A Ready Reckoner : Human Milk Fortifier
- Part 1 -

Pankaj Garg / Hijam Rajendra Singha *

To ensure long-term health and development of preterm infants, an early nutritional support is utmost important. Breast milk is undoubtedly an ideal food for a preterm infant. However, the human milk fortifiers protein, calcium, phosphorus, carbohydrate, vitamins and minerals. All infants with a birth weight below 1800g would benefit from the additional fortification of breast milk as per ESPGHAN recommendations 2009.The said fortification of breast milk aims to increase the optimum level of concentration of nutrients to meet the requirements of all nutrients for preterm infants including those who are at the customary feeding volumes.

As no classification of infants who should receive fortified human milk (FHM) has been recommended by any study in India and abroad, there is a general worldwide consensus amongst the Neonatologists to prefer abovementioned recommendation of ESPGHAN 2009. The results of a systematic review of ten randomized controlled trials1 generally support the use of HM fortification as a common practice in neonatal intensive care units. Other trials2, 3 have not come out with any significant differences. Caution is also required as feeding these enriched diets may lead to disproportionate growth.

Rapid “catch-up” growth has been proposed as a potential contributor to a “metabolic syndrome” that results in long-term adverse cardiovascular outcomes. Brief Analysis of Contents Protein: The most common approach is multi-nutrient packaged powdered fortifiers. Protein replacement in VLBW poses the most difficult challenge. Preterm infants accrete protein at a higher rate than term infants and, therefore, the protein requirements of preterm infants are higher. ESPGHAN Committee on Nutrition recommends aiming at 4.0 to 4.5 g kg/day protein intake for infants up to 1000 g, and 3.5 to 4.0 g for infants from 1000 to 1800 g that will meet the needs of most preterm infants.

However, human milk alone provides inadequate amounts of protein, energy and minerals to meet the high needs for preterm infant growth. It has been shown that adequate protein intake has impact not only on short term growth but also on long term neurological outcome. A Cochrane analysis showed that protein supplementation of human milk in preterm infants lead to increase in short term weight gain (WMD 3.6 g/kg/day, 95% CI 2.4 to 4.8 g/kg/day), linear growth (WMD0.28cm/week, 95% CI 0.18 to 0.35 cm/week) and head growth (WMD 0.15 cm/week,95% CI 0.06 to 0.23 cm/week). As HM shows variability in protein content, it often results in an unpredictable nutrient intake.

Actual intakes of protein by preterm infants fed fortified human milk are substantially lower than assumed intakes. The discrepancy may in part explain why preterm infants who are fed fortified HM also frequently show postnatal growth failure. Individualized fortification is now emerging as the best solution to the problem of protein under nutrition with standard fortification of HM. Given the large variability in nutrient composition of breast milk it is difficult to know how much fortifier to provide. Some have proposed analyzing individual aliquots of breast milk it is difficult to know how much fortifier to provide.

Some have proposed analyzing individual aliquots of breast milk but this technique is not routinely available. Adjusting fortification uses periodic determinations of serum urea as a guide to protein intake, and adjusting the intake of fortifier and supplemental protein accordingly. This technique resulted in better weight gain and head growth compared to a control group receiving standard fortification. Also, protein and energy needs should be considered concurrently. Protein to energy ratio (P: E ratio) should be in the optimal range. It has been recommended that 2.8g/100 kcal to 3.4 g/100 kcal should be the minimum and maximum and maximum P: E ratio.

The energy content of HMF could influence the gastric emptying, with implications for the management of premature infants at greater risk of feed intolerance. Carbohydrate: The expert panel for LSRO has based its carbohydrate intake recommendations in relation to the needs of other macronutrients and has recommended a minimum of 9.6 g/100 kcal and a maximum of 12.5g/100 kcal. So the fortifier should aim to provide this amount of carbohydrate. Iron: The quantity of iron in human milk fortifiers differs and directly affects the activity of lactoferrin.

Lactoferrin is a glycoprotein that binds iron so bacteria cannot use it for metabolism. If lactoferrin binds iron, it is rendered inactive; thus, lactoferrin needs to be in a state that is not found to be active. A few studies have shown that addition of iron decreases the antimicrobial property of the human milk and therefore, iron supplementation should be given separate from HM feedings.

However, it has also been demonstrated that using the iron-fortified product may reduce the need for blood transfusions in VLBW infants. This study also demonstrated low rates of suspected and confirmed NEC and sepsis and refuted the premise that the inclusion of iron in fortifiers will increase the incidence of sepsis and NEC. So further research is needed regarding the optimum content of iron in HMF. Mineral: Human Milk fortifiers contain different quantity and quality of minerals and their effect on bone mineral content is still unclear.

Calcium absorption is dependent on the quantity and the source of calcium salt and quality and quantity of fat content of the diet. In using human milk fortifiers, it has been suggested that soluble calcium salts bind the fatty acids in the fortified human milk, thus impairing fat absorption, lowering energy intake, and decreasing the rate of growth. Schanler and Abrams reported that preterm infants receiving that powdered HMF containing highly soluble calcium and phosphorus demonstrated poorer at absorption, compared with similar infants fed powdered HMF containing insoluble calcium and phosphorus.

So insoluble calcium salts like calcium phosphate tribasic and calcium carbonate should be used to optimize fat absorption. As per W H O guidelines there is low quality evidence that routine calcium and phosphate supplementation reduces the risk of metabolic bone disease in preterm VLBW infants. Also there is no evidence of reduction in the risk of rickets of prematurity.

So, fortification with minerals, trace mineral and vitamins presents few problems. Although the exact requirement for many of these nutrients is unknown, aiming at meeting or, more often, exceeding the presumed requirements has proved successful. This is so because neither modest degree of shortfalls nor of excesses of these nutrients appears to pose any problems.

None of these nutrients are limiting growth. Osmolality: Osmolality is a critical determinant of feed tolerance. Cochrane meta-analysis has shown an increased tendency for feed intolerance with fortified milk. Various studies have demonstrated that Osmolality of breast milk increases significantly on fortification with HMF and LBW formula. The rise of Osmolality observed in human milk supplemented with HMF can be explained by the fact that polysaccharides, present in the HMF, are broken down into their constituent mono and oligosaccharides and the difference observed between the various HMF could be related to the different carbohydrate content and the use of dextrin of different origin and equivalent glucose content.

So we expect an ideal fortifier to alter the Osmolality of human milk to minimum. The lower Osmolality may improve the feeding tolerance, thereby providing indirect benefits to growth. Some fat may be used in place of carbohydrate to reduce the Osmolality of the fortifier. The commonly used fortifiers are powdered products that are different from liquid fortifiers in that they do not further dilute maternal milk when added. Recently liquid ultra-concentrated fortifier has been used.

This new LHMF with higher protein has been shown to enhance both lengths as well as weight growth in preterm infants with birth weight less than 1250 g, with minimal metabolic and host defense impact compared with currently available powdered fortifier.

to be continued.....