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Formula feeding based on human milk composition
Human milk fed directly from the mother to the infant is the optimal nutrition source that serves as the gold standard for the manufacturing of formula feeding. The composition of human milk however is complex and sofar only the main macro- and micronutrients are represented in formula feeding. Recently new dynamic measurement methods such as the use of substrate labelling with stable isotopes have given evidence for a revision of the views on the composition of normal and special formula feeding for low birthweights infants. The latter category of infants may benefit from human milk and will still receive sufficient nutrients if the milk is fortified with specially developed fortifier.
Human milk composition changes rapidly over the first weeks of lactation. This is certainly true for many factors involved in humoral and cellular immunity. Examples are the presence of factors that directly influence phagocytosis and the complement system, the presence of lymphocytes, macrophages and lysozyme. The levels of secretory immuno-globuline A and of lactoferrin, a component that facilitates iron transport and stimulates bacterial breakdown in the gut, both drop substantially over the first four weeks after birth.
Sofar it has not proven to be possible to adapt formula composition according to this changing situation since most of the human milk components mentioned above are not yet available for formula production. The main source of carbohydrates in formula is lactose with use of polysac-charides in some special formula. Most of the new develop-ments are concen-trated around the protein composition of human milk, in particular the non protein nitrogen fraction and the special protein needs of very low birth weight infants. Regarding fat new information is available indicating the benefits of the presence of long chain poly unsaturated fatty acids in special formula feeding for preterm infants. The use of medium chain triglycerides has been abandoned. Regarding micronu-trients the increased require-ments of calcium, phosphorus and vitamine D in very low birth weight infants can be fully met by adding human milk fortifier to expressed human milk or the use of special low birth weight formula feeding.
Proteins in human milk and formula
Based on metabolic balance studies together with estimates of intake and changes in body composition the recommended daily energy and protein intake of preterm and term infants were estimated to be 65 kcal with 1.4 g. protein / 100 ml in term infants and 80 kcal with 1.8 g. protein / 100 ml in preterm infants. New measurements based on the use of stable isotope dilution have demon-strated however that the nutritional intake of breast fed term infants has been overesti-mated. Energy intake calculated from protein has also been overestima-ted because of the non protein nitrogen fraction of human milk that may contribute to 25% of total nitrogen. The energetic contribution of this fraction can be neglected, the compo-nents however are of great importance to the functioning of the gastro intestinal mucosa. The most important components of the non nitrogen fraction are: urea, ammonia, creatinine, uric acid, free amino acids, growth factors (IGF 1), thyroxine, somatostatin, nucleotides and polyami-nes.
The protein composition of formula has always been debated due to the changes seen in term and preterm breast milk over the first four weeks of lactation. The whey fraction is approximately 80% at birth (20% casein fraction) but drops to 55% (45% casein fraction) within three weeks. Therefore in practice most human milk based formula use 60% whey and 40% casein. Of the non protein nitrogen fraction only nucleotides have been introduced in some formula with a suggested beneficial effect on local mucosa functio-ning. At present it is suggested to create a standard starting formula containing only 1.0 - 1.2 g. protein / 100 ml for the first two months of life, a standard formula containing 1.4 g. protein / 100 ml and a follow on formula (after 6 months of life) containing 1.8 g. protein / 100 ml.
Over the last ten years many clinical studies were performed in preterm infants using stable isotope labelled amino acids in combination with nitrogen balances ( reviewed by Mi-cheli et al. 1993). These studies have shown that in order to reach the in utero protein gain of 2-3 g protein/kg/day deposited in the body, a metabolizable protein intake of 3-4 g/kg/day should be aimed for. Preterm human milk containing on average 1.3-1.7 g protein / 100 ml is not sufficient in reaching this goal in low birth weight in-fants. Use of human milk fortifier however containing approximately 0.7 g. pro-tein added to 100 ml human milk has proven to be adequate in feeding low birth weight infants. Special low birth weight formula has recently been adapted to contain 2.4 g pro-tein / 100 ml.
