What is the recommended protocol for initiating and managing parenteral nutrition in preterm infants who cannot receive adequate enteral feeds?

Parenteral Nutrition in Preterm Infants

In preterm infants who cannot receive adequate enteral feeds, initiate parenteral nutrition immediately after birth or no later than day 2 of life, starting with amino acids at 1.5-2.5 g/kg/day on day 1, glucose at 4-8 mg/kg/min, and lipid emulsions at 1-2 g/kg/day, then advance rapidly over 2-3 days to target amino acids 3.5 g/kg/day, glucose 8-10 mg/kg/min (max 12), and lipids 3-4 g/kg/day to prevent cumulative nutrient deficits that impair neurodevelopmental outcomes. 1, 2

Timing of Initiation

• Start PN within 8 hours of birth in preterm neonates, as delayed initiation leads to negative nitrogen balance and growth failure that cannot be recovered. 2
• Lipid emulsions can be started immediately after birth and no later than day 2 of life (strong recommendation, Level 1 evidence). 1
• Do not wait for enteral feeding attempts to fail before initiating PN—preterm infants require PN as complementary support even when minimal enteral feeds are given. 1, 3

Amino Acid Protocol

Day 1: Start at minimum 1.5 g/kg/day to achieve anabolic state and prevent negative nitrogen balance. 2

Day 2 onwards: Advance to target of 3.5 g/kg/day for optimal growth and neurodevelopmental outcomes. 1, 2, 4

• The maximum safe dose is 3.5 g/kg/day based on ESPGHAN 2018 guidelines; do not exceed this outside clinical trials as evidence for higher doses (up to 4 g/kg/day) lacks strong support. 2, 4
• When providing high protein doses, ensure non-protein energy exceeds 65 kcal/kg/day to optimize nitrogen retention and protein utilization. 2, 4
• Higher amino acid intakes (3.5-4 g/kg/day) are well tolerated when started early and prevent the protein deficits that lead to poor neurodevelopmental outcomes. 3, 5

Glucose (Carbohydrate) Protocol

Day 1: Start at 4-8 mg/kg/min (5.8-11.5 g/kg/day) in preterm infants, adjusted based on blood glucose monitoring. 1

Day 2 onwards: Target 8-10 mg/kg/min (11.5-14.4 g/kg/day) to support growth. 1

• Maximum: Do not exceed 12 mg/kg/min (17.3 g/kg/day). 1
• Minimum: Generally maintain at least 4 mg/kg/min (5.8 g/kg/day) to prevent hypoglycemia. 1
• Monitor blood glucose frequently (every 4-6 hours initially) and maintain levels between 2.5-8 mmol/L (45-145 mg/dL). 4
• If acute illness or sepsis develops, temporarily reduce to day 1 glucose rates guided by blood glucose levels. 1

Lipid Emulsion Protocol

Day 1-2: Start at 1-2 g/kg/day immediately after birth or by day 2. 1

Day 2 onwards: Advance to 3-4 g/kg/day. 1, 4

• Maximum: Do not exceed 4 g/kg/day in preterm infants. 1, 4
• Provide minimum linoleic acid intake of 0.25 g/kg/day to prevent essential fatty acid deficiency. 1
• Use composite lipid emulsions (containing medium-chain triglycerides, olive oil, or fish oil) rather than pure soybean oil for PN lasting more than a few days, as they reduce infection risk and may decrease PN-associated liver disease. 1, 5
• Use 20% lipid emulsions as first choice (strong recommendation). 1
• Administer lipids continuously over 24 hours in preterm infants. 1
• Use light-protected tubing to prevent lipid peroxidation and generation of toxic oxidants. 1

Total Energy Targets

• Day 1: Minimum 45-55 kcal/kg/day to meet basal metabolic requirements. 2
• Stable growing period: Target 90-120 kcal/kg/day parenterally, with most practitioners aiming for at least 120 kcal/kg/day to facilitate maximal protein accretion during catch-up growth. 2, 4
• At typical fluid intake of 150 mL/kg/day, standard PN solutions deliver approximately 90-93 kcal/kg/day. 4

Fluid Management

• Start with restricted fluids (60-80 mL/kg/day) on day 1, then advance by 20-30 mL/kg/day. 6
• Target 140-170 mL/kg/day by day 3-5 to maintain sodium balance and support growth. 6
• At lower fluid intakes (100 mL/kg/day), energy delivery may be insufficient for optimal growth; adjust concentration accordingly. 4

