13
4. Physiological development of the infant and its implications for complementary feeding From the standpoint of nutritional needs, physiological maturation, and immunological safety the provision of foods other than breast milk before about four months of age is unnecessary and may also be harmful. On the other hand, many infants require some complementary feeding by about six months of age. There are a number of known disadvantages and risks involved in too early complementary feeding, including interference with the infant's feeding behaviour, reduced breast-milk production, decreased iron absorp- tion from breast milk, increased risk of infections and allergy in infants, and increased risk of a new pregnancy. With many complementary foods, including undiluted cow's milk, there is also a risk of a water deficit with a resultant hyperosmolarity and hypernatraemia that, in extreme cases, can lead to lethargy, convulsions, and even residual brain damage. Other possible implications include the development of obesity, hypertension, and arteriosclerosis in later life. The decision about when to start complementary feeding depends not only on age but also on the developmental stage of the individual infant, the type of food available, the sanitary conditions in which the food is prepared and given, and family history of atopic disease. Introduction During the intrauterine period, the fetus is "fed" through the placental circulation. As briefly discussed in chapter 1, the placenta transmits from the mother's blood all required nutrients, which directly enter the fetal circulation in an immediately usable form. Glucose is the main source of energy, while free amino acids are used for protein synthesis. Owing to this mechanism the fetus does not have to ingest, digest and absorb food, nor is an excretory system required. Whatever waste is produced goes back into the mother's circulation. The gastrointestinal tract and renal functions develop progressively prior to birth, in preparation for the day when they will be needed. There is evidence that, late in pregnancy, the fetus demonstrates swallowing movements and takes in amniotic fluid; this has very little, if any, nutritional significance, though it is of importance for the anatomical and functional development of the fetal gastrointestinal system. Similarly, the fetus produces and excretes urine, which passes into the amniotic fluid even though the kidneys are still developing and are not yet playing a vital role. The situation changes radically at birth, after which the infant must take food by mouth, digest and absorb the nutrients, and have functioning kidneys to excrete metabolic wastes and maintain water and electrolyte homeostasis. However, since neither the digestive nor excretory system is as yet fully developed, the margin of tolerance for water, overall solute load, and specific solutes is very narrow com- pared with the older infant and young child. Because of the inability of the kidneys to concentrate urine at birth and for several months thereafter, the neonate and young infant require food with a higher water content than that taken by the older infant in order to be able to excrete a comparable solute load. The process of adaptation to these drastic changes occurs during the first few months of extrauterine life, during which the infant is also growing rapidly and therefore has high nutritional requirements. Both the sucking and extrusion reflexes, present at birth and active throughout the first months of life, prime the infant to receive only liquid nourishment. If other foods are given at this time, they are usually regur- gitated. Appropriate feeding practices during the first months of life are thus conditioned by the infant's nutritional needs and degree of functional maturity, particularly as regards the types of food, mechanism of excretion and defences against infection. This chapter reviews the development of the gastrointes- tinal tract and renal functions during early extra- uterine life and the corresponding nutritional needs. It also considers infant-feeding practices, particularly complementary feeding. Gastrointestinal-tract functions Food Ingestion At birth the normal infant is able to suck from the mother's breast, conduct the milk thus obtained to the back of the mouth and swallow it. The infant can do this for five to ten minutes continuously while breathing normally. As discussed in chapter 2, the sucking and swallowing functions are vital for the newborn and the infant during the first months of life. They are achieved by a special morphological confi- guration of the mouth, with, in particular, a propor- WHO Bulletin OMS: Supplement Vol. 67 1989 5S

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4. Physiological development of the infant and itsimplications for complementary feeding

From the standpoint of nutritional needs, physiological maturation, and immunological safety the provisionof foods other than breast milk before about four months of age is unnecessary and may also be harmful.On the other hand, many infants require some complementary feeding by about six months of age. Thereare a number of known disadvantages and risks involved in too early complementary feeding, includinginterference with the infant's feeding behaviour, reduced breast-milk production, decreased iron absorp-tion from breast milk, increased risk of infections and allergy in infants, and increased risk of a newpregnancy. With many complementary foods, including undiluted cow's milk, there is also a risk of a waterdeficit with a resultant hyperosmolarity and hypernatraemia that, in extreme cases, can lead to lethargy,convulsions, and even residual brain damage. Other possible implications include the development ofobesity, hypertension, and arteriosclerosis in later life. The decision about when to start complementaryfeeding depends not only on age but also on the developmental stage of the individual infant, the type offood available, the sanitary conditions in which the food is prepared and given, and family history of atopicdisease.

IntroductionDuring the intrauterine period, the fetus is "fed"through the placental circulation. As briefly discussedin chapter 1, the placenta transmits from the mother'sblood all required nutrients, which directly enter thefetal circulation in an immediately usable form.Glucose is the main source of energy, while freeamino acids are used for protein synthesis. Owing tothis mechanism the fetus does not have to ingest,digest and absorb food, nor is an excretory systemrequired. Whatever waste is produced goes back intothe mother's circulation. The gastrointestinal tractand renal functions develop progressively prior tobirth, in preparation for the day when they will beneeded.

There is evidence that, late in pregnancy, thefetus demonstrates swallowing movements and takesin amniotic fluid; this has very little, if any,nutritional significance, though it is of importance forthe anatomical and functional development of thefetal gastrointestinal system. Similarly, the fetusproduces and excretes urine, which passes into theamniotic fluid even though the kidneys are stilldeveloping and are not yet playing a vital role.

The situation changes radically at birth, afterwhich the infant must take food by mouth, digest andabsorb the nutrients, and have functioning kidneys toexcrete metabolic wastes and maintain water andelectrolyte homeostasis. However, since neither thedigestive nor excretory system is as yet fullydeveloped, the margin of tolerance for water, overallsolute load, and specific solutes is very narrow com-pared with the older infant and young child. Becauseof the inability of the kidneys to concentrate urine atbirth and for several months thereafter, the neonate

and young infant require food with a higher watercontent than that taken by the older infant in orderto be able to excrete a comparable solute load.

The process of adaptation to these drastic changesoccurs during the first few months of extrauterine life,during which the infant is also growing rapidly andtherefore has high nutritional requirements. Both thesucking and extrusion reflexes, present at birth andactive throughout the first months of life, prime theinfant to receive only liquid nourishment. If otherfoods are given at this time, they are usually regur-gitated.

Appropriate feeding practices during the firstmonths of life are thus conditioned by the infant'snutritional needs and degree of functional maturity,particularly as regards the types of food, mechanismof excretion and defences against infection. Thischapter reviews the development of the gastrointes-tinal tract and renal functions during early extra-uterine life and the corresponding nutritional needs.It also considers infant-feeding practices, particularlycomplementary feeding.

