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Nutrition for the Neonate

Growth Failure in the VLBW Infant


on 24 November 2012

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Transcript of Nutrition for the Neonate

When NPO... When NPO... Nutrition for the Neonate Goal Growth for the very low birth weight infant should approximate in utero growth rates. "Postnatal growth failure is the norm for extremely low birth weight infants, especially the sickest infants." Pediatrics 2006;117;1253 Two weeks Growth Failure Five weeks "Impaired neurocognitive development is closely linked to impaired growth during the neonatal period." Pediatrics 1985;76;976-986 Pediatrics 2006;117;1253 Head circumference catch up growth is associated with improved neurocognitive development. Brain growth is key J Perinat Med. 2011 Sep;39(5):579-86 When NPO... reduced gut growth and atrophy with increased apoptosis and proteolysis
decreased gut DNA, protein mass, cell proliferation, villous height
decreased gut hormone secretion (gastrin, GIP)
decreased growth factors Low intestinal lactase activity
More feeding intolerance gastrointestinal barrier remains immature
bacterial colonization with pathogens more likely
increased intestinal permeability
increased gut-derived septicemia Early Aggressive Nutrition Nutritional requirements do not stop at birth Unfortunately, some changes in brain growth are irreversible J Maternal-Fetal and Neonatal Medicine, 2009;22(3):191-197 Fetal hypoxia
reduces protein synthesis more than protein breakdown
decreases activity of amino-acid transporters
prevents insulin from stimulating eIF4e expression Anemia
fetal or neonatal growth rates diminish Oxygen toxicity
Transfusion risk vs. growth
restriction Oxygen Glucose Whole body glucose utilization is twice as high in early gestation compared to term
Early in gestation, the brain accounts for nearly all of whole-body glucose utilization Glucose production rates... 28 weeks - 6-8 mg/kg/min
Term infants - 3-5 mg/kg/min Neonatology 2008;94(4):245-254 Lipids Hyperglycemia excessive glucose administration
thermal instability
sepsis (release of endotoxin)
dopamine, dobutamine, epinephrine
intravenous lipids Hyperglycemia managment Decreasing glucose infusion rate
Normalizing physiology
Decreasing endogenous catecholamines
Limiting lipid infusion
Start amino acids early
Insulin Little is known of the normal requirements of lipids for fetal growth and development. Lipids are a source of energy but little used by the fetus until late gestation. Lipids are variously used... Early or late
Low dose or high Nutritional goal Essential Fatty acid deficiency may be prevented by lipid infusions as small as 0.5 gm/kg/day Lipid emulsions are unbalanced toward the omega-6 rather than the omega-3 PUFAs. PUFAs are needed for neurologic development and visual development Protein Protein Requirements "At mid-gestation, fetal animals require from 3.5 to 4.6 gm/kg/day to sustain normal rates of fractional protein synthesis and growth." Am J Physiol 1981;240:E320-E324
Am J Physiol 1996;270:E491-E503 "This rate of requirement is ongoing. There is no justification for short- or long-term interruption of amino acid supply..." Neonatology, 2008;94(4):245-254 Minimum protein intake of premature infants is 3.4 g/kg/day with a protein/energy ratio of 2.5 g/100 kcal/kg/day J Nutr 2002;132 (Suppl 1):1395S-577S (the rate limiting step for growth) Why are protein intakes still so low? At 14 days of age, the overall mean protein intake was 2.5 g/kg/day. At 21 days of age, mean intake was still 2.5 g/kg/day Pediatrics 2002;110:1125 Enteral Nutrition After Thoughts Not a rate limiting factor! Energy seldom limits growth as long as intakes are at least 90 kcal/kg to 100 kcal/kg Leftovers... "Fear of amino acid toxicity, uremia, and metabolic acidosis lingers, a problem left over from the earliest days of IV amino acid nutrition when solutions were unbalanced away from essential amino acids towards non-essential and the potentially toxic glycine, methionine and phenylalanine." Neonatology, 2008;94(4):245-254 "Some increase in blood urea nitrogen is expected when the amino acids are oxidized..." Neonatology, 2008;94(4):245-254 To prevent amino acid toxicity, but provide enough for protein synthesis, net protein accretion, and growth must give the right amount at the right time. 24 to 30 weeks gestation - 3.6 to 4.8 g/kg/day
30 to 36 weeks gestation - 2 to 3 g/kg/day
