Caballero B. (ed.) Encyclopaedia of Food Science, Food Technology and Nutrition. Ten-Volume Set

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Feeding Problems

E M E Poskitt, Department of Public Health Nutrition,

London School of Hygiene and Tropical Medicine, UK

Introduction

0001 Nutrition is of great importance in infancy. Infants

are entirely dependent on others for their nutrition

and carers may have difficulty recognizing their

needs. This dependence and infants’ high nutritional

requirements for growth and development make mal-

nutrition a relatively common problem. Prolonged

malnutrition can impair both somatic growth and

brain development.

Failure to Thrive

000 2 Failure to thrive (Figure 1) is failure to gain in height

and weight at the expected rates (determined from

recognized growth data). The causes are numerous

(Table 1) but if the precipitating causes can be

successfully treated, failure to thrive is followed by

accelerated or ‘catch-up’ growth (Figure 1a), pro-

vided extra food meets the nutritional needs of accel-

erated growth. Without extra nutrients, catch-up

growth is likely to be incomplete. Affected infants

may then resume normal growth rates, but along

lower growth centiles than previously (Figure 1b).

0003Some children with growth below the third centile

or 2sd weight-for-age or below (outside the rec-

ognized ‘normal’ range) may be labeled as failure-

to-thrive although growing at more or less normal

rates for age. They may have been low-weight for

gestational age at birth and always small (Figure 1c).

These constitutionally small children may show

delayed bone age, delayed adolescence, and some-

times late catch-up to more normal adult size.

0004Careful dietary histories should indicate which

infants are failing to thrive because of inadequate

intakes, inappropriately constituted feeds, or in-

appropriate weaning practices. Average milk or

formula intakes are 150 ml kg

1

day

1

(441 kJ kg

1

day

1

) for full-term normal infants. Around 6–8

weeks of age intakes often stabilize despite continuing

Weight

Age

fig0001Figure 1 Weight of children with (a) failure to thrive and com-

plete catch-up growth; (b) failure to thrive and failure of complete

catch-up growth; and (c) constitutional small size plotted against

the 3rd, 50th, and 97th weight-for-age centiles.

3300 INFANTS/Feeding Problems

increases in weight and intakes kg

1

day

1

thus

decrease.

0005 It may be difficult to assess the adequacy of milk

intake in breast-fed infants. Normal growth velocities

and general contentment after feeding suggest intakes

are adequate. If there is concern, weighing infants in

clean diapers prior to breast-feeding and then

weighing them again after feeding without diaper

change provides some indication of the weight, and

thus the volume, of milk consumed. This test

weighing must be for all feeds over 24 h since infants

may consume large feeds early in the morning and in

the evening, but relatively small amounts at other

times of day.

0006 When breast milk output seems insufficient for an

infant’s needs, improving maternal nutrition and in-

creasing the frequency of suckling may improve milk

secretion. Current recommendations are that infants

should be exclusively breast-fed until at least 4

months of age and preferably until 6 months of age.

Usually breast-feeding failure arises because of

inappropriate feeding practices (e.g., infrequent

suckling, especially in early lactation, or incorrect

positioning and failure by the infant to latch on).

Advice on feeding technique may resolve the

problems. However, mothers who are sick or very

malnourished may sometimes fail to produce suffi-

cient milk to support normal infant growth. The

decision whether to continue struggling to increase

breast milk production, to introduce infant formula

feeds, or to introduce weaning foods early is deter-

mined by individual circumstances such as the age of

the child and cause of breast-feeding failure. Failure

to thrive without evidence of nutritional inadequacy,

or secondary to persistent anorexia and vomiting,

requires urgent medical investigation.

0007Occasionally failure to thrive occurs without evi-

dence of clinical disease or nutritional inadequacy.

Children with such nonorganic failure to thrive may

eat well, sometimes excessively, but grow poorly.

Typically they are apathetic, showing little social

interaction, although some are restless and inatten-

tive. Developmental delay, particularly in social and

cognitive skills, is common. These children come

from home environments of social and/or emotional

deprivation. Environmental stress and lack of love

inhibit normal growth. Changing the home environ-

ment without necessarily changing the diet can induce

accelerated growth giving a dramatically improved

effect – confirming the diagnosis.

Vomiting

0008Most normal infants vomit occasionally and some

vomit frequently. Probably the most common cause

of persistent vomiting in infancy is laxity of the

gastroesophageal sphincter. The sphincter is the

spiral muscular area, 2–3 cm in length, at the lower

end of the esophagus. Sphincter competence is related

to the length of intraabdominal sphincter (which in-

creases with age) and to intragastric pressure. Com-

petence tends to be poor at birth but improves after

the first 2 weeks of life, regardless of gestational age.

The fluid diets of young infants and the high volumes

of liquid needed to meet nutritional requirements

produce gastric distension, high intraabdominal

tension, and easy regurgitation. Thickening feeds

to increase resistance to regurgitation, feeding

smaller feeds more frequently, and raising the head

end of the cot help reduce gastric distension and

regurgitation. As infants grow, consume more solid

food and adopt an upright posture, reflux ceases to be

a problem.

0009Feeding problems, including gastroesophageal

reflux, are common in children with neurological

handicap. Failure to thrive can be severe and may

improve with intragastric feeding through gastro-

stomy, but this exacerbates gastroesophageal reflux.

