Q, et al; NICHD Neonatal Research Network. Human milk intake and retinopathy of prematurity in extremely low birth weight infants. Pediatrics. 2007;120(1):1-9.
2. Meinzen-Derr J, Poindexter B, Wrage L, Morrow AL, Stoll B, Donovan EF. Role of human milk in extremely low birth weight infants' risk of necrotizing enterocolitis or death. J Perinatol. 2009; 29(1):57-62.
3. Vohr BR, Poindexter BB, Dusick AM, et al; National Institute of Child Health and Human Development National Research Network. Persistent beneficial effects of breast milk ingested in the neonatal intensive care unit on outcomes of extremely low birth weight infants at 30 months of age. Pediatrics. 2007; 120(4):e953-e959.
4. Vohr BR, Poindexter BB, Dusick AM, et al; NICHD Neonatal Research Network. Beneficial effects of breast milk in the neonatal intensive care unit on the developmental outcome of extremely low birth weight infants at 18 months of age. Pediatrics. 2006;118(1):e115-e123.
5. Christensen RD, Gordon PV, Besner GE. Can we cut the incidence of necrotizing enterocolitis in half--today? Fetal Pediatr Pathol. 2010;29(4): 185-98.
6. Senterre T,Rigo J. Optimizing early nutritional support based on recent recommendations in VLBW infants and postnatal growth restriction. J Pediatr Gastroenterol Nutr. 2011;53(5):536-542.