Early nutrition for the very low birthweight infant (VLBW)

1. 
   

   Nutritional strategies for VLBW infants should minimize the interruption of growth and development as the fetus transitions to extrauterine life.

   
   
2. 
   

   The initial phase of management with total parenteral nutrition (TPN) improves growth by

   
   
   
   
   1. 
      

      Reducing postnatal weight loss

      
      
   2. 
      

      Promoting earlier return to birthweight (RTBW)

      
      
   3. 
      

      Facilitating catch-up growth

   
   
3. 
   

   When TPN is used exclusively for the provision of nutrients with no enteral nutrition, morphologic and functional changes occur in the gut including

   
   
   
   
   1. 
      

      Significant decrease in intestinal mass

      
      
   2. 
      

      Decrease in mucosal enzyme activity

      
      
   3. 
      

      Increase in gut permeability

   
   
4. 
   

   The changes are due primarily to the lack of luminal nutrients.

   
   
5. 
   

   The earlier initiation of enteral feedings has direct trophic effects on the gastrointestinal tract and indirect effects secondary to release of intestinal hormones.

   
   
6. 
   

   Initiation of TPN with early enteral feedings the first days of life allows feedings to be advanced slowly, which may increase the tolerance and safety of enteral feedings.

Postnatal growth failure

1. 
   

   Many VLBW infants experience extrauterine growth restriction (EUGR).

   
   
2. 
   

   Figure 11-1 is based on data from the National Institutes of Child Health and Human Development (NICHD) Neonatal Research Network demonstrating the differences between normal intrauterine growth and the postnatal growth failure among the VLBW infants in the NICHD study.

   
   
3. 
   

   This “growth faltering” is most common among extremely low birthweight infants (ELBW) (birthweight <1000 g).

   
   
4. 
   

   Nutrient intakes received by VLBW infants during the first weeks of life in particular are much lower than what the fetus received in utero.

   
   
5. 
   

   Although nonnutritional factors (comorbidities) contribute to slower growth of these infants, suboptimal nutrient intakes are critical in explaining their poor growth outcomes.

   
   
6. 
   

   Figure 11-2 suggests that postnatal growth failure or EUGR is a “surrogate” for inadequate nutrition. The observation of postnatal growth failure suggests that inadequate nutrition has taken place and the infant is at risk for poor neurodevelopmental outcomes.

   
   
7. 
   

   Considerable evidence links inadequate nutrition and long-lasting effects including short stature and poor neurodevelopmental outcomes.

   
   
   
   
   1. 
      

      Preterm infants receiving a preterm formula containing more protein and other enrichment, versus a term formula, over the first month of life had higher neurodevelopmental indices at 18 months, 7 to 8 years, and as adolescents. The difference in protein between the two diets was thought to be the important dietary difference as well as taurine found only in breast milk and added to only preterm formula, not term formula. Taurine is neurotrophic and exerts specific neurodevelopmental effects in these infants.

      
      
   2. 
      

      ELBW infants in the NICHD cohort with the highest growth velocity by weight (21.2 g/kg/d) and head circumference (1.17 cm/wk) from RTBW to discharge 12 g/kg/d and 0.67 cm/wk, respectively, had a lower incidence of cerebral palsy, mental developmental index scores >70, and were less likely to demonstrate abnormal neurologic findings at 18 to 22 months corrected age. The lowest growth quartile (12 g/kg/d and 0.67 cm/wk), respectively, had the highest risk for morbidity; therefore, inadequate nutrition is responsible for the poor outcomes observed here.

   
   
8. 
   

   These studies emphasize the importance of closely monitoring nutritional intake and growth inhospital for VLBW infants.

   
   
9. 
   

   Because weight gain and head circumference growth are associated with better neurodevelopmental and growth outcomes at 18 to 22 months corrected age, goals of growth from BW to discharge include

   
   
   
   
   1. 
      

      Weight ≥18 g/kg/d

      
      
   2. 
      

      Head circumference ≥0.9 cm/wk

   
   
10. 
    

    If those rates are not being achieved, the infant’s diet should be reviewed and steps taken to ensure adequate nutrition support such as increasing protein intake and dietary protein-energy ratio (P/E).

Protein in enteral feeding strategies

1. 
   

   Nutrient requirements for VLBW infants should promote postnatal growth that not only approximates in utero growth rate but should also allow for catch-up to make up for the early growth faltering. The goals listed above should provide for catch-up growth.

   
   
2. 
   