Electrolytes and Minerals

• Sodium: 4-7 mEq/kg/day (consider 4-5 mmol/kg/day supplementation in infants <35 weeks during first 2 weeks for better neurocognitive outcomes). 2, 6
• Potassium: 2-4 mEq/kg/day. 2
• Calcium: 2-3 mmol/kg/day (80-120 mg/kg/day) with calcium:phosphorus ratio of 0.8-1.2. 2
• Phosphorus: Calculate as [calcium intake (mmol/kg)/1.67] + [protein accretion (g) × 0.3]. 2
• Magnesium: 0.12-0.20 mmol/kg/day (2.9-4.8 mg/kg/day). 2

Administration and Safety

• Administer PN through central venous access when osmolality exceeds peripheral vein tolerance (typically >900 mOsm/L). 3
• Use terminal filters: 1.2-1.5 μm for lipid-containing solutions, 0.22 μm for aqueous solutions. 1
• Administer with accurate flow control using infusion pumps with free-flow prevention and lockable settings. 1
• Check peripheral infusions frequently for extravasation or signs of infection. 1

Monitoring Protocol

• Frequency: Daily laboratory assessment initially, then 2-3 times per week once stable. 1
• Blood glucose: Monitor every 4-6 hours initially, maintain 2.5-8 mmol/L (45-145 mg/dL). 4
• Anthropometrics: Monitor weight daily, length and head circumference weekly. 1, 2
• Target weight gain: 17-20 g/kg/day after initial postnatal weight loss to prevent dropping across centiles. 2, 6
• Weight gain below 9 g/kg/day requires immediate intervention. 2
• Birth weight should be regained by 7-10 days; if not regained by day 14, exclude pathology and intensify feeding. 6

Enteral Feeding Integration

• Never provide complete enteral starvation—give minimal enteral feeds ("trophic feeds") whenever possible, even if only small volumes, to maintain gut structure and function. 1, 7
• Breast milk is the preferred enteral feed and reduces necrotizing enterocolitis risk. 1, 7
• Start enteral feeds as continuous infusion over 4-24 hours using volumetric pump. 1
• Increase enteral volumes slowly (20-30 mL/kg/day) according to tolerance, making only one change at a time. 1, 6
• Reduce PN in proportion to or slightly more than the increase in enteral nutrition. 1
• Enteral volumes <25 mL/kg/day have negligible absorption; do not reduce PN significantly at these volumes. 2

Multidisciplinary Team Oversight

• PN should be supervised by a multidisciplinary nutrition support team (physician, nurse, dietitian/nutritionist, pharmacist) to promote optimal care, reduce errors, and improve outcomes. 1
• Accurate anthropometrics and clinical evaluation should be performed by skilled practitioners. 1

Critical Pitfalls to Avoid

• Do not delay PN initiation—waiting beyond day 2 results in irreversible nutrient deficits. 1, 2, 3
• Do not underdose amino acids—starting below 1.5 g/kg/day or failing to advance to 3.5 g/kg/day leads to negative nitrogen balance and poor neurodevelopmental outcomes. 1, 2
• Do not provide high protein without adequate non-protein energy—ensure >65 kcal/kg/day to optimize protein utilization. 2, 4
• Do not use pure soybean oil emulsions for PN lasting more than a few days—switch to composite emulsions to reduce infection and liver complications. 1
• Do not restrict fluids below 140 mL/kg/day once stable, as this compromises energy intake and growth. 6
• Do not ignore light protection—lipid emulsions must use validated light-protected tubing to prevent oxidant generation. 1
• Do not withhold minimal enteral feeds—complete bowel rest leads to villous atrophy and feeding intolerance. 1, 7

Special Consideration: Critically Ill Preterm Infants

• In critically ill preterm infants requiring intensive care (mechanical ventilation, vasopressors), consider withholding PN for up to 1 week while providing micronutrients intravenously, as the PEPaNIC trial showed this reduces infections, ventilator days, and kidney injury compared to early PN. 1
• This applies only to the acute resuscitation phase; once stabilized, advance to full PN as outlined above. 1
• This recommendation is controversial and should be weighed against the risk of cumulative nutrient deficits in extremely preterm infants. 1, 3