Gastrointestinal-tract functions

Food IngestionAt birth the normal infant is able to suck from themother's breast, conduct the milk thus obtained tothe back of the mouth and swallow it. The infant cando this for five to ten minutes continuously whilebreathing normally. As discussed in chapter 2, thesucking and swallowing functions are vital for thenewborn and the infant during the first months of life.They are achieved by a special morphological confi-guration of the mouth, with, in particular, a propor-

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Chapter 4

tionately longer soft palate than is found later in life,and by the sucking and swallowing reflexes, whichdirect a series of coordinated movements of the lips,cheeks, tongue and pharynx. By six months of age,the ability to swallow fluids offered by cup has begunto develop.

If solid or semi-solid food is placed in the younginfant's mouth, it is normally vigorously rejected bythe action of another of the infant's normal reflexes.It is only at four to six months of age, when thetongue thrust, or extrusion reflex, is normally nolonger present, that the infant is able to cope withsemi-solid foods; hence the food can be transportedto the rear of the mouth and swallowed (1). The seriesof movements needed for this purpose are differentfrom those needed for sucking and swallowingliquids. Later, at seven to nine months of age,rhythmic biting movements start to appear at thesame time as the first teeth are erupting; masticationhas begun.

For the first four to six months of life the normalinfant is thus at a stage of functional developmentthat allows the acceptance of an essentially liquiddiet. This is a period of transition between the fetalnutrition in utero and the mixed, mainly solid, diet oflater life. While a young infant can be forced to takesoft semi-solid foods from the first days after birth,for example by a mother who learns how to utilizethe infant's sucking movements to feed such foods,this cannot be considered either normal or desirable.

Food digestionCarbohydrates. The process of food digestion starts inthe mouth; during mastication foods are mixed withsaliva allowing the action of amylase to begin thedigestion of starches. Although amylase has beenfound in infant saliva, no digestion of carbohydratestakes place in the mouth or oesophagus during thefirst months of life.

Carbohydrates are digested mainly in the proxi-mal small intestine. Polysaccharides, like starches, aredegraded into mono- and disaccharides, primarily bythe action of delta-amylase secreted by the pancreas.Glucoamylase secreted by the intestinal mucosa mayalso contribute to the digestion of starches, but itacts primarily on oligosaccharides and some disac-charides. The small intestine's mucosa also secretesdisaccharidases, which hydrolyse disaccharides intomonosaccharides, the only form in which carbo-hydrates can be absorbed.

It has been determined that infants born at termhave approximately 10% of adult amylase activity intheir small intestine (2) and this seems to be mainlyglucoamylase activity. Present information indicatesthat pancreatic amylase is not secreted during the

first three months of life; it has been found to bepresent only at very low levels, or absent altogether,up to six months of age (3).

There is, however, some evidence that infantscan digest starches before three months of age. This isprobably due to the activity of glucoamylase, whichis not normally active at this time, but which isactivated by the presence and nature of the substanceor substrate on which the enzyme acts (4). It is alsopossible that pancreatic amylase could be producedas a reaction to the presence of starches in the smallintestine, although this has not been proved. In anycase, a process of adaptation is required for theyoung infant to be able to digest starches. This cantake days or weeks and might explain the frequencywith which gastrointestinal disturbances, particularlydiarrhoea, are observed in small infants fed starch-containing foods. It has also been suggested thatundigested starches may interfere with the absorptionof other nutrients and result in failure to thrive ininfants fed diets containing a large proportion ofstarches (5).

Contrary to the evident immaturity of theinfant's system for the digestion and utilization ofstarches during the first months of life, the activity ofthe disaccharidases is fully developed at birth. Bothdelta-glucosidase, which hydrolyses sucrose and mal-tose, and beta-galactosidase, which hydrolyses lac-tose, are present at birth at the same activity levels asthose found in older infants (6). The digestion andutilization of milk sugar, therefore, poses no problemat this age.

Proteins. The gastric secretion of hydrochloric acidand pepsin is already well developed in the newbornat term; concentrations are low, however, andincrease progressively during the first months of life(7,8). In any case, the digestion of proteins takesplace mainly in the small intestine, where proteolyticactivity in the newborn has reached the same concen-tration as in adults (9). Thus, while the young infantmay have some difficulty with proteins like casein forwhich gastric activity can be important to initiatedigestion, the infant's capacity to digest proteins isotherwise fully developed at birth. Nevertheless, veryhigh protein intake should be avoided, particularly inthe pre-term and very young infant, in whom anexcessive renal solute load may produce acid-baseimbalances and metabolic acidosis.

Another problem related to the young infant'suse of proteins is the permeability of the intestinalmucosa to large molecules. In older infants, as inadults, proteins are absorbed as amino acids andsmall peptides. Most of the latter are further digestedduring their passage through the mucosa, and it is

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Physiological development of the Infant

mainly the free amino acids which enter the circula-tion. Large molecules, which can act as antigens, donot normally cross the intestinal mucosa. During theneonatal period, however, and for a variable timethereafter, the infant is able to absorb proteinmolecules intact (10), as demonstrated by the absorp-tion of antibodies and the immunological response toprotein antigens administered orally.

This physiological characteristic of the younginfant seems to be one mechanism by which anallergic reaction to cow's milk sometimes develops inchildren. Its implications for the development ofother food allergies is not clear but should be bornein mind when decisions about the feeding of younginfants are being made.

Fats. As mentioned above, glucose is the main sourceof energy for fetal development during the intra-uterine period. After birth, however, dietary fatsbecome an important energy source. Some 40-50%of energy in human milk is in the form of fats. Adrastic adjustment in energy metabolism is thereforerequired after birth, starting with the digestion andabsorption of fats.

In older infants and adults, dietary fats are firsthydrolysed, mainly by the activity of the pancreaticlipases in the small intestine. The products of lipolysisare then solubilized for absorption by the action ofthe bile salts. In the newborn at term, the pancreaticand hepatic functions are not yet fully developed andthe concentrations of both pancreatic lipase and bilesalts are very low (11, 12).

It has been observed, however, that younginfants adequately absorb fats, particularly thosefrom human milk. This is somewhat surprising con-sidering that milk-fat droplets are particularly resis-tant to the lipolytic activity of pancreatic lipasesbecause they are enveloped by a layer of phos-pholipids and proteins. It is known that fat digestionand absorption in young infants are enhanced by theaction of lingual lipases (13) and by the action of alipase contained in human milk (14). Lingual lipasesare secreted by papillae on the posterior part of thetongue; they start to act in the stomach and theproducts of lipolysis (fatty acids and monoglycerides)contribute to the emulsification of the mixture, there-by compensating for low bile-salt content. This impor-tant mechanism of preduodenal lipolysis in the younginfant is further complemented by the lipase con-tained in breast milk (bile-salt stimulated lipase),which also plays an important role during earlyinfancy in fat digestion and absorption. The breast-milk lipase also has esterase activity, which is vital forutilization of vitamin A that is present in milk in theform of retinol esters.

