Challenges of providing human milk to premature infants
Providing human milk to very premature infants presents a variety of challenges. To maximize milk supply, new mothers should begin frequent pumping shortly after delivery. Mothers whose babies are in the NICU should be encouraged to begin pumping within 6–12 hours of delivery and to pump 8 – 12 times per day, ensuring that they empty the breast each time. These interventions significantly increase the likelihood that a premature infant will receive his mother’s own milk.45
Perhaps the biggest concern in providing human milk to premature infants is growth. Term infants undergo rapid growth in the third trimester of pregnancy receiving nutrition through the placenta and swallowed amniotic fluid with no need to expend calories for temperature regulation or gas exchange. Premature infants miss out on much or all of the third trimester and thus have higher nutritional requirements on a per kilogram basis than term infants. Human milk evolved/was designed to nourish the term infant who can tolerate large fluid volumes, whereas premature infants are less tolerant of high fluid volumes.
For these reasons, human milk is generally fortified for premature infants with birth weight less than 1500 grams. Human milk fortifier powders were developed from bovine milk to supplement key nutrients with particular emphasis on protein, calcium, phosphorus, and vitamin D. Fortification of human milk leads to improved growth in weight,46 length and head circumference47 however improvements in bone mineralization and neurodevelopmental outcomes are unclear.47 Recent studies suggest that higher protein intake is beneficial for premature infants.48 There is large variation in the energy and protein content of human milk (between mothers, over time in a given mother, and between foremilk and hindmilk).49Protein content decreases over time of lactation and is likely to be much lower in donor human milk than milk from mothers delivering prematurely. Current NICU practices are often based on the clearly misleading assumption that human milk has approximately 0.67 kcal/ml with stable protein content. “Assumed” protein intake from standard fortification is significantly lower than actual protein intake.50These observations have led to clinical trials of “individualized” fortification, that is, adjusting the amount of added protein based on actual measurements of milk samples51 or based on metabolic parameters indicative of protein accretion in the neonate (e.g. blood urea nitrogen).52 Both methods led to increased protein intake and improved growth. A recent trial of a human milk fortifier with higher protein content demonstrated increased growth and fewer infants with weight below the 10th per centile.53
Use of commercial human milk fortifiers, however, is not without complications as demonstrated by the observation of a marked increase in metabolic acidosis associated with the introduction of a new fortifier.54Human milk fortifiers have also been associated with increased markers of oxidative stress compared to unfortified human milk and to infant formula.55 In addition, bacterial contamination56 of powdered infant formulas and associated sepsis57 has been well documented, resulting in more than 100 cases of neonatal Cronobacter (Enterobacter sakazakii) infections leading to high mortality rates. This association has led to calls for “powder-free” NICUs and the development of new liquid human milk fortifiers. Unfortunately, one of the challenges of liquid fortifiers is displacement of the volume of mother’s own milk, so that the infant receives less total volume of human milk. Table 1 provides a comparison of the nutrient content and volume of human milk displaced by the liquid formulations of several commercial human milk fortifiers available in North America. Note that the use of the bovine liquid fortifiers means that 17–50% of the volume ingested is formula. The table also demonstrates the significant variation in macro and micronutrients among these products.