   The growth limiting nutrient for VLBW infants is almost always protein.

   
   
3. 
   

   Energy seldom limits growth as long as intakes of energy reach 90 to 100 cal/kg/d.

   
   
4. 
   

   The nutritional “responsibility” for postnatal growth failure and, therefore, inadequate nutrition is about 80% inadequate protein intake and 20% inadequate energy.

   
   
5. 
   

   Recommendations for protein intake should take into account a number of factors because the requirement changes over time, these variables include

   
   
   
   
   1. 
      

      Promotion of lean body mass

      
      
   2. 
      

      Protein/energy ratio of diet

      
      
   3. 
      

      Postmenstrual age

      
      
   4. 
      

      Need for catch-up growth

   
   
6. 
   

   Protein requirement is dynamic and responsible for body composition and even future health outcomes; therefore, in these VLBW infants the following are the important principles:

   
   
   
   
   1. 
      

      Lean body mass (LBM) gain is a more suitable reference than weight gain in terms of nutritional goals.

      
      
   2. 
      

      An additional supply of protein is necessary for catch-up growth compensating for the cumulative protein deficit, which develops the first weeks of life.

      
      
   3. 
      

      An increase in the P/E is mandatory to improve LBM accretion and limit fat deposition.

      
      
   4. 
      

      Recommended dietary protein allowance needs to be adapted for postmenstrual age instead of gestational age or birthweight to integrate the dynamic aspect of growth and protein metabolism.

   
   
7. 
   

   Figure 11-3 shows the relationships to increase LBM and Table 11-1 provides revised recommendations for protein intakes and P/E for premature infants requiring catch-up growth.

   
   
8. 
   

   These recommendations and requirements come from analysis of nitrogen retention, and fat mass deposition in studies evaluating preterm infants fed human milk, human milk fortifiers, and a variety of term and preterm formulas.

Preterm formulas for VLBW infants

1. 
   

   Preterm formulas provide between 3.0 and 3.6 g/100 kcal. This is the P/E.

   
   
2. 
   

   The higher protein containing preterm formulas more closely meet both the P/E and protein requirement when fed at 120 cal/kg/d.

   
   
3. 
   

   The standard protein preterm 24 cal formulas can be fed at higher volumes to meet protein requirements. However, the energy provided with the volume reaches approximately 144 cal/kg/d.

   
   
4. 
   

   This is excessive energy when considering that the goal is to promote LBM while limiting fat deposition.

   
   
5. 
   

   To provide 4.3 g/kg/d of protein when fed at 120 cal/kg/d requires P/E of 3.6 g/100 kcal.

Human milk for VLBW infants

1. 
   

   Although breast milk is considered the ideal food for the term infant, it provides inadequate amounts of several nutrients for the VLBW infant, especially

   
   
   
   
   1. 
      

      Protein

      
      
   2. 
      

      Vitamin D

      
      
   3. 
      

      Calcium

      
      
   4. 
      

      Phosphorus

      
      
   5. 
      

      Sodium

   
   
2. 
   

   The calcium and phosphorus content is low in unsupplemented human milk regardless of large volumes in comparison with that required to achieve intrauterine accretion rates. Inadequate intakes may result in poor bone mineralization and metabolic bone disease.

   
   
3. 
   

   While large volumes of human milk (>180 mL/k/d) provide sufficient energy for VLBW infants, the protein content is still suboptimal.

   
   
4. 
   

   In the 1980s prior to the use of fortifiers, a group of ELBW infants fed unfortified human milk were less than 2 standard deviations below the mean for weight for age when they reached 2.0 kg.

   
   
5. 
   

   Therefore, ELBW infants fed unfortified human milk would be expected to take 3 weeks longer to reach a weight of 2.0 kg than infants receiving preterm formulas.

Benefits of human milk for VLBW infants.

1. 
   

   Preterm infants receiving breast milk—either their own mother’s milk or donor milk—demonstrated higher intelligence quotients at 8 years of age versus formula fed. These studies included infants receiving unfortified donor milk.

   
   
2. 
   

   A subset of these same infants at age 13 to 16 showed increase in white matter volume on MRI and sustained higher IQ scores particularly relating to verbal scores.

   
   
3. 
   

   Improved visual outcomes have been reported for human milk fed VLBW infants as well as for infants fed with formula containing higher levels of docosahexaenoic acid (DHA) and arachidonic acid (ARA). DHA and ARA are naturally found in human milk and have been added to preterm formulas and fortifiers using single cell oils.