In spite of the immaturity of the pancreatic and

hepatic functions, the young infant is thus wellequipped to make use of both the fat in breast milk,which provides close to half of energy requirements,and its other important fat-soluble components.These compensatory, or complementary, mechanismsfor fat utilization are less efficient when cow's-milk fator other fats are introduced into the young infant'sdiet (15).

Vitamins and minerals. There appear to be no majorproblems in the utilization of dietary vitamins andminerals in early life. However, the subject has notbeen studied as much as the digestion and utilizationof the macronutrients already discussed. The absorp-tion of fat-soluble vitamins is closely linked to fatabsorption. For vitamin A in particular, not enoughis known about the utilization by young infants ofthe different forms in which it or its precursors canoccur ifi foods. The particularly high absorbability ofvitamin A in human milk has already been men-tioned.

The situation is similar for iron, the absorptionof which is higher in infants than in older childrenand adults. This seems to be related to a greater needfor the mineral in early life. In addition, the bio-availability of iron is much higher from breast milkthan from cow's milk or preparations added to food(16). The responsible mechanism is not known,although it has been observed that the high bio-availability of breast-milk iron decreases drasticallywhen solid complementary foods of vegetable originare given to the breast-fed infant. This situation hasbeen confirmed experimentally by measuring, inadults, the iron absorption from breast milk alone orwhen fed together with a common complementaryinfant food (strained pears). Iron absorption wasfound to be 23.8% in the former and 5.7% in thelatter case (17).

Water and electrolytes. The permeability of the intes-tinal mucosa to water and electrolytes is higherduring infancy than in later life. This is of no sig-nificance under normal conditions but becomesimportant in situations of high osmolarity in theintestinal contents. Under these circumstances theinfant tends to develop water and electrolyteimbalances more easily than later in life, and theimplications for infant feeding should thus becarefully borne in mind.

Excretory systemMaintaining the amount and composition of bodyfluids and excreting metabolic wastes are among thekidneys' vital functions. In utero urine formationstarts early in fetal development, i.e., by the ninth or

WHO Bulletin OMS Supplement Vol. 67 1989 S7

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Chapter 4

tenth week of gestation. Urine excretion at this stageplays a role in amniotic-fluid maintenance and theembryogenesis of the urinary system. The regulatoryand excretory functions of the kidneys are minimalbefore birth, however, as the task of maintaining fetalhomeostasis is carried out by the placenta. Metabolicwastes are practically nil, since fetal metabolismis fundamentally anabolic; whatever waste there ispasses through the placenta into the maternal cir-culation. This is confirmed by the fact that no renalinsufficiency is initially evident in infants born withrenal agenesis.

At birth the kidneys are performing all theirfunctions but at a limited capacity. They meet theneeds of the normal newborn, who continues with apredominantly anabolic metabolism provided that abalanced, fully utilizable, low-residue food, namelybreast milk, continues to be fed. The kidneys' func-tional capability rapidly increases during the first fewmonths of life, as illustrated by their near doubling insize from 12.5 g per kidney at birth to about 20 g at13 months of age.

The newborn's kidneys are characterized by alow glomerular filtration rate and low concentrationcapability (18). They function very efficiently, how-ever, as a water-conservation mechanism to preventdehydration and have no difficulty in eliminating thelow metabolic residues of a breast-fed infant. Thesystem can fail when the water intake is markedlyreduced or solute intake is noticeably increased.Because the human infant has very differentnutritional requirements compared to those of a calf,the giving of undiluted cow's milk can lead tohyperosmolarity with hypernatraemia in the younginfant. If not checked, this can result in lethargy,convulsions and even damage to the central nervoussystem. A cow's-milk diet for the young infant canlead to a water deficit of 80ml/day. The situationbecomes particularly critical when there areextrarenal water losses such as occur with fever orhigh ambient temperature.

The young infant's kidneys have a limited abilityto eliminate hydrogen ions (19), and hence are moresusceptible to develop acidosis. Phosphate excretionis a good example of how they adapt their functionalcapacity to demand. At this age, the kidneys nor-mally function with a low-phosphate intake, as wasthe case in utero, and should continue this wayprovided the infant is breast-fed. However, when theinfant is put on a high-phosphate diet-cow's milkfor instance-the kidneys have to adjust to anotherlevel of functioning. Although they usually respondto this demand, it does take time. Meanwhile, theinfant may develop transitory hyperphosphataemiaas a result of both renal immaturity and functionalhypoparathyroidism, which may be associated with

hypocalcaemia and neonatal tetany (20).The relative immaturity of the newborn's renal

system seems to be due only to the fact that the levelof functioning corresponds to expected demand. Thekidneys subsequently mature very rapidly during thefirst few months of life and are able to adapt tosignificant variations in diet. Thus, starting at aboutfour months, the solute load resulting from themetabolism of newly introduced foods is acceptable.In fact, progressive modifications in dietary intake,with increments in urea and other solutes to beexcreted, stimulate the kidneys to attain higher func-tional levels. The immature renal system is easilyoverburdened by such stress situations as disease,dehydration and sudden or too-drastic dietarychanges such as the inclusion of foods with highsodium (minerals) or solute loads (proteins), whichwould require water supplements (see Table 4.1,parts A and B). The use of water with a high mineralcontent to prepare infant formula is thus undesirable.

Infant feeding

Nutritional requirementsEarly life is a period of very rapid growth, with theweight of the normal infant doubling by four monthsof age. Energy and nutrients are needed not only formaintenance of bodily functions and activity butalso, in large proportion, for tissue deposition. Boththe quantitative and qualitative nutritional require-ments of the infant are consequently different fromthose of older children and adults. For example, therequirements for both energy and protein during thefirst month of life are, on a per kilogram basis, aboutthree times those of the adult. There are also otherimportant differences, related either to actual nutri-tional needs or to the particular physiologicalcharacteristics of the infant.

Where proteins are concerned, the requirementsof infants for essential amino acids are proportion-ately much higher than in older children and adults(21,22). It would therefore by very difficult, if notimpossible, to satisfy their nitrogen needs withproteins of low biological value. Fats as such are notrequired, except for very small amounts of essentialfatty acids. Nevertheless, they are extremely impor-tant for the infant as a source of concentrated energy,allowing as they do the high-energy intake requiredwithin a reasonable volume of food. Mineral require-ments are particularly critical at this age; iron andcalcium, needed for haemoglobin formation andbone calcification, are notable examples.