Surgical fundoplication is usually performed, prior to

gastrostomy, to control reflux.

0010Vomiting can be a symptom of serious gastrointest-

inal or parenteral disorder. When infants vomit and

fail to thrive, vomit bile or blood, or vomit to the

extent of causing dehydration, medical investigation

is required urgently.

tbl0001 Table 1 Classification of nutritional problems associated with

failure to thrive

Basic problem Examples

Inadequate intake Poverty; famine; ignorance of nutrient

needs

Vomiting: all causes

Feeding problems, including

neurological damage

Anorexia

Increased losses Protein-losing enteropathy

Glycosuria; proteinuria

Exfoliative skin conditions

Suppuration

Failure to absorb food Cystic fibrosis

Gluten-sensitive enteropathy

Giardiasis

Lactose intolerance

Failure to utilize food Inborn errors of metabolism

Endocrine problems

Micronutrient deficiencies, e.g., zinc

Chronic renal failure

Emotional deprivation

Increased requirements Small-for-dates and premature infants

Catch-up growth

Congenital heart disease: left-to-right

shunt

INFANTS/Feeding Problems 3301

Diarrhea

0011 Diarrhea is an increase in total stool output, usually

from increase in water content, volume, and frequency

of stools. The color, consistency, and frequency of

stools vary widely both between different infants

and in the same infant on different occasions. Exclu-

sively breast-fed infants tend to have frequent watery

yellow stools. Formula-fed infants have less frequent,

greenish, drier-looking stools.

0012 In infancy diarrhea is commonly part of either

a specific gastrointestinal or a generalized (usually

viral) infection. Infectious diarrhea has an acute

onset but is usually short-lived and associated with

other signs of infection: pyrexia, vomiting, anorexia,

and general malaise. Weight loss from anorexia and

dehydration are common. Weight recovery is gener-

ally rapid and complete. Acute diarrhea has little

effect on long-term weight-for-age and even less

impact on long-term height-for-age. However, chronic

diarrhea and significant growth faltering are common

with some gastrointestinal infections (especially rota-

virus, Giardia lamblia, and Entamoeba histolytica).

0013 Malnutrition causes profound changes to gastro-

intestinal mucosal structure and function. This pre-

disposes malnourished children to severe diarrheal

infection and high mortality from diarrheal illness.

0014 All diarrhea should be managed with extra fluids,

usually in the form of oral rehydration solution

(ORS). ORS suitable for most infant diarrhea has

lower sodium and chloride content than that intended

for rehydration in adults.

0015 Diarrhea which is persistent and associated with

failure to thrive, dehydration, bleeding or other

obvious illness, requires medical investigation.

Toddler diarrhea

0016 Some young children persistently pass watery stools

or have bouts of loose watery stools alternating with

episodes of constipation without evidence of infec-

tion, malnutrition, or other ill health. The diarrhea

stools are typically voluminous and watery with bits

of undigested food in them, indicating the visible bean

husks, tomato skins, and other vegetable matter pre-

sent, although less obviously so, in normally formed

stools. Children with toddler diarrhea are active and

thriving but their parents are usually very concerned.

0017 Toddler diarrhea has no recognized specific path-

ology and probably has many causes. Whole-gut

transit time is reduced but there is no evidence of

abnormal duodenal or jejunal secretion, nor of mal-

absorption. Minor infection may set off bouts of

diarrhea and in some children there is a family history

of response to stress with diarrhea. Poor hygiene and

low-grade infection associated with constant pacifier

(dummy) sucking and prolonged bottle-feeding may

contribute to the problem.

0018Many affected children have high intakes of

sweetened fruit juices and/or low intakes of dietary

fat. High fluid intakes with high simple carbohydrate

content encourage rapid intestinal transit which over-

whelms small intestinal function, so sugars reach the

large intestine unabsorbed. These and their fermenta-

tion products in the colon stimulate osmotic diarrhea.

Reducing fluid intakes, particularly of sweetened

juices and carbonated drinks, reduces the symptoms

in some toddlers. Changing to more adult diets with

higher concentrations of complex carbohydrates

and fats can also reduce diarrhea. Lipids in the

ileum slow duodenal and jejunal transit time (the

ileal brake) and may modulate mucosal contact time

and the absorption of intestinal luminal contents.

Graduating to cup-feeding usually results in less ex-

cessive fluid intakes and, particularly if pacifiers are

avoided, encourages more hygienic feeding practices.

0019Toddler diarrhea usually resolves as children move

on to more mature diets and develop continence. It is

unusual after the age of 6 years.

Micronutrient Deficiencies

0020Significant micronutrient deficiencies, other than for

iron, are rare in normal-weight, full-term healthy infants

in developed countries. Vitamin D deficiency rickets

can be a problem in low-birth-weight (LBW) infants

and noncaucasian infants. In developing countries low

levels of vitamin A are associated with high morbidity

and mortality from diarrheal diseases, respiratory infec-

tions, and measles. Iodine deficiency is also common.

Many countries now have supplementation programs to

prevent vitamin A and iodine deficiency.

Iron Deficiency

0021The human fetus has high hemoglobin levels to

accommodate low oxygen tension in utero. After

birth, in response to the high oxygen tension in the

extrauterine environment, the bone marrow becomes

relatively quiescent and hemoglobin levels decline.

