3 Nutritional Challenges in Special Conditions and Diseases Koletzko B, et al. (eds): Pediatric Nutrition in Practice. World Rev Nutr Diet. Basel, Karger, 2015, vol 113, pp 214–217 DOI: 10.1159/000360342
3.14 Preterm and Low-Birth-Weight Infants Ekhard E. Ziegler
Growth failure · Parenteral nutrition · Gastrointestinal priming · Human milk fortification
Key Messages • Nutrient administration, though technically difficult, must be initiated promptly after birth to avoid adverse effects of undernutrition • Because of immaturity of the intestinal tract, the use of parenteral nutrition is necessary until feeds can be given • Trophic feeding (gastrointestinal priming) should be started promptly and advanced as permitted by maturation of intestinal motility • The preferred feed is breast milk (the mother’s own or donated) because of its protective effect against sepsis and necrotizing enterocolitis. Formulas for preterm infants are the second choice • Breast milk must be fortified with nutrients to meet the high nutrient needs of preterm infants. Fortifiers raise the nutrient content to adequate levels, compensating for shortfalls © 2015 S. Karger AG, Basel
Postnatal (extrauterine) growth failure is common among prematurely born infants. It used to be considered inevitable as well as innocuous. But it has become clear that far from being inevitable, it is largely if not exclusively the result of inadequate intakes of nutrients. Ehrenkranz et al. [1], among others, have shown in a landmark study that it is not innocuous. The study established that growth failure is associated with impairment of neurocognitive development in a dose-dependent fashion. The more severe the growth failure, the more severe is the neurocognitive impairment. There are mainly two reasons for the occurrence of growth failure in premature infants. One is that there are physiological limitations that prevent the provision of nutrients in the usual way, i.e. through enteral feeding. The other reason is that the nutrient needs are exceedingly high, as summarized in table 1. These needs cannot be met by human milk alone without nutrient fortification. Thus, providing nutritional support to preterm infants presents unique challenges as failure to provide adequate nutrient intakes at all stages of development places them at risk of impaired neurodevelopment. Every effort must therefore be made to provide complete nutrition beginning from birth [2].
Downloaded by: Kellogg Health Sciences Libr. 198.143.38.97 - 6/20/2015 11:34:34 PM
Introduction
Key Words
Provision of nutrients has to overcome the immaturity of the intestinal tract; this is the most important physiological limitation in these infants. This necessitates the use of parenteral nutrition during the early days and often weeks of life. Although parenteral nutrition carries risks, especially that of infection, failure to provide nutrients parenterally would place these infants at high risk of impaired neurodevelopment or impaired host defenses. Immaturity of the intestinal tract is also the main reason why preterm infants are susceptible to necrotizing enterocolitis (NEC). While nutrients are provided parenterally, small trophic feedings (gastrointestinal priming) are given with the sole purpose of stimulating the intestinal tract to undergo maturation. Breast milk is the most effective and safest feed to bring about intestinal maturation. Once maturation has occurred, nutrients can be delivered enterally and parenteral nutrition may be phased out. Nutritional support of preterm infants occurs in four distinct phases, each with its own risks and challenges. During the early phase, nutrients are almost exclusively provided via the parenteral route, while small enteral feedings (gastrointestinal priming) are used to prod the immature intestinal tract into undergoing maturation. During the subsequent transition phase, enteral feeding is slowly advanced as the intestinal tract shows evidence of maturation, and parenteral nutrition is gradually phased out. During the late phase, infants are on exclusive enteral feeding and are expected to grow normally. If provided the necessary nutrients, preterm infants may also show catch-up growth, that is, they may be making up for lost time during the early phase. Preterm infants continue to have special nutritional needs after discharge from hospital.
