What is the initial approach to feeding in neonates with Inborn Errors of Metabolism (IEM)?

Initial Feeding Approach in Neonates with Inborn Errors of Metabolism

In neonates with suspected or confirmed IEM, immediately discontinue all protein-containing feeds and initiate intravenous glucose at 10-12 mg/kg/min (14.4-17.3 g/kg/day) to prevent catabolism and maintain anabolism while diagnostic workup proceeds. 1

Immediate Management Protocol

Stop Protein Intake Immediately

• Halt all enteral feeds containing protein (breast milk or formula) as soon as IEM is suspected, particularly in neonates presenting with lethargy, poor feeding, apnea, tachypnea, or recurrent vomiting 2, 3
• This applies especially to intoxication-type disorders (urea cycle defects, organic acidemias, amino acid metabolism disorders) where substrate accumulation causes toxicity 4

Initiate Intravenous Glucose

• Start IV glucose at 10 mg/kg/min (14.4 g/kg/day) immediately to prevent catabolism and provide energy without protein load 1
• In critically ill neonates, glucose can be increased up to 12 mg/kg/min (17.3 g/kg/day) but should not exceed this rate to avoid hyperglycemia and lipogenesis 1
• Maintain blood glucose >70 mg/dL (3.9 mmol/L) to suppress endogenous protein breakdown 1

Monitor Blood Glucose Rigorously

• Use blood gas analyzers for glucose measurements rather than handheld meters in critically ill neonates, as handheld devices are inaccurate due to high hemoglobin and bilirubin levels 1
• Check glucose every 2-4 hours initially to avoid both hypoglycemia (which worsens catabolism) and hyperglycemia (>145 mg/dL or 8 mmol/L), which increases morbidity 1

Diagnostic Workup During NPO Period

Baseline Metabolic Assessment

• Obtain GALAK panel immediately (Glucose, Arterial blood gas, Lactate, Ammonia, Ketones) before any feeding modifications 4
• Metabolic acidosis and/or hyperammonemia are present in many IEMs, though notable exceptions include nonketotic hyperglycinemia and molybdenum cofactor deficiency 2
• Send tandem mass spectrometry (TMS) and gas chromatography-mass spectrometry (GCMS) for definitive diagnosis 4

Hydration Management

• Provide IV fluids at 150-180 mL/kg/day to maintain adequate hydration and support renal clearance of toxic metabolites 3
• Add electrolytes as needed based on serum levels, typically sodium 4-7 mEq/kg/day and potassium 2-4 mEq/kg/day 1

Reintroduction of Feeds

Timing of Feed Reintroduction

• Do not restart protein-containing feeds until metabolic derangements normalize (ammonia <100 μmol/L, pH >7.35, lactate <2.5 mmol/L) and specific diagnosis guides therapy 3, 4
• This typically occurs within 24-72 hours of stopping protein intake and initiating IV glucose 3

Specialized Formula Selection

• Initiate disease-specific medical foods once the specific IEM is identified (e.g., phenylalanine-free formula for PKU, branched-chain amino acid-free formula for maple syrup urine disease) 5
• Start at 25-50% of calculated protein requirements and advance gradually over 3-5 days while monitoring metabolic parameters 4

Route of Administration

• Use nasogastric tube feeding initially rather than oral feeding to reduce energy expenditure and ensure precise intake measurement 6
• Continuous nasogastric feeds lower resting energy expenditure compared to bolus feeds in metabolically stressed neonates 6

Four Principles of Dietary Therapy

1. Substrate Reduction

• Restrict the specific amino acid or substrate that accumulates (e.g., phenylalanine in PKU, leucine/isoleucine/valine in MSUD) 4

2. Provision of Deficient Metabolites

• Supplement downstream products that cannot be synthesized (e.g., arginine in urea cycle defects, carnitine in organic acidemias) 4

3. Disposal of Toxic Metabolites

• Use scavenger medications (e.g., sodium benzoate, sodium phenylbutyrate for hyperammonemia) in conjunction with dietary restriction 4

4. Increase Enzyme Activity

• Provide cofactor supplementation where applicable (e.g., thiamine for MSUD, biotin for biotinidase deficiency, vitamin B12 for methylmalonic acidemia) 4

Critical Pitfalls to Avoid

• Never delay stopping protein feeds while awaiting confirmatory testing in a neonate with suspected IEM presenting with encephalopathy, as hours matter for neurological outcome 2, 3
• Never use standard infant formula during the acute phase of suspected IEM, as this provides uncontrolled protein load and worsens intoxication 4
• Never assume sepsis alone in a full-term infant with no risk factors presenting with lethargy, poor feeding, and metabolic acidosis—always consider IEM simultaneously 2
• Avoid hypoglycemia at all costs during the NPO period, as this triggers endogenous protein catabolism and worsens the metabolic crisis 1, 3