   
   
4. 
   

   Human milk has many nonnutritional advantages. For example, human milk contains immunocompetent cellular components including secretory IgA, which has a protective effect on the intestinal mucosa.

   
   
5. 
   

   These types of immunoprotective functions and the promotion of a “healthier” colonization or microbiome of the gastrointestinal tract with lactobacillus or bifidobacteria may be part of the explanation of how human milk prevents NEC.

   
   
6. 
   

   Most of the human milk fortifiers contain bovine antigen and concerns are raised if the microbiome is affected adversely when human milk is fortified with bovine-derived products, which may alter the microbiome and lead to colonization with potential pathogenic enteric bacteria.

Human milk fortification strategies.

1. 
   

   Optimization of human milk fortification for VLBW infants remains challenging, though nutrient fortification of human milk is necessary.

   
   
2. 
   

   VLBW infants receiving fortified human milk still showed slower growth versus those fed preterm formula despite the fortification.

   
   
   
   
   1. 
      

      Inadequate protein is most likely responsible for the slow growth.

      
      
   2. 
      

      Donor human milk has even less protein than mother’s own milk.

   
   
3. 
   

   Postnatal growth failure with human milk is still adverse for neurodevelopment despite the many advantages with human milk.

   
   
4. 
   

   Human milk fortifiers have been either liquid or powder.

   
   
   
   
   1. 
      

      The Centers for Disease Control has recommended that all formulas used with high-risk infants be sterile because powder formulas that are not sterile may become contaminated and convey infections with enteric bacteria.

      
      
   2. 
      

      Liquid formulations are processed to be sterile but powder formulations are not.

      
      
   3. 
      

      There is a liquid fortifier made from human donor milk, which provides an exclusively human milk–based diet. This fortification was associated with lower rates of medical and surgical NEC versus human milk supplemented with preterm formula or a powdered fortifier.

Human milk protein and fortification.

1. 
   

   The main reason preterm infants fed fortified human milk in standard fashion grow slower than preterm formula fed infants is inadequate protein.

   
   
2. 
   

   The main reason for protein undernutrition despite fortification is that standard fortification is based on customary assumptions about the composition of preterm human milk containing protein at 1.5 g/dL. The mother’s milk for many of these infants does not provide this amount of protein and the protein decreases in quantity as lactation continues during the course of hospitalization.

   
   
3. 
   

   The protein concentration of banked donor milk most often provided by mothers of term infants is even lower at 0.8 to 1.0 g/dL.

   
   
4. 
   

   Hence most of the human milk fed to VLBW infants during the fortification period is likely to have an inadequately low protein concentration.

   
   
5. 
   

   Studies looking at comparing the assumed and actual protein intakes in VLBW infants have confirmed the lower and inadequate protein content when the actual sample is analyzed.

   
   
6. 
   

   Human milk fortification to provide additional protein poses substantial challenges. Protein is limiting for growth.

   
   
7. 
   

   Novel fortification models have been devised to deal with the problem of ongoing protein undernutrition and, therefore, the prevention of poor neurocognitive development. Shortfalls of protein, even modest ones, are not acceptable. However, protein intakes in excess of needs have been considered dangerous as well.

Human milk analyses.

1. 
   

   Protein fortification of human milk is complicated by the fact that the protein concentration of expressed maternal milk is variable.

   
   
2. 
   

   Protein content of human milk decreases with the duration of lactation and also varies in an unpredictable fashion from sample to sample.

   
   
3. 
   

   This variability has the potential to introduce problems for the preterm infant that is exclusively fed expressed milk.

   
   
4. 
   

   For example, current neonatal practice “blindly” assumes mother’s milk content to be 20 cal/oz.

   
   
5. 
   

   New methods that analyze milk with point-of-care devices show there is a risk that both clinically significant under- and overestimation of actual nutrients take place.

   
   
6. 
   

   In clinical practice, this means that the protein and energy concentration of maternal milk is unknown (unless the milk is analyzed).

   
   
7. 
   

   The ability to precisely monitor the nutrient intake of the extremely preterm infant allows individualization and customization of nutritional management.

   
   
8. 
   

   Near-infrared spectrophotometers (NIRS) have been studied recently as point-of-care devices that provide rapid analysis of human milk content.

   
   
9. 
   

   NIRS and midinfrared spectrophotometers (MIRS) have several distinct advantages over other technologies or methods including the creamatocrit and ultrasonic analyzers.

