b. Esophageal sphincter present by 28 weeks of gestation.

c. GI tract resembles that of a term newborn infant by 20 weeks of gestation.

d. Gut lengthens to 250 to 300 cm by term; gastric capacity is about 30 mL.

b. By 28 weeks, biochemical and physiologic capacities for limited digestion and absorption are present.

c. Major gut-regulating polypeptides—gastrin, motilin, cholecystokinin, pancreatic polypeptide, and somatostatin—are present in limited amounts by the end of the first trimester; act locally to regulate growth and development of the gut; reach adult distribution by term gestation.

d. Intestinal transport of amino acids seen by 14 weeks, glucose by 18 weeks, and fatty acid by 24 weeks of gestation.

e. Lactose is a predominate source of carbohydrate in breast milk and formula. Lactase reduces lactose to glucose.

f. Lactase activity is first seen at 9 weeks of gestation; at 24 weeks of gestation, less than one fourth the activity level of term infant; dramatically increases between 32 and 34 weeks of gestation to the activity level of term infant.

g. Disaccharidases, such as salivary amylase and mucosal glucoamylase, are functionally active after 27 to 28 weeks of gestation. Some formulas contain glucose polymers, likely hydrolyzed by salivary amylase or absorbed directly at the mucosal level via mucosal glucoamylase.

h. Fat (lipid) emulsification and hydroxylation to free fatty acids and monoglycerides result from lipase and bile acid activity.

i. Lingual and gastric lipases present by 26 weeks of gestation; limited in volume and function. Additional lipases also in breast milk; function well in conditions with low bile acid synthesis and stores such as seen in premature infants.

j. Bile acid secretion observed by 22 weeks of gestation.

k. Bile acid synthesis and stores of premature infant decreased when compared to term infant synthesis and stores, which is in turn one half that seen in adult synthesis and stores.

l. Gastric gland secretion activity seen by 20 weeks of gestation; gastric acid secretion lower than adult levels even at term gestation; activated with introduction of enteral feeding.

m. Ingested proteins are denatured by gastrin and cleaved by pepsin; further reduced by pancreatic proteolytic enzymes into oligopeptides and amino acids. Pepsin activity induced by increased gastric acid resulting from initiation of enteral feedings.

b. Hormonal regulatory mechanisms have a critical role in mediating gut development after birth. Gut development stimulated by increases in specific GI hormones and enteric neuropeptides such as enteroglucagon, promoting intestinal mucosa growth; gastrin, stimulating gastric mucosa and exocrine pancreas growth; motilin and neurotensin, stimulating development of gut motility; and gastric inhibitory peptide, promoting glucose tolerance.

c. Initiation of enteral feeding is a major stimulus for hormonal regulatory mechanisms in both premature and term infants; response delayed in premature and high-risk infants receiving only PN without enteral feedings.

d. Type of enteral feeding has an influence on gut maturation; breast milk contains high levels of GI trophic factors, which enhance the postnatal maturation of gut.

(b) Brown adipose tissue: accumulates in the neck, scapulae, axillae, mediastinum, and perirenal tissues; critical for nonshivering thermogenesis, a major method of neonatal heat production.

(2) Protein catabolism contributes approximately 10% of postnatal caloric intake.

(2) Fat is a major source of stored calories for term infant; preferred energy source for high energy demands of such tissues as the heart and the adrenal cortex.

2. Vitamins and minerals.

(2) Vitamin E gradually increases throughout pregnancy with direct correlation between vitamin E level and body weight and adipose tissue; stored primarily in liver, adipose tissue, and skeletal muscle; at low levels after birth and through infancy, dependent on diet (breast milk, formula) for adequate supply; provides protection from oxidant free-radical damage.

(2) Fetal phosphorus levels higher than maternal levels during the third trimester; important role in fetal intermediary metabolism and bone mineralization.

(3) Eighty percent of the magnesium in term infants is accrued in the third trimester; important to plasma membrane excitability, regulatory role in numerous biological processes involved in energy storage, transfer, and production, significant in calcium and bone homeostasis.

b. Enteral: 120 to 150 mL/kg/day.

2. Energy (caloric) intake requirements.

b. Enteral: 100 to 120 kcal/kg/day.

(2) Fat.

b. Individual premature infant nutritional needs vary with gestational age and health status.

b. Enteral: 150 to 200 mL/kg/day.

c. Varies with hydration state (e.g., dehydration to overhydration/edematous states), estimated insensible water losses, gestational age, postmenstrual age, generalized health status, and underlying disease state of the infant (e.g., presence of patent ductus arteriosus, bronchopulmonary disease, postrecovery phase of necrotizing enterocolitis [NEC], and short bowel syndrome).

3. Energy (caloric) intake requirements.

b. Parenteral: 80 to 100 kcal/kg/day.

c. Enteral: 110 to 130 kcal/kg/day.

d. Varies depending on day of life, fluid intake, thermal environment, activity, maturation, health status, underlying disease state, and growth rate.

(2) Enteral: 8 to 12 g/kg/day; primarily lactose.

(3) Glucose intake must be adequate to maintain serum levels greater than 45 mg/dL.

(4) Premature infants rapidly become hypoglycemic with inadequate glucose intake. Hyperglycemia can also be a problem with extremely premature infants. Hyperglycemia contributes to hyperosmolality and may be a risk factor for intracranial hemorrhage in those infants.

b. Fat.

(2) Enteral: 3 to 4 g/kg/day.

(3) Medium-chain triglycerides are easier to absorb than long-chain triglycerides; medium-chain triglycerides are absorbed by passive diffusion and do not require bile salts.

(b) Linoleic acid is an essential fatty acid and should account for at least 3% of total calories; achieved with adequate intake of human milk and commercial premature infant formulas.

