In a pre‑term infant less than 32 weeks gestational age who has developed bronchopulmonary dysplasia after mechanical ventilation and supplemental oxygen, which nutritional supplements have proven benefit or are routinely used?

Nutritional Supplements in Bronchopulmonary Dysplasia

Vitamin A supplementation at 700-1500 IU/kg/day administered intramuscularly or with lipid emulsion is the only supplement with proven mortality and morbidity benefit in preterm infants <32 weeks with BPD, specifically reducing oxygen requirements and chronic lung disease. 1, 2

Vitamin A: The Evidence-Based Supplement

Vitamin A is the single supplement with Level 1 evidence demonstrating clinical benefit in BPD prevention and management. 1

Dosing and Administration

• Preterm infants (<32 weeks) require 700-1500 IU/kg/day (227-455 µg/kg/day) 1, 2
• Must be administered with lipid emulsion, NOT water-based solutions (>60% is lost in aqueous preparations) 2
• Intramuscular dosing regimens of 4000-5000 IU three times weekly have also shown benefit 1
• Continue supplementation through the acute phase and recovery period 1

Clinical Benefits

• Reduces death or oxygen requirement at one month of age 1
• Decreases oxygen requirement at 36 weeks postmenstrual age, particularly in infants <1000g 1
• Reduces days on mechanical ventilation and supplemental oxygen 1
• May reduce retinopathy of prematurity incidence 1
• No adverse effects on neurodevelopmental outcomes at 18-22 months 1

Monitoring

• Serum levels <200 µg/L (0.7 µmol/L) indicate deficiency 2
• Levels <100 µg/L (0.35 µmol/L) indicate severe deficiency with depleted liver stores 2
• Routine monitoring not required except in long-term parenteral nutrition 2

Important caveat: The benefit is most pronounced in vitamin A-deficient infants; approximately 76% of VLBW neonates are deficient. 1

Standard Multivitamin Supplementation

All infants with BPD should receive standard multivitamin supplementation at 0.5-1.0 mL daily to meet baseline requirements. 1

Key Vitamins Beyond Vitamin A

• Vitamin D: 400 IU/day for breastfed infants 3
• Vitamin K: 0.5-1.0 mg at birth (mandatory for all newborns) 3
• Vitamin E: 2.8-3.5 mg/kg/day (conflicting evidence for BPD-specific benefit; early reports suggested benefit but not confirmed in subsequent trials) 1
• Vitamin C: 15-25 mg/kg/day 1

Minerals and Electrolytes

Calcium and Phosphorus

Infants with BPD are at high risk for osteopenia due to chronic diuretic therapy causing calciuresis. 1

• Ensure adequate calcium and phosphorus intake to prevent skeletal demineralization 1
• Monitor bone health in infants on chronic furosemide or other loop diuretics 1

Iron

Iron supplementation at 1-2 mg/kg/day starting at 2-6 weeks of age and continuing until at least 6 months. 3

• Critical for catch-up growth in these infants 3

Nutrients with Insufficient Evidence

Inositol

• One trial showed 80 mg/kg/day for 5 days increased survival and lowered BPD incidence in respiratory distress syndrome 1
• Insufficient evidence for routine use in established BPD 4, 5

Selenium

• Theoretical antioxidant benefit but no proven clinical efficacy 6
• Remains speculative 4

Long-Chain Polyunsaturated Fatty Acids (LCPUFAs)

• Some evidence suggests potential BPD prevention 6
• Not yet standard of care; requires further study 6

L-Citrulline/L-Arginine

• May help treat pulmonary hypertension associated with BPD 6
• Not routinely recommended for BPD itself 6

Macronutrient Strategy

High-calorie, high-protein nutrition is essential but not technically a "supplement"—it's foundational management. 1

Energy Requirements

• 120-150 kcal/kg/day (higher than healthy preterm infants due to increased work of breathing) 1
• Caloric density: 24-30 kcal/oz formula 1
• Macronutrient balance: 8-12% protein, 40-50% carbohydrate, 40-50% fat 1

Protein

• 3 g/kg/day in early infancy, decreasing to 1.2 g/kg/day in early childhood 1
• Maximum 4 g/kg/day to avoid acidosis in immature kidneys 1
• Critical caveat: Corticosteroid therapy (often used in severe BPD) causes significant protein catabolism 1

Fluid Management

• Often restricted to 75-150 mL/kg/day depending on severity 1
• Fluid retention significantly limits pulmonary function 1
• Reconciling adequate calories with fluid restriction is a major challenge requiring concentrated formulas 1

Clinical Pitfalls to Avoid

1. Never use water-based vitamin A preparations—losses exceed 60% 2
2. Never use adult multivitamin formulations due to propylene glycol and polysorbate toxicity 3
3. Monitor for vitamin A toxicity (narrow therapeutic window): acute symptoms include increased intracranial pressure, headache, vomiting; chronic symptoms include bone abnormalities, dermatitis, alopecia 2
4. Don't forget calcium/phosphorus in infants on chronic diuretics 1
5. Gastroesophageal reflux is common and may worsen with theophylline/beta-agonists, complicating enteral feeding 1

Post-Discharge Considerations

Close follow-up after NICU discharge is mandatory to monitor growth and ensure adequate protein and calorie intake. 4

• Growth failure is predominantly due to malnutrition and worsens BPD by compromising lung growth 4
• Supplemental nutrition benefits extend to 3 months corrected age but require prolonged support for sustained catch-up growth 5