Eventually (usually at 4–6 weeks of age) the bone

marrow becomes more active again but by then

infants have grown and their blood volumes have

expanded. Hemoglobin levels remain below adult

levels, at 11–12 g dl

1

, until late childhood.

0022Where infants are small and growing very rapidly

(e.g., premature and small-for-dates infants), with

initially low total blood volume and low total body

iron, the need for iron for new blood formation may

soon exceed the iron stored, so anemia results. Once

body weight has doubled, all infants are at risk of iron

deficiency since, without good external sources of

3302 INFANTS/Feeding Problems

iron, iron stores of the body will be distributed over

twice the blood volume, and hemoglobin levels will

have halved. However, iron supplementation should

probably be avoided in exclusively breast-fed infants

unless they show clinical evidence of deficiency, since

lactoferrin is a major immunological component of

breast milk. It binds iron in the small intestine,

speeding absorption and inhibiting multiplication of

iron-dependent bacterial pathogens. Iron fortification

of infant formulas reduces the prevalence of severe

iron deficiency in nonbreast-fed infants.

0023 Iron sufficiency is important. Table 2 lists some

factors predisposing to iron-deficiency anemia. The

frequency of iron-deficiency problems is an indication

of the small margin of safety between requirements

for iron and the quantity of iron young children are

likely to ingest and absorb from their diets. Low-

grade iron deficiency can impair growth rates, intel-

lectual function, and the immunological response to

infection. In countries where malaria is common,

anemia resulting from iron deficiency puts infants at

great risk of life-threatening severe malarial anemia.

Vitamin D Deficiency: Rickets

0024 Rickets used to be common in weanlings. The Clean

Air Act (1956) probably did as much to reduce rickets

in the UK as any medical intervention, since vitamin

D metabolites are predominantly derived from irradi-

ation of 7-dehydrocholesterol in the skin by sunlight

of wavelength around 300 nm.

0025 Rickets is still seen in the UK in newborn Asian

infants and mothers. The mothers have both inad-

equate absorption of dietary vitamin D and inadequate

skin synthesis of endogenous vitamin D because of

indoor habits and clothing cover when out of doors.

Low calcium absorption due to low dietary intake

and the high phytate content of traditional flours

exacerbates the need for vitamin D to optimize calcium

absorption from the small intestine. Skin pigmentation

increases the need for sunlight exposure when levels of

ultraviolet light of appropriate wavelength are low

(e.g., winter in northern latitudes).

0026Infants born to vitamin D-deficient mothers may

present with hypocalcemic tetany and convulsions

soon after birth or with rickets in the weaning period.

The incidence of rickets in Asian children is diminish-

ing in the UK as Asian women in this country adopt

lifestyles more suited to northern latitudes and their

need for vitamin D supplementation is better recog-

nized. However, signs of vitamin D deficiency in

mothers and children are widely reported from the

Middle East where there is plenty of sunshine of

vitamin D synthesizing wavelength, but little social

opportunity for women and children to expose their

bodies to the sunlight.

Vegetarian Diets in Infancy

0027Infants weaned on to vegetarian diets may become

deficient in a variety of nutrients. If diets include eggs

and milk, it is not difficult to achieve dietary require-

ments, particularly if breast milk or infant formula is

continued as a milk source beyond the first year of

life. Milk usually provides a substantial proportion of

riboflavin, calcium, and total energy intake in wean-

ling children. Infant formula can provide a fairly

absorbable dietary source of iron which may other-

wise be deficient.

0028Vegetarian diets tend to be of low energy density

because of high-fiber and low-fat content. Children

should be fed frequently (at least four times a day) to

enable them to consume the volumes of food neces-

sary to meet nutrient needs. No vegetable protein

contains the full range of essential amino acids so

diets should include a variety of protein sources

(e.g., beans, lentils, cereals, dark green leaves, soya

and homogenized nut products).

0029It is difficult to achieve adequate nutrition in very

young children with vegan, macrobiotic, and other

strict vegetarian diets. These diets are not recom-

mended for infants unless there is close pediatric

dietetic supervision.

Low-birth-weight Infants

0030The problems of both premature and LBW for gesta-

tional age (small-for-dates or SFD) infants are similar,

although the greater immaturity of the premature

infants’ gastrointestinal tracts and of other organs

makes the nutrition of the former more difficult

than that of the latter. In both groups there is a need

for more nutrients per unit of body weight to cope

tbl0002 Table 2 Classification of problems predisposing to iron

deficiency in childhood

Basic nutritional problem Example

Inadequate intake Early introduction to cows’ milk

Prolonged exclusive breast-feeding

Poor quality of weaning diet

Strict vegetarian diet

Increased losses Bleeding disorders

Reflux esophagitis

Failure to absorb Celiac disease

Pyrexia

Iron in ferric form

High-phytate diet

Failure to utilize Chronic infection

Hypothyroidism

Riboflavin deficiency

Increased requirements Rapid growth: low-birth-weight infants

Catch-up growth

INFANTS/Feeding Problems 3303

with the rapid growth to parallel intrauterine growth

in premature infants and catch-up growth in SFD

infants. The small stomach volumes of LBW infants

restrict the volumes which can be fed at any one time

without causing apnea, vomiting, or necrotizing

enterocolitis. Respiratory problems in premature

infants may also restrict the amount of enteral food

tolerated. Thus there is a conflict between increased

(proportionate to body weight) nutrient needs, espe-

cially for protein, calcium, phosphate, fluid, and

energy, and the amounts of food that can be adminis-

tered safely. Even when LBW infants are fed paren-

terally there are restrictions on the fluid volumes, and

thus the quantity of nutrients, that can be given safely.

