Portal de Periódicos da CAPES

Improving Infant Milk Formulas: Near the End of the Trail for the Holy Grail?

2003; Lippincott Williams & Wilkins; Volume: 36; Issue: 3 Linguagem: Inglês

10.1097/00005176-200303000-00002

1536-4801

Lawrence T. Weaver,

Digestive system and related health

ArticlePlus Click on the links below to access all the ArticlePlus for this article. Please note that ArticlePlus files may launch a viewer application outside of your web browser. https://links.lww.com/MPG/A1 The past ten years have seen acceleration in the trend away from formula feeding. More and more mothers are electing to breast-feed their babies from birth and are receiving support and encouragement to do so. This welcome change was set in motion, in part, by the natural childbirth movement and given momentum by WHO and UNICEF through their Baby Friendly Initiative (BFI). Neonatologists and pediatricians have been slow to throw their weight behind it. Nevertheless the number of hospitals that are baby-friendly worldwide now exceeds 14,500, although less than 2% are in industrialized countries (http://www.babyfriendly.org.uk/world.asp). One effect of the BFI has been to limit the influence of infant formula companies on hospitalized post partum mothers, through the WHO code (1). However, rising breast-feeding rates have done little to dampen the enthusiasm of manufacturers to continue the effort to develop new infant milk formulas more and more closely resembling human milk. Numico (embracing Nutricia, Milupa, Cow & Gate, and other companies) started to adapt cow milk in the manufacture of formulas for babies in the 1890s (http://www.numico.com/uk/history) at a time when the circumstances surrounding infant feeding differed greatly from those of the present day. The decades that spanned the end of the nineteenth century were a period of high infant mortality. In most of Europe, death rates had remained stubbornly at around 150 per 1000 live births for 50 years of more. Infant mortality was closely related to diarrheal disease and malnutrition, and `clean milk' was thought to be the answer. Gouttes de Laits in France, Milk Depots in Great Britain, Milchsammelstellen in Germany, and Milk Stations in the U.S.A. sprang up to meet the needs of poor urban mothers and infants (2). CLEAN MILK FOR BABIES Milk Depots were usually set up under local governmental direction, sometimes with charitable and public support. With an abundance of milk, and the technology to pasteurize and bottle it, their purpose was to supply `clean, harmless, palatable cow's milk' to mothers to feed their infants. Simple mixtures were made up by varying the amounts of milk, cream, water, salt, and sugar. However, the principle behind milk depots was `to encourage and aid breast-feeding, to supply good-quality sterilized milk if required, and to provide weekly infant care and supervision of infants during first two years'. They were, in effect, the prototypes for infant welfare clinics, which spread throughout the world and are alive and well today (2). Pierre Budin, the French pioneer of `consultations de nourissons', stressed the central importance of breast-feeding: `Nous encouragions de toutes nos forces l'allaitement au sein. . . . Dans tous nos écrits, nous avons insisté sur l'importance de l'allaitement maternal. Le nouveau-né doit être mis au sein, il doit être nourri par sa mère' (3). These public health initiatives ran parallel to the development of infant food companies, which catered more to the upper end of the market (4). In the absence of effective remedies, improvements in infant nutrition through the application of rational, scientifically derived principles, were strong forces behind the rise of pediatrics, particularly in Germany, Great Britain, and the U.S.A. Those physicians who looked after sick children collaborated with those scientists who manufactured new formulas to feed them. Together they tested them in baby's wards, clinics, and children's hospitals and presented their results at medical and scientific meetings. The emergence of pediatrics as a subspecialty owes much to the interest its pioneers took in infant feeding (5). Knowledge of the differences between human and bovine milk was well advanced by the turn of the nineteenth century, and formed the basis of the processes involved in `humanizing' cow milk (6). The techniques of drying and condensing milk were in place, and evaporated milk had an obvious advantage over fresh milk in resisting bacterial contamination. The term `formula' arose from the move away from simple recipes for mixtures based on cow milk—some described in textbooks, some passed on by word of mouth, and some recommended by physicians—to more scientific prescriptions that defined their nutritional composition. Thomas Rotch of Harvard refined this process with his percentage feeding method, which involved diluting cow milk to lower its relatively