Richard Cooke, MD
Vanderbuilt University
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PRE-TEST QUESTIONS
Q1. Greatest pre term weight gain per kg of body weight is from
a. 20 to 24 weeks gestation
b. 24 to 28 weeks gestation
c. 28 to 32 weeks gestation
d. 32 to 36 weeks gestation
Q2. Pick best completion to: Feeding of very low birth Weight Infants should be begun with an early introduction of
a. a high energy glucose solution provided enterally
b. a delay in feeding until evaluation is complete
c. a balanced enteral formulae
d. a parentally provided nutrition support
Q3. True or False Most otherwise 'normal' preterm infants born at 28 or after weeks gestation should regain birth weight by 2 weeks of age.
Q4. True or False infants born before 28 weeks gestation it may take 3 weeks to gain to birth weight.
Q5. True or False once birth weight has been regained, weight gain should be gaining at 25-30 g/d.
Q6. Energy and protein requirements are interrelated. Chose the best answer describing this interrelationship
a. With low energy intakes, catabolized fat stores provide energy needed for metabolism
b. Sufficient energy will not prevent protein from being catabolized in a VLBW infant
c. Protein will be endogenously catabolized to meet basal energy requirements unless sufficient energy is provided.
OBJECTIVES
On completion of this module, learners will be able to:
1. Establish how nutrient requirements of the neonate are determined
2. Recognize that early Parenteral Nutrition is critical even in the 'sick' unstable preterm infant.
3. Establish a rationale for early introduction of Enteral Nutrition
4. Develop a rationale approach towards meeting nutritional requirements during Enteral Nutrition
5. Provide guidance for nutritional management of the preterm infant after hospital discharge.
FACILITATOR PREPARATION
SUGGESTED READING:
1. Klein CJ. Nutrient requirements for preterm infant formulas. J Nutr 2002;132(6 Suppl 1):1395S-577S.
2. Ziegler EE, Thureen PJ, Carlson SJ. Aggressive nutrition of the very low birth weight infant. Clin Perinatol 2002;29(2):225-44.
3. Embleton NE, Pang N, Cooke RJ. Postnatal malnutrition and growth retardation: an inevitable consequence of current recommendations in preterm infants? Pediatrics 2001;107(2):270-3.
4. Cooke RJ, Griffin IJ, McCormick K, Wells JCK, Smith JS, Robinson SJ, et al. Feeding preterm infants after hospital discharge: Effect of dietary manipulation on nutrient intake and growth. Pediatric Research 1998;43(3):355-360.
INTRODUCTION
The fundamental principle of nutritional support is to ensure that nutritional intake meets requirements thereby ensuring appropriate growth and optimal health. This is difficult in the preterm infant. It takes time to establish adequate intakes during early life in the sick infant. Requirements are also not well defined. Moreover, changes in body weight may be confounded by fluid and electrolyte shifts during early life or later by the effects of therapeutic intervention; e.g., steroid, diuretics, etc.
Yet, it is generally agreed that nutritional support should be provided in phases (see Table 1). During stabilization (0-2 d of age), intake must meet needs for maintenance, while the primary route of nutritional support is parenteral nutrition (PN). During transition (3-6 d), intake must be advanced to also meet needs for growth. During this time, support is provided by a combination of PN and enteral nutrition (EN). During the growth phase (6 d+), intake must meet needs for maintenance and growth, support is primarily provided by EN.
1. Determination of nutrient requirements in preterm infants
Objective: To establish how nutrient requirements are determined
Key points: Requirements
1. Are related to the rte and composition of fetal growth and based on needs for maintenance and growth.
2. Will vary depending upon the phase of infant development and the method of nutrient delivery.
In term infants, nutrient requirements are determined by examining intakes of breast-fed infants of a well-nourished mother or intakes of a formula-fed infant. This is not possible in the preterm infant. Suck, swallow and breathing coordination and satiety are rarely fully functional before 34 w gestation. Furthermore, neither mature human milk nor a term infant formula was designed to meet the nutritional needs of the preterm infant.
