Fluid

Fluid management is a challenging component of early-life neonatal care because requirements must be balanced with expected losses and rapidly changing serum electrolyte status. Weight loss is expected within the first 1 to 2 weeks of life due to the transition to the extrauterine environment and contraction of the extracellular fluid. As illustrated in Table 20.7 , extracellular fluid volume increases with the degree of prematurity, resulting in greater expected weight loss after birth. ^,

Term infants typically experience 5% to 10% weight loss from birth weight in the first 7 to 10 days of life; preterm infants may experience up to 15% weight loss and may take up to 14 days to regain birth weight. More significant weight loss and a longer time to regain birth weight may be concerning for improper fluid and nutrition management.

Premature infants have increased fluid requirements due to elevated energy needs, high rates of insensible water loss, and immature renal function. Insensible water losses are caused from respiration and immature skin membranes but may be reduced with administration of antenatal steroids and use of double-wall incubators. Premature infants have an impaired ability to concentrate urine due to a reduced nephron count and immature tubular function causing decreased glomerular filtration; this puts them at an increased risk of dehydration and electrolyte abnormalities.

Many disease states may necessitate modifications to fluid administration so as to not contribute to disease progression while preventing dehydration ; disease states include patent ductus arteriosus and bronchopulmonary dysplasia. ^,

A gradual increase of fluid intake is recommended in preterm and term neonates after birth. The smaller and more premature the infant, the higher the fluid requirements. An example of fluid progression in neonates is depicted in Table 20.8.

Energy

Energy requirements of preterm infants receiving parenteral nutrition are determined by the basal metabolic rate, growth requirements, and severity of illness. Meeting energy goals is necessary to meet growth goals and improve clinical and developmental outcomes in neonates. Research has shown that meeting ideal nutrition administration in the first week of life is associated with improved growth and neurodevelopment in preterm infants. ^{, ,} Additionally, achieving energy intake goals in the first week of life may decrease the risk of adverse outcomes from critical illness in extremely low birth weight infants. Excess energy administration may cause hyperglycemia, which may increase the risk of infection, impaired liver function, and long-term metabolic consequences and thus should be avoided.

Energy provided should promote appropriate, symmetric growth. A commonly used goal for weight gain is 17 to 20 g/kg/day. A full discussion of growth goals and assessment can be found in the nutrition assessment chapter ( Chapter 22 ).

Protein

Protein is required for growth in the preterm infant. Reaching protein goals in the first days of life may lessen hyperglycemia and reduce the need for insulin therapy. ^, Achieving protein goals in this critical window may also improve postnatal growth and neurodevelopmental outcomes in preterm infants. ^,

Protein requirements of parenterally fed infants are lower than those of infants receiving enteral nutrition due to the bypassing of intestinal uptake and utilization of amino acids. Protein administration should not exceed 4 g/kg/day, because exceedingly high protein has not been shown to be an effective therapy in improving any nutritional or clinical outcomes.

Preterm infants have altered metabolic requirements and have a higher need for conditionally essential amino acids including arginine, glycine, proline, tyrosine, cysteine, and glutamine. Specialized amino acid solutions are used to meet preterm infants’ parenteral needs ( Table 20.9 ).

Carbohydrates

Dextrose (D-glucose) is the source of carbohydrate in parenteral nutrition and provides 3.4 calories per gram. Dextrose should be given at a level to meet energy needs while preventing excessive administration and hyperglycemia. Table 20.10 reviews dextrose and glucose infusion rate (GIR) recommendations and associated line requirements. Minimum GIRs have been estimated to ensure that organs that preferentially use glucose for energy (the brain, renal medulla, and erythrocytes) are able to receive a sufficient amount.

Excessive dextrose administration can cause hyperglycemia, which is associated with an increased risk of multiple morbidities including poor postnatal growth, severe intraventricular hemorrhage, increased need for respiratory support, and poor neurologic outcomes. Hyperglycemia is also associated with a higher rate of mortality among preterm infants.