The high demands for growth and development,

particularly for the brain, lead to deficiencies of

some nutrients which are usually synthesized by the

body. This critical nutrient status applies to the long-

chain polyunsaturated fatty acids, docosahexaenoic

and arachidonic acids, and possibly also carnitine,

nucleotides, and other nutrients. For this reason

breast milk, which has high levels of these nutrients,

may have advantages over infant formulas for the

nutrition of LBW infants, if supplemented with

energy to meet the high requirements of these infants.

However, manufacturers, aware of the physiological

needs of LBW infants, are gradually developing

formulas which aim to meet these special needs.

0031 Table 3 lists the problems of LBW infants which

are discussed elsewhere. LBW infants should be

supplemented at least with vitamins A, C, D, and

folate over the first year of life. Iron supplementation

in the neonatal period risks encouraging bacterial

infection and damage by free iron radicals, since

iron stores are replete following temporary bone

marrow inactivity associated with high hemoglobin

levels at birth. However, iron supplementation is ad-

visable in formula-fed infants after the first 4 weeks.

Iron supplements should probably not be given at all

to wholly breast-fed infants unless they show hema-

tological evidence of iron deficiency, since free iron in

the gastrointestinal tract can counteract the protect-

ive effects of lactoferrin.

Allergy

Cows’ Milk Protein Intolerance (CMPI)

0032Food allergies, particularly CMPI, are frequently diag-

nosed in infants. True CMPI affects between 1.5% and

5% of the population of western Europe. In families

with a strong atopic history the incidence may be much

higher. Cows’ milk protein intolerance most commonly

develops in children under 2 months of age, although

it may develop at a later age after gastrointestinal

surgery, malnutrition, or gastrointestinal infection.

0033Children with diarrhea and/or blood loss in associ-

ation with CMPI may show villous atrophy and

increased inflammatory cell infiltrations on jejunal

biopsy, or acute colitis on sigmoidoscopy. Those

with respiratory symptoms may present with pul-

monary hemosiderosis which resolves on removal of

all cows’ milk-containing products from the diet.

However, for most children, manifestations of CMPI

are varied and nonspecific.

0034Infants who vomit, have diarrhea, have a rash, or

cry a lot, are liable to be diagnosed as CMPI. They are

put on to commercial cows’ milk-free formulas and

may seem to improve. Improvements may have

been coincidental or as a result of mothers feeling

reassured that ‘something was being done.’

0035Commercial cows’ milk protein-free formulas are

also lactose-free. Excluding formula and cows’ milk

products from the diet does not distinguish between

CMPI and lactose intolerance. Children with lactose

intolerance commonly have a preceding history of

gastrointestinal infection, surgery, or malnutrition.

They have loose stools, weight loss, and abdominal

distension. Stools are acid and contain reducing sub-

stances. Thus, if infants’ stools show pH > 5.1 and

have no reducing substances in them and symptoms

resolve on cows’ milk protein-free diet but recur when

milk protein is reintroduced, CMPI is likely.

0036Where the child’s symptoms have been dramatic

(e.g., angioneurotic edema; profuse life-threatening

tbl0003 Table 3 Nutritional problems of low-birth-weight infants

Problem Precipitating factors

Immediate

hypoglycemia

Limited liver glycogen

Delay in mobilizing fat stores

Problems with supplying nutrition

Immediate

hypocalcemia

Loss of high calcium flux across

placenta

Immaturity of calcium homeostasis

Occasionally maternal vitamin D

deficiency

Later poor growth Low energy density of breast milk

Poor tolerance of other

energy/nutrient-dense feeds

Poor fat absorption by immature infants

Increased needs due to

bronchopulmonary dysplasia

Bone disease of

prematurity

Substrate deficiency, especially

phosphate

Renal calcium loss from acidosis

and/or diuretics

Vitamin D, protein, or copper

deficiency

Anemia Vitamin E deficiency increasing early

hemolysis

Folate deficiency

Iron deficiency

3304 INFANTS/Feeding Problems

diarrhea), challenging the diagnosis of CMPI by

reintroduction of milk and milk products can be

dangerous. Children should only be challenged with

milk under hospital supervision and even then with

great care.

0037 The particular elements of the cows’ milk protein

causing allergenic responses vary. At least 18 com-

ponents that can induce antibody formation have

been identified. When purified protein fractions are

used as challenges, b-lactoglobulin levels and casein

produce symptoms in over 60% of affected individ-

uals. Antibodies to cows’ milk protein are widespread

and neither their presence, nor their levels in the

blood, correlate well with reactions to cows’ milk.