Requirements, therefore, have been based on the rate and compositional nature of fetal growth between 24-40 w gestational ages (2). Growth of the fetus between 24-40 w is presented in Figure 1. Body weight increases from ~ 650 g to 3300 g, almost six-fold in 16 weeks. Expressed as function of body weight, the rate of gain is greatest between 24-28 w, making this a 'period of particular nutritional vulnerability'.
The changes in body composition are presented in Figure 2. Increases in body weight largely reflect those in body water, protein and fat. However, increments in protein are greatest before 32 w, underpinning the importance of adequate protein intakes in the smaller, more immature infant. Increments in body fat are greater after 32 w, indicating subtle changes in protein-energy needs with advancing gestation.
Using the factorial approach, requirements can be simply split into needs for maintenance and needs for growth. Allowance is then made for the method of nutrient delivery. For example, during PN dietary nutrients are 100% metabolically available. During EN, metabolic availability depends upon absorption rate that will vary depending upon the nutrient.
Protein requirements are estimated using the factorial approach in Table 2. During Stabilization, requirements must balance needs for maintenance; i.e., obligatory losses in the urine =1.0 g/kg/d. Obligatory losses may also be noted in secretions and from the skin but this is exceptional. Since PN is the primary route of nutrient supply during this period, a minimum intake of ?1.0 g/kg/d is required.
Table 2. Estimation of Dietary Protein Intakes in Preterm Infants.
During Transition, intake must be advanced to also meet needs for growth. For an infant weighing 500-700 g, requirements for growth rate are 2.5 g/kg/d. Allowing for maintenance needs of 1.0 g/kg/d, then requirements during Growth are 1.0 + 2.5 g or 3.5 g/kg/d. With PN, 100% of the protein is metabolically available. The requirement is 3.5 g/kg/d. With EN, ~ 90% is available. The requirement is 3.5/0.9 or 3.9 g/kg/d.
Table 3. Estimation of Dietary Energy Intakes in Preterm Infants.
Energy requirements can also be estimated using the factorial approach, although the energy balance equation is a little more complicated. This is illustrated in Figure 3. Energy intake must meet needs for maintenance (resting metabolism, activity, thermoregulation) and growth (new tissue synthesis + deposition).
Energy requirements are presented in Table 3. During Stabilization, intake must meet a basal energy expenditure of 35-45 kcal/kg/d. With PN as the primary route of nutrient delivery; i.e., 100 % absorbed, then an infant must receive 35-45 kcal/kg/d. During Transition, intake must be increased to meet both miscellaneous (15 kcal) and growth (29-39) kcal/kg/d.
Daily Caloric Requirement = Basal + Miscellaneous + Growth
During Growth with EN as the main route of nutrient delivery; i.e., 90% energy is absorbed, needs = (35-45 + 15 + 29)/0.9 = 93-105 kcal/kg/d.
Energy and protein requirements are interrelated. With low energy intakes, as is commonly seen during Stabilization, protein will be endogenously catabolized to meet basal energy requirements. Sufficient energy is necessary to prevent this occurring.
Protein accretion is an energy consuming process. For each gram of protein deposited ~12 kcal are expended at low protein intakes energy will not be expended to accrete protein but will be stored as fat, an important consideration in infants with chronic lung disease.
CASE STUDY - PART I
Part 1
Objective: To establish why early PN is critical even in the 'sick' unstable preterm infant.
Key points:
1. Early provision of adequate energy, protein and essential fatty acid intakes is critical to minimize endogenous catabolism and negative protein balance
2. During Stabilization requirements are a function of needs for Maintenance, while the primary route of nutrient delivery is PN
Clinical History: Baby boy X was born at 25 w gestation weighing 505 g. He was the product of a pregnancy complicated by severe pre-eclampsia necessitating Caesarian Section because of non-reassuring fetal heart rate tracings. Because of poor respiratory effort he was intubated soon after birth. Apgar scores were 3 at 1 minute and 8 at 5 minutes. He was subsequently admitted to the neonatal intensive care unit, received artificial surfactant and placed on ventilator support. Umbilical arterial and venous lines were placed, a septic work-up was performed and antibiotic therapy begun.