More than 50 nutrients are known to be neededby human beings, although information is lacking onthe requirements in respect of more than half of them.

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Physiological development of the Infant

For most nutrients there is not only a minimumintake level below which a deficiency occurs but alsoa maximum level above which they could haveundesirable consequences. While the range betweenthese minimum and maximum desirable intakes isquite wide in most cases, it is rather narrow in others.For example, energy-intake levels even slightly belowthose normally required result in a deficiency whilethose above will, in time, produce obesity.

A delicate balance of energy and a large numberof nutrients is therefore required to ensureappropriate infant nutrition and health. Fortunately,an adequate diet depends less on a consideration ofindividual nutrients than on the range of foods to begiven. For infants up to at least the age of 4-6months, breast milk is a complete and perfectlybalanced mixture of all required nutrients (see chap-ter 2, on the nutritional quality of breast milk). If theinfant's energy needs are satisfied with breast milk, allother nutritional requirements will automatically bemet. Exceptions to this rule are infants with very lowbirth weight who may need iron supplementation (seechapter 5) and infants born of mothers with specificvitamin and mineral deficiencies. In the latter case, amother's milk may have low values for a givennutrient and her infant may have to be given it as asupplement. The situation is different for infants fedwith breast-milk substitutes, who would normallyrequire early supplementation with vitamin C as wellas with iron (when the breast-milk substitute used isnot enriched with this mineral) and vitamin D (when,because of environmental or other reasons, infantsare not exposed to sufficient sunlight) (see Table 4.1,parts B and C).

Energy requirementsEnergy requirements can be defined as the level ofenergy intake from food that will balance the energyexpenditure in healthy individuals. Energy expen-diture includes the basic metabolism, energy expen-ded in activity, and the energy cost of food utiliza-tion. For pregnant and lactating women, the energycost of pregnancy and lactation has to be added, andfor children the energy required for growth.

Ideally, the energy requirement should be deter-mined by accurately measuring all dietary compo-nents. While this can usually be done in the case ofolder children and adults, no reliable informationis available on the energy needed by infants foradequate growth and physical activity. However,since it is generally accepted that healthy infants,growing within accepted standards, are in energybalance, the energy intake of such infants has beenused as the basis for establishing this group's energyrequirements.

Table 4.2: Energy requirements of Infants (23)

Age (months) kcal/kg/day MJ

0-3 120 0.5023-6 115 0.4816-9 110 0.4609-12 105 0.439

To estimate the energy requirements for infantsunder 6 months of age, an FAO/WHO Ad HocExpert Committee on Energy and Protein Require-ments (23) in 1971 used data on the intake of infantsfed breast milk by bottle and teat (24). For infants 6-12 months of age, data were used concerning healthychildren from the USA and the United Kingdomwho were fed on a mixed diet (25). Although theinformation had its limitations, it was the best thatwas available. The Committee recommended 120kcal (0.502 MJ) per kg per day for infants 0-3months of age, decreasing progressively to 105 kcal(0.439 MJ) per kg per day for infants 9-12 months ofage (see Table 4.2). It was on this basis that the breastmilk of healthy mothers was judged to be insufficientto satisfy the energy requirements of normal infantsbeyond three months of age (26).

A second consultation, which was jointly spon-sored by FAO, WHO and the United NationsUniversity, took place in 1981 to review energy andprotein requirements once again (27). This group hadaccess to a much larger collection of food-intakemeasurements from Canada, Sweden, the UnitedKingdom and the USA for infants, who were healthyand growing within recommended WHO standards(28). Data from developing countries were inten-tionally not used in order to exclude any infantsgrowing below the recommended standard, which isassociated more with inadequate diet and frequentinfections than with genetic differences (29). Theinteresting results of an analysis of the data used bythe 1981 Committee are summarized in Table 4.3.

Although energy intake values start at a levelsimilar to those of the 1971 recommendations, theydrop rapidly during the first months of life, beginningto rise again after the tenth month. This U-shapedcurve is very different from the progressively decreas-ing line followed by the 1971 values; it is consideredto be more accurate, however, and is probably relatedto a rapid decline in the energy required for growth. Incontrast, energy expenditure through activity, which isinitially low, increases progressively to assume greatersignificance during the latter part of the first yearof life. The differences between these observed intakevalues and the 1971 recommendations are consider-able, particularly during the critical period when theweaning process starts. They explain why, under

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Chapter 4

Table 4.3: Energy Intake of Infants"

Intake

Age (months) kcal/kg/day MJ

0.5 118 0.4941-2 114 0.4772-3 107 0.4483-4 101 0.4234-5 96 0.4025-6 93 0.3906-7 91 0.3817-8 90 0.3378-9 90 0.3779-10 91 0.38110-11 93 0.39011-12 97 0.40612 102 0.427

' Based on reference 28.

normal conditions, breast milk alone satisfies theenergy requirements of the average infant for the first6 months of life (30).

Complementary feedingBy "weaning process" is meant the progressive trans-fer of the infant from breast milk to the usual familydiet. From the standpoint of physiological matura-tion and nutritional need, giving foods other thanbreast milk to the infant before about 4 months ofage is usually unnecessary and may entail risks, forexample making the infant more vulnerable to diar-rhoeal and other diseases (see chapter 6). Moreover,because of its effect on the infant's feeding behaviour,and therefore breast-milk secretion, any other food ordrink given before complementary feeding is nutri-tionally required may interfere with the initiation ormaintenance of breast-feeding.

On the other hand, by around 6 months of agemany breast-fed infants require some complementaryfeeding and are fully developed functionally to copewith it. Traditionally, the period between 4 and 6months of age has been seen as suitable for infants tobegin to adapt to different foods, food textures andmodes of feeding.

When to start complementary feeding for breast-fed infants cannot be decided exclusively on the basisof age, however. The types of food that are normallyconsumed at home or are easily available, and theenvironmental conditions and facilities to prepareand feed them safely, should also be considered. Forexample, if the available foods for the infant are lowin nutritional value and are too coarse or difficult toprepare in a soft semi-solid form, or if environmentalconditions favour contamination with either micro-

organisms or undesirable substances, it is preferableto delay the introduction of complementary foodsuntil they become strictly necessary on nutritionalgrounds.