   
   
10. 
    

    These spectrophotometers are now available commercially and have been used to measure carbohydrate, fat, and protein content of cow’s milk by the dairy industry. They have been used to measure sheep, donkey, and goat milk as well.

    
    
11. 
    

    These devices have been recently validated for analysis of carbohydrates, fat, and protein in human milk.

    
    
12. 
    

    Studies show the method to be feasible and offer the potential to evaluate human milk before feedings. This would allow adjustable individualized fortification to optimize nutrition.

    
    
13. 
    

    The analyses have confirmed that human milk composition varies greatly between individuals, with the volume of the milk, the type of milk (foremilk or hindmilk), and the stage of lactation.

    
    
14. 
    

    The range of actual protein concentrations in human milk is very large and is the most important growth nutrient. It is the macronutrient that “lactoengineering” will be modifying with new protein supplements and fortifiers to customize fortification.

    
    
15. 
    

    The practical implications are that expressed breast milk supplied by mothers of VLBW infants frequently contains far less protein, energy, and other nutrients than has been assumed.

    
    
16. 
    

    The current strategy of “blind” fortification is not supporting growth rates nor providing enough protein for prioritizing lean body mass.

    
    
17. 
    

    The widely used creamatocrit may not be accurate and does not measure carbohydrate or protein.

Discharge

1. 
   

   Discharge diet

   
   
   
   
   1. 
      

      Timing

      
      
      
      
      • 
        

        Infants should be transitioned to home diet 1 week prior to discharge in order to evaluate ability to demonstrate adequate growth.

        
        
      • 
        

        Infants should demonstrate at least a weight growth velocity of ≥16 g/kg/d.

      
      
   2. 
      

      Diet of primarily breast milk

      
      
      
      
      • 
        

        A diet of exclusive breast milk should be reserved for preterm infants with a weight growth velocity of ≥16 g/kg/d, serum alkaline phosphatase <400 IU/L, and serum phosphorous >4.2 mg/dL, steady linear growth, and weight and head circumference >10th percentile on growth curve.

        
        
      • 
        

        The majority of preterm infants receiving primarily breast milk at discharge should have postdischarge formula (PDF) powder added to the breast milk in order to meet the energy needs of the infant.

        
        
        
        
        1. 
           

           1/4 tsp of PDF formula powder added to 50 mL of breast milk adds an additional 2 kcal/oz.

           
           
        2. 
           

           Typically, at least 1/2 tsp of PDF powder/50 mL breast milk is needed for steady catch-up growth.

           
           
        3. 
           

           If mom is transitioning to breast-feeding, continue to fortify the expressed breast milk that is given by bottle.

      
      
   3. 
      

      Diet of primarily formula

      
      
      
      
      • 
        

        Infants should be switched to a PDF (see below) prior to discharge.

        
        
      • 
        

        ELBW infants, infants with morbidities having increased metabolic demands (BPD, CHD, etc), and infants with poor oral feeding skills often need the formula mixed to greater than the standard 22 kcal/oz PDF (see Appendix D).

      
      
   4. 
      

      Transitioning to breast-feeding

      
      
      
      
      • 
        

        See Chapter 12, Breast-feeding in the NICU

        
        
      • 
        

        If mom’s goal is to transition to more frequent breast-feeding attempts postdischarge, infants should have a discharge plan in place prior to going home. In general, breast-feeding attempts should be about as frequent as the inhospital feeding schedule for the first week postdischarge. Attempts may then increase every 1 to 2 weeks, supplementing by bottle, as long as the infants demonstrate appropriate catch-up growth and stable bone health indices.

      
      
   5. 
      

      Infants with suboptimal growth (weight, length, or head circumference) or abnormal bone health indices (serum calcium, phosphorous, alkaline phosphatase) on breast milk

      
      
      
      
      • 
        

        Babies who show poor growth or laboratory findings suggestive of poor bone mineralization on breast milk (with or without formula powder added) need additional fortification or formula supplementation.

        
        
        
        
        1. 
           

           May discharge home using human milk fortifiers (can be expensive if not covered by insurance and takes preplanning of how/where to obtain as an outpatient).

           
           
        2. 
           

           May supplement breast milk feeds with two to four formula feeds of PDF daily.

           
           
        3. 
           

           Growth as well as serum calcium, phosphorous, and alkaline phosphatase levels should be monitored every 2 weeks as an outpatient if going home on HMF. Once they have normalized, switching to formula powder added to breast milk is recommended.