What are early nutritional considerations for this infant?
Between 24-40 w, body size increases six-fold as the infant grows and nutrient reserves are established (Figures 2, 3). Infants born prematurely do not establish these stores; the more immature the infant the greater the deficit. In addition, many preterm infants are growth retarded at birth, further complicating the issue.
Energy reserves in the preterm infant are illustrated in Figure 4. Liver glycogen content remains low until 34-35 w. Stores then increase but are rapidly depleted within 6 hours of delivery. Fat mass is also low, increasing from ~ 1.5% at 24 w to 8.5% at 40 w gestation. Before 28 w, much of the lipid is structural in nature; i.e., contained in cell membranes, and may not be available as an energy source. Immediate provision of an adequate energy intake is crucial, and estimated at 35-45 kcal/kg/d (see TABLE 3).
An additional consideration is protein needs. Total body content is low in a 500 g infant, amounting to ~ 44 g or 88 g/kg. Obligatory losses amount to ? 1.0 g/kg/d or ~ 1.2% of protein mass. Immediate provision of an adequate protein intake is also crucial if protein mass is to be maintained and estimated at 1-1.5 g/kg/d (see TABLE 2).
Consideration must also be given to essential fatty acid (EFA) requirements. EFA, linoleic and linolenic, are precursors in arachidonic acid (AA) and docosahexaenoic acid (DHA) synthesis (Figure 5). AA plays a critical role in prostaglandin synthesis and other metabolic processes, while DHA is a critical component of brain and retinal cell membranes. Early provision of intravenous lipids as a source of EFA's and calories is also critical.
An additional consideration is metabolic mass of the preterm or term infant when compared to the adult. This is illustrated in Figure 6. The metabolic masses of the brain, liver and lungs are substantially greater in the preterm and the term infant. Whether increased mass is a marker of vulnerability is not clear. What is clear is that undernutrition has been identified as a critical problem in a group of infants in whom chronic lung disease and poorer developmental outcome are a major source of morbidity and mortality.
It is, therefore, critical to provide adequate energy, protein and EFA intakes immediately from birth in this infant. This is best accomplished by starting PN on admission to the neonatal intensive care unit. A stock PN solution containing dextrose (10%) and amino acids (2-3 g/100 ml) administered at 75 ml/kg/d coupled with a 10% intravenous lipid solution administered in a dosage of 0.5 g/kg/d will meet basic requirements.
The provision of an adequate:
1. Energy intake may be limited by the development of hyperglycemia; i.e., blood glucose = 150 mg/dl. It is reasonable to initiate insulin therapy once glucose intake has been decreased to 6 mg/kg/min, below which point energy intake will be less than requirements and protein will be catabolized to meet energy requirements. Insulin is required to enhance glucose as well as protein utilization.
2. Protein intake may be confounded by the development of metabolic acidosis; i.e., base deficit ? -8.0 mmol. This is commonly due to hyperchloremia. Substituting acetate for chloride in the PN solution can minimize this problem.
3. EFA intake may be limited by the development of hyper-triglyceridemia; i.e., serum triglycerides > 250 mg/dl. However, this is rare at an intake of 0.5 g/kg/d, which is administered over 18-24 hrs.
Part 1
Objective: To establish why early PN is critical even in the 'sick' unstable preterm infant.
Key points:
3. Early provision of adequate energy, protein and essential fatty acid intakes is critical to minimize endogenous catabolism and negative protein balance
4. During stabilization requirements are a function of needs for maintenance, while the primary route of nutrient delivery is PN
Clinical History: Baby boy X was born at 25 w gestation weighing 505 g. He was the product of a pregnancy complicated by severe pre-eclampsia necessitating Caesarian Section because of non-reassuring fetal heart rate tracings. Because of poor respiratory effort he was intubated soon after birth. Apgar scores were 3 at 1 minute and 8 at 5 minutes. He was subsequently admitted to the neonatal intensive care unit, received artificial surfactant and placed on ventilator support. Umbilical arterial and venous lines were placed, a septic work-up was performed and antibiotic therapy begun.
What are early nutritional considerations for this infant?