An infant's developmental stage can be deter-mined by observing neuromuscular capabilities.When the head is held erect, hands are put to themouth and semi-solid foods are accepted withoutdifficulty (indicating the disappearance of theextrusion reflex), an infant is ready to begin receivingcomplementary foods. Obviously, growth velocityshould also be considered. If a breast-fed infant is notgrowing properly and no other reason can be foundto account for it, it may be time to start complemen-tary feeding. In practice, there is no need either tobegin complementary feeding before it is nutritionallynecessary, or to wait for growth faltering to occurbefore initiating it.

Breast milk is the only "standard" food for thehuman infant. Once other foods are given, they canbe as varied as are family diets prepared at home inthe normal manner. From the nutritional point ofview, complementary foods progressively replacebreast milk, which is a complete and balanced food.At the onset of complementary feeding, when theinfant is still predominantly breast-fed, these foodsare important primarily as an additional source ofenergy. At the same time, however, they should alsohelp to satisfy requirements for all essential nutrientsto which breast milk will be making a progressivelydecreasing contribution. Particular attention shouldbe given to proteins, iron, and vitamins A and C;these nutrients are frequently found to be deficient inthe diet of young infants.

Table 4.1 provides a few examples of the verylarge number of commercial and home-made com-plementary foods that are available. The home-madevarieties are frequently more in accordance with afamily's cultural and economic conditions, in addi-tion to being generally low in sodium.

Rlsks of too early complementary feedingIt is generally recognized today that infants areneither ready to receive semi-solid foods before about4 months of age, nor, except under exceptional cir-cumstances (see chapter 3), are these foods necessaryas long as infants are breast-fed. Not so very longago, however, it was customary in some indus-trialized countries to start complementary feedingbefore one month of age with cereal preparations,strained vegetables and fruits, and eggs and meat.While this practice has been largely abandoned, it isstill common to give semi-solid foods to infantsbefore three months of age.

There is no question that, in terms of functional

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capabilities, most infants can adapt to this situation.They may initially refuse the food, vomit or haveloose stools, but they will finally take it withoutmajor problems. They and their mothers quicklylearn how to manage semi-solid foods, even if thereflex movements of the infant's mouth are not yetready for them. As discussed earlier in this chapter,the production of digestive enzymes, amylases inparticular, is still normally low at this age; but thepotential to react to stimuli is there, and thus enzymeproduction increases when starches or other sub-strates are included in the diet. The kidneys, stimu-lated by the presence of urea derived from excessiveprotein, can also react by increasing their excretoryand filtering capacity.

Of course, the mere fact that the physiologicallyimmature organism can adapt to a feeding mode thatis nutritionally unnecessary hardly justifies its use.On the contrary, a number of immediate disadvan-tages or risks of too early complementary feedingare recognized, and the possibility of longer-termundesirable effects-including a contribution to thepathogenesis of such conditions as obesity, hyperten-sion, arteriosclerosis and food allergy-is suspectedeven if it is extremely difficult to prove. The followingare among the possible immediate problems.

Short-term risksIt is well demonstrated that the introduction of foodsother than breast milk into the young infant's dietdecreases the frequency and intensity of sucking andthat, as a consequence, breast-milk production alsodecreases. Under these circumstances the food givenwill be not so much a complement to breast milk asa partial replacement. Since in most instances thenutritional value of the "complement" is lower thanthat of breast milk, the child will be at a disadvan-tage; the opposite of the desired intention will beachieved.

It has also been observed that the introductionof cereals, and particularly vegetables, can interferewith the absorption of breast-milk iron (17), which isnormally low in concentration but high in absorb-ability. Because iron balance is extremely delicate inthe young infant, this can result in iron deficiency andanaemia. A deficiency can be avoided, of course, ifiron-enriched cereal preparations are used, but thiswould only serve to prevent a problem that was notthere at the outset.

Because large sections of populations indeveloping countries have restricted diets and live inunsanitary environments, the greatest immediate riskto the breast-fed infant of giving complementaryfoods too early is diarrhoeal disease (31) (see chapter 6).Longitudinal studies done in rural Bangladesh (32),

where 41% of the food, and 50% of the water, samplesexamined were contaminated with Escherichia coli,demonstrate an association between the early intro-duction of contaminated foods and intestinal infec-tions in children. The proportion of water samplesthat contained E. coli was directly associated with achild's annual rate of diarrhoea due to enterotoxi-genic E. coli. Ambient temperatures and the durationof storage after food preparation were directly cor-related with bacterial counts. Moreover, the monthlyrates of diarrhoea associated with enterotoxigenic E.coli in the community correlated directly with theenvironmental temperature.

In another study in Kenya, where complemen-tary feeding was started at 3 months of age,Enterobacteriaceae were found in the feeds at a levelof up to 104 bacteria per g. The counts increased afterstorage of the food for periods as short as three hours(33).

Enteropathogenic microorganisms do not neces-sarily have to be present in weaning foods before theyare consumed; they may in fact enter the child'salimentary tract at the time of feeding. For example,rotaviruses were detected in hand-washings from79% of the attendants of Bangladesh patients whowere hospitalized because of rotavirus-associateddiarrhoea (34). The importance of microbial con-tamination of hands in the genesis of diarrhoea hasalso been demonstrated by the interruptionof the transmission of Shigella simply by institut-ing washing procedures, after defecation and beforemeals, for family members of confirmed casesof shigellosis (35). In the final analysis, waterquality and quantity may be the most importantfactors determining morbidity due to diarrhoealdiseases in children under three years of age (36,37).

Long-term risksInappropriate complementary feeding practices mayalso have a negative impact on health in the longterm through two mechanisms. One is the cumulativeeffect of changes which, while starting early in life,result in clinical evidence of morbidity only yearslater. The other is the creation of food habits leadingto undesirable dietary practices, which finally con-tribute to health problems. In practice these twomechanisms may be interrelated. For example, anadult's taste for salty foods may be the result of earlyexperiences, and therefore a learned practice, whilethe cumulative effect of hypernatraemia over manyyears contributes to the development of hyperten-sion.Obesity. Although the health risks of adult obesity arewell known, its etiology is complex given its multiple

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origins. A better understanding of the etiology andnatural history of obesity is important since treat-ment is difficult once the condition has developed.One of the important questions that has not yet beenanswered concerns the relationship between feedingpractices and overweight in infancy and childhood,and obesity in adulthood. Although no long-termprospective studies have been done, retrospective andshort-term prospective studies tend to support thehypothesis of a close link.

Studies of the relationship between overweight atbirth and obesity in childhood have generally showna very low correlation (38). A higher correlation hasbeen found, however between obesity at 12 months ofage and later in life (39), while it has also beendetermined that cases of severe obesity at this agehave a greater tendency to persist. One limitation ofthese studies is that they use as a basis for compari-son situations prevailing at one point during infancy,for example at birth or at 12 months of age; there aremany non-dietary factors, however, that may help toexplain the situation at any given moment.