0038 Breast-fed infants often show circulating cows’ milk

protein antibodies. Changing from breast-feeding to

cows’ milk formula feeding can, very rarely, precipi-

tate dramatic anaphylactic symptoms of angioneuro-

tic edema with acute and very dangerous swelling of

tissues around the neck and airway. Relevant proteins

from the cows’ milk consumed by the mother are

thought to be transferred to affected infants either

across the placenta or in breast milk, causing sensi-

tization. The infants are then desensitized by the

small amounts of antigen in maternal milk but are

overwhelmed when confronted with a large load of

antigen from formula feeding.

0039 The management of CMPI involves removal of all

cows’ milk protein-containing products from the diet.

Pediatric dietetic advice is advisable since milk and

milk products continue to contribute significant

amounts of energy and other nutrients to normal

children’s diets, even after the start of mixed feeding.

Difficulties in meeting nutritional needs on milk-free

weaning diets can lead to undernutrition. Soya-based

infant formulas can be helpful but infants with CMPI

may also develop soya protein intolerance. Hydro-

lyzed cows’ milk protein formulas are more suitable

for treatment of CMPI but are rather unpalatable (to

mothers anyway), not available in supermarkets in

the UK, and costly.

0040 Tolerance to cows’ milk protein usually develops as

children move into the second or third year of life.

Eczema

0041 The extent to which food intolerance is relevant to

the development of infantile eczema remains contro-

versial. Some infants with atopic eczema show signifi-

cant improvement in their skin problem when all milk

products are withdrawn from the diet. Others only

improve when put on very restricted lists of foods.

Studies of infants with familial high risk of atopic

eczema suggest that eczema may be prevented in

some infants by exclusive breast-feeding for the first

6 months of life. Moreover, exclusively breast-fed

infants who do develop eczema may have become

sensitized to foreign proteins transferred through the

breast milk.

Other Food Allergens

0042Other food allergies are quite common in infancy,

especially in those with an atopic family history.

Common precipitants are egg protein, citrus fruits,

nuts (not advised for young children anyway because

of the risks of inhalation), and the food colorants

tartrazine and quinoline yellow. Diarrhea, vomiting,

rashes, wheezing and – rarely – behavioral disturb-

ances may occur. (Most behavioral problems are dis-

ciplinary rather than allergic.) The pattern of

response in each child is usually repeated on subse-

quent contact with the allergen but there is great

variation in the pattern of individual responses.

Colic

0043Around 3 months of age healthy infants often develop

bouts of fractiousness and inconsolable crying, usu-

ally in the early evening. Their abdomens become

tight and distended, probably because of the air swal-

lowed whilst crying. Infants tend to flex their legs

when crying and this may be interpreted as abdom-

inal pain. ‘Three-month colic’ is an ill-defined prob-

lem with a wide range of symptomatology. In the long

term, colic resolves without specific treatment. It may

be a behavioral rather than a medical problem.

Nevertheless, it causes great distress to the child and

parents. Removal of cows’ milk formula and substi-

tution with nonallergenic formula or soya protein

formula has sometimes been associated with im-

provement. However it is difficult to know if this

has anything to do with resolution of symptoms in a

benign self-limiting condition.

Cot Death: Sudden Infant Death

Syndrome

0044Sudden unexpected infant death (SUID) affects about

1 in 500 infants in the UK. The condition is of mixed

etiology, since detailed history and autopsy reveal cause

of death or evidence of illness in many of the infants.

There remains a group of SUID infants for whom

detailed investigation shows no adequate explanation

for death. These are the cases of true ‘sudden infant

death syndrome’ (SIDS). In the past, anaphylactic

shock from acute CMPI was sometimes cited as pos-

sible etiology for SIDS since SUID is more common in

formula- than in breast-fed infants. Some infants have

postmortem evidence of milk/formula in the respira-

tory tract, perhaps as a terminal event. However, true

SIDS is probably not more common in formula-fed

INFANTS/Feeding Problems 3305

than breast-fed infants. It now seems likely that a major

component of death in SIDS relates to impaired cardi-

orespiratory arousal. Putting infants to sleep supine,

rather than prone or on their sides, has reduced SIDS

by about 35% in many countries.

0045 Another nutritional explanation proffered for

some forms of SUID is undiagnosed inborn errors of

metabolism involving inhibition of breakdown of

long-chain fatty acids. Children with inborn errors

of this kind are unable to metabolize fats to cope

with the stress of fasting and die of hypoglycemia.

Postmortem examination reveals acute fatty degener-

ation of the liver. In such very rare cases, SUID may be

familial since inborn errors of metabolism involving

fatty acid breakdwon are inherited, usually by auto-

somal recessive genes.

Teething Problems

0046 Teeth are erupting more or less continuously between

6 and 30 months. Teething children may show exces-

sive salivation, gingival swelling, and general irrit-

ability. These symptoms may exacerbate existing

illness but there is no evidence that teething causes

fever or diarrhea. Rubbing the gums with cool cloths

or giving infants firm objects to bite may reduce

teething discomfort.

0047 Most children develop their first teeth around 6

months of age but some do not develop teeth until

around 2 years. Late tooth erupters usually cope well

with chewing and should be encouraged to progress

in the weaning process in the normal way.

Nursing Bottle Syndrome: Rampant Caries in

Infancy

0048 Nursing bottle syndrome is the rampant carious de-

struction of the upper incisors in young children.