Early Phase During the immediate postnatal period, the objective of nutritional support is twofold: to provide an uninterrupted flow of nutrients so that the anabolic state that existed in utero can continue with minimal or no interruption, and to stimulate the immature gastrointestinal tract to undergo maturation. As gastrointestinal maturation progresses, a gradual shift occurs from exclusive parenteral nutrition to predominant, and finally exclusive, enteral nutrition. The early phase ends when enteral feedings exceed about 20 ml/kg/day. Parenteral Nutrition In immature infants, parenteral nutrition must begin immediately (within 2 h of birth), and as a minimum must provide glucose, amino acids, electrolytes, Ca, P and Mg (starter parenteral nutrition) until full parenteral nutrition can be started. It is acceptable for the amount of amino acid to be less than 3.5 g/kg/day for a few days. Initiation of lipid emulsion is somewhat less urgent, and a delay of 24 h is acceptable. The initial rate should be 1.0 g lipids/kg/day. The efficacy and safety of parenteral nutrition starting immediately after birth have been established [3]. Full parenteral nutrition should be maintained until enteral feedings of 20 ml/kg/day are regularly tolerated. As the feedings are increased, the amount of parenteral nutrition is tapered, with total (parenteral plus enteral) intake of nutrients always remaining at full level. Enteral Nutrition The anatomically and functionally immature intestine can undergo maturation in a relatively short time if the necessary stimulation is provided in the form of trophic feedings (gastrointestinal priming). Gastrointestinal priming should be started on the first day of life. Feeding volumes initially may be as low as 2 ml every 6 or 4 h. Stimulation of the gut is initially the sole objective of enteral feeding. Motility serves as a marker of gut maturation and is monitored clinically by assessment of gastric residuals. As gastric emptying im-
Preterm and Low-Birth-Weight Infants
Koletzko B, et al. (eds): Pediatric Nutrition in Practice. World Rev Nutr Diet. Basel, Karger, 2015, vol 113, pp 214–217 DOI: 10.1159/000360342
215
3
Downloaded by: Kellogg Health Sciences Libr. 198.143.38.97 - 6/20/2015 11:34:34 PM
Nourishing Preterm and Low-Birth-Weight Infants
Table 1. Requirements for protein and energy (best estimates by factorial and empirical methods)
Body weight 1,000 – 1,500 g
1,500 – 2,200 g
2,200 – 3,000 g
19.0 4.0 106 3.8
17.4 3.9 115 3.4
16.4 3.7 123 3.0
13.4 3.4 130 2.6
proves, it is assumed that the ability to digest and absorb nutrients is also improving. Gastric emptying thus serves as an important clinical guide in early enteral feeding. The risk of NEC is quite low with trophic feedings, but it somewhat increases subsequently as feeding volumes increase. The preferred feed for gastrointestinal priming is maternal milk or, if not available, donor milk. Donor milk is pasteurized and free of viruses such as HIV and cytomegalovirus. Although pasteurization diminishes some of the protective and trophic factors of human milk, donor milk retains its protective effect against NEC [4] and sepsis and has strong trophic effects. When human milk is not available, formulas can also be used for gastrointestinal priming. Transition Phase Feeding volumes are usually kept low for several days and are gradually increased as gastric residuals diminish. At each new level, the adequacy of gastric emptying (absence of gastric residuals) must be ascertained before the feeding volume is further increased. The presence of gastric residuals does not require cessation of feedings as long as there are no signs suggestive of NEC. The use of gastrointestinal priming has been shown to lead to earlier establishment of full feedings and to earlier hospital discharge without an increase in NEC [5]. In fact, earlier achievement of full feedings has been shown to decrease the risk of sepsis [6]. Feeding volumes can be increased by 20 ml/kg each day as gastric residuals permit. Al-
216