There is a better correlation between weight gainduring infancy and overweight later in life (40). Forexample, a recent prospective study showed that,while breast-fed and artificially fed infants hadsimilar growth patterns during the first three months,weight gain was greater for the artificially fed infantswith a difference at one year of 410 g more in boysand 750 g in girls (41). Overfeeding is one of the mainrisks associated with bottle-feeding and too earlycomplementary feeding.

Breast-fed infants appear to regulate their foodintake in accordance with their needs (see Chapter 2).Once a mother assumes responsibility of the amount offood her child receives, overfeeding becomes a possibility.Undue concern about infant nutrition can contributeto overfeeding, particularly in societies where theimage of a healthy baby is a plump one. The con-sequences later in life may be related either tothe infant's excess weight or to the acquisition ofundesirable eating habits, or both.

Hypertension. High sodium intake is certainly one ofthe principal factors in the etiology of essentialhypertension. A direct relationship is not easy toprove because there also appear to be contributinggenetic factors, which make some individuals morevulnerable than others. However, the relationshipbetween high sodium intake and hypertension hasbeen proved experimentally in rats. Of greatest con-cern are experimental data showing that sensitiverats with a high sodium intake only during the firstsix weeks of life still developed hypertension one yearlater (42).

Breast milk is low in sodium (about 15 mg/

100 ml or 6.5 mmol/1). However, an infant's sodiumintake can drastically increase when complementaryfoods are introduced (see Table 4.1, part B), inparticular when they are prepared according to thetaste of a mother whose own salt intake is high.Although there are no data to show that early highsodium intake has the same consequences later in lifefor humans as have been demonstrated in experimen-tal animals, it has been suggested that the taste forsalt may be established with the introduction of foodsother than breast milk. The maintenance of this habitmay in turn have a cumulative effect that results in illhealth many years later.

Experimental and epidemiological evidence indi-cates that potassium plays a protective role wherehigh sodium intake related to hypertension is con-cerned (43). While most fresh fruits and vegetablesare high in potassium, their processing for use ascomplementary foods may drastically reduce theirvalue as a source of this mineral as well as vitamin C.

An association has also been found betweenhypertension and obesity, although they may beetiologically unrelated and observed independently.Early feeding practices may be a common factorcreating food habits that favour the development ofboth conditions.

ArterlosclerosIs. The role of dietary factors in thepathogenesis of arteriosclerosis and ischaemic heartdisease, which are major health problems in indus-trialized countries and, increasingly, in developingcountries, is no longer in doubt. The nutritionalfactors involved include diets high in energy and richin cholesterol and saturated fats, but low in poly-unsaturated fats. High protein intake has alsobeen found to be associated with these conditions,although diet is only contributory in otherwise pre-disposed individuals. The relationship between dietaryfactors and the development of the disease has beenproved through both prospective and cross-sectionalcomparisons among different populations.

It is difficult to establish this link at theindividual level, however, both because people res-pond differently to a diet rich in saturated fats andthe fact that many other variables are involved. Itwould be still more difficult to establish a linkbetween infant-feeding practices and a disease thatmanifests itself only some 30-40 years later. It hasbeen shown, however, that infants in the upper cen-tiles of lipid blood levels tend to maintain those samelevels two years later (44). Thus, it only makes goodsense to avoid, in complementary feeding, the samedietary excesses that have proved to be undesirablelater in life.

Food allergy. There is evidence that prolonged breast-feeding and the timely introduction of carefully selec-

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ted complementary foods contribute to the preven-tion of food allergies, particularly in predisposedinfants (45). This is true not only in respect ofcow's-milk allergy but also where other foods areconcerned. Cow's-milk allergy is manifested clinicallyby gastrointestinal, dermatological or respiratorysymptoms of varying severity, and even by anaphy-lactic shock.

Using sensitive immunological methods, it hasbeen demonstrated that the majority of infants fedartificially with cow's-milk-based formulas do indeedreact to the foreign proteins. However, since only afew infants show clinical manifestations, and usuallyonly those with severe symptomatology are diag-nosed as having cow's-milk allergy, it is very difficultto know the disease's real incidence. In industrializedcountries, where the majority of infants in questionreceived cow's-milk-based formulas since very earlyin life, various studies show an estimated prevalenceof clinical manifestation of about 1% (46). In mostinstances, the condition can be prevented altogetherby avoiding the use of cow's-milk preparations dur-ing the first months of life.

It has been shown that prolonged breast-feedingalso has a protective value where allergies to otherfoods are concerned. For example, in a study ofinfants born of parents suffering from eczema, it wasdemonstrated that a significant reduction in theincidence of the disease could be achieved byfeeding breast milk exclusively for at least threemonths and avoiding allergenic foods during the initialstages ofcomplementary feeding (47). In another pros-pective study of children followed from birth to threeyears of age, it was shown that infants who werebreast-fed for six months, particularly those with afamily history of allergies, had a lower incidence ofatopic diseases than those who were artificially fed.In the latter group, complementary feeding wasstarted at three and a half months with cookedvegetables and fruits, cereals were introduced at fivemonths, and meat and eggs were given at six; a morevaried diet was given by nine months of age (45). Astudy of 135 exclusively breast-fed children of familieswith a history of atopic disease showed that giving nosolid foods before six months greatly reduced therates of eczema and food intolerance at 12 months;matched controls were children with similar familyhistories who received solids when 4-6 months ofage. Relative rates for the study groups and controlswere 35% vs. 14% for eczema, and 37% vs. 7% forfood intolerance (48).

R6sum6Le d6veloppement physiologique dunourrisson et ses Implications sur

I'alimentation de compl6mentDurant la periode intra-uterine le foetus estalimente par la circulation sanguine maternellepar l'intermediaire du placenta. Le tractus gastro-intestinal et l'appareil renal se developpentprogressivement mais ne sont pas fonctionnels.Apres la naissance la croissance rapide du nour-risson entraine une elevation proportionnelle desbesoins nutritionnels, il faut donc que l'alimenta-tion soit adaptee. La maniere de nourrir 1'enfantest conditionnee par son degre de maturite fonc-tionnelle, en particulier en ce qui concerne l'utilisa-tion des nutriments, les mecanismes d'excretion etla lutte contre les infections.

L'ingestion des aliments est limitee au debutaux liquides grace au reflexe de succion et a laconfiguration particuliere du palais du nouveau-neet aussi a cause du reflexe lingual ou d'expulsionqui disparalt entre4 et 6 mois. Plus tard, entre 6 et 9mois apparait la mastication qui facilite l'absorp-tion d'aliments solides. Le processus de digestiondes sucres se realise dans la partie proximale del'intestin grele pendant les premiers mois de lavie. C'est Ia et non pas dans la bouche que lespolysaccharides comme l'amidon sont attaques; lasecretion amylasique a ce niveau ne representecependant que 10% de celle de l'adulte. Pendantles 3 premiers mois de la vie il n'y a pas desecretion d'amylase pancreatique.