Although associated with offering bottles of juice/

milk or pacifiers sweetened with sugary solutions to

infants when they are ready to sleep, rampant caries

in this age group probably also reflects underlying

enamel hypoplasia in the primary teeth which is

secondary to prematurity or to maternal nutritional

deficiencies in pregnancy.

0049 Constant bathing of upper incisors with sugary

fluids, together with reduced salivary secretion and

reduced mouth movements at night, encourages the

development of plaque. Streptococcus mutans, which

survives well at low pH, collects under plaque and

adheres to tooth enamel. Enamel is eroded, allowing

opportunity for further tooth infection by other bac-

teria. Excessive vomiting, by creating an acid environ-

ment in the mouth, may contribute to the risk. Teeth

in the front of the upper jaw are reduced to carious

discolored stumps. Children may become faddy

eaters due to the discomfort of chewing meat and

biting vegetables and fruit.

0050Fluoridation of water supplies with one part per

million of fluoride protects against dental caries. If

water is not fluoridated, children can be supple-

mented with fluoride 1.25 mg day

1

in infancy and

1.5 mg day

1

between 1 and 3 years. Regular, at least

daily, tooth brushing should be taught from the first

appearance of teeth. Adults should supervise loading

children’s toothbrushes with small pea-sized lumps of

toothpaste since small children may eat toothpaste

rather than spit it out after cleaning their teeth. As

much as 1.66 mg of fluoride could be consumed by

small children brushing their teeth inexpertly twice

a day with fluoridated toothpaste.

0051All food, and particularly sweetened drinks, should

be discouraged after tooth brushing at night.

See also: Anemia (Anaemia): Iron-deficiency Anemia;

Cholecalciferol: Properties and Determination, Dental

Disease: Etiology of Dental Caries; Food Intolerance:

Types; Growth and Development; Inborn Errors of

Metabolism: Overview; Malnutrition: The Problem of

Malnutrition; Preterm Infants – Nutritional

Requirements and Management; Tocopherols:

Properties and Determination; Vegetarian Diets

Further Reading

Department of Health (1994) Weaning and the Weaning

Diet. Report on Health and Social Subjects, no. 45.

London: Her Majesty’s Stationery Office.

Hunt CE (2000) Sudden infant death syndrome. In:

Behrman RE, Kliegman RM and Jenson HB (eds)

Nelson’s Textbook of Pediatrics, 16th edn, pp.

2139–2143. Philadelphia: WB Saunders.

Filer LJ, Jr. (ed) (1989) Dietary Iron. Birth to Two Years.

New York: Raven Press.

Johnson D and Tinanoff N (2000) Dental caries. In: Behr-

man RE, Kliegman RM and Jenson HB (eds) Nelson’s

Textbook of Pediatrics, 16th edn, pp. 1114–1116.

Philadelphia: WB Saunders.

Simeon DT and Grantham-McGregor SM (1991) Nutri-

tional deficiencies and children’s behaviour and mental

development. Nutrition Reviews 3: 1–24.

Skuse D, Reilly S and Wolfe D (1994) Psychosocial adver-

sity and growth during infancy. European Journal of

Clinical Nutrition 48 (suppl. 1): S113–S130.

Standing Committee on Nutrition, British Paediatric Asso-

ciation (1988) Vegetarian weaning. Archives of Disease

in Childhood 63: 470–478.

Stevenson RD and Allaire JH (1991) The development of

normal feeding and swallowing. Pediatric Clinics of

North America 38: 1439–1453.

Walker-Smith J and Murch S (1999) Toddler diarrhoea. In:

Diseases of the Small Intestine in Childhood, 4th edn,

pp. 364–366. Oxford: Isis Medical Media.

Widdowson EM (1947) Mental contentment and physical

growth. Lancet i: 1316–1318.

3306 INFANTS/Feeding Problems

INFECTION, FEVER, AND NUTRITION

C J Field, University of Alberta, Edmonton, Alberta,

Canada

Background

0001 Infection is a broad term that encompasses a number

of pathological situations initiated by invasion of in-

fectious organisms. An effort to reduce the number of

infectious incidences is a primary focus for those who

work in public health but also for those who work in

the clinical setting. Infections are responsible for

worsening the nutritional status of patients, doubling

the length of hospital stay, increasing the number of

medical and surgical procedures required, delaying

the provision of adjuvant therapies, and significantly

reducing patients’ quality of life. This article will

briefly review the immune response/role in infection

and fever, the importance of nutrition to the immune

system, and the role of nutrition and specific nutrients

on the response to fever and infection.

The Immune Response to Infection

0002 The immune system (cells and molecules responsible

for immunity) is defined as part of the host’s defense

against destructive forces from outside the body (i.e.,

bacteria, viruses, and parasites) and those from

within, such as malignant and autoreactive cells.

Appropriate interactions between the different cells

of the immune system are necessary to eliminate

infectious organisms (Table 1). The purpose is to

disadvantage and destroy invading organisms, while

protecting healthy tissue from the damaging

influences of the compounds produced during the

response. Cytokines and other compounds play a

central role orchestrating the immune response to

infectious organisms. However, the proinflammatory

cytokines and other molecules produced during

the inflammatory response also pose a danger to the

host. The host response (cytokines and acute phase

response) designed to fight infection is partially

responsible for a serious and life-threatening meta-

bolic condition called sepsis. Sepsis is characterized

by an unregulated host inflammatory response and

the presence of bacteria (though primary invasion or

secondary to other infections) or their products in the

bloodstream.