though more rapid increases are safe, intestinal maturation requires time and therefore more rapid increases are not necessary. When feeding volumes are 80–100 ml/kg/day, fortification of breast milk is usually initiated, although in some units fortification is started much earlier. Parenteral nutrition can be discontinued when enteral feedings are at least 90% of the full amount. Late Phase The late phase begins when full feedings are established and parenteral nutrition is discontinued. The objective of nutrition is to allow growth to proceed parallel to intrauterine growth. The energy and protein intakes listed in table 1 are needed to support growth at the intrauterine rate. If the infant is to catch up in growth, intakes must be increased by perhaps 10–20%. Intakes below those listed in table 1 lead to extrauterine growth failure with all its negative consequences. Feedings are fortified human milk or, when not available, special formulas. With standard preterm formulas with a protein/energy ratio (3.0 g/100 kcal) protein intakes are marginally adequate. Formulas with higher protein content (3.3–3.6 g/100 kcal) are therefore preferable in order to achieve appropriate ‘catch up’ growth of lean body mass. Breast milk must be fortified (supplemented) with nutrients in order to meet the preterm infant’s high needs (table 1). Fortifiers are available as powders and as liquids. Commercially available fortifiers provide the necessary nutrients in suffi-
Ziegler
Koletzko B, et al. (eds): Pediatric Nutrition in Practice. World Rev Nutr Diet. Basel, Karger, 2015, vol 113, pp 214–217 DOI: 10.1159/000360342
Downloaded by: Kellogg Health Sciences Libr. 198.143.38.97 - 6/20/2015 11:34:34 PM
Fetal weight gain, g/kg/day Protein, g/kg/day Energy, kcal/kg/day Protein/energy, g/100 kcal
500 – 1,000 g
cient amounts with the exception of protein, which is inadequate in most fortifiers. Protein intakes are therefore often inadequate. The reason why powder fortifiers, and some liquid fortifiers, are too low in protein is that they were designed at a time when the overriding consideration was the avoidance of ‘high’ protein intakes in the face of variable protein concentrations of expressed human milk. The inevitable consequence is that protein intakes are too low most of the time. Today the ill effects of inadequate protein intakes are better known. Fortifiers (liquid) with higher protein content are available and should be used. With their use, protein intakes are adequate most of the time, albeit being somewhat high at times when the protein content of expressed milk is relatively high. Customizing approaches to fortification have been developed with the aim of overcoming the
inadequacy of protein intakes with powder fortifiers. A method for BUN-guided fortification has been described by Arslanoglu et al.[7]. The method is somewhat cumbersome, which may be the reason for its limited use. Approaches based on periodic analysis of expressed milk (targeted fortification) also have been shown to lead to more adequate nutrient intakes and improved growth [8]. After Discharge When preterm infants leave the hospital their nutrient needs are still high. In addition, they often have accrued deficits in bone mineral content. This is the reason why there is a need for continued fortification of human milk. In the case of formula feeding, the use of enriched post-discharge formulas is necessary.
References 4 Boyd CA, Quigley MA, Brocklehurst P: Donor breast milk versus infant formula for preterm infants: systematic review and meta-analysis. Arch Dis Child Fetal Neon Ed 2007;92:F169–F175. 5 Tyson JA, Kennedy KA: Trophic feedings for parenterally fed infants (Review). Cochrane Database Syst Rev 2005;CD000504. 6 Ronnestad A, Abrahamsen TG, Medbø S, Reigstad H, Lossius K, Kaaresen PI, et al: Late-onset septicemia in a Norwegian national cohort of extremely premature infants receiving very early full human milk feeding. Pediatrics 2005;115:e269– e276.
7 Arslanoglu S, Moro GE, Ziegler EE: Adjustable fortification of human milk fed to preterm infants: does it make a difference? J Perinatol 2006;26;1–8. 8 Polberger S, Räihä NCR, Juvonen P, Moro GE, Minoli I, Warm A: Individualized protein fortification of human milk for preterm infants: comparison of ultrafiltrated human milk protein and a bovine whey fortifier. J Pediat Gast Nut 1999;29:332–338.
Preterm and Low-Birth-Weight Infants
Koletzko B, et al. (eds): Pediatric Nutrition in Practice. World Rev Nutr Diet. Basel, Karger, 2015, vol 113, pp 214–217 DOI: 10.1159/000360342
217
3
Downloaded by: Kellogg Health Sciences Libr. 198.143.38.97 - 6/20/2015 11:34:34 PM
1 Ehrenkranz RA, Dusick AM, Vohr BR, Wright LL, Wrage LA, Poole WK: Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth weight infants. Pediatrics 2006;117: 1253–1261. 2 Ziegler EE: Meeting the nutritional needs of the low-birth-weight infant. Ann Nutr Metab 2011;58(suppl 1):8–18. 3 te Braake FWJ, van den Akker CHP, Wattimena DJL, Huijmans JGM, van Goudoever JB: Amino acid administration to premature infants directly after birth. J Pediatr 2005;147:457–461.