Pour la digestion des proteines on sait que lasecretion gastrique d'acide chlorhydrique et depepsine existe chez le nouveau-ne a terme mais ade basses concentrations. Les proteines sont prin-cipalement digerees dans le grele ou l'activiteproteolytique est equivalente A celle de l'adulte.Neanmoins des apports proteiques eleves sont adeconseiller dans la mesure oiu un desequilibremetabolique peut se produire au niveau du reinentrainant une acidose. La permeabilite parti-culiere de la muqueuse intestinale du jeune enfantaux grosses molecules proteiques pourrait avoirdes consequences antigeniques qui expliqueraientcertaines allergies au lait de vache.

Les graisses relaient le glucose comme sourceprincipale d'energie apres la naissance. Lalipolyse preduodenale est assuree par les lipaseslinguales et elle est renforcee par la lipase du laitmaternel. II ne semble pas qu'il y ait de problememajeur avec les vitamines et les mineraux. Le laitmaternel etant de ce point de vue particulierementfavorable pour l'absorption de la vitamine A et du

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fer entre autres. On ignore les mecanismes quiaugmentent la biodisponibilite du fer dans le laitmaternel mais on a constate qu'elle diminuaitlorsque l'on supplementait la ration par desaliments d'origine vegetale. La grande per-meabilite de l'intestin a I'eau et aux electrolytespeut entrainer plus facilement des desequilibresdangereux en cas d'hyperosmolarite du bol intes-tinal. La capacite fonctionnelle du rein augmenterapidement pendant les premiers mois de la viemais elle est limitee chez le nouveau-ne parce quela filtration glomerulaire et la capacite de concen-tration sont basses.

Besoins nutritlonnels. Ils sont quantitativement etqualitativement diff&rents de ceux des enfants plusages et des adultes. Durant le premier mois parexemple, ils sont en calories et en proteines 3 foisplus importants par kilogramme de poids que chezl'adulte. Cependant le lait maternel est l'alimentideal pour les enfants jusqu'a 4 a 6 mois, saufpour les nouveau-nes de tres petit poids de nais-sance qui doivent etre supplement6s en fer entreautres nutriments. Pour les enfants nourris avecdes substituts du lait maternel la situation estdifferente. A titre indicatif des tables de compo-sition de certains aliments de complement sontfournies. Les besoins en energie sont difficilesa apprecier, les recommandations du comited'experts FAO/OMS de 1971 sur les besoins enproteines et en energie representaient une esti-mation des besoins a 120 kcal/kg/j entre 0 et 3mois diminuant regulierement pour atteindre105 kcal/kg/j entre 9 et 12 mois. Une consulta-tion plus recente (FAO/OMS/UNU, 1981) partantdes memes valeurs aboutit a des besoins net-tement plus bas aux ages intermediaires pourremonter sensiblement a 12 mois. Les differencesconstatees expliquent pourquoi dans des circons-tances normales, le lait maternal seul couvre lesbesoins des nourrissons au moins pour les 4premiers mois de la vie et souvent jusqu'ausixieme.

Alimentation de compl6ment et sevrage. Par sevrage ilfaut entendre le passage progressif du nourrissondu lait de sa mere au regime habituel de la famille.Aux environs de 6 mois les enfants doiventrecevoir d'autres aliments et ils sont physio-logiquement et fonctionnellement en mesure deles utiliser. Une diversification alimentaire tropprecoce pr6sente des risques a court terme: dimi-nution de la production de lait chez la mere, malcompensee dans certains cas par la valeurnutritive du "complement"; les cereales peuventlimiter I'absorption du fer du lait maternel; et le

risque de maladies diarrheiques augmente, enparticulier dans les pays en developpement. Abeaucoup plus long terme les effets n6gatifs surla sante peuvent se traduire par une morbidited'origine nutritionnelle due aux modificationsdietetiques introduites durant le jeune ageintriquee avec la creation d'habitudes alimentairesentrainant des pratiques dietetiques nefastes. Lefait par exemple d'aimer les aliments sales a l'ageadulte pourrait etre le resultat d'experiencesacquises durant la petite enfance. Ainsi obesite,hypertension et arteriosclerose semblent pouvoiretre associees a ces situations. De meme lesallergies d'origine alimentaire peuvent etreprevenues par un allaitement maternel prolongecomme certaines etudes l'ont demontre.

References1. Herbst, J.J. Development of sucking and swallowing.

In: Lebenthal, E., ed. A textbook of gastroenterologyand nutrition in infancy, Vol. 1. New York, RavenPress, 1981, p. 102.

2. Auricchlo, S. et al. Intestinal glycosidase activities inthe human embryo, fetus, and newborn. Pediatrics,35: 944-954 (1965).

3. Lebenthal, E. & Lee, P.C. Development of functionalresponse in human exocrine pancreas. Pediatrics,66: 556-560 (1980).

4. Lebenthal, E. & Le, P.C. Glucoamylase and disac-charidase activities in normal subjects and inpatients with mucosal injury of the small intestine. J.pediatr., 97: 389-393 (1980).

5. LIlibridge, C.B. & Townes, P.L. Physiologic deficiencyof pancreatic amylase in infancy: a factor iniatrogenic diarrhea. J. pediatr., 82: 279-282 (1973).

6. Lebenthal, E. et al. Development of disaccharidase inpremature, small-for-gestational-age and full-terminfants. In: Lebenthal, E., ed. A textbook of gastroen-terology and nutrition in infancy, Vol. 1. New York,Raven Press, 1981, p. 417.

7. Agunod, M. et al. Correlative study of hydrochloricacid, pepsin and intrinsic factor secretion in new-borns and infants. Am. j. dig. dis., 14: 400-414 (1969).

8. Deren, J.S. Development of structure and function inthe fetal and newborn stomach. Am. j. clin. nutr., 24:144-159 (1971).

9. Hadorn, B. Developmental aspects of intraluminalprotein digestion. In: Lebenthal, E., ed. A textbook ofgastroenterology and nutrition in infancy, Vol. 1. NewYork, Raven Press, 1981, p. 368.