Between 24-40 w, body size increases six-fold as the infant grows and nutrient reserves are established (Figures 2, 3). Infants born prematurely do not establish these stores; the more immature the infant the greater the deficit. In addition, many preterm infants are growth retarded at birth, further complicating the issue.
Energy reserves in the preterm infant are illustrated in Figure 4. Liver glycogen content remains low until 34-35 w. Stores then increase but are rapidly depleted within 6 hours of delivery. Fat mass is also low, increasing from ~ 1.5% at 24 w to 8.5% at 40 w gestation. Before 28 w, much of the lipid is structural in nature; i.e., contained in cell membranes, and may not be available as an energy source. immediate provision of an adequate energy intake is crucial, and estimated at 35-45 kcal/kg/d (see TABLE 3).
An additional consideration is protein needs. Total body content is low in a 500 g infant, amounting to ~ 44 g or 88 g/kg. Obligatory losses amount to ? 1.0 g/kg/d or ~ 1.2% of protein mass. immediate provision of an adequate protein intake is also crucial if protein mass is to be maintained and estimated at 1-1.5 g/kg/d (see TABLE 2).
Consideration must also be given to essential fatty acid (EFA) requirements. EFA, linoleic and linolenic, are precursors in arachidonic acid (AA) and docosahexaenoic acid (DHA) synthesis (Figure 5). AA plays a critical role in prostaglandin synthesis and other metabolic processes, while DHA is a critical component of brain and retinal cell membranes. early provision of intravenous lipids as a source of EFA's and calories is also critical.
An additional consideration is metabolic mass of the preterm or term infant when compared to the adult. This is illustrated in Figure 6. The metabolic masses of the brain, liver and lungs are substantially greater in the preterm and the term infant. Whether increased mass is a marker of vulnerability is not clear. What is clear is that undernutrition has been identified as a critical problem in a group of infants in whom chronic lung disease and poorer development outcome are a major source of morbidity and mortality.
It is, therefore, critical to provide adequate energy, protein and EFA intakes immediately from birth in this infant. This is best accomplished by starting PN on admission to the neonatal intensive care unit. A stock PN solution containing dextrose (10%) and amino acids (2-3 g/100 ml) administered at 75 ml/kg/d coupled with a 10% intravenous lipid solution administered in a dosage of 0.5 g/kg/d will meet basic requirements.
The provision of an adequate:
4. Energy intake may be limited by the development of hyperglycemia; i.e., blood glucose ? 150 mg/dl. It is reasonable to initiate insulin therapy once glucose intake has been decreased to 6 mg/kg/min, below which point intake will be less than basal energy needs.
5. Protein intake may be confounded by the development of metabolic acidosis; i.e., base deficit ? -8.0 mmol. This is commonly due to hyperchloremia. Substituting acetate for chloride in the PN solution can minimize this problem.
6. EFA intake may be limited by the development of hyper-triglyceridemia; i.e., serum triglycerides > 250 mg/dl. However, this is rare at an intake of 0.5 g/kg/d, which is administered over 18-24 hrs.
CASE STUDY - PART 2
Objectives: To establish a rationale for early introduction of EN
Key points:
1. Early EN is critical to if the immature gut is to successfully adapt to extra-uterine existence.
2. During Transition nutrient intake must be advanced to also meet needs for growth.
3. Advancement of enteral feeds should be consistent enough that outcomes can be systematically evaluated within any neonatal intensive care unit.
Clinical History: By the third day of life, this 505 g infant continues on ventilator support with good gas exchange. His blood pressure, urine output and serum electrolytes are within normal limits. He is receiving 100 ml/kg of PN solution containing 10% dextrose and 2.5% protein and 5 ml/kg of an intravenous lipid solution containing 10% lipid. He is also receiving 20 ml/kg of an IV solution containing dextrose 10%.
What are the nutritional considerations now in this infant?
At his current PN intake, he is receiving 41 kcal of non-protein energy, 2.5 g of protein and 0.5 g of lipid; i.e., intake is meeting maintenance requirements for energy, protein and lipid. The major question now is whether EN should be begun.