high casein (protein) content, adding sugar and cream to increase the carbohydrate and fat contents. Rotch argued that a `changing combination of the different elements of milk (fat, carbohydrate and protein) made it the best food during the first year of life, and since human milk varied to meet the needs of the individual infant, so too must any substitute be flexible enough to allow alteration of the percentages of its nutritive parts'. His prescriptions went into immense detail specifying precise and minute variations according to infant age, medical condition and growth rate, and his textbook of pediatrics even contained pictures of the best diary cows from which milk should be obtained (7). Rotch established his own `milk laboratory', which echoed those of the infant milk formula companies. Rotch was not working alone, and many pediatricians in Europe and America were preoccupied with developing the science of infant feeding. His ideas were taken up in London by Vincent (who opened his own milk lab and dedicated his book (8) to Rotch) and both were in contact with Finkelstein in Berlin, developer of Eiweissmilch (protein milk) and popularizer of maltodextrins as partially digested alternatives to starch in infant foods, an advance that was quickly taken up by the formula manufacturers of the day (9). The rise of biochemistry and metabolic research added impetus to the transatlantic and pan-European interchange of scientific advances and commercial enterprise. One of the effects (and intentions) of Rotch's work was to retain control of infant feeding practices in the hands of pediatricians. Nevertheless some physicians ` revolted at doing algebraic or even considerable arithmetical sums at the bedside' and complained that ` you cannot bring up a baby by mathematics' (5). On the other hand as commercialization and marketing of infant formulas became increasingly independent of pediatricians, with advertising directly to the public, doctors feared loss of influence over their patients, and some publicly resisted the trend. The first decade of the century was an exciting time for those scientists trying to control infant mortality and interested in improving the feeding of babies. One hundred years ago the interaction of those scientists working in the field, at international meetings, and through the pages of journals, was well developed and helped to create the science base of pediatric nutrition. Infant milk formulas that in gross composition resembled human milk began to be mass-produced and marketed, dedicated to the cause of reducing infant mortality and childhood malnutrition. NECESSITY IS THE MOTHER OF HABIT If necessity is the mother of invention, necessity is also the mother of habit. High infant mortality rates demanded measures to reduce them, which included better infant feeding practices. These practices found expression through both the milk depot movement and artificial feeds. By the end of the interwar years infant mortality rates were under control, and milk depots had faded away (2). The child welfare movement was well established, yet the practice of formula feeding had taken hold. The frontiers of pediatrics moved on from infant nutrition, which had preoccupied its founders (5) as new subspecialties opened up. Formula-feeding rates rose quietly and steadily through the 1950s, 60s and 70s until the voices of the natural childbirth movement, pediatricians working in the developing world (10), and those scientists researching the benefits of beast feeding beyond its provision of nutrition alone (not all in unison), began to influence the trend in the other direction. It has been argued, within the general hypothesis that improved nutrition at a public health level accounted for the decline in mortality rates, that milk made a major contribution (11). Success in reproducing the gross constituents of human milk has been followed by concentration on subtler aspects of composition—refining the polyunsaturated fatty acid and amino acid balance and the antigenicity for instance (12). The latest phase of formula development has been to focus on the non-nutritional `bioactive' components, and there has been interest in trying to add protective factors, such as IgA, lactoferrin, and nucleotides. But the constituents that are currently receiving most attention are oligosaccharides. Oligosaccharides are found in human milk at concentrations of around 5 to 10 g/l. There are thought to be hundreds, perhaps thousands, of different oligosaccharides, varying in size, monosaccharide core structure, and glycoconjugates (13). A common feature of most human milk oligosaccharides (HMO) is inclusion of lactose and fucose in their structure. This huge diversity is thought to reflect the wide range of bacterial cell surface receptors, which use the oligosaccharide portion of glycolipids and glycoproteins as targets. HMOs have therefore been postulated to