The Innate Immune System and Infection

0003The innate immune system comprises defenses that

are present early in life that function without

depending on previous exposure to a particular

pathogen, thereby providing the first line of defense

that protects the host during the 4–5 days it takes

for lymphocytes in the acquired immune system to

become activated. The major components of the

innate immunity are illustrated in Figure 1. The resist-

ance to bacterial invasions is thought to depend

primarily on nonT-cell branches of immunity such

as physical barriers (skin and mucous membranes),

tbl0001 Table 1 Immune responses to some common infectious agents

Infection type Examples Immuneresponse

Viruses HIV, influenza, rhinovirus

Humoral immune system blocks initial infection and recruits

other immune cells

Cell-mediated response is most effective at destroying cells

once infected with virus

Parasites Tr i c h in e ll a , Helminths

Low immune response, as there is no of the infectious agent

inside the host’s cells

May be some humoral and inflammatory response from B-cells

and macrophages/neutrophils near the invasion site

Protozoa Malaria

Bloodborne protozoa are destroyed by B-cell antibodies

Once cells are infected, cells are destroyed by cell-mediated

functions

Intracellular bacteria Listeria monocytogenes,

Mycobacterium tuberculosis

Cell-mediated, delayed-type hypersensitivity response

important in destroying intracellular bacteria

Stimulates a type-2 helper T-cell response (pattern of

cytokines)

Extracellular bacteria Streptococcus pneumoniae

Humoral immune system (located in lymphoid tissues

throughout the body) secretes antibodies

Sepsis (systemic inflammatory

response system)

Endotoxin, lipopolysaccharides

Caused by a dysregulated inflammatory response to an

infectious agent

INFECTION, FEVER, AND NUTRITION 3307

neutrophils, macrophages, complement, and acute

phase proteins. If infectious organisms penetrate this

barrier, the innate immune system responds immedi-

ately by activating the acquired immune system. If the

pathogens are bloodborne, the reticuloendothelial

system becomes involved.

The Acquired Immune System and Infection

0004 The acquired (or adaptive) immune response de-

velops over one’s lifetime in response to environ-

mental challenges (pathogens/antigens). The cells

that comprise the acquired immune defense are illus-

trated in Figure 2. T- and B-lymphocytes (cells) are the

primary cells of this arm of immune system. The T-

cell population is divided into two basic subsets CD4

(helper/inducer) and CD8 (cytotoxic/suppressor)

cells. T-cells play multiple roles functions including

providing help to B-cells, stimulating the inflamma-

tory response, maintaining antigen-specific memory

and producing cytokines. Once activated, some

T-cells can directly destroy cells (via cytotoxic killing)

infected with intracellular pathogens. B-cells produce

and secrete antibodies for the elimination of extracel-

lular pathogens and parasites. B-cells can also serve as

antigen-presenting cells and activate T-cells.

The Mucosal Associated Lymphoid Tissue

0005 Mucosal tissues (contain components of both the

innate and acquired immune system) are strategically

located in areas where external pathogens enter the

body. Immune cells that reside in mucosal tissues

protect against the entry of infectious agents. The

immune responses arising in these regions must be

very selective so as to avoid mucosal damage that

would impair functions such as gas exchange (lungs).

The gastrointestinal system serves as a primary reser-

voir for bacteria that have the potential, if not prop-

erly controlled, to induce life-threatening infections.

A vast immune system exists in the gastrointestinal

tract with immune cells located in intraepithelial and

lamina propria regions of the gut and in specialized

lymph tissues, Peyer’s patches, lining the large and

small intestine. The main defense in the gut comes

from the large number of activated B-cells present in

the lamina propria region that secrete IgA.

Mediators of the Immune System

0006The response of immune cells to infectious agents is

mediated by a number of compounds. Cytokines are

glycoproteins that are secreted by immune and other

cell types and are a means of communication between

cells of the immune system and with other cells in the

body. The localized concentration of various cyto-

kines will determine what immune cells are activated.

T-helper cells type 1 cells (Th1 CD4þ cells) produce

interleukin (IL)-2 and interferon-g (IFN-g), which

generally promote a cell-mediated inflammatory re-

sponse. Th2-type CD4þ cells produce IL-4, IL-5, IL-

10, and IL-13, which support a humoral antibody

response. It has been hypothesized that the balance

of these cytokines offers a mechanism by which the

immune system can respond appropriately to a

specific type of infection.

0007Other important mediators of immune function

include epinephrine, glucagon, and cortisol, which

are released in response to stress and infection.

These hormones have been shown to have immuno-

suppressive effects on immune cells. Lipid-derived

factors such as eicosanoids, leukotrienes, and plate-

let-activating factor, made by a variety of cell types in

response to cytokines and other signals, also modu-

late immune function. When tissue is injured during

infection, the complement cascade is activated, and

fibronectin, vasoactive amines, and chemoattractants

are released. The complement cascade is important in

mediating inflammation and promoting phagocytosis

of microorganisms. Nitric oxide is a potent immuno-

biological compound produced by macrophages and

neutrophils to combat intracellular pathogens (i.e.,

parasitic fungi, protozoa, helminths, and mycobac-

teria) and viruses.