Gut mass is decreased in the preterm infant. This is illustrated in Figure 7. As gestation increases so does small intestinal length. At any given gestation, intestinal length is significantly less in the small for gestational age (SGA) when compared to appropriately grown (AGA) infant. Reduced mass is paralleled by poor function; decreased gastric emptying, increased intestinal permeability and decreased intestinal motility.
Feeding maintains gut mass. This is illustrated in Figure 8. It provides direct local nutrition and stimulates cell turnover, thereby intestinal growth. Through hormonal release and stimulation of intestinal secretions and motility and nerves, it also promotes intestinal growth. On the other hand, fasting leads to gut atrophy.
EN is, therefore, crucial if the immature gut is to successfully adapt to extra-uterine existence. Initiation of early EN is tempered by concerns necrotizing entercolitis (NEC). Yet, withholding EN has not been shown to prevent NEC. Furthermore, early small volume EN has been shown to improve gut function without an increased incidence of NEC. Initiation of EN at a volume of 10-20 ml/kg/d is, therefore, indicated.
What remains uncertain is how fast EN can be advanced to meet needs for maintenance and growth; i.e., 150 ml/kg/d with a standard preterm infant formula. Further studies are needed to examine this issue. In the meantime, once feeding tolerance has been established it is reasonable to advance feeds at a rate of 10-20 ml/kg/d, closely monitoring clinical status throughout. Whichever approach is taken it should be consistent enough that it can be systematically evaluated within each neonatal intensive care unit.
CASE STUDY- PART 3
Objective: To establish a rationale approach towards meeting nutritional requirements during EN
Key Points:
1. During Growth, intake must meet needs for maintenance and growth.
2. Unfortified human milk will not meet needs for maintenance and growth.
3. Growth, protein-energy status and mineral bone status must be closely monitored throughout hospital stay, particularly in infants fed human milk.
Clinical History
By 14 d of age, he was weaned from the ventilator and placed on continuous positive air pressure using nasal prongs and was receiving a combination of PN and EN. Between 14 and 21 d, PN was discontinued when an enteral intake of 150 ml/kg/d of human milk was tolerated. By 21 d, he had regained birth weight. Between 28 d of age, he was gaining weight at a rate of 5 g/kg/d.
What are the nutritional considerations now in this infant?
Most otherwise 'normal' preterm infants should regain birth weight by 2 weeks of age. For infants born before 28 weeks gestation it may take 3 weeks. Whether this is 'normal' or not is not clear. However, once birth weight has been regained, weight gain should parallel that of the fetus at the same gestational age; i.e., 25-30 g/d. This infant is failing to thrive.
This is not surprising. Mature human milk does not meet the needs of the preterm infant. This is illustrated in Table 4. At an energy intake of 120 kcals/kg, mature human will provide a protein intake of 2.7 g/kg/d, 2.24 X 1,2, substantially less than 3.9 g/kg/d (see Table 2). It is, therefore, recommended the human milk be fortified with a nutrient supplement. Even with fortification intake, 3.4 g/kg/d (2.8 X 1.2), may not meet the requirements of infants of these infants. It should also be noted that fortified human milk barely meets requirements for calcium, phosphorus and sodium.
Table 4. Nutrient Density of Mature Unfortified Human Milk Compared to Fortified Human Milk and Standard Preterm Infant Formula and Current Recommendations
Preterm infants fed fortified human milk do not grow as well as infants fed a preterm infant formula. Yet, fortified human milk may provide some non-nutritional advantages vis-à-vis defense against infection and development. When fortified milk is fed it is important to serially monitor not only protein-energy but also metabolic bone status using anthropometry (weight, length, head circumference) and serum chemical analyses (blood urea nitrogen, serum albumin, serum calcium, phosphorus, alkaline phosphatase).
NOTE: It is common practice to volume limit infants with chronic lung disease to 120-130 ml/kg/d, while adding medium chain triglycerides to maintain an energy intake of 120 kcal/kg/d. In doing so, protein-energy ratio decreases from 3.0 to 2.4 g/100 kcal and protein intake decreases 3.6 to 2.9 g/kg/d. At these energy intakes, weight gain but not lean mass may be maintained as body fat is accreted. It is, therefore, important to monitor linear growth as well as serum chemical analyses vis-à-vis blood urea nitrogen, total serum protein and albumin.