There may be a risk of long-term metabolic consequences of persistent hyperglycemia and high glucose infusion rate in the neonatal period. In pediatric studies, beta-cell dysfunction has been observed in children with prolonged hyperglycemia in the critically ill state. Excess glucose administration causes lipogenesis and fat deposition; this may cause steatosis and impair liver function. This metabolic outcome may contribute to development of parenteral nutrition–related liver disease in the preterm infant.

Providing a balanced parenteral administration that meets carbohydrate, lipid, and amino acid goals helps minimize hyperglycemia and electrolyte abnormalities in preterm infants. ^,

Lipids

Lipids provide energy and essential fatty acids and aid in delivery of lipid-soluble vitamins. Infants receiving parenteral nutrition should receive 25% to 50% of nonprotein calories from a lipid source. Initiation of lipids in the first 2 days of life is believed to be safe and well tolerated in very low birth weight infants. ^, Additionally, early initiation of intravenous lipid emulsions has been shown to improve growth in the neonatal population and may reduce the incidence of retinopathy of prematurity. ^,

There is little research on the ideal dosing of intravenous lipid emulsions in the first days of life or in infants with sepsis or infection. In critically ill infants, monitoring of plasma triglycerides and adjustment of lipid infusion rates is recommended. An example of dosing of commonly discussed intravenous lipid emulsion products in the United States can be seen in Table 20.11 .

Intralipid is a 20% lipid emulsion, is entirely soybean-oil based, and provides 10 calories per gram of fat. Intralipid is highly concentrated in essential fatty acids, thus allowing a minimum dose of0.5–1 g/kg/day to meet essential fatty acid requirements. This product has historically been the only intravenous lipid emulsion product used in the neonatal population in the United States. Although Intralipid is effective in providing nonprotein calories and essential fatty acids, prolonged use is associated with negative clinical outcomes including increased oxidative stress, pulmonary vascular resistance, impaired pulmonary gas exchange, and increased rates of infection.

Omegaven is an entirely fish oil–based intravenous lipid emulsion that is approved for use in neonatal populations for treatment of parenteral nutrition associated cholestasis (PNAC), as diagnosed by a direct bilirubin level ≥2 mg/dL. Use of Omegaven is effective in reversing PNAC in neonates requiring prolonged parenteral nutrition administration. Although Omegaven is an intravenous lipid emulsion, it is intended to be used for PNAC management and treatment; Omegaven does not contain sufficient essential fatty acids to meet the neonate’s requirements.

SMOFlipid is a mixed oil lipid emulsion that has recently been approved for use in neonates in the United States by the Food and Drug Administration. SMOFlipid is a 20% lipid emulsion composed of 30% soybean oil, 30% midchain triglycerides, 25% olive oil, and 15% fish oil; and it provides 10 calories per gram of fat. Due to the decreased content of the essential fatty acid–rich soybean oil, a minimum dose of 2 g/kg/day is needed to avoid essential fatty acid deficiency. Composite intravenous lipid emulsions such as SMOFlipid may have fewer proinflammatory components, thus causing less immune suppression, and a greater antioxidant effect than intravenous lipid emulsions composed of only soybean oil, such as Intralipid. A reduction in phytosterol content in mixed-oil lipid emulsions has been proposed as a possible reasoning for the hepatoprotective effects of mixed-oil and soy lipid emulsions. However, the reduction of cholestasis in preterm infants due to SMOFlipid use has been inconclusive in the neonatal population. The medium chain triglyceride (MCT) content of SMOFlipid is beneficial because it has faster plasma clearance, more rapid oxidation, and less dependency on carnitine for beta oxidation. The increased vitamin E content in SMOFlipid may have antiinflammatory benefits but may require increased monitoring of serum alpha-tocopherol levels to prevent hypervitaminosis. Although further research must be completed to discern the full impact of SMOFlipid on neonates, there are significant potential benefits related to SMOFlipid use in this population, including reduction of PNAC, improved growth, reduction of retinopathy of prematurity, and reduction of bronchopulmonary dysplasia. ^, Infants with prolonged exposure to parenteral nutrition likely have the greatest potential to benefit from SMOFlipid administration.