10. Walker, W.A. et al. Intestinal uptake of macro-molecules: effect of oral immunization. Science, 177:608-610 (1972).

11. Zoppl, G. et al. Exocrine pancreas function in prema-ture and full-term neonates. Pediatr. res., 6: 880-886(1972).

12. Poley, J.R. et al. Bile acids in infants and children. J.lab. clin. med., 63: 838-846 (1964).

13. Hamosh, M. & Burns, W.A. Lipolytic activity of human

66 WHO Bulletin OMS: Supplement Vol. 67 1989

Page 13: 4. Physiological development of infant implications for

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lingual glands (Ebner). Lab. invest., 37: 603-608(1977).

14. Hall, B. & Muller, D.P.R. Studies on the bile saltstimulated lipolytic activity of human milk usingwhole milk as source of both substrate and enzyme.I. Nutritional implications. Pediatr. res., 16: 251-255(1982).

15. Wellers, H.A. et al. Analysis and interpretation of thefat-absorption coefficient. Acta pediatr. (Uppsala), 49:615-625 (1960).

16. Saarlnen, U.M. et al. Iron absorption in infants: highbioavailability of breast-milk iron as indicated by theextrinsic tag method of iron absorption and by theconcentration of serum ferritin. J. pediatr., 91: 36-39(1977).

17. OskI, F.A. Development of the small intestine'scapacity to absorb iron and folic acid. In: Lebenthal,E., ed. Textbook of gastroenterology and nutrition ininfancy, Vol. 1. New York, Raven Press. 1981, p. 612.

18. Aperla, A. et al. Development of renal control of saltand fluid homeostasis during the first year of life.Acta paediatr. scand., 64: 393-398 (1975).

19. Svenningsen, N.W. & Llndqulst, B. Postnatal develop-ment of renal hydrogen ion excretion capacity inrelation to age and protein intake. Acta paediatr.scand., 63: 721-731 (1974).

20. Oppe, T.E. et al. Calcium and phosphorus levels inhealthy newborn infants given various types of milk.Lancet, 1: 1045-1048 (1968).

21. Fomon, S.J. & Flier, L.J. Amino acid requirements fornormal growth. In: Nyhan, W.L., ed. Amino acidmetabolism and genetic variation. New York,McGraw-Hill, 1967, p. 391.

22. WHO Technical Report Series No. 724, 1985 (Energyand protein requirements: report of a Joint FAO/WHO/UNU Expert Consultation), pp. 64-66.

23. WHO Technical Report Series No. 522, 1973 (Energyand protein requirements: report of a Joint FAO/WHOAd Hoc Expert Committee).

24. Fomon, S.J. Infant nutrition, Philadelphia, Saunders,1967.

25. FAO Nutritional Studies No. 15, 1957 (Calorierequirements: report of the Second Committee onCalorie Requirements).

26. Waterlow, J.C. & Thomson, A.M. Observations on theadequacy of breast-feeding. Lancet, 2: 238-241(1979).

27. WHO Technical Report Series No. 724 (see ref. 22),op. cit., pp. 90-92.

28. Whltehead, R.G. et al. A critical analysis of measuredfood intakes during infancy and early childhood incomparison with current international recommenda-tions. J. human nutr., 35: 339-348 (1981).

29. Habicht, J.P. et al. Height and weight standardsfor preschool children. How relevant are ethnic dif-ferences in growth potential? Lancet, 1: 611-614(1974).

30. Ahn, C.H. & Maclean Jr. W.C. Growth of theexclusively breast-fed infant. Am. j. clin. nutr., 33:183-192 (1980).

31. Gordon, J.E. et al. Weanling diarrhea, Am. j. med.sci., 245: 345-377 (1963).

32. Black, R.E. et al. Contamination of weaning foods andtransmission of enterotoxigenic Escherichia colidiarrhoea in children in rural Bangladesh. Trans.Roy. Soc. Trop. Med. Hyg., 76: 259-264 (1982).

33. Van Steenbergen, W.M. et al. Agents affecting healthof mother, infant and child in a rural area of Kenya.XXII. Bacterial contamination of foods commonlyeaten by young children in Machakos, Kenya. Trop.geogr. med., 35: 193-197 (1983).

34. Samadl, A.R., et al. Detection of rotavirus in hand-washing of attendants of children with diarrhoea. Br.med. j., 286: 188 (1983).

35. Khan, M.V. Interruption of shigellosis by hand-wash-ing. Trans. Roy. Soc. Trop. Med. Hyg., 76: 164-168(1982).

36. Hobert, J.R. Effects of water quality and water quan-tity on nutritional status: findings from a south Indiancommunity. Bull. Wld Hlth Org., 63: 143-155 (1985).

37. Jlwa. S. et al. Enterotoxigenic bacteria in food andwater from an Ethiopian community. Appl. environ.microbiol., 41: 1010-1019 (1981).

38. Fisch, R.O. et al. Obesity and leanness at birth andtheir relationship to body variations in later child-hood. Pediatrics, 56: 521-528 (1975).

39. Johnston, F.E. & Marck, R.W. Obesity in urban blackadolescents of high and low relative weight at oneyear of age. Am. j. dis. child., 132: 862-864 (1978).

40. Eld, E.E. Follow-up study of physical growth of chil-dren who had excessive weight gain in first sixmonths of life. Br. med. j., 2: 74-76 (1970).

41. Hitchcock, N.E. et al. The growth of breast-fed andartificially fed infants from birth to twelve months.Acta paediatr. scand., 74: 240-245 (1985).

42. Dahl, L.K. et al. Effects of chronic excess salt inges-tion: evidence that genetic factors play an importantrole in susceptibility to experimental hypertension. J.exp. med., 115: 1173-1190 (1962).

43. James, W.P.T. Diseases of Western civilization. In:McLaren, D.S. & Burman, D., ed. Textbook ofpaediatric nutrition, 2nd ed. Edinburgh, ChurchillLivingstone, 1982, p. 419.

44. MellIes, M. & Glueck, C. Infant feeding practices andthe development of atherosclerosis. In: Lebenthal, E.,ed. Textbook of gastroenterology and nutrition ininfancy, Vol. 2. New York, Raven Press, 1981, p. 722.

45. Saarlnen, U.M. et al. Prolonged breast-feeding asprophylaxis for atopic disease. Lancet, 2: 163-166(1979).

46. Savilahtl, E. et al. Cow's-milk allergy. In: Lebenthal,E., ed. Textbook of gastroenterology and nutrition ininfancy, Vol. 2. New York, Raven Press, 1981, p. 690.

47. Matthew, D.J. et al. Prevention of eczema. Lancet, 1:321-324 (1977).

48. Kayosasrl, M. & Sasrlnen, V. Prophylaxis of atopicdisease by six months' total solid food elimination.Evaluation of 135 exclusively breast-fed infants ofatopic families. Acta paediatr. scand., 72: 411-414(1983).

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