CASE STUDY - PART 4
Objective: To establish a rationale for the nutritional management of the preterm infant after hospital discharge.
Key points:
1. Preterm infants are uniformly growth-retarded at hospital discharge
2. Preterm infants fed a nutrient-enriched infant formula will show greater catch-up growth than infants fed a standard term infant formula.
3. Growth must be closely monitored in preterm infants during the first year of life.
At 90 d of age, this infant has been weaned from CPAP and oxygen therapy. He is taking ad-lib feeds of 160-180 ml/kg/d and growing at 17 g/kg/d. A decision has been made to discharge him home.
What are the nutritional considerations now in this infant?
It takes time to establish adequate dietary intakes in preterm infants. This is illustrated in a study conducted by Embleton et al, in which dietary intakes and growth were monitored in a group of preterm infants admitted to a neonatal intensive care unit. Throughout hospital stay, protein and energy intakes were determined daily, while weight was measured every other day.
Daily intake was subtracted from recommended intake to calculate the daily deficit. Daily deficits were then summed to estimate cumulative deficit. Body weight was converted to Z-scores. Z-score at birth was subtracted from post-natal z-score; a score below zero indicating poor growth, the more negative the score the greater the postnatal growth deficit.
The protein intake data and z-scores are presented in Figure 9. It took 2-3w to establish the RDI for protein. During this time, infants accrued a major deficit that was not recouped before hospital discharge. A similar pattern was noted for energy intake. This was paralleled by a fall in z-score growth, indicating significant postnatal growth retardation. The cumulative protein and energy deficits accounted for ~ 50% of the postnatal growth deficit.
Other studies have shown similar findings. It has, therefore, been suggested that preterm infants may require a nutrient-enriched formula designed not only to meets needs for maintenance and normal growth but also 'catch-up' growth. Only recently has this issue been addressed.
In one study, preterm infants were randomized to either a preterm or term formula between hospital discharge and 6 months corrected age. The results are presented in Figure 10. Although z-scores decreased between birth and discharge, scores improved in both study groups between discharge-6 m, indicating 'catch-up' growth. However, the amount of 'catch-up' was greater in infants fed the preterm formula indicating that it preterm formula more closely met requirements in these growth-retarded infants.
This and other studies support the idea that preterm infants be fed a nutrient-enriched formula after hospital discharge, at least until 6m corrected age. However, growth must be closely monitored throughout the first year of life. It is not clear whether breast-fed infants should or should not receive some form of nutrient supplementation.
SUMMARY
The information provided here emphasizes aggressive refeeding of low birth weight neonate in the context of a careful monitoring. Nutritional needs in the three phases of early life - Stabilization, Transition, and Growth.
It is essential to recognize that early Parenteral Nutrition is critical even in the 'sick' unstable preterm infant. Enteral nutrition must be introduced early in the life of a pre-term infant to meet nutritional requirements. There must be careful follow-up after discharge. Issues of early feeding are addressed elsewhere in the Teacher's Guide.
ANNOTATED ANSWERS
A1. The answer is B. Expressed as function of body weight, the rate of gain is greatest between 24-28 w, making this a 'period of particular nutritional vulnerability'.
A2. The answer is D. Nutient and energy needs are too great during the "Stabilization" and "Transition" periods in the liofe of a premature neonate.
A3. The answer is True. Vigerous monitored feeding of a low birth weight premature should bring the infant back to birth weight when the gestational age is greater than 28 weeks.
A4. The answer is True. Lowest weight babies may require three weeks to regain weight.
A5. The answer is True. Once the low birth weight infant reaches the growth phase, it will proceed as with full or near term babies.
A6. The answer is C. Energy sufficiciency is critical to protein sparing at all ages. A is a half truth in that some fat will be metabolized. B is simply false. The infant will lay down protein if given sufficient energy and protein substrate - e.g., essential amino acids.