3.14 Preterm and Low-Birth-Weight Infants Ekhard E. Ziegler
Growth failure · Parenteral nutrition · Gastrointestinal priming · Human milk fortification
Key Messages • Nutrient administration, though technically difficult, must be initiated promptly after birth to avoid adverse effects of undernutrition • Because of immaturity of the intestinal tract, the use of parenteral nutrition is necessary until feeds can be given • Trophic feeding (gastrointestinal priming) should be started promptly and advanced as permitted by maturation of intestinal motility • The preferred feed is breast milk (the mother’s own or donated) because of its protective effect against sepsis and necrotizing enterocolitis. Formulas for preterm infants are the second choice • Breast milk must be fortified with nutrients to meet the high nutrient needs of preterm infants. Fortifiers raise the nutrient content to adequate levels, compensating for shortfalls © 2015 S. Karger AG, Basel
Postnatal (extrauterine) growth failure is common among prematurely born infants. It used to be considered inevitable as well as innocuous. But it has become clear that far from being inevitable, it is largely if not exclusively the result of inadequate intakes of nutrients. Ehrenkranz et al. [1], among others, have shown in a landmark study that it is not innocuous. The study established that growth failure is associated with impairment of neurocognitive development in a dose-dependent fashion. The more severe the growth failure, the more severe is the neurocognitive impairment. There are mainly two reasons for the occurrence of growth failure in premature infants. One is that there are physiological limitations that prevent the provision of nutrients in the usual way, i.e. through enteral feeding. The other reason is that the nutrient needs are exceedingly high, as summarized in table 1. These needs cannot be met by human milk alone without nutrient fortification. Thus, providing nutritional support to preterm infants presents unique challenges as failure to provide adequate nutrient intakes at all stages of development places them at risk of impaired neurodevelopment. Every effort must therefore be made to provide complete nutrition beginning from birth [2].
Downloaded by: Kellogg Health Sciences Libr. 198.143.38.97 - 6/20/2015 11:34:34 PM
Introduction
Key Words
Provision of nutrients has to overcome the immaturity of the intestinal tract; this is the most important physiological limitation in these infants. This necessitates the use of parenteral nutrition during the early days and often weeks of life. Although parenteral nutrition carries risks, especially that of infection, failure to provide nutrients parenterally would place these infants at high risk of impaired neurodevelopment or impaired host defenses. Immaturity of the intestinal tract is also the main reason why preterm infants are susceptible to necrotizing enterocolitis (NEC). While nutrients are provided parenterally, small trophic feedings (gastrointestinal priming) are given with the sole purpose of stimulating the intestinal tract to undergo maturation. Breast milk is the most effective and safest feed to bring about intestinal maturation. Once maturation has occurred, nutrients can be delivered enterally and parenteral nutrition may be phased out. Nutritional support of preterm infants occurs in four distinct phases, each with its own risks and challenges. During the early phase, nutrients are almost exclusively provided via the parenteral route, while small enteral feedings (gastrointestinal priming) are used to prod the immature intestinal tract into undergoing maturation. During the subsequent transition phase, enteral feeding is slowly advanced as the intestinal tract shows evidence of maturation, and parenteral nutrition is gradually phased out. During the late phase, infants are on exclusive enteral feeding and are expected to grow normally. If provided the necessary nutrients, preterm infants may also show catch-up growth, that is, they may be making up for lost time during the early phase. Preterm infants continue to have special nutritional needs after discharge from hospital.
