Preterm vs Term Milk

Introduction: Biological Specificity of Human Milk

Human milk is recognized not only as "species-specific" but also as "baby-specific." The mammary gland responds to the gestational age of the neonate, producing milk with a composition uniquely adapted to meet the physiological limitations and rapid growth requirements of the preterm infant.

• Preterm Milk (PTM) is defined as the milk secreted by a mother who has delivered before 37 weeks of gestation.
• Term Milk is the milk secreted by a mother delivering after 37 weeks.
• PTM is distinct from term milk in its concentration of macronutrients, micronutrients, and immunological factors, particularly during the first few weeks of lactation.

Nitrogen and Protein Composition

The most significant difference between preterm and term milk lies in the protein content. Preterm infants have extremely high growth velocities (aiming to match intrauterine growth rates) and limited stomach capacity, necessitating a higher protein density.

• Total Nitrogen: PTM has a significantly higher concentration of total nitrogen compared to term milk.
• Protein Concentration:
  • Preterm Milk: Contains up to 2.3 g/100 mL in the first week of life.
  • Term Milk: Contains approximately 1.1 g/100 mL,.
• Dynamic Changes: The protein content in PTM is highest immediately after birth and gradually declines over time. By the 6th week of lactation, the protein levels in PTM drop to approximately 1.3 g/100 mL, approaching the levels found in term milk,.
• Protein Quality:
  • Human milk is whey-predominant (Whey:Casein ratio of 60:40 to 80:20),.
  • Whey protein is richer in cysteine and taurine. This is critical for preterm infants because the enzyme cystathionase (required to convert methionine to cysteine) is developmentally immature, making cysteine an essential amino acid for them.
  • PTM contains lower amounts of aromatic amino acids (phenylalanine and tyrosine), which is beneficial as preterm infants have immature enzymes for degrading these amino acids.

Lipid Composition and Energy

Lipids provide the major fraction of energy (approximately 50%) in human milk. While the total fat content can be variable, the specific fatty acid profile is crucial for the preterm infant's developing brain and retina.

• Fat Content: Generally, human milk contains about 3.8 g fat/100 mL. PTM fat content is comparable to term milk, though energy density may vary slightly (approx. 67 kcal/100 mL).
• Long Chain Polyunsaturated Fatty Acids (LCPs):
  • Rapid accumulation of LCPs (specifically Docosahexaenoic acid [DHA] and Arachidonic acid [ARA]) occurs in the brain during the third trimester.
  • Preterm delivery interrupts this placental transfer.
  • PTM is rich in these LCPs, which are essential for neural and visual development and membrane fluidity,.
• Digestibility:
  • Preterm infants have reduced pancreatic lipase and bile salt pool sizes, leading to potential steatorrhea.
  • Bile Salt Stimulated Lipase (BSSL): Present in human milk, this enzyme is crucial for preterm infants as it compensates for their pancreatic insufficiency, facilitating fat absorption,.
• Carnitine: PTM is rich in carnitine, which is required for the transport of long-chain fatty acids across mitochondrial membranes for oxidation. Preterm infants have defective synthesis of carnitine.

Electrolyte Composition

The electrolyte content of PTM is markedly higher than term milk, reflecting the immature renal conservation mechanisms and higher requirements of the preterm neonate.

• Sodium:
  • Preterm Milk: High concentration, starting at 1.7 mmol/100 mL in the first week.
  • Term Milk: Low concentration, approximately 0.6 mmol/100 mL.
  • Significance: Preterm infants are prone to hyponatremia due to high urinary sodium losses (immature tubular reabsorption). The higher sodium in PTM helps compensate for these losses.
• Chloride:
  • Preterm Milk: Values are higher in the first week and decline gradually (e.g., matching sodium trends).
  • Term Milk: Lower values consistent with mature milk profiles.
• Potassium:
  • Preterm Milk: Approximately 1.7 mmol/100 mL in the first week.
  • Term Milk: Approximately 1.5 mmol/100 mL.

Minerals and Trace Elements

While PTM has higher concentrations of certain minerals compared to term milk, the absolute amounts may still be insufficient to meet the extreme demands of the very low birth weight (VLBW) infant's rapid bone mineralization.

• Calcium and Phosphorus:
  • The accretion of calcium and phosphorus primarily occurs in the third trimester.
  • PTM contains higher levels of calcium and phosphorus compared to term milk, but these levels are often insufficient to match intrauterine accretion rates, predisposing unsupplemented preterm infants to osteopenia of prematurity,.
  • PTM (Week 1) Calcium: ~0.7 mmol/100 mL vs Term: 0.8 mmol/100 mL (Note: Source 71 indicates Term may be slightly higher or comparable in some fractions, but bioavailability is the key).
• Iron:
  • PTM has higher concentrations of iron compared to term milk.
  • However, iron stores are low in preterm infants, and deficiency can occur by 6-12 weeks; supplementation is usually required from 6-8 weeks.
• Zinc and Copper:
  • PTM contains higher concentrations of zinc and copper compared to term milk.
  • Despite higher levels, the rapid growth rate of preterms often necessitates further fortification.

Immunological Factors

Preterm infants are immunocompromised and highly susceptible to sepsis and necrotizing enterocolitis (NEC). PTM provides enhanced immunological protection.

• Secretory IgA: PTM contains significantly higher concentrations of secretory IgA (SIgA) compared to term milk. This provides critical surface protection to the immature GI and respiratory tracts.
• Anti-inflammatory Factors: PTM is rich in anti-inflammatory cytokines and growth factors that promote gut maturation and reduce the risk of NEC,.
• Cellular Components: PTM contains higher numbers of leukocytes and macrophages, offering direct immunity.

Temporal Changes in Preterm Milk Composition

The composition of PTM is not static; it changes rapidly over the first few weeks of lactation.

Table: Compositional Changes of Preterm Milk vs. Term Milk (per 100 mL)

Source: Adapted from Table 1.4

Clinical Implications: The Need for Fortification

Despite PTM being richer in protein and sodium than term milk, it may still be nutritionally incomplete for the Very Low Birth Weight (VLBW) infant (<1.5 kg) or the sick preterm infant due to:

1. Volume Restrictions: Preterm infants often cannot tolerate the volumes required to meet their nutrient needs solely through unfortified breast milk.
2. Rapid Growth Demands: The protein and mineral requirements for "catch-up growth" exceed what PTM provides alone.

Therefore, Human Milk Fortifiers (HMF) are often added to PTM. HMFs supplement protein, calcium, phosphorus, sodium, and vitamins to meet the specific RDA of the preterm infant (e.g., Protein 3-4 g/kg/day, Calcium 100-200 mg/kg/day),.

Summary of Key Differences

• Protein: PTM >>> Term Milk (Critical for rapid somatic growth).
• Sodium: PTM >>> Term Milk (Compensates for renal salt wasting).
• Immunology: PTM > Term Milk (Protects against NEC and sepsis).
• Duration: The "preterm" characteristics of the milk persist for about 4-6 weeks before composition adjusts to resemble mature term milk.