(c) Very-long-chain fatty acids—arachidonic acid and docosahexaenoic acid—are derivatives of linoleic and linolenic acids and are found in human milk but not cow’s milk; associated functionally with cognition and vision.

(b) Very low birth weight (VLBW) infants, that is, 1000 to 1500 g birth weight: 3.0 to 3.5 g/kg/day.

(2) Enteral: 3.0 to 4.3 g/kg/day; higher protein amounts for low birth weight (LBW) infants.

(3) Protein requirements for VLBW infants controversial owing to uncertainty related to ability to tolerate protein and what is actually needed to provide for growth and development.

(b) Good evidence that early amino acid intake compensates for potential protein losses; 1.5 to 2 g/kg/day as soon as possible after birth preserves limited body protein stores in ELBW infants even at low caloric intakes; increasing caloric intake will improve protein accretion.

(c) Ultimate goal of parenteral amino acid administration is to achieve a rate of fetal protein accretion; recent evidence shows that 3.5 to 4.0 g/kg/day are tolerated for ELBW infants.

(d) Protein and energy intakes should be determined concurrently to optimize nitrogen retention and promote proportionate body composition (lean-to-fat mass ratio) growth; protein-to-energy intake ratio recommendations for VLBW infants range from 2.25 to 3.6 g/100 kcal.

(e) In addition to the eight essential amino acids necessary for cell growth, premature infants require four conditionally essential amino acids: histidine, taurine, cysteine, and tyrosine.

b. Premature infants, especially VLBW infants, have increased urine sodium and obligatory water loss during the transitional neonatal period.

c. After reduction of the extracellular fluid, loss of body weight slows and urinary excretion of sodium chloride decreases. VLBW infants may require sodium supplements until renal tubular function matures.

d. Premature infant formulas provide higher amounts of sodium, potassium, and chloride than term infant formulas; milk from mothers of premature infants (premature human milk) has higher sodium and chloride levels than that from mothers of term infants (mature human milk) (after 4 weeks); may still need to supplement until renal tubular function matures.

2. Short bowel syndrome.

3. Acute GI conditions, such as NEC or intestinal perforation.

4. Renal failure.

5. Insufficient caloric or nitrogen (protein) content of enteral feeds.

6. Severe respiratory or cardiac disease.

B. PN administration.

b. Provides up to 90 kcal/kg/day with dextrose and lipid emulsions and adequate fluid intake.

2. Central route.

b. Complications of central catheters: sepsis; thrombosis of large vessels; pleural or pericardial effusions due to malposition outside the vessel; hemorrhage associated with erosion of central vessels; thrombophlebitis.

c. Peripherally inserted central catheters provide prolonged venous access; inserted at the bedside with a strictly aseptic technique by qualified personnel.

d. Surgically placed central venous catheters (i.e., Broviac or Hickman) provide long-term venous access; require anesthesia; and are recommended for home PN use.

e. All central venous catheters require radiographic confirmation for placement prior to initiation of PN.

b. Varies with gestational and postnatal age and environmental conditions, such as incubator versus radiant heat source and phototherapy. Incubators and heat shields can reduce insensible water losses, whereas radiant warmers and phototherapy increase these losses.

2. Calories

(2) Activity and catabolic states can cause a 25% to 75% increase in metabolic demands.

(2) Guidelines for carbohydrate administration:

(b) Gradual increase in GIR to 13 to 17 g/kg/day (9 to 12 mg/kg/min) over 2 to 7 days usually tolerated in the presence of amino acid administration; maintain serum glucose 40 to 150 mg/dL; maximum GIR recommended: 18 g/kg/day (12.5 mg/kg/min); higher rates exceed glucose oxidative capacity, cause extensive lipogenesis.

(c) In some VLBW infants, severe hyperglycemia may present and continue despite reduced carbohydrate intakes; continuous insulin infusion may be used; routine use not advised because of side effects. The usual infusion of insulin is 0.01 to 0.1 unit/kg/hr to maintain blood glucose levels between 100 and 200 mg/dL.

b. Fat: 20% lipid preparations, 2.2 kcal/mL.

(2) IV lipid emulsions have a fatty acid profile substantially different from human milk.

(3) Lipid emulsions of 0.5 to 1 g/kg/day prevent deficiency of essential fatty acids; should be introduced as a component of PN by 24 to 48 hours of age; increase by 0.5 to 1 g/kg/day to 3 g/kg/day.

(4) Premature infants less than 28 weeks of gestational age have limited lipoprotein lipase activity and triglyceride clearance; may require slower advances in IV lipid infusion rate to improve tolerance.

(5) Although heparin releases lipoprotein lipase from the endothelium into circulation, there is no evidence that this increases lipid utilization in premature infants; therefore, routine addition of heparin into lipid infusion is not recommended.

c. Protein: amino acids, 4 kcal/g. Recommended intake: 2.25 to 4 g/kg/day.

(2) Pediatric amino acid solutions designed to mimic plasma amino acid concentrations in healthy 20-day-old breastfed infant (Trophamine) or fetal or neonatal cord blood amino acid concentrations (Primine); no evidence to support superiority of one solution over the other.

(b) Tyrosine has limited solubility, and so a small amount is included; Trophamine contains a soluble derivative of tyrosine but appears to have poor bioavailability; current research suggests that tyrosine supply in amino acids is suboptimal for VLBW infants.

(c) Cysteine unstable for long periods; cysteine hydrochloride supplement can be added to PN just prior to administration; there is conflicting evidence as to whether cysteine improves protein accretion.

d. Calcium and phosphorus.

(2) Precipitation of calcium and phosphorus remains an issue in the United States owing to commercially available solutions; not possible to supply VLBW infants with adequate amounts of parenteral calcium and phosphorus to support optimal bone mineralization.