Early Phase During the immediate postnatal period, the objective of nutritional support is twofold: to provide an uninterrupted flow of nutrients so that the anabolic state that existed in utero can continue with minimal or no interruption, and to stimulate the immature gastrointestinal tract to undergo maturation. As gastrointestinal maturation progresses, a gradual shift occurs from exclusive parenteral nutrition to predominant, and finally exclusive, enteral nutrition. The early phase ends when enteral feedings exceed about 20 ml/kg/day. Parenteral Nutrition In immature infants, parenteral nutrition must begin immediately (within 2 h of birth), and as a minimum must provide glucose, amino acids, electrolytes, Ca, P and Mg (starter parenteral nutrition) until full parenteral nutrition can be started. It is acceptable for the amount of amino acid to be less than 3.5 g/kg/day for a few days. Initiation of lipid emulsion is somewhat less urgent, and a delay of 24 h is acceptable. The initial rate should be 1.0 g lipids/kg/day. The efficacy and safety of parenteral nutrition starting immediately after birth have been established [3]. Full parenteral nutrition should be maintained until enteral feedings of 20 ml/kg/day are regularly tolerated. As the feedings are increased, the amount of parenteral nutrition is tapered, with total (parenteral plus enteral) intake of nutrients always remaining at full level. Enteral Nutrition The anatomically and functionally immature intestine can undergo maturation in a relatively short time if the necessary stimulation is provided in the form of trophic feedings (gastrointestinal priming). Gastrointestinal priming should be started on the first day of life. Feeding volumes initially may be as low as 2 ml every 6 or 4 h. Stimulation of the gut is initially the sole objective of enteral feeding. Motility serves as a marker of gut maturation and is monitored clinically by assessment of gastric residuals. As gastric emptying im-
Preterm and Low-Birth-Weight Infants
Koletzko B, et al. (eds): Pediatric Nutrition in Practice. World Rev Nutr Diet. Basel, Karger, 2015, vol 113, pp 214–217 DOI: 10.1159/000360342
215
3
Downloaded by: Kellogg Health Sciences Libr. 198.143.38.97 - 6/20/2015 11:34:34 PM
Nourishing Preterm and Low-Birth-Weight Infants
Table 1. Requirements for protein and energy (best estimates by factorial and empirical methods)
Body weight 1,000 – 1,500 g
1,500 – 2,200 g
2,200 – 3,000 g
19.0 4.0 106 3.8
17.4 3.9 115 3.4
16.4 3.7 123 3.0
13.4 3.4 130 2.6
proves, it is assumed that the ability to digest and absorb nutrients is also improving. Gastric emptying thus serves as an important clinical guide in early enteral feeding. The risk of NEC is quite low with trophic feedings, but it somewhat increases subsequently as feeding volumes increase. The preferred feed for gastrointestinal priming is maternal milk or, if not available, donor milk. Donor milk is pasteurized and free of viruses such as HIV and cytomegalovirus. Although pasteurization diminishes some of the protective and trophic factors of human milk, donor milk retains its protective effect against NEC [4] and sepsis and has strong trophic effects. When human milk is not available, formulas can also be used for gastrointestinal priming. Transition Phase Feeding volumes are usually kept low for several days and are gradually increased as gastric residuals diminish. At each new level, the adequacy of gastric emptying (absence of gastric residuals) must be ascertained before the feeding volume is further increased. The presence of gastric residuals does not require cessation of feedings as long as there are no signs suggestive of NEC. The use of gastrointestinal priming has been shown to lead to earlier establishment of full feedings and to earlier hospital discharge without an increase in NEC [5]. In fact, earlier achievement of full feedings has been shown to decrease the risk of sepsis [6]. Feeding volumes can be increased by 20 ml/kg each day as gastric residuals permit. Al-
216