All infants receiving intravenous lipid emulsions should have their triglyceride levels checked every 2 weeks. If the triglyceride level is >265 mg/dL, reduction of lipids may be considered. ^, For infants receiving SMOFlipid, testing of serum alpha tocopherol levels should be considered to monitor for hypervitaminosis due to increased vitamin E content in this product.

Sodium, Potassium, Magnesium, and Chloride

Administration of electrolytes (Na, Cl, and K) should be adjusted to maintain appropriate serum values on laboratory measurements and per the infant’s clinical status. Fluctuation of fluid status in the first days of life often requires several changes to electrolyte supplementation. Example dosing of electrolytes can be viewed in Table 20.12 . Chloride levels should be monitored to avoid iatrogenic metabolic acidosis. Potassium supplementation in early life should be closely monitored to avoid nonoliguric hyperkalemia.

While weaning off PN, serum sodium should be closely monitored to ensure adequate status with enteral supplementation provided as needed. Late-onset hyponatremia after discontinuing parenteral nutrition inhibits appropriate growth in preterm infants.

Magnesium is an important cation that is required for DNA, RNA, and protein synthesis and plays a crucial role in bone matrix development. Neonates are at risk for hypermagnesemia in the first days of life if their mothers were treated with magnesium sulfate prior to delivery; this population may not immediately require supplementation parenterally. If a neonate has hypermagnesemia at birth, magnesium should be added into the parenteral solution after neonatal serum levels have normalized.

Calcium and Phosphorus

Calcium and phosphate are essential minerals that play an important function in bone health and development. Phosphate plays a critical role in energy metabolism, whereas calcium is essential for muscle contractions.

The challenges of calcium and phosphate solubility in parenteral nutrition have been well studied, with numerous published solubility curves available for standard use of pediatric pharmacists. Most commonly, the ideal ratio of calcium to phosphorus appears to be 1 mmol Ca to 1 mmol P (or 2 mEq Ca to 1 mmol P). The percentage of amino acid in solution, inclusion of cysteine, pH, volume of PN, and temperature of the PN solution all increase the solubility of calcium and phosphorus in solution ; see Table 20.13 for further discussion of compatibility, and see Table 20.14 for example dosing of calcium and phosphorus with parenteral nutrition volume and amino acid content in mind.

Metabolic bone disease and serum calcium and phosphorus abnormalities can be common problems in the preterm infant. Inadequate and unbalanced parenteral nutrition administration in the first days of life may exacerbate these abnormalities. This “placental incompletely restored feeding syndrome” was first proposed by Bonsante et al. in 2013; they showed that excessive amino acid and energy administration without adequate mineral administration drove hypokalemia, hypophosphatemia, and hypercalcemia in preterm infants. Neonatal refeeding syndrome may be prevented by introducing phosphorus at physiologic rates in the first 24 hours of life, rather than providing phosphate-free starter total parenteral nutrition (TPN) for the first few days of life.

Prolonged use of parenteral nutrition puts neonates at an increased risk for metabolic bone disease of prematurity. This is discussed in depth in the “Complications of Parenteral Nutrition” section of this chapter.

Iron

Iron plays a critical role in neurodevelopment and erythropoiesis. Iron deficiency in infancy can cause anemia and significant neurocognitive deficits later in life. ^, Enteral iron is nearly always the preferred method of administration, as parenterally administered iron bypasses the absorption regulation present in the gastrointestinal tract. When administered parenterally, there is a risk of iron overload because there is no mechanism for excretion or absorption regulation. Iron overload can increase oxidative stress and risk of infection. For patients on long-term parenteral nutrition, ferritin and hemoglobin should be monitored to assess iron status and avoid iron deficiency and toxicity.