Nutrition In Preterm & Role Of HMF

schedule 8 min read
Topic(s): Low Birth Weight

Preterm infants often demand intensive care due to associated risks and their unique demand for nutrition during hospitalizations and post-discharge. Although the mother’s milk has been universally accepted as the best feed for an infant it might not suffice the needs of a preterm infant. This article discusses the importance of preterm nutrition along with the factors that need to be considered during the fortification of human milk.

Human Milk Fortifiers (HMF) are multi-nutrient formulas that enhance the nutritional content of human milk feed. The objective of neonatal care of preterm infants is to achieve growth and development comparable to in utero growth of the fetus. The structural and functional growth of preterm infants requires increased protein supply and adequate energy in the form of carbohydrates and fats. Since the premature breast milk may not suffice the demands of energy, proteins, and minerals for optimum growth and development outcomes, HMF play a vital role in enhancing the nutritional content of human milk feed enabling to meet the increased nutritional requirements of preterm infants.
Importance of fats, proteins quantity as a part of preterm nutrition
1. Fats: Lipids constitute the main source of energy for infants. ESPHAGAN suggests a total fat intake for preterm infants in the range of 4.8 to 6.6 g/kg/day. Saturated fatty acids aid as a primary energy source while the polyunsaturated fatty acids (PUFA) serve as components of structural lipids. Long-chain polyunsaturated fatty acids (LC-PUFAs) are crucial for normal development of the central nervous system. Preterm infants have very limited fat stores and are dependent on external nutrition for the same. LC-PUFA status in preterm infants depends on the amount of supplementation, intestinal absorption, and the capacity of the preterm infant for endogenous synthesis from parent fatty acids i.e. linoleic acid (LA) and alpha-linolenic acid (ALA). Preterm infants excrete around 20-30% of dietary lipids via stools owing to reduced intestinal fat digestion and absorption due to low enzyme secretion and low concentration of bile salts. Moreover, the pasteurization of human milk inactivates the bile salt-stimulated lipase (BSSL) in the milk that changes the structure of milk fat globule. These structural changes decrease the nutritional and biological quality of human milk. Therefore, to compensate for the impaired absorption and retention of fats, HMF is critical in preterm infant nutrition. Clinical findings suggest that substituting fats in place of carbohydrates as an energy source also minimizes the risk associated with an 
increased osmolality of the formula.

2. Proteins: Proteins and amino acids form the structural and functional foundation for the growth and development and preterm neonates need the high protein intake to meet the demands of high growth rate. ESPGHAN recommends 3.5–4.5 g/kg/day of target protein intake for preterm infants. Metabolism of proteins and amino acids consumes less energy and their adequate intake is known to drive weight gain by increasing the lean body mass in neonates. Early administration of high dose amino acids benefits the synthesis of essential proteins such as albumin and glutathione. According to a meta-analysis decreased serum albumin is an independent risk factor for mortality and morbidity. Clinical findings suggest that an attained albumin level of more than 30 g/L is associated with a shorter time to regain birth weight and fewer illnesses; improved nutritional status; reduced hospitalizations with a lower incidence of septicemia and pneumonia; and greater resolution of hypotension. Glutathione is reported to be the most important intracellular antioxidant and is suggested to play a significant role in lung protection in preterm infants.  According to a recent study, early administration of amino acids (within 24 h of birth) is associated with improved weight gain in extremely low weight infants (<1500 g) preterm infants.

3. Importance of DHA, LA, ALA and LA/ALA ratio in preterm nutrition
Linoleic acid (LA) and alpha-linolenic acid (ALA) are essential fatty acids that have influential metabolic roles like lowering of plasma cholesterol. LA and ALA, precursor fatty acids for endogenous synthesis of LC-PUFA, compete for desaturases and elongases in the PUFA conversion pathway. Therefore, an optimum LA/ALA ratio is important to endogenous PUFA synthesis, as a high LA/ALA ratio may reduce the conversion of ALA to PUFA whereas a lower ratio may reduce the synthesis of LA-based PUFAs. Extremely high levels of LA in formulas have also been reported to hamper development up to 18 months in preterm infants.

a) Docosahexaenoic acid (DHA)
DHA is long chain PUFA synthesized from ALA and is important for normal retinal and neurodevelopment in humans. The formation of DHA is highly variable and limited, moreover, low energy levels in preterm infants lead to DHA oxidation. Therefore, its supplementation becomes essential during early development of preterm neonates. Studies have demonstrated that supplementation of larger amounts of DHA (levels higher than breast milk) in preterm infants, yields better visual development and neurological outcomes as compared with non-DHA fortified formulae. A study, which examined the effect of DHA supplementation (0.50% of total fatty acids) for up to 9 months after term, showed that DHA improved growth in the whole cohort of preterm infants with improved mental development. DHA is also reported to be associated with other health benefits such as reduced incidence of bronchopulmonary dysplasia.

4. Importance of MCTs in preterm nutrition
Clinical findings have reported that medium chain triglycerides (MCTs) are rapidly absorbed even in the presence of low intraluminal bile salts and pancreatic lipases. They are directly absorbed into the portal vein and then transported to the liver. Moreover, the transport of MCTs across the mitochondrial membrane is independent of carnitine, that makes them easily available for oxidation, more rapidly than long chain fatty acids. Therefore, owing to a rapid absorption and metabolism MCTs are a quick source of energy.  A study shows that the preterm infants fed on formula with higher content of MCT (38%) gained higher body mass in comparison to those fed on a formula with the relatively small quantity of MCT (6%).

5. Importance of optimal osmolality of the feed for preterm infants
An increased osmolality of preterm feed formulas is presumably due to the breakdown of glucose polymers by endogenous breast milk amylase. A high osmolality feed for preterm infants is associated with delayed gastric emptying & risk of development of necrotizing enterocolitis, therefore, an osmolality of <450 mOsm/kg has been recommended for preterm infants by AAP (1976). There are no other recommendations for preterms which specify the guidelines for the osmolality. Fortifiers can be helpful in maintaining a lower osmolality along with high nutrient content as fortifiers are associated with lower propensity to increase osmolality.
Overall, HMF is of vital importance for providing the optimal nutrition to preterm infants to support their catch-up growth and development. Evidence suggests that partially hydrolyzed proteins may offer a beneficial preventive effect in conditions like allergies etc. However, it is important to consider the osmolality and clinical evidence before selection of HMF for preterm infants.


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