Fat in human milk and formula
The gastrointestinal tract, even of preterm infants shows rapid adaptation from intra- to extra-uteri-ne life. The lipase activity in saliva, stomach and pancreas shows a rapid adaption enabling the use of long chain triglycerides as a fat source that comprises up to 40% of the macronutrients even in preterm infants. Recent investigations in preterm infants fed with formula containing medium chain triglycerides ( with the possible benefit of an easier absorption) have shown that the MCT fat is rapidly absorbed but to a large extent takes over the role of carbohy-drates as a rapid energy source. The surplus of carbohydrate nutrients is oxidized and used in the energy consuming process of lipogene-sis with unwanted effects on body composition (i.e. increased fat deposition). Use of long chain triglycerides in preterm infants shows sufficient absorption of fat and adequate calcium and phosphorus uptake leading to better balanced body composition (Sulkers et al. 1994). The use of MCT fat has recently been abandonded in most preterm formula.
Over the last decade much has become known from clinical studies investigating the possible beneficial role of adding long chain poly unsaturated fatty acids (LC-PUFA's) to the nutrition of (pre)term infants. Some of the LC-PUFA's, such as docosa-hexaenoic acid (DHA) are essential precursors of neuro-tissue components such as for instance the receptors of the retina. Human milk contains these LC-PUFA's in ready form. All neonates are capable of synthetizing LC-PUFA's from C-18 linoleic / alpha linolenic acid. Elongation from these C-18 fatty acids in preterm infants however is limited during the first postnatal weeks. In preterm infants fed a special formula not containing DHA, evidence has been found of a delay in vision and neuro deve-lop-ment at 3 months corrected age in comparison with a formula containing DHA ( Carlson et al. 1993). Addition of 0.3-0.4 g. DHA / 100 g. fat together with 0.5-0.6 g. arachido-nic acid / 100 g. fat in the special formula for preterm infants is at present considered benificial regarding their LC-PUFA status (ESPGAN recommendation 1991). The addition of these LC-PUFA's in the correct combination of omega 3 and omega 6 fatty acids is essential since addition of fish oil, containing large amounts of eicosapentanoic acid has been shown to impair growth due to a lowering effect on arachidonic acid.
Micronutrients in human milk and formula
Resorption of calcium, phosphorus and vitamine D is related to fat digestion. Digestion and resorption of human milk fats is much better than that of the triglycerides in formula feeding. Only if mother and child have a low exposure to UV sunlight it is advisable to supplement approxima-tely 400 IU of vitamine D / day. In formula feeding calcium and phosphorus contant must be substantially higher. Very low birth weight infants are at risk of osteopenia and therefore these infants require an even higher intake of these micronu-trients. All formula for low birth weight infants are adapted for these requirements while human milk can be adapted by the use of human milk fortifier.
Large variations exist in serum iron content in term and preterm infants and therefore the recommended iron intake from infant nutrition is considered to be variable for most infants. High concentrati-on of iron in the nutrition may cause bacterial overgrowth in the gut, while high supple-mentations of iron in preterm infant may have the risk of stimulati-on of free radical formation in the lungs during oxygen treatment. Most formula therefore do not contain high iron concentra-tions and supplementation should take place on a individual basis.
Energy and macro-/micronutrient composition of human milk per 100 ml in comparison with recent recommendations and standard / special formula feeding.
-? linolenic acid
-a linolenic acid
-docosa hexanoic acid
Folic acid (µg)
Vitamine C (mg)
1. Micheli JL and Schutz Y (1993) Protein. In: Nutritional needs of the preterm infant. Tsang R et al eds. Williams and Wilkins, Baltimore, pp.29-46
2. Sulkers EJ, Lafeber HN, Goudoever JB et al. (1993) Decreased glucose oxidation in preterm infants fed a formula containing medium chain triglycerides. Pediatr Res 26,294-297
3. Carlson SE, Werkman SH, Rhodes PG et al. (1993) Visual acuity development in healthy preterm infants: effect of marine-oil supplementation Am J Clin Nutr 58,35-42
References in table:
1. Nutritional needs of the preterm infant. (1993) Tsang R etal. editors, Williams and Wilkins, Baltimore, Hong Kong, Sydney, ISBN 683084259
2. Friesland Nutrition, Leeuwarden, The Netherlands: composition of Frisolac and FrisoprÃ©