Fever

0008Fever is a host response that is characterized by an

elevation of core body temperature. The most

Cellular components

Phagocytes Natural killer

cells

Mucous

membranes

Skin

Physical barriers

Reticuloendothelial

system

NeutrophilsMacrophages

(activated

monocytes)

fig0001 Figure 1 Defenses of the innate immune system.

Cell-mediated

CD4

helper/inducer

T lymphocytes

CD8

cytotoxic/suppressor

T lymphocytes

Humoral

B-lymphocytes

(plasma cells)

Antibody production

(extracellular bacteria)

T helper type 1 T helper type 2

Delayed type hypersensitivity

response

(intracellular bacteria)

fig0002 Figure 2 Defenses of the acquired immune system.

3308 INFECTION, FEVER, AND NUTRITION

frequent cause of fever in acutely ill patients is infec-

tion (by bacteria, viruses, and/or their toxins). In most

cases, fever is initiated by the production of cytokines

(IL-1, IL-6, tumor necrosis factor (TNF)-a) from

macrophages and neutrophils. In general, it is be-

lieved that proinflammatory cytokines stimulate the

production of arachidonic acid metabolites (PGE

and thromboxane A

), which affect the temperature-

regulating areas in the brain (hypothalamus, me-

dulla). Subsequently, the brain signals mechanisms

that generate heat and reduce heat loss, thus increas-

ing core body temperature.

0009 It is widely accepted that fever has three distinct

phases. The first is known as the chill phase where the

individual experiences shivering and feeling cold. The

second phase is a plateau phase when the thermo-

static set point and body temperature are at the

same level. This is followed by a third phase known

as ‘defervescence’ when the fever ‘breaks,’ resulting in

flushing and sweating. This increase in body tempera-

ture is important as it increases the speed at which

neutrophils move and secrete antibacterial sub-

stances, increases B-cell and T-cell replication, and

results in a higher production of IFN-g (antiviral

and antibacterial properties). High fever, however, is

clearly maladaptive to the host resulting in loss of

appetite, increased sleepiness, muscle aches, and

hypermetabolism. Resting energy expenditure rises

by as much as 10–15% for each degree Celsius

increase in body temperature.

Interaction Between Nutrition, Infection

and the Immune System

0010 In children and adults with marginal or poor nutri-

tional status, episodes of infectious diseases are more

severe and result in more complications. Almost any

nutrient deficiency, if sufficiently severe, will impair

resistance to infection. The impact of infection on

nutritional status depends on the previous nutritional

health of the individual, the nature and duration of

the infection, and the diet consumed during the

recovery period. Thus, infections themselves promote

malnutrition (appetite loss and anorexia, malabsorp-

tion, and elevated metabolism of energy, and other

nutrients), creating a complex cycle of immunosup-

pression and worsened nutritional status. Worsened

nutritional status will then further suppress immunity

and predispose the individual to opportunistic infec-

tions (Figure 3).

0011The interaction between nutrition and infection is

complex. The physiological mechanisms responsible

for metabolic changes during infection are not

completely understood, although cytokines are clearly

involved. Some degree of appetite loss (anorexia) is

present during most infections. In some cases, this

anorexia is due to nausea and vomiting; in others,

gastrointestinal lesions. Additionally, the presence of

a fever can result in appetite loss (anorexia) resulting

in a 10–40% decrease in dietary intake, not only of

protein and energy but also of most nutrients. Anor-

exia will precipitate clinical nutrient deficiencies of

any nutrient in which body stores are limited. The

extent of the depletion of nutrient status will subse-

quently increase the risk of damage to the host’s

tissues from the inflammatory response. To sustain a

hypermetabolic rate (i.e., in fever), there is an acute

mobilization of endogenous energy stores (glucose

and fat). However, during infections, there is also an

impaired ability to use these substrates. If body stores

are used to provide for the metabolic needs of infec-

tion and fever, weight loss occurs. In fact, this sort of

observation led to the introduction of the lay-term

‘consumption’ to describe tuberculosis, the classic

chronic wasting infectious disease. The high preva-

lence of infections among children living in poor areas

of developing countries results in impaired linear

growth. In addition, the acute phase response (e.g.,

proinflamatory cytokine release) to fever directly

affects bone remodeling that is required for long

bone growth.

Nutrition and the Immune System

0012The past 25 years have resulted in an explosion of

scientific literature defining the role of specific nutri-

ents on immunity. Most host defenses are breached

in protein-energy malnutrition, particularly cell-

mediated immunity. It is now generally accepted

that nutrition is an important determinant of the

immune response. It appears that almost every

known nutrient deficiency can affect disease resist-

ance if it is sufficiently severe, and this may also be

true for many nutrients consumed in excess. Nutri-

tional state and specific nutrients may impact on the

immune system directly (e.g., triggering immune cell

activation, or altering immune cell interactions) or

INFECTION

Immune

suppression

IMPAIRED IMMUNITY

MALNUTRITION

Barrier function

Cell mediated immunity

Fever

anorexia

metabolism

fig0003 Figure 3 Relationship between malnutrition, immunity, and

infection.

INFECTION, FEVER, AND NUTRITION 3309