though more rapid increases are safe, intestinal maturation requires time and therefore more rapid increases are not necessary. When feeding volumes are 80–100 ml/kg/day, fortification of breast milk is usually initiated, although in some units fortification is started much earlier. Parenteral nutrition can be discontinued when enteral feedings are at least 90% of the full amount. Late Phase The late phase begins when full feedings are established and parenteral nutrition is discontinued. The objective of nutrition is to allow growth to proceed parallel to intrauterine growth. The energy and protein intakes listed in table 1 are needed to support growth at the intrauterine rate. If the infant is to catch up in growth, intakes must be increased by perhaps 10–20%. Intakes below those listed in table 1 lead to extrauterine growth failure with all its negative consequences. Feedings are fortified human milk or, when not available, special formulas. With standard preterm formulas with a protein/energy ratio (3.0 g/100 kcal) protein intakes are marginally adequate. Formulas with higher protein content (3.3–3.6 g/100 kcal) are therefore preferable in order to achieve appropriate ‘catch up’ growth of lean body mass. Breast milk must be fortified (supplemented) with nutrients in order to meet the preterm infant’s high needs (table 1). Fortifiers are available as powders and as liquids. Commercially available fortifiers provide the necessary nutrients in suffi-
Ziegler
Koletzko B, et al. (eds): Pediatric Nutrition in Practice. World Rev Nutr Diet. Basel, Karger, 2015, vol 113, pp 214–217 DOI: 10.1159/000360342
Downloaded by: Kellogg Health Sciences Libr. 198.143.38.97 - 6/20/2015 11:34:34 PM
Fetal weight gain, g/kg/day Protein, g/kg/day Energy, kcal/kg/day Protein/energy, g/100 kcal
500 – 1,000 g
cient amounts with the exception of protein, which is inadequate in most fortifiers. Protein intakes are therefore often inadequate. The reason why powder fortifiers, and some liquid fortifiers, are too low in protein is that they were designed at a time when the overriding consideration was the avoidance of ‘high’ protein intakes in the face of variable protein concentrations of expressed human milk. The inevitable consequence is that protein intakes are too low most of the time. Today the ill effects of inadequate protein intakes are better known. Fortifiers (liquid) with higher protein content are available and should be used. With their use, protein intakes are adequate most of the time, albeit being somewhat high at times when the protein content of expressed milk is relatively high. Customizing approaches to fortification have been developed with the aim of overcoming the
inadequacy of protein intakes with powder fortifiers. A method for BUN-guided fortification has been described by Arslanoglu et al.[7]. The method is somewhat cumbersome, which may be the reason for its limited use. Approaches based on periodic analysis of expressed milk (targeted fortification) also have been shown to lead to more adequate nutrient intakes and improved growth [8]. After Discharge When preterm infants leave the hospital their nutrient needs are still high. In addition, they often have accrued deficits in bone mineral content. This is the reason why there is a need for continued fortification of human milk. In the case of formula feeding, the use of enriched post-discharge formulas is necessary.
References 4 Boyd CA, Quigley MA, Brocklehurst P: Donor breast milk versus infant formula for preterm infants: systematic review and meta-analysis. Arch Dis Child Fetal Neon Ed 2007;92:F169–F175. 5 Tyson JA, Kennedy KA: Trophic feedings for parenterally fed infants (Review). Cochrane Database Syst Rev 2005;CD000504. 6 Ronnestad A, Abrahamsen TG, Medbø S, Reigstad H, Lossius K, Kaaresen PI, et al: Late-onset septicemia in a Norwegian national cohort of extremely premature infants receiving very early full human milk feeding. Pediatrics 2005;115:e269– e276.
7 Arslanoglu S, Moro GE, Ziegler EE: Adjustable fortification of human milk fed to preterm infants: does it make a difference? J Perinatol 2006;26;1–8. 8 Polberger S, Räihä NCR, Juvonen P, Moro GE, Minoli I, Warm A: Individualized protein fortification of human milk for preterm infants: comparison of ultrafiltrated human milk protein and a bovine whey fortifier. J Pediat Gast Nut 1999;29:332–338.
Preterm and Low-Birth-Weight Infants
Koletzko B, et al. (eds): Pediatric Nutrition in Practice. World Rev Nutr Diet. Basel, Karger, 2015, vol 113, pp 214–217 DOI: 10.1159/000360342
217
3
Downloaded by: Kellogg Health Sciences Libr. 198.143.38.97 - 6/20/2015 11:34:34 PM
1 Ehrenkranz RA, Dusick AM, Vohr BR, Wright LL, Wrage LA, Poole WK: Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth weight infants. Pediatrics 2006;117: 1253–1261. 2 Ziegler EE: Meeting the nutritional needs of the low-birth-weight infant. Ann Nutr Metab 2011;58(suppl 1):8–18. 3 te Braake FWJ, van den Akker CHP, Wattimena DJL, Huijmans JGM, van Goudoever JB: Amino acid administration to premature infants directly after birth. J Pediatr 2005;147:457–461.
