What is the optimal glucose‑to‑sodium ratio in parenteral fluids for a preterm neonate ≤32 weeks gestation (birth weight 800–1500 g) to provide adequate calories while maintaining safe serum sodium levels?

Glucose-to-Sodium Ratio in Parenteral Fluids for Preterm Neonates ≤32 Weeks

The optimal approach prioritizes adequate caloric delivery through glucose while maintaining sodium at 3-5 mmol/kg/day, with the glucose-to-sodium ratio varying by postnatal phase rather than being a fixed target—during Phase I (days 1-3), restrict sodium to allow physiologic extracellular fluid contraction while providing glucose for calories, then increase sodium to 4-5 mmol/kg/day during Phase II (after day 3) to support growth and neurodevelopment. 1, 2

Phase-Based Approach to Fluid and Electrolyte Management

Phase I: Initial Adaptation (Days 1-3)

During the first 2-3 postnatal days, sodium should be restricted to allow a negative sodium balance of 2-3 mmol/kg/day while glucose is provided for caloric needs. 1

• Target weight loss of 5-10% of birth weight is physiologic and represents extracellular fluid contraction 1
• Serum sodium should remain in the high normal range (<150 mmol/L) during this contraction phase 1
• Sodium concentrations <140 mmol/L combined with 10% weight loss indicate sodium depletion requiring clinical reassessment 1

Critical monitoring parameters during Phase I:

• Serum sodium every 4-6 hours until stable to detect both hypernatremia and depletion 3
• Urine output maintained >1 ml/kg/hour 2
• Avoid oliguria (diuresis <1 ml/kg/h for >12 hours) which signals inadequate fluid intake 1

Phase II: Intermediate Phase (After Day 3 Through Birth Weight Recovery)

After initial weight loss, increase sodium to 4-5 mmol/kg/day to support growth and neurodevelopment while maintaining adequate glucose for calories. 1, 2

• Sodium supplementation of 4-5 mmol/kg/day during the first 2 weeks improves neurocognitive performance at 10-13 years compared to 1-1.5 mmol/kg/day 1
• Birth weight should be regained by 7-10 days of life 1
• Fluid intake should be maintained at 140-160 ml/kg/day rather than exceeding 170 ml/kg/day, as higher volumes cause negative sodium balance even with 10 mmol/kg/day sodium intake 1

Electrolyte Composition Strategy

Use predominantly acetate-based sodium and potassium salts rather than chloride salts to prevent hyperchloremic metabolic acidosis. 1, 2, 4

Specific Electrolyte Targets:

• Sodium: 3-5 mmol/kg/day, provided primarily as sodium acetate 2
• Potassium: 2-3 mmol/kg/day as potassium acetate or potassium phosphate 2
• Chloride: Limited to 3-5 mmol/kg/day maximum 2
• Target anion gap: Maintain Na + K - Cl = 1-2 mmol/kg/day 2

Rationale for acetate-based salts: High chloride intake induces hyperchloremic metabolic acidosis in VLBW infants and is a causative factor for intraventricular hemorrhage and other morbidities. 1 The use of "chloride-free" sodium and potassium solutions should be considered in preterm infants on parenteral nutrition. 1

Glucose Delivery for Adequate Calories

While the question asks about glucose-to-sodium ratio, the critical principle is that glucose delivery must provide adequate calories (typically starting at 6-8 mg/kg/min and advancing) while sodium is adjusted based on postnatal phase and serum levels. 1

• Endogenous water production from glucose oxidation is 0.6 ml per gram of carbohydrate oxidized, which must be factored into total fluid calculations 1
• Recent studies show increased incidence of hypokalaemia and hypophosphatemia when optimizing protein and energy intakes in VLBW infants, representing a refeeding-like syndrome 1

Special Considerations for Growth-Restricted and ELBW Infants

In growth-restricted and extremely low birth weight (<1000g) infants with low mineral stores, potassium supplementation may be initiated from day 1 to reduce hypokalaemia risk and enable adequate phosphorus supply. 1

• Close monitoring is necessary during the oliguric phase to prevent hyperkalemia 1
• Deferment of potassium may be required in some ELBW infants at high risk for non-oliguric hyperkalemia 1
• Sodium and potassium supply should start before serum concentrations drop below recommended values 1

Critical Pitfalls to Avoid

Excessive chloride administration: Using equal amounts of sodium chloride and potassium chloride creates an unphysiologic high chloride load leading to metabolic acidosis, potential intraventricular hemorrhage, and impaired growth. 1, 2

Excessive fluid administration: Fluid intake exceeding 200 ml/kg/day does not maintain sodium balance regardless of sodium amount provided, and increases risk of patent ductus arteriosus, necrotizing enterocolitis, and death. 1

Ignoring large variations in serum sodium: Significant fluctuations in serum sodium concentration impair later neurocognitive outcomes in preterm infants. 1

Rapid correction of hypernatremia: If hypernatremia develops, correct slowly at 10-15 mmol/L per 24 hours to prevent cerebral edema and seizures. 3