Term infants - 1.5 to 2 g/kg/day Specifically, infants fed additional 22:6n-3 (DHA) have better visual acuity and improved developmental testing at 12 months. Am J Clin Nutr 1993;58:35-42 Parenteral Nutrition Insulin Insulin is the principal anabolic hormone in the fetus Insulin production begins around 15 weeks gestation Insulin enhances protein synthesis and reduces protein breakdown Without optimal amounts of amino acids and energy, insulin cannot by itself promote growth "For the most part, insulin treatment to increase growth will simply make the baby fatter." Neonatology 2008;94(4):245-254 J Pediatr 1998;132:948-953 However... Adults in the ICU have increased risk of sepsis and death associated with hyperglycemia In the PICU, high glucose levels are associated with increased mortality Neonatal hyperglycemia is associated with ROP, NEC, IVH and increased mortality N Engl J Med 2001; 345(19):1359-1367 J Pediatr 2005;146(1):30-34 J Perinatology 2006;26:730-736 Insulin infusion for hyperglycemia in very preterm infants appears safe with no effect on morbidity, mortality and long-term neurodevelopmental outcome. Recommended glucose range is 55 to 150 J Matern Fetal Neonatal Med 2012 Jun 29 [Epub ahead of print] Hours, not days, are the longest an infant should be allowed to be without nutrition, IV or PO. At birth the continuous transfer of nutrients to the fetus is interrupted. Stock TPN Impossible for the immature gut to absorb all the nutrients required to match in utero growth rates. D7.5
4 g AA/100 ml
Na Acetate 2 mEq/100 ml
Ca gluconate 1 mEq/100 ml
Heparin 0.5 units/ml < 30 weeks EGA > 30 weeks EGA D10
3 g AA/100 ml
Na Acetate 2 mEq/100 ml
Ca gluconate 1 mEq/100 ml
Heparin 0.5 units/ml Lipids may be started safely on day one at 0.5 up to 3 g/kg/day Lipoproteinase activity is independent of intake so that slowly increasing IL is likely unnecessary J Perinatology 2004;24:482-486
J Matern Fetal Neonatal Med, March 2009;22(3):191-197 J Perinatology 2005;25:130-133 Minimal Enteral Nutrition (MEN) Breast milk does not provide enough PUFAs to equal the essential fatty acids that accumulate in the developing fetal brain. prevent essential fatty acid deficiency
prevent limitation of neurologic development What is known? Direct and Indirect trophic effects of MEN Enhanced DNA synthesis
Epidermal growth factor
Gastric inhibitory peptide Maturation of gut mucosa
Nutrient absorption
Enhanced motor responses of small intestine
Enhanced mixing and churning
Increased forward propulsion Safe to feed on day 1 - no later than day 2
No increased risk of NEC
Decreases risk of sepsis and NEC
Shorter times to full feedings
Safe even in sick infants Pediatrics in Review 1999;20;e45 Neonatology 2008;94(4):245-254
Acta Paediatrica, 2006;95:1341-1344 aka Trophic Feedings Leading to... Amino acids are provided in excess of what the fetus can use.
Excess amino acids are oxidized for fuel
Glucose is taken up and used to meet energy needs
Little fetal lipid uptake at 70% of gestation Normal Fetal Nutrition Typical Nutrition of the Preterm Infant Glucose is pumped in at rates higher than the infant can use
Excess glucose produces hyperglycemia
Amino acids are provided at rates less than needed for normal growth
Lipids are a major source of energy To mimic in utero nutrition Supply amino acids at levels just higher than the infant can use (<30 weeks gestation)
Excess amino acids are oxidized for energy
Provide just enough glucose (6-10 mg/kg/min)
Provide just enough lipids to meet additional energy needs (and EFA) 2-3 g/kg/day Infants with IUGR Decreased pancreatic development
Decreased insulin secretion capacity
Decreased amino acid synthesis into protein and cell growth
Regulators of protein translation are decreased
Inhibitors of protein translation are increased
Poor growth in spite of adequate amino acid supply Infants with IUGR Up-regulated capacity to take up glucose
Higher rates of glucose may lead to lactic acidosis and fat production (more than in the normal fetus) Birth weight and rate of weight gain predict childhood overweight status
More energy (given normal protein and calorie intake) only produces fatter infants without increased growth of bone length, body length, or OFC.
Excess growth and catch up growth is associated with the metabolic syndrome Special Considerations Asphyxia Typical to keep infant NPO for at least 48 hours
Consider feedings by no later than 5 days even for severe asphyxia
Neurologically intact term infants may feed ad lib Sepsis Work Up NPO status is appropriate for poor perfusion states (decreased urine output, hypotension or shock
Consider continuing feedings if stable
Resuming feedings at previously tolerated levels is acceptable Post Operative Period Increased catabolism following surgery
Nutrition should be maintained by TPN if infant is NPO
Amino acid infusion is safe and will prevent significant catablolism J Pediatr 2008;152:63-67 "Even when every effort was made to meet recommended energy and protein intakes, most infants accumulated significant deficits in the first 2 weeks of life." J Perinatology 2006;26:436-442 NEC Feedings may be re-started with clinical signs of motility How much is needed?
At what age?
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