be homologues for bacterial receptor molecules, and thereby to defend the gastrointestinal tract mucosa by competing with intestinal ligands for attachments by enteropathogens (14). Most HMOs resist digestion in the upper gut, and pass into the colon where they are available for fermentation by the resident bacteria. More than a century ago, in the pioneering days of infant formula development, oligosaccharides were observed to be growth factors for the bifidus flora of breast fed infants (15). It is this feature of oligosaccharides that has caught the attention of infant formula manufacturers, and in this issue of JPGN the results of a randomized, double-blind trial of the nutritional efficacy and bifidogenicity of an infant formula containing partially hydrolyzed protein, a high beta-palmitic acid level, and non-digestible oligosaccharides are reported. Galacto and fructo-oligosaccharides (GOS and FOS) are synthetic non-digestible carbohydrates that have a comparable `prebiotic' effect to HMOs. Prebiotics are defined as non-digestible food ingredients that selectively stimulate the growth and/or activity of one or more bacteria in the colon and thereby beneficially affect the host (16). A number of studies (referred to in the report) have shown that the fecal flora of infants fed milks containing them can be modified to contain comparable counts of Bifidobacteria as the stools of breast-fed infants and that they may protect the baby from gastroenteritis and atopic sensitization. In the current study the stools of the babies receiving the formula containing FOS and GOS had a higher proportion of bifidobacteria than those of the babies receiving a formula devoid of them. The rationale for the structured triglyceride with a high palmitic acid level is that this fatty acid, particularly abundant in human milk, is largely found at the beta (sn-2) position on the glycerol molecule. Pancreatic lipases preferentially and selectively hydrolyze the fatty acids at the sn-1 and 3 positions, releasing the 2-monoglyceride, which is easily taken up because it readily forms micelles with bile acids (17). This characteristic commends it for inclusion in Omneo/Comformil, by making palmitic acid unavailable to form insoluble soaps with cations like calcium and magnesium, a problem that has long been recognized with conventional formulas based on cow milk that contain palmitic acid predominantly at the sn-1 and 3 positions of triglyceride. The inclusion of partially hydrolyzed protein recognizes the quest for a feed that evokes no antigenic reaction (18), and here the aim is to ensure that the type chosen is nutritionally optimal. The biochemical data published are reassuring, and overall the new formula was well tolerated by babies and accepted by mothers. TESTING NEW FORMULAS The process of developing, testing, and marketing a new or modified infant formula can be lengthy and expensive. In the early days, criteria for adequacy were little more than improved survival of babies fed on one. Long-term outcomes, including ponderal and linear growth, biochemical and metabolic measures, are now required. The UK Committee of Medical Aspects of Food and Nutrition Policy (COMA) and the Committee on Nutrition of ESPGHAN have produced guidelines for the nutritional and safety assessment of breast-milk substitutes (19,20). The design of Omneo/Comformil therefore represents the latest step in more than a century of improvements to infant formula. The paper by Schmelzle et al. observes many of these guidelines and is a model of how such studies should be performed and reported. It is fitting that it should be published in this journal in which the guidelines of the ESPGHAN Committee on Nutrition were also published (20), so that pediatricians, child public health specialists, dieticians, nutritionists, and all those dedicated to ensuring the optimal health, nutrition, and feeding of children can assess the potential value of this new formula. The scientific foundations of infant nutrition and feeding are much more fully understood than they were a century ago. Infant mortality rates are now lower by an order of magnitude in Europe and North America (1), and one of the prime stimuli for better infant formulas has now well and truly gone. In the developing world, where mortality rates remain high and infant malnutrition is one of the principal causes of growth faltering and early death, there is little nutritional justification for breast milk substitutes. Habits die hard. The Holy Grail in the quest for the perfect infant formula is of course something that already exists—human milk. It is logically possible and desirable that refinement of the perfect breast milk substitute and achievement of universal breast-feeding will coincide, and the holy grails of both industry and child public health will be realized at once and in one, when all babies are fed by their mothers on the breast.