Unit 3: Nutrition and Feeding Practice in Preterm Infants

Preterm infant formulas have been developed to meet the special nutritional needs of these infants. Although, HM is always best for the preterm infant, many NICU's still do not have access to a HM bank or DHM, making the use of these specifically adapted formulas necessary (Senterre 2014).

Preterm infant formulas offer higher caloric content, proteins and other nutrients, when compared to term infant formulas. These formulas should be used when the mother's own milk or pasteurized donor milk are unavailable. There are numerous preterm infant formulas available throughout the world. With some modifications, they are formulated to resemble human milk and almost all are supplied in liquid form.

Preterm infant formulas are high in energy, generally providing approximately 80 kcal/100ml (about 24 kcal/fluid oz). This represents about 15 kcal/100ml more than typically found in human milk or term infant formula and reflects the particularly high energy needs of growing preterm infants.

The protein content of preterm formulas, ranging from 2.8-3.6 g/100kcal, is also higher than in term formulas or in human milk, since preterm infants need especially high amounts of protein for growth. Nonetheless, the protein content of many preterm formulas still falls short of the 3.2-4.1 g/100kcal of protein that is recommended for the fully enterally-fed VLBW infant (Koletzko et al. 2014a).

Modern preterm infant formulas have been developed to try to be as similar as possible to human milk. Concerning protein content, both human milk and preterm infant formulas have a high whey-to-casein ratio. Higher amounts of whey protein in human milk and preterm infant formula are advantageous to the neonate. These benefits include: easier protein digestion, faster gastric emptying with whey-dominant milk compared to casein-dominant milk (Billeaud et al. 1990), and production of plasma free amino acids more similar to  human milk than the casein-formulas (Rassin et al. 1977).   

Preterm formula milks generally contain only about half as much lactose as human milk. The rationale for this is that lactase activity is thought to be lower in very preterm infants relative to term infants and reducing the lactose content in feeds might therefore increase feeding tolerance. Although one study (Griffin & Hansen 1999) with a very low lactose formula has given some support to this idea, the addition of exogenous lactase to feeds has not shown beneficial effects. Enteral feeding itself induces lactase activity in the intestine (Hay et al. 2014). Standard term formulas usually do not have reduced lactose.

Relative to human milk, many preterm formulas contain much higher proportions of medium chain triglycerides (MCT). MCT are better absorbed than the long chain fatty acids predominantly found in human milk and in natural oils and fats (please refer to Lesson 5 of Unit 2 -Lipids). In spite of better absorption, addition of MCT did not lead to an improved energy balance or weight gain because the energy content per g of MCT is about 15% lower than long chain triglycerides due to the different carbon chain length (Senterre 2014).

The LC-PUFAs DHA and ARA (please refer to Lesson 5 of Unit 2 -Lipids) are added to standard preterm formulas. However, the amounts provided in most currently-available products do not meet the more recent recommendations (Koletzko et al. 2014b) for higher intakes. DHA and ARA precursors LA and ALA are also found in most preterm infant formulas, whereas they are currently supplied only in some formulas for term infants.

Preterm formula, like human milk and term formula, has a low sodium concentration. Given that sodium requirements are higher in preterm than term infants, it may be necessary to supplement sodium.

There are slight differences in the amounts of vitamins, minerals and microminerals in the various available preterm formulas. Although the vitamin content of preterm formulas is generally higher than in term formulas, amounts may still not be adequate. Nutrition information provided for a particular formula should be compared with recommended intakes. Vitamin A and D in particular may require additional supplementation (Leaf & Lansdowne 2014).

Calcium and phosphate, especially important for bone mineralization in the preterm infant, are included at higher concentrations in preterm formulas than in human milk or term infant formulas.

With the exception of iron, most micronutrients will be adequately provided by a typical preterm formula. The 1.8 mg/100kcal of iron contained in many preterm formulas, while higher than the amount recommended for standard term formulas (Koletzko et al. 2005), may be insufficient for many preterm infants, who are estimated to require 1.8-2.7 mg/100kcal iron (Koletzko et al. 2014a). Additional supplementation should be performed.

The developing intestinal microbiome: Probiotics and Prebiotics

Recent investigation has shown that human intestine microbes and its interaction in early life with the host (meaning us human beings), is crucial for immune system development and metabolic function. Aberrant intestinal colonization or erratic interactions with the host may contribute to post-natal diseases (such as NEC) or have implications in life-long health outcomes (Neu 2014).  

Wang and collaborators analyzed fecal samples of preterm infants (25 to 32 weeks of gestation) with or without NEC. All preterm infants showed a limited diversity of the intestinal flora compared to either adult or term flora. Preterm infants with NEC, who also received antibiotic treatment for longer than non-NEC controls, showed an even more reduced diversity with a predominance in Gammaproteobacteria (Wang et al. 2009). Taken together with another study that showed a higher incidence of NEC and death in ELBW infants that received a prolonged duration of initial empirical antibiotic treatment (Cotten et al. 2009), it has been suggested that:

Probiotics - Live microorganisms that lead to health benefits when administered to a host. These benefits include (Neu 2014):

• A protective barrier against pathogenic bacteria through competition.
  
• Antimicrobial actions
  
• May interfere to pathogenic bacteria adherence
  
• Confers an increased immunological and physical barrier to the intestine
  
• Higher mucus production
  
• Reduced risk of ischemic injury
  
• Inflammatory response modulation
  
• Evidence of improved intestinal mobility

Probiotics and NEC - The number of studies of probiotics in preterm infants has increased dramatically over the past few years and available evidence implies that probiotics do have the potential to reduce NEC. An updated Cochrane Review from 2014 concluded:

Although these results seem encouraging, concerns have been raised surrounding controversial proposals to use probiotics routinely in preterm infants (Neu 2014). First, there may be risks to the use of probiotics: one study showed a trend towards an increased risk of sepsis in the subgroup of infants with a birth weight of 500-750g (Lin et al. 2008).

Moreover, study results showing the benefits of probiotics may not be generalizable because many different preparations (single species or mixtures of probiotic organisms) were used in the various studies (Neu 2014). To obtain the most reliable results, a study would have to be done with formula-fed preterm infants with a standard preterm infant formula and a standard probiotic preparation (Panigrahi 2014). To design such a study, researchers would have to include only preterm infants who have no access to human milk (maternal or donor), because human milk intake is associated with lower rates of NEC (Ziegler 2014) and should be used if available.

Another serious concern is the overall safety of available probiotic preparations. In the US, probiotics are neither drugs nor medical devices and thus are not regulated by the Food and Drug Administration (Neu 2014, AlFaleh & Anabrees 2014). Given that the infants most at risk for NEC are also the smallest and most fragile, rigorous quality and safety standards for any probiotics would be desirable. The use of probiotics in preterm infants has not yet been endorsed by either the American Academy of Pediatrics or the ESPGHAN, more data about which type of probiotics to be used, long-term outcomes and neonatal population are still awaited.  

Prebiotics - Generally are:

They can modulate the intestinal colonic microbiota increasing specific bacteria. They include the oligosaccharides inulin, fructose, galactose, acidic oligosaccharides. Between their benefits, increased fecal bifidobacteria and improved gastric mobility would be the most important for the prevention of NEC in the neonate. There are only few studies of prebiotics and NEC in premature infants. None has shown a significant benefit of prebiotics in the prevention of NEC, though some have demonstrated increased numbers of bifidobacteria after administration of oligosaccharides. More and larger studies are warranted (Neu 2014, Panigrahi 2014).

Please refer to Module 3 - Infant Formula Feeding, Unit 3 Lesson 3.1 Probiotics, Prebiotics & Synbiotics for